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Increased risk of meningioma with cyproterone acetate use
.
Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.
The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.
These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.
“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.
“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.
Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.
The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.
Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.
“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”
Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
Strong dose-effect relationship
For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.
All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).
Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.
When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.
In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.
However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.
Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.
“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”
“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
Use only when necessary
Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”
Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.
The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”
Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.
This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.
The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.
These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.
“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.
“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.
Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.
The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.
Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.
“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”
Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
Strong dose-effect relationship
For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.
All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).
Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.
When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.
In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.
However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.
Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.
“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”
“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
Use only when necessary
Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”
Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.
The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”
Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.
This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Cyproterone acetate is a synthetic progestogen and potent antiandrogen that has been used in the treatment of hirsutism, alopecia, early puberty, amenorrhea, acne, and prostate cancer, and has also been combined with an estrogen in hormone replacement therapy.
The new findings were published online in the BMJ. The primary analysis showed that, among women using cyproterone acetate, the rate of meningiomas was 23.8 per 100,000 person years vs. 4.5 per 100,000 in the control group. After adjusting for confounders, cyproterone acetate was associated with a sevenfold increased risk of meningioma.
These were young women – the mean age of participants was 29.4 years, and more than 40% of the cohort were younger than 25 years. The initial prescriber was a gynecologist for more than half (56.7%) of the participants, and 31.6% of prescriptions could correspond to the treatment of acne without hirsutism; 13.1% of prescriptions were compatible with management of hirsutism.
“Our study provides confirmation of the risk but also the measurement of the dose-effect relationship, the decrease in the risk after stopping use, and the preferential anatomical localization of meningiomas,” said lead author Alain Weill, MD, EPI-PHARE Scientific Interest Group, Saint-Denis, France.
“A large proportion of meningiomas involve the skull base, which is of considerable importance because skull base meningioma surgery is one of the most challenging forms of surgery and is associated with a much higher risk than surgery for convexity meningiomas,” he said in an interview.
Cyproterone acetate products have been available in Europe since the 1970s under various trade names and dose strengths (1, 2, 10, 50, and 100 mg), and marketed for various indications. These products are also marketed in many other industrialized nations, but not in the United States or Japan.
The link between cyproterone acetate and an increased risk of meningioma has been known for the past decade, and information on the risk of meningioma is already included in the prescribing information for cyproterone products.
Last year, the European Medicines Agency strengthened the warnings that were already in place and recommended that cyproterone products with daily doses of 10 mg or more be restricted because of the risk of developing meningioma.
“The recommendation from the EMA is a direct consequence of our study, that was sent to the EMA in summary form in 2018 and followed up with a very detailed with a report in summer 2019,” said Dr. Weill. “In light of this report, the European Medicines Agency recommended in February 2020 that drugs containing 10 mg or more of cyproterone acetate should only be used for hirsutism, androgenic alopecia, and acne and seborrhea once other treatment options have failed, including treatment with lower doses.”
Dr. Weill pointed out that two other epidemiologic studies have assessed the link between cyproterone acetate use and meningioma and showed an association. “Those studies and our own study are complementary and provide a coherent set of epidemiological evidence,” he said in the interview. “They show a documented risk for high-dose cyproterone acetate in men, women, and transgender people, and the absence of any observed risk for low-dose cyproterone acetate use in women.”
Strong dose-effect relationship
For their study, Dr. Weill and colleagues used data from the French administrative health care database. Between 2007 and 2014, 253,777 girls and women aged 7-70 years had begun using cyproterone acetate during that time period.
All participants had received at least one prescription for high-dose cyproterone acetate and did not have a history of meningioma, benign brain tumors, or long-term disease. They were considered to be exposed if they had received a cumulative dose of at least 3 g during the first 6 months (139,222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114,555 participants).
Overall, a total of 69 meningiomas were diagnosed in the exposed group (during 289,544 person years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up). All were treated by surgery or radiotherapy.
When the analysis was done according to the cumulative dose, it showed a dose-effect relation, with a higher risk associated with a higher cumulative dose. The hazard ratio was not significant for exposure to less than 12 g of cyproterone acetate, but it jumped rapidly jumped as the dose climbed: The hazard ratio was 11.3 for 36-60 g and was 21.7 for 60 g or higher.
In a secondary analysis, the authors looked at the cohort who were already using cyproterone acetate in 2006 (n = 123,997). Women with long-term exposure were also taking estrogens more often (55.5% vs. 31.9%), and the incidence of meningioma in the exposed group was 141 per 100,000 person years, which was a risk greater than 20-fold (adjusted hazard ratio 21.2.) They also observed a strong dose-effect relationship, with adjusted hazard ratio ranging from 5.0 to 31.1.
However, the risk of meningioma decreased noticeably after treatment was stopped. At 1 year after discontinuing treatment, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.
Dr. Weill noted the clinical implications of these findings: clinicians need to inform patients who have used high-dose cyproterone acetate for at least 3-5 years about the increased risk of intracranial meningioma, he said.
“The indication of cyproterone acetate should be clearly defined and the lowest possible daily dose used,” he said. “In the context of prolonged use of high-dose cyproterone acetate, magnetic resonance imaging screening for meningioma should be considered.”
“In patients with a documented meningioma, cyproterone acetate should be discontinued because the meningioma might regress in response to treatment discontinuation and invasive treatment could be avoided,” Dr. Weill added.
Use only when necessary
Weighing in on the research, Adilia Hormigo, MD, PhD, director of neuro-oncology at The Tisch Cancer Institute at Mount Sinai Health System in New York, noted that, “it is well known that there are sex differences in the incidence of meningiomas, as they are more frequent in women than men, and there is an association between breast cancer and the occurrence of meningiomas.”
Progesterone and androgen receptors have been found in meningiomas, she said in an interview, and there is no consensus regarding estrogen receptors. “In addition, hormonal therapy to inhibit estrogen or progesterone receptors has not produced any decrease in meningiomas’ growth,” she said.
The current study revealed an association between prolonged use of cyproterone acetate with an increased incidence of meningiomas, and the sphenoid-orbital meningioma location was specific for the drug use. “It is unclear from the study if all the meningiomas were benign,” she said. “Even if they are benign, they can cause severe morbidity, including seizures.”
Dr. Hormigo recommended that an MRI be performed on any patient who is taking a long course of cyproterone acetate in order to evaluate the development of meningiomas or meningioma progression. “And the drug should only be used when necessary,” she added.
This research was funded by the French National Health Insurance Fund and the Health Product Epidemiology Scientific Interest Group. Dr. Weill is an employee of the French National Health Insurance Fund, as are several other coauthors. The other authors have disclosed no relevant financial relationships. Dr. Hormigo has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Novel blood test detects precancerous colorectal adenomas
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Shaukat has relationships with Freenome and Iterative Scopes.
Help your patients understand colorectal cancer prevention, and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
A version of this article first appeared on Medscape.com.
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Shaukat has relationships with Freenome and Iterative Scopes.
Help your patients understand colorectal cancer prevention, and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
A version of this article first appeared on Medscape.com.
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Shaukat has relationships with Freenome and Iterative Scopes.
Help your patients understand colorectal cancer prevention, and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.
A version of this article first appeared on Medscape.com.
High cost of pancreatic enzymes a barrier for patients with cancer
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.
“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.
This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.
In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.
“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.
Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.
The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).
The findings were presented at the 2021 Gastrointestinal Cancers Symposium.
Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”
These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.
One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
Study details
For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.
Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.
Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.
The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.
Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”
Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”
The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”
The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
First mammography guidelines for older breast cancer survivors
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
Novel blood test detects precancerous colorectal adenomas
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.
This article was updated 2/2/21.
A version of this article first appeared on Medscape.com.
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.
This article was updated 2/2/21.
A version of this article first appeared on Medscape.com.
A novel blood test has shown promise for colorectal cancer screening.
The “multiomics” test, under development by Freenome, has previously been shown to detect early-stage (I/II) colorectal cancer with a sensitivity of 94% and a specificity of 94%.
A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (AAs).
“The ability to detect advanced adenomas is incredibly important because we can remove them before they become cancerous,” senior author Aasma Shaukat, MD, MPH, chief of gastroenterology at Minneapolis VA Health Care System and professor of medicine at the University of Minnesota, Minneapolis, said in a statement.
At the Gastrointestinal Cancers Symposium 2021, she presented data showing that the novel test was able to detect AAs with a sensitivity of 41% and a specificity of 90%.
This sensitivity of the new test is better than or similar to that of currently available stool tests, noted study author C. Jimmy Lin, MD, PhD, MHS, chief scientific officer at Freenome.
The new test had almost double the sensitivity for detecting AAs (41% vs. 24%) as the fecal immunochemical test (FIT), and its sensitivity was comparable to that of FIT-DNA testing (41% vs. 42%).
In addition, it showed much higher sensitivity (41% vs 22%) for detecting AAs than the Epi proColon, a screening blood test that has been approved by the U.S. Food and Drug Administration for detecting methylated septin 9 DNA (mSEPT9).
“What’s special about our company is ... that we use a multinomic technology, meaning we look at DNA, RNA, protein, and other biomarkers – all of these things together,” Dr. Lin told this news organization.
Their platform integrates assays for circulating free DNA, methylation, and proteins using advanced computational biology and machine-learning techniques, which provide a multidimensional view of both tumor- and immune-derived signatures that enable the early detection of cancer.
In contrast to other blood tests that are under development for cancer screening, some of which claim to detect several common cancer types, Freenome is focusing on only colorectal cancer. “There are other companies in the early-detection space, but some of them are doing multicancer screening and have a generalized product,” said Dr. Lin. “Our approach is to focus on a specific cancer type, and we are beginning with colorectal cancer screening, and then will expand to other types.”
Better sensitivity
The study that was presented at the meeting evaluated the novel multiomics blood test for AA detection.
Blood samples were obtained from participants in the AI-EMERGE study, a prospective, multicenter study that included primarily average-risk screening patients from 30 clinical sites in the United States and Canada. The study included a total of 542 samples, including 122 histopathologically confirmed AAs and 420 colonoscopy-confirmed negative control samples.
AA sensitivity of the novel test was greater than that with the mSEPT9 test, which is the only blood test currently available for colorectal cancer screening. The new test’s sensitivity was much higher than that of FIT and was comparable to that of FIT-DNA. Sensitivity increased with increasing lesion size and was consistent across location and histology except for serrated lesions, the authors noted in the abstract.
“By combining signatures from both tumor and non–tumor-derived sources, our multiomics signatures detect twice as many AAs as methylation only or single-protein approaches,” Dr. Lin said. “And we have now shown that sensitive AA detection at a level similar to or better than currently available stool tests is achievable in blood, which is necessary for effective early detection and prevention of colorectal cancers.”
The company has begun the regulatory process for having the test approved by the FDA. The company’s goal is to enroll 14,000 participants and have prospectively collected data.
The research was funded by Freenome. Dr. Lin is the chief scientific officer at Freenome and has relationships with Labroots, Natera, and Neon Therapeutics. Dr. Shaukat has relationships with Freenome and Iterative Scopes.
This article was updated 2/2/21.
A version of this article first appeared on Medscape.com.
No benefit seen with radiotherapy in borderline resectable pancreatic cancer
Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.
Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.
This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.
These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.
“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.
Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.
The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.
The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).
Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.
In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours).
The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.
“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”
At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.
The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.
For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.
“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
Further investigation needed
The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.
She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.
“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.
“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.
She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”
The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.
The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.
Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.
This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.
These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.
“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.
Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.
The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.
The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).
Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.
In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours).
The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.
“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”
At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.
The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.
For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.
“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
Further investigation needed
The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.
She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.
“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.
“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.
She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”
The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.
The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are often treated with chemotherapy, radiotherapy, or both before undergoing surgery, but the optimal regimen in this setting is controversial.
Results from the Alliance A021501 study suggest the reference regimen should be neoadjuvant therapy with modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours), according to Matthew Katz, MD, FACS, chief of the pancreatic surgery service at the University of Texas MD Anderson Cancer Center, Houston.
This regimen improved survival for patients with PDAC, relative to historical data. For patients who received mFOLFIRINOX, the overall 18-month survival rate was 66.4%. However, when this regimen was combined with hypofractionated radiotherapy, the survival benefit was significantly lower, at 47.3%.
These findings were presented at the 2021 Gastrointestinal Cancers Symposium (GICS), which was held online this year.
“ASCO guidelines recommend that preoperative therapy be administered to patients with localized pancreatic adenocarcinoma who have tumors that have a significant radiographic interface with the major mesenteric blood vessels, as these patients are at high risk for a margin-positive operation and short survival when pancreatectomy is performed de novo,” Dr. Katz explained.
Although both chemotherapy and radiotherapy are used in these patients, there is no consensus as to the best approach, he commented.
The goal of Alliance A021501 “was to define a reference preoperative regimen for future trials of preoperative therapy,” he said.
The cohort included 126 patients who were randomly assigned to receive either mFOLFIRINOX (arm A) or mFOLFIRINOX plus radiotherapy (arm B).
Patients in arm A received eight cycles of neoadjuvant mFOLFIRINOX. Patients in arm B received seven cycles of mFOLFIRINOX followed by 5 days of hypofractionated radiotherapy with either stereotactic body radiotherapy or hypofractionated image-guided radiotherapy.
In either arm, patients who did not experience disease progression underwent pancreatectomy followed by four cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and infusional 5-fluorouracil 2,400 mg/m2 over 46 hours).
The study’s primary endpoint was 18-month overall survival in comparison to a historical control of 50%. “An interim futility analysis was scheduled to be conducted following treatment of 30 patients on each arm,” Dr. Katz said. “Either arm in which 11 or fewer patients underwent [curative] R0 resection on protocol was to be declared futile and closed to further enrollment.
“With 62 evaluable patients in each arm, the final efficacy analysis was powered to detect an improvement in 18-month overall survival of 13% over the historical rate of 50%,” said Dr. Katz. “The two arms would be compared only if both were declared efficacious.”
At the interim analysis, 57% of the first 30 patients in arm A had undergone a resection, vs. 33% in arm B. Therefore, arm B was considered futile and was closed to accrual.
The median overall survival in arm A was 29.8 months. The median event-free survival was 15 months. Nearly half (49%) of patients proceeded to pancreatectomy following neoadjuvant therapy. The R0 resection rate was 88%, the pathologic complete response rate was 0%, and the 18-month overall survival rate was 93.1%.
For the patients in arm B, which had been closed to accrual, the median overall survival was 17.1 months, and the median event-free survival was 10.2 months. About one-third (35%) of patients were able to proceed to pancreatectomy. The R0 resection rate was 74%, the pathologic complete response rate was 11%, and the 18-month overall survival rate was 78.9%.
“Preoperative mFOLFIRINOX was associated with favorable overall survival relative to historical criteria in patients with borderline resectable PDAC, and mFOLFIRINOX with radiation therapy met the predefined futility boundary for R0 resection at interim analysis,” Dr. Katz concluded. “Therefore, mFOLFIRINOX represents a reference perioperative regimen for patients with borderline resectable PDAC.”
Further investigation needed
The paper’s discussant, Rebecca A. Snyder, MD, MPH, of the Brody School of Medicine, East Carolina University, Greenville, N.C., emphasized that this study was not designed or powered to directly compare chemotherapy alone with chemotherapy plus radiotherapy in the neoadjuvant setting.
She noted that it is surprising that the radiotherapy arm was closed early. She said the reasons for this remain unclear, although a few possible reasons can be speculated.
“Based on multiple studies in both the adjuvant and neoadjuvant setting, including the Alliance [A021501] trial presented today, there is no convincing randomized data that radiation therapy prolongs survival in any population of unselected patients with pancreatic cancer,” said Dr. Snyder.
“Certainly, follow-up questions still remain, specifically regarding the role for non-SBRT radiation in the preoperative setting, which may be answered by the ongoing PREOPANC-2 and PRODIGE 44 trials,” she said.
She added that the “addition of SBRT in the preoperative setting does not appear to be justified.”
The role of radiotherapy for subsets of patients remains unknown, and future investigation should focus on patient-centered endpoints, such as symptomatic local control rates, Dr. Snyder concluded.
The study was funded by the National Institutes of Health. Dr. Katz has had a consulting or advisory role for AbbVie and Alcresta Therapeutics. Dr. Snyder has disclosed no relevant financial relationships.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Better survival with S-1 plus docetaxel in stage III gastric cancer
A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.
, say the researchers.
The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.
“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”
Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
S-1 widely used in Asia
S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.
“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.
The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.
The data presented at the meeting are the final results from GC-07. They confirm earlier data.
Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.
That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).
Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).
At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.
In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).
No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).
However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.
The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.
However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.
“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.
She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.
“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.
The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.
A version of this article first appeared on Medscape.com.
A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.
, say the researchers.
The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.
“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”
Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
S-1 widely used in Asia
S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.
“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.
The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.
The data presented at the meeting are the final results from GC-07. They confirm earlier data.
Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.
That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).
Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).
At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.
In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).
No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).
However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.
The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.
However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.
“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.
She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.
“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.
The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.
A version of this article first appeared on Medscape.com.
A new recommendation for the treatment of patients with gastric cancer has been proposed on the basis of final results from the phase 3 trial GC-07, which showed survival benefit. The trial was conducted by the Japan Clinical Cancer Research Organization.
, say the researchers.
The 3-year relapse-free survival (RFS) and 3-year overall survival rates were significantly superior among patients treated with S-1/docetaxel, compared with those treated with S-1 alone, commented lead study author Kazuhiro Yoshida, PhD, MD, director of Gifu University Hospital and professor and chairman of the department of surgical oncology, Gifu (Japan) University.
“The study met its primary endpoint and improved the RFS [recurrence-free survival],” he said. “Postoperative S-1 plus docetaxel was safe and manageable.”
Dr. Yoshida presented the updated findings of the GC-07 trial at the Gastrointestinal Cancers Symposium (GICS) 2021, which was held online this year.
S-1 widely used in Asia
S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine. The drug, which is a biochemical modulation of 5-fluorouracil, comprises tegafur and two types of enzyme inhibitor. It is widely used to treat various solid tumors in Asia.
“S1 is a standard postoperative adjuvant chemotherapy for patients with p-stage II/III gastric cancer in Asia,” said Dr. Yoshida, but the “outcome in p-stage III is unsatisfactory,” he added.
The GC-07 trial set out to further investigate the use of this drug in this patient population. Dr. Yoshida and colleagues included 915 patients with stage III gastric cancer who had undergone R0 resection and D2 lymphadenectomy and who tested negative on peritoneal-washing cytology. The patients were randomly assigned to receive either S-1 plus docetaxel or S-1 alone for up to 1 year in the postoperative setting.
The data presented at the meeting are the final results from GC-07. They confirm earlier data.
Previously, a second interim analysis showed that the trial had met its primary endpoint. As a result of that analysis, the study was terminated.
That interim analysis showed that the 3-year RFS of the S-1/docetaxel arm was significantly superior to that of the S-1 arm (65.9% vs. 49.6%; hazard ratio, 0.632; P = .0007).
Now, the final results, at a median follow-up of 48.2 months, show that there were 400 recurrences and 324 deaths. The 3-year RFS was 67.7% in the S-1/docetaxel group, which was significantly superior to the 57.4% reported in the S-1 group (HR, 0.715; P = .0008). Similarly, 3-year overall survival was 77.7% in the S-1/docetaxel group, vs. 71.2% in the S-1 group (HR, 0.742; P = .0076).
At 12 months, 62.7% of patients in the S-1 group had experienced treatment failure, compared with 56.2% in the combination-therapy group.
In addition to reducing overall relapse, treatment with combination therapy also decreased the incidence of relapse at specific sites, compared with S-1 alone. These included reductions in lymphatic recurrence (6.4% vs. 15.0%), hematogenous recurrence (9.7% vs. 15.5%), local recurrence (2.9% vs. 4.4%), and peritoneal recurrence (18.8% vs. 21.4%).
No new safety signals were observed, Dr. Yoshida commented. Grade 3/4 adverse events that occurred more frequently with S-1/docetaxel than with S-1 alone included neutropenia (39.2% vs. 16.4%), leukopenia (22.4% vs. 2.7%), and febrile neutropenia (5.7% vs. 0.4%).
However, the authors noted that, in a subgroup analysis, patients with stage IIIB disease did not derive the same benefit in RFS and overall survival with combination therapy as the patients with stage IIIA or IIIC disease.
The discussant for this paper, Rutika Mehta, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., highlighted differences in benefit among the subgroups, as well as the finding that patients with stage IIIB appeared to benefit less.
However, she noted that the seventh edition of the American Joint Committee on Cancer TNM classification, which distinguishes patients on the basis of prognostic subgroups, is inaccurate for stage III disease, and this might have affected the study results. Dr. Mehta pointed to a previous analysis in which more than 33% of individuals with stage IIIB disease, determined in accordance with the seventh edition of the AJCC staging system, were reclassified as having stage IIIC disease, as determined using the more recent eighth edition.
“There were also few T2, N0, and N1 patients, making meaningful deductions in these subgroups not possible,” she said.
She said that despite these limitations, these “results are meaningful and impactful, and the combination of docetaxel and S-1 showed better RFS and overall survival than S-1 alone.
“These results do favor a new recommendation for the use of docetaxel plus S-1 for stage III gastric cancer patients after D2 lymphadenectomy,” she concluded.
The study was funded by the Japan Clinical Cancer Research Organization. Dr. Yoshida has received honoraria and research funding from many pharmaceutical companies, as listed in the abstract.
A version of this article first appeared on Medscape.com.
Gut microbiome may predict nivolumab efficacy in gastric cancer
Researchers have demonstrated bacterial invasion of the epithelial cell pathway in the gut microbiome and suggest that this could potentially become a novel biomarker.
“In addition, we found gastric cancer–specific gut microbiome predictive of responses to immune checkpoint inhibitors,” said study author Yu Sunakawa, MD, PhD, an associate professor in the department of clinical oncology at St. Marianna University, Kawasaki, Japan.
Dr. Sunakawa presented the study’s results at the 2021 Gastrointestinal Cancers Symposium.
The gut microbiome holds great interest as a potential biomarker for response. Previous studies suggested that it may hold the key to immunotherapy responses. The concept has been demonstrated in several studies involving patients with melanoma, but this is the first study in patients with gastric cancer.
Nivolumab monotherapy has been shown to provide a survival benefit with a manageable safety profile in previously treated patients with gastric cancer or gastroesophageal junction (GEJ) cancer, Dr. Sunakawa noted. However, fewer than half of patients responded to therapy.
“The disease control rate was about 40%, and many patients did not experience any tumor degradation,” he said. “About 60% of the patients did not respond to nivolumab as a late-line therapy.”
In the observational/translational DELIVER trial, investigators enrolled 501 patients with recurrent or metastatic adenocarcinoma of the stomach or GEJ. The patients were recruited from 50 sites in Japan.
The primary endpoint was the relationship between the genomic pathway in the gut microbiome and efficacy of nivolumab and whether there was progressive disease or not at the first evaluation, as determined in accordance with Response Evaluation Criteria in Solid Tumors criteria.
Genomic data were measured by genome shotgun sequence at a central laboratory. Biomarkers were analyzed by Wilcoxon rank sum test in the first 200 patients, who constituted the training cohort. The top 30 biomarker candidates were validated in the last 300 patients (the validation cohort) using the Bonferroni method.
Clinical and genomic data were available for 437 patients (87%). Of this group, 180 constituted the training cohort, and 257, the validation cohort.
The phylogenetic composition of common bacterial taxa was similar for both cohorts.
In the training cohort, 62.2% of patients had progressive disease, as did 53.2% in the validation cohort. The microbiome was more diverse among the patients who did not have progressive disease than among those who did have progressive disease.
The authors noted that, although there was no statistically significant pathway to be validated for a primary endpoint using the Bonferroni method, bacterial invasion of epithelial cells in the KEGG pathway was associated with clinical outcomes in both the training cohort (P = .057) and the validation cohort (P = .014). However, these pathways were not significantly associated with progressive disease after Bonferroni correction, a conservative test that adjusts for multiple comparisons.
An exploratory analysis of genus showed that Odoribacter and Veillonella species were associated with tumor response to nivolumab in both cohorts.
Dr. Sunakawa noted that biomarker analyses are ongoing. The researchers are investigating the relationships between microbiome and survival times, as well as other endpoints.
Still some gaps
In a discussion of the study, Jonathan Yeung, MD, PhD, of Princess Margaret Cancer Center, Toronto, congratulated the investigators on their study, noting that “the logistical hurdles must have been tremendous to obtain these data.”
However, Dr. Yeung pointed out some limitations and gaps in the data that were presented. For example, he found that the ratio of the training set to the validation set was unusual. “The training set is usually larger and usually an 80/20 ratio,” he said. “In their design, the validation set is larger, and I’m quite curious about their rationale.
“The conclusion of the study is that a more diverse microbiome was observed in patients with a tumor response than in those without a response,” he continued, “but they don’t actually show the statistical test used to make this conclusion. There is considerable overlap between the groups, and more compelling data are needed to make that conclusion.”
Another limitation was the marked imbalance in the number of patients whose condition responded to nivolumab in comparison with those whose condition did not (20 vs. 417 patients). This could have affected the statistical power of the study.
But overall, Dr. Yeung congratulated the authors for presenting a very impressive dataset. “The preliminary data are very interesting, and I look forward to the final results,” he said.
The study was funded by Ono Pharmaceutical and Bristol-Myers Squibb, which markets nivolumab. Dr. Sunakawa has received honoraria from Bayer Yakuhin, Bristol-Myers Squibb Japan, Chugai, Kyowa Hakko Kirin, Lilly Japan, Nippon Kayaku, Sanofi, Taiho, Takeda, and Yakult Honsha. He has held a consulting or advisory role for Bristol-Myers Squibb Japan, Daiichi Sankyo, and Takeda and has received research funding from Chugai Pharma, Daiichi Sankyo, Lilly Japan, Sanofi, Taiho Pharmaceutical, and Takeda. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Researchers have demonstrated bacterial invasion of the epithelial cell pathway in the gut microbiome and suggest that this could potentially become a novel biomarker.
“In addition, we found gastric cancer–specific gut microbiome predictive of responses to immune checkpoint inhibitors,” said study author Yu Sunakawa, MD, PhD, an associate professor in the department of clinical oncology at St. Marianna University, Kawasaki, Japan.
Dr. Sunakawa presented the study’s results at the 2021 Gastrointestinal Cancers Symposium.
The gut microbiome holds great interest as a potential biomarker for response. Previous studies suggested that it may hold the key to immunotherapy responses. The concept has been demonstrated in several studies involving patients with melanoma, but this is the first study in patients with gastric cancer.
Nivolumab monotherapy has been shown to provide a survival benefit with a manageable safety profile in previously treated patients with gastric cancer or gastroesophageal junction (GEJ) cancer, Dr. Sunakawa noted. However, fewer than half of patients responded to therapy.
“The disease control rate was about 40%, and many patients did not experience any tumor degradation,” he said. “About 60% of the patients did not respond to nivolumab as a late-line therapy.”
In the observational/translational DELIVER trial, investigators enrolled 501 patients with recurrent or metastatic adenocarcinoma of the stomach or GEJ. The patients were recruited from 50 sites in Japan.
The primary endpoint was the relationship between the genomic pathway in the gut microbiome and efficacy of nivolumab and whether there was progressive disease or not at the first evaluation, as determined in accordance with Response Evaluation Criteria in Solid Tumors criteria.
Genomic data were measured by genome shotgun sequence at a central laboratory. Biomarkers were analyzed by Wilcoxon rank sum test in the first 200 patients, who constituted the training cohort. The top 30 biomarker candidates were validated in the last 300 patients (the validation cohort) using the Bonferroni method.
Clinical and genomic data were available for 437 patients (87%). Of this group, 180 constituted the training cohort, and 257, the validation cohort.
The phylogenetic composition of common bacterial taxa was similar for both cohorts.
In the training cohort, 62.2% of patients had progressive disease, as did 53.2% in the validation cohort. The microbiome was more diverse among the patients who did not have progressive disease than among those who did have progressive disease.
The authors noted that, although there was no statistically significant pathway to be validated for a primary endpoint using the Bonferroni method, bacterial invasion of epithelial cells in the KEGG pathway was associated with clinical outcomes in both the training cohort (P = .057) and the validation cohort (P = .014). However, these pathways were not significantly associated with progressive disease after Bonferroni correction, a conservative test that adjusts for multiple comparisons.
An exploratory analysis of genus showed that Odoribacter and Veillonella species were associated with tumor response to nivolumab in both cohorts.
Dr. Sunakawa noted that biomarker analyses are ongoing. The researchers are investigating the relationships between microbiome and survival times, as well as other endpoints.
Still some gaps
In a discussion of the study, Jonathan Yeung, MD, PhD, of Princess Margaret Cancer Center, Toronto, congratulated the investigators on their study, noting that “the logistical hurdles must have been tremendous to obtain these data.”
However, Dr. Yeung pointed out some limitations and gaps in the data that were presented. For example, he found that the ratio of the training set to the validation set was unusual. “The training set is usually larger and usually an 80/20 ratio,” he said. “In their design, the validation set is larger, and I’m quite curious about their rationale.
“The conclusion of the study is that a more diverse microbiome was observed in patients with a tumor response than in those without a response,” he continued, “but they don’t actually show the statistical test used to make this conclusion. There is considerable overlap between the groups, and more compelling data are needed to make that conclusion.”
Another limitation was the marked imbalance in the number of patients whose condition responded to nivolumab in comparison with those whose condition did not (20 vs. 417 patients). This could have affected the statistical power of the study.
But overall, Dr. Yeung congratulated the authors for presenting a very impressive dataset. “The preliminary data are very interesting, and I look forward to the final results,” he said.
The study was funded by Ono Pharmaceutical and Bristol-Myers Squibb, which markets nivolumab. Dr. Sunakawa has received honoraria from Bayer Yakuhin, Bristol-Myers Squibb Japan, Chugai, Kyowa Hakko Kirin, Lilly Japan, Nippon Kayaku, Sanofi, Taiho, Takeda, and Yakult Honsha. He has held a consulting or advisory role for Bristol-Myers Squibb Japan, Daiichi Sankyo, and Takeda and has received research funding from Chugai Pharma, Daiichi Sankyo, Lilly Japan, Sanofi, Taiho Pharmaceutical, and Takeda. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Researchers have demonstrated bacterial invasion of the epithelial cell pathway in the gut microbiome and suggest that this could potentially become a novel biomarker.
“In addition, we found gastric cancer–specific gut microbiome predictive of responses to immune checkpoint inhibitors,” said study author Yu Sunakawa, MD, PhD, an associate professor in the department of clinical oncology at St. Marianna University, Kawasaki, Japan.
Dr. Sunakawa presented the study’s results at the 2021 Gastrointestinal Cancers Symposium.
The gut microbiome holds great interest as a potential biomarker for response. Previous studies suggested that it may hold the key to immunotherapy responses. The concept has been demonstrated in several studies involving patients with melanoma, but this is the first study in patients with gastric cancer.
Nivolumab monotherapy has been shown to provide a survival benefit with a manageable safety profile in previously treated patients with gastric cancer or gastroesophageal junction (GEJ) cancer, Dr. Sunakawa noted. However, fewer than half of patients responded to therapy.
“The disease control rate was about 40%, and many patients did not experience any tumor degradation,” he said. “About 60% of the patients did not respond to nivolumab as a late-line therapy.”
In the observational/translational DELIVER trial, investigators enrolled 501 patients with recurrent or metastatic adenocarcinoma of the stomach or GEJ. The patients were recruited from 50 sites in Japan.
The primary endpoint was the relationship between the genomic pathway in the gut microbiome and efficacy of nivolumab and whether there was progressive disease or not at the first evaluation, as determined in accordance with Response Evaluation Criteria in Solid Tumors criteria.
Genomic data were measured by genome shotgun sequence at a central laboratory. Biomarkers were analyzed by Wilcoxon rank sum test in the first 200 patients, who constituted the training cohort. The top 30 biomarker candidates were validated in the last 300 patients (the validation cohort) using the Bonferroni method.
Clinical and genomic data were available for 437 patients (87%). Of this group, 180 constituted the training cohort, and 257, the validation cohort.
The phylogenetic composition of common bacterial taxa was similar for both cohorts.
In the training cohort, 62.2% of patients had progressive disease, as did 53.2% in the validation cohort. The microbiome was more diverse among the patients who did not have progressive disease than among those who did have progressive disease.
The authors noted that, although there was no statistically significant pathway to be validated for a primary endpoint using the Bonferroni method, bacterial invasion of epithelial cells in the KEGG pathway was associated with clinical outcomes in both the training cohort (P = .057) and the validation cohort (P = .014). However, these pathways were not significantly associated with progressive disease after Bonferroni correction, a conservative test that adjusts for multiple comparisons.
An exploratory analysis of genus showed that Odoribacter and Veillonella species were associated with tumor response to nivolumab in both cohorts.
Dr. Sunakawa noted that biomarker analyses are ongoing. The researchers are investigating the relationships between microbiome and survival times, as well as other endpoints.
Still some gaps
In a discussion of the study, Jonathan Yeung, MD, PhD, of Princess Margaret Cancer Center, Toronto, congratulated the investigators on their study, noting that “the logistical hurdles must have been tremendous to obtain these data.”
However, Dr. Yeung pointed out some limitations and gaps in the data that were presented. For example, he found that the ratio of the training set to the validation set was unusual. “The training set is usually larger and usually an 80/20 ratio,” he said. “In their design, the validation set is larger, and I’m quite curious about their rationale.
“The conclusion of the study is that a more diverse microbiome was observed in patients with a tumor response than in those without a response,” he continued, “but they don’t actually show the statistical test used to make this conclusion. There is considerable overlap between the groups, and more compelling data are needed to make that conclusion.”
Another limitation was the marked imbalance in the number of patients whose condition responded to nivolumab in comparison with those whose condition did not (20 vs. 417 patients). This could have affected the statistical power of the study.
But overall, Dr. Yeung congratulated the authors for presenting a very impressive dataset. “The preliminary data are very interesting, and I look forward to the final results,” he said.
The study was funded by Ono Pharmaceutical and Bristol-Myers Squibb, which markets nivolumab. Dr. Sunakawa has received honoraria from Bayer Yakuhin, Bristol-Myers Squibb Japan, Chugai, Kyowa Hakko Kirin, Lilly Japan, Nippon Kayaku, Sanofi, Taiho, Takeda, and Yakult Honsha. He has held a consulting or advisory role for Bristol-Myers Squibb Japan, Daiichi Sankyo, and Takeda and has received research funding from Chugai Pharma, Daiichi Sankyo, Lilly Japan, Sanofi, Taiho Pharmaceutical, and Takeda. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A version of this article first appeared on Medscape.com.
Risk of HPV-related oropharyngeal cancer linked to number of oral sex partners
Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.
The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.
The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.
Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.
“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”
The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.
“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
Reinforces the need for vaccination
Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.
These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.
“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.
He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.
“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”
These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
Details of the new findings
The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.
All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.
The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).
Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).
Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).
Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).
After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.
The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.
The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.
The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.
The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.
Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.
“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”
The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.
“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
Reinforces the need for vaccination
Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.
These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.
“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.
He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.
“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”
These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
Details of the new findings
The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.
All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.
The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).
Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).
Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).
Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).
After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.
The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.
The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having oral sex with more than 10 previous partners was associated with a 4.3 times’ greater likelihood of developing human papillomavirus (HPV)–related oropharyngeal cancer, according to new findings.
The study also found that having more partners in a shorter period (i.e., greater oral sex intensity) and starting oral sex at a younger age were associated with higher odds of having HPV-related cancer of the mouth and throat.
The new study, published online on Jan. 11 in Cancer, confirms previous findings and adds more nuance, say the researchers.
Previous studies have demonstrated that oral sex is a strong risk factor for HPV-related oropharyngeal cancer, which has increased in incidence in recent decades, particularly cancer of the base of the tongue and palatine and lingual tonsils.
“Our research adds more nuance in our understanding of how people acquire oral HPV infection and HPV-related oropharyngeal cancer,” said study author Gypsyamber D’Souza, PhD, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “It suggests that risk of infection is not only from the number of oral sexual partners but that the timing and type of partner also influence risk.”
The results of the study do not change the clinical care or screening of patients, Dr. D’Souza noted, but the study does add context for patients and providers in understanding, “Why did I get HPV-oropharyngeal cancer?” she said.
“We know that people who develop HPV-oropharyngeal cancer have a wide range of sexual histories, but we do not suggest sexual history be used for screening, as many patients have low-risk sexual histories,” she said. “By chance, it only takes one partner who is infected to acquire the infection, while others who have had many partners by chance do not get exposed, or who are exposed but clear the infection.”
Reinforces the need for vaccination
Approached for comment, Joseph Califano, MD, physician-in-chief at the Moores Cancer Center and director of the Head and Neck Cancer Center at the University of California, San Diego, noted that similar data have been published before. The novelty here is in the timing and intensity of oral sex. “It’s not new data, but it certainly reinforces what we knew,” he said in an interview.
These new data are not going to change monitoring, he suggested. “It’s not going to change how we screen, because we don’t do population-based screening for oropharyngeal cancer,” Dr. Califano said.
“It does underline the fact that vaccination is really the key to preventing HPV-mediated cancers,” he said.
He pointed out that some data show lower rates of high-risk oral HPV shedding by children who have been appropriately vaccinated.
“This paper really highlights the fact we need to get people vaccinated early, before sexual debut,” he said. “In this case, sexual debut doesn’t necessarily mean intercourse but oral sex, and that’s a different concept of when sex starts.”
These new data “reinforce the fact that early exposure is what we need to focus on,” he said.
Details of the new findings
The current study by Dr. D’Souza and colleagues included 163 patients with HPV-related oropharyngeal cancer who were enrolled in the Papillomavirus Role in Oral Cancer Viral Etiology (PROVE) study. These patients were compared with 345 matched control persons.
All participants completed a behavioral survey and provided a blood sample. For the patients with cancer, a tumor sample was obtained.
The majority of participants were male (85% and 82%), were aged 50-69 years, were currently married or living with a partner, and identified as heterosexual. Case patients were more likely to report a history of sexually transmitted infection than were control participants (P = .003).
Case patients were more likely to have ever performed oral sex compared to control persons (98.8% vs 90.4%; P < .001) and to have performed oral sex at the time of their sexual debut (33.3% of case patients vs 21.4% of control persons; P = .004; odds ratio [OR], 1.8).
Significantly more case patients than control persons reported starting oral sex before they were 18 years old (37.4% of cases vs. 22.6% of controls; P < .001; OR, 3.1), and they had a greater number of lifetime oral sex partners (44.8% of cases and 19.1% of controls reported having more than 10 partners; P < .001; OR, 4.3).
Intensity of oral sexual exposure, which the authors measured by number of partners per 10 years, was also significantly higher among cases than controls (30.8% vs 11.1%; P < .001; OR, 5.6).
After adjustment for confounders (such as the lifetime number of oral sex partners and tobacco use), ever performing oral sex (adjusted odds ratio [aOR], 4.4), early age of first oral sex encounter (20 years: aOR, 1.8), and oral sex intensity (aOR, 2.8) all remained significantly associated with increased odds of HPV-oropharyngeal cancer.
The type of sexual partner, such as partners who were older (OR, 1.7) and having a partner who engaged in extramarital sex (OR, 1.6), were also associated with increased odds of developing HPV-oropharyngeal cancer. In addition, seropositivity for antibodies to HPV16 E6 (OR, 286) and any HPV16 E protein (E1, E2, E6, E7; OR, 163) were also associated with increased odds of developing the disease.
The study was supported by the National Institute of Dental and Craniofacial Research and the National Institute on Deafness and Other Communication Disorders. Dr. D’Souza and Dr. Califano have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CRC risk in young adults: Not as high as previously reported
Implications for CRC screening.
New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.
They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.
Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.
However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).
But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.
The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”
The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.
These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”
This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.
This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.
The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia – call for action based on the new findings.
“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.
They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”
However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.
Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.
“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”
“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out.
“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.
Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.
Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
Steepest changes in adenocarcinomas in younger groups
In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.
A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.
The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.
The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).
There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.
Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.
The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”
They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
Calls for next steps
The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.
They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.
“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.
This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested. “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.
“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.
The study authors concluded somewhat differently.
“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.
They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”
Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.
This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”
The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Implications for CRC screening.
Implications for CRC screening.
New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.
They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.
Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.
However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).
But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.
The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”
The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.
These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”
This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.
This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.
The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia – call for action based on the new findings.
“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.
They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”
However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.
Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.
“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”
“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out.
“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.
Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.
Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
Steepest changes in adenocarcinomas in younger groups
In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.
A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.
The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.
The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).
There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.
Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.
The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”
They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
Calls for next steps
The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.
They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.
“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.
This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested. “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.
“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.
The study authors concluded somewhat differently.
“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.
They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”
Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.
This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”
The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New estimates for the risk of CRC in young adults, which differentiate colorectal adenocarcinoma from other types, are reported in a study published Dec. 15, 2020, in Annals of Internal Medicine.
They are important because this finding has implications for CRC screening, say a trio of experts in an accompanying editorial.
Reports of an increase in the incidence of CRC in younger adults have led to changes in screening for this cancer in the United States. The age for starting CRC screening has been lowered to 45 years (instead of 50 years) in recommendations issued in 2018 by the American Cancer Society, and also more recently in preliminary recommendations from the U.S. Preventive Services Task Force.
However, that 2018 ACS recommendation to lower the starting age to 45 years was based to a large extent on a report of a higher incidence of CRC in younger adults from a 2017 study that used the SEER (Surveillance, Epidemiology, and End Results) database).
But that SEER-based study considered “colorectal cancer” as a homogeneous group defined by topology, the editorialists pointed out.
The new study, the editorialists said, uses that same SEER database but has “disentangled colorectal adenocarcinoma, the target for screening, from other histologic CRC types, including neuroendocrine (carcinoid) tumors, for which screening is not recommended.”
The study authors explained that adenocarcinoma is a target for prevention through screening because it arises from precancerous polyps. Those growths can be detected and removed before cancer develops. That doesn’t apply to carcinoid tumors, which are frequently incidental findings on flexible sigmoidoscopy or colonoscopy.
These carcinoid tumors typically are indolent, with a better prognosis than most other cancer types, the editorialists added. “Most likely, the majority of carcinoid tumors identified by screening represent incidental findings with little health benefit from detection. In fact, many may be characterized as overdiagnosed tumors, which by definition increase the burden and harms of screening without the balance of additional benefit.”
This new analysis showed that 4%-20% of the lesions previously described as CRC were not adenocarcinoma but carcinoid tumors, the editorialists pointed out.
This figure rose even higher in the subgroup of findings pertaining to the rectum, the colonic segment with the largest reported increase in early-onset CRC. Here, up to 34% of lesions (depending on patient age) were carcinoid tumors rather than adenocarcinoma, they noted.
The three editorialists – Michael Bretthauer, MD, PhD, and Mette Kalager, MD, PhD, both of the University of Oslo, and David Weinberg, MD, MSc, of Fox Chase Cancer Center, Philadelphia – call for action based on the new findings.
“The ACS’s 2018 estimate of about 7,000 new CRC cases among persons aged 45-49 years in the United States (the justification for screening) needs to be adjusted downward on the basis of the new evidence,” the trio wrote.
They conclude that “caution is warranted when promoting the benefits of CRC screening for persons younger than 50 years.”
However, the senior author of the new study, Jordan Karlitz, MD, of Tulane University, New Orleans, strongly disagreed.
Contrary to the editorialists, Dr. Karlitz said in an interview that he and his colleagues firmly believe that colorectal cancer screening for average-risk patients should begin at age 45 and that their new research, despite its clarification about carcinoid tumors, provides evidence for that.
“There are a number of other studies that support screening at age 45 as well,” he said. “This [new] finding supports the presence of a large preclinical colorectal cancer case burden in patients in their 40s that is ultimately uncovered with screening initiation at age 50. Many of these cancers could be prevented or diagnosed at an earlier stage with screening at age 45.”
“This is the first study to analyze early-onset colorectal cancer by specific histologic subtype,” Dr. Karlitz also pointed out.
“Although colorectal carcinoids are increasing at a faster rate than adenocarcinomas, adenocarcinomas constitute the overwhelming majority of colorectal cancers in people in their 40s and are also steadily increasing, which has implications for beginning screening at age 45,” he said.
Adenocarcinomas also make up the “overwhelming majority” of colorectal cancers in patients under 50 overall and “are the main driving force behind the increased colorectal cancer burden we are seeing in young patients,” Dr. Karlitz added.
Furthermore, “modeling studies on which the USPSTF screening recommendations were based [which recommended starting at age 45] were confined to adenocarcinoma, thus excluding carcinoids from their analysis,” he said.
Steepest changes in adenocarcinomas in younger groups
In their study, Dr. Karlitz and colleagues assessed the incidence rates of early colorectal cancer, using SEER data from 2000 to 2016, and stratifying the data by histologic subtype (primarily adenocarcinoma and carcinoid tumors), age group (20-29, 30-39, 40-49, and 50-54 years), and subsite.
A total of 123,143 CRC cases were identified in 119,624 patients between the ages of 20-54 years during that time period.
The absolute incidence rates in the younger age groups (20-29 and 30-39 years) were very low, compared with those aged 40-49 and 50-54 years.
The greatest 3-year average annual incident rate changes in adenocarcinoma (2000-2002 vs. 2014-2016) for any age group or subsite were for rectal-only cases in the 20-29 years group (+39%), as well as rectal-only cases in those aged 30-39 years (+39%), and colon-only cases in the age 30-39 group (+20%).
There was also significant increase in rectal-only adenocarcinoma in individuals aged 50-54 years (+10%). A statistically significant increase in the annual percentage change for adenocarcinomas was observed for all age groups, except for colon-only cases in the 20-29 years group (0.7%) and for both colorectal (0.2%) and colon-only cases (–0.1%) in those aged 50-54 years.
Even though the absolute carcinoid tumor incidence rates were lower than for adenocarcinoma in all age groups and subsites, a statistically significant increase was observed in the 3-year average annual incidence rate of combined-site colorectal carcinoid tumors in all age groups from 2000–2002 and 2014–2016. This increase was largely the result of increases in rectal carcinoid tumors, the authors note.
The authors also highlighted the results in the 40- to 49-year age group “because of differing opinions on whether to begin average-risk screening at age 45 or 50 years.”
They reported that rates of rectal and colon adenocarcinoma are increasing “substantially,” whether measured by changes in 3-year average annual incidence rate or by annual percentage changes. The change in average annual incidence rate of colon-only adenocarcinoma for persons aged 40-49 years was 13% (12.21 to 13.85 per 100,000), and that of rectal adenocarcinoma was 16% (7.50 to 8.72 per 100,000). Corresponding annual percentage changes were 0.8% and 1.2%, respectively. “These significant increases in adenocarcinoma incident rates add to the debate over earlier screening at age 45 years,” they commented.
Calls for next steps
The editorialists emphasize restraint when promoting the benefits of colorectal screening for persons younger than 50 years.
They point out that the USPSTF released a provisional update of its CRC screening recommendations about lowering the age to initiate screening to 45 years, as reported by this news organization.
“No new empirical evidence has been found since the USPSTF update in 2016 to inform the effectiveness of screening in persons younger than 50 years,” they write, adding that similar to the American Cancer Society in 2018, the task force has relied exclusively on modeling studies.
This new data from Dr. Karlitz and colleagues “should prompt the modelers to recalculate their estimates of benefits and harms of screening,” they suggested. “Revisiting the model would also allow competing forms of CRC screening to be compared in light of new risk assumptions.
“Previous assumptions that screening tests are equally effective in younger and older patients and that screening adherence will approach 100% may also be reconsidered,” the editorialist commented.
The study authors concluded somewhat differently.
“In conclusion, adenocarcinoma rates increased in many early-onset subgroups but showed no significant increase in others, including colon-only cases in persons aged 20-29 and 50-54 years,” the investigators wrote.
They also observed that “rectal carcinoid tumors are increasing in young patients and may have a substantial impact on overall CRC incident rates.”
Those findings on rectal carcinoid tumors “underscore the importance of assessing histologic CRC subtypes independently,” the researchers said.
This new approach, of which the current study is a first effort, “may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of the outcomes of adenocarcinoma risk reduction efforts, and can guide future research.”
The study had no outside funding. Dr. Karlitz reported personal fees from Exact Sciences, personal fees from Myriad Genetics, and other fees from Gastro Girl and GI OnDEMAND, outside the submitted work. Dr. Bretthauer reports grants from Norwegian Research Council, grants from Norwegian Cancer Society for research in colorectal cancer screening. Dr. Weinberg and Dr. Kalager have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.