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VIDEO: Low testosterone common after testicular cancer
CHICAGO – More than one-third of testicular cancer survivors have hypogonadism, according to an analysis of nearly 500 male patients conducted by the Platinum Study Group.
Lead author Mohammad Abu Zaid, MBBS, of Indiana University, Indianapolis, discusses the implications for long-term health, screening during follow-up, testing, and testosterone replacement therapy in a video interview at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – More than one-third of testicular cancer survivors have hypogonadism, according to an analysis of nearly 500 male patients conducted by the Platinum Study Group.
Lead author Mohammad Abu Zaid, MBBS, of Indiana University, Indianapolis, discusses the implications for long-term health, screening during follow-up, testing, and testosterone replacement therapy in a video interview at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – More than one-third of testicular cancer survivors have hypogonadism, according to an analysis of nearly 500 male patients conducted by the Platinum Study Group.
Lead author Mohammad Abu Zaid, MBBS, of Indiana University, Indianapolis, discusses the implications for long-term health, screening during follow-up, testing, and testosterone replacement therapy in a video interview at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
VIDEO: Single dose of RT suffices, but will radiation oncologists adopt the strategy?
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
Infections up the risk for pregnancy-associated stroke in preeclampsia
A host of factors, some of them preventable or treatable, increase the risk of pregnancy-related stroke among women hospitalized for preeclampsia, according to findings from a case-control study of nearly 800 preeclamptic women in New York.
Women who experienced a stroke were roughly seven times more likely to have severe preeclampsia or eclampsia, and about three to four times more likely to have an infection, a prothrombotic state, a coagulopathy, or chronic hypertension, according to the findings (Stroke. 2017 May 25. doi: 10.1161/STROKEAHA.117.017374).
“Prospective studies are needed to confirm these findings and develop interventions aimed at preventing strokes in this uniquely vulnerable group,” they added.
For the study, the investigators used billing data from the 2003-2012 New York State Department of Health inpatient database to identify women aged 12-55 years admitted with preeclampsia.
They matched each woman who experienced pregnancy-associated stroke with three randomly selected controls of the same age, race/ethnicity, and insurance status. They then compared the groups on a set of predefined risk factors.
Results showed that of 88,857 women admitted for preeclampsia during the study period, 0.2% experienced pregnancy-associated stroke, translating to a cumulative incidence of 222 per 100,000 preeclamptic women, a value more than six times that seen in the general pregnant population, the investigators noted.
The majority of strokes occurred post partum (66.5%), but more than a quarter occurred before delivery (27.9%). The single most common type of stroke was hemorrhagic (46.7%).
The 197 women with preeclampsia who experienced pregnancy-associated stroke had a sharply higher rate of in-hospital mortality (13.2%), compared with the 591 controls (0.2%).
In multivariate analysis, women with preeclampsia experiencing stroke were more likely to have severe preeclampsia or eclampsia (odds ratio, 7.2; 95% confidence interval, 4.6-11.3), or infections at the time of admission (OR, 3.0; 95% CI, 1.6-5.8), predominantly genitourinary infections.
Other risk factors for pregnancy-associated stroke included prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5).
The findings were similar when women were matched by the severity of preeclampsia, when women with eclampsia were excluded, or when women with only postpartum stroke were included.
Heart disease, multiple gestation, and previous pregnancies were not significantly independently associated with the risk of pregnancy-associated stroke.
“The ethnic and regional diversity of New York State increases the generalizability of our findings,” the investigators wrote. “Matching of cases and controls allowed for nuanced analysis of other risk factors.”
But the study may have missed some cases of preeclampsia not formally diagnosed, and the timing of infections relative to stroke was unknown, they acknowledged. Additionally, they noted that causality cannot be inferred from the observational study, and therefore the results should be interpreted cautiously.
The investigators reported research support from the National Institutes of Health. They had no other financial disclosures.
A host of factors, some of them preventable or treatable, increase the risk of pregnancy-related stroke among women hospitalized for preeclampsia, according to findings from a case-control study of nearly 800 preeclamptic women in New York.
Women who experienced a stroke were roughly seven times more likely to have severe preeclampsia or eclampsia, and about three to four times more likely to have an infection, a prothrombotic state, a coagulopathy, or chronic hypertension, according to the findings (Stroke. 2017 May 25. doi: 10.1161/STROKEAHA.117.017374).
“Prospective studies are needed to confirm these findings and develop interventions aimed at preventing strokes in this uniquely vulnerable group,” they added.
For the study, the investigators used billing data from the 2003-2012 New York State Department of Health inpatient database to identify women aged 12-55 years admitted with preeclampsia.
They matched each woman who experienced pregnancy-associated stroke with three randomly selected controls of the same age, race/ethnicity, and insurance status. They then compared the groups on a set of predefined risk factors.
Results showed that of 88,857 women admitted for preeclampsia during the study period, 0.2% experienced pregnancy-associated stroke, translating to a cumulative incidence of 222 per 100,000 preeclamptic women, a value more than six times that seen in the general pregnant population, the investigators noted.
The majority of strokes occurred post partum (66.5%), but more than a quarter occurred before delivery (27.9%). The single most common type of stroke was hemorrhagic (46.7%).
The 197 women with preeclampsia who experienced pregnancy-associated stroke had a sharply higher rate of in-hospital mortality (13.2%), compared with the 591 controls (0.2%).
In multivariate analysis, women with preeclampsia experiencing stroke were more likely to have severe preeclampsia or eclampsia (odds ratio, 7.2; 95% confidence interval, 4.6-11.3), or infections at the time of admission (OR, 3.0; 95% CI, 1.6-5.8), predominantly genitourinary infections.
Other risk factors for pregnancy-associated stroke included prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5).
The findings were similar when women were matched by the severity of preeclampsia, when women with eclampsia were excluded, or when women with only postpartum stroke were included.
Heart disease, multiple gestation, and previous pregnancies were not significantly independently associated with the risk of pregnancy-associated stroke.
“The ethnic and regional diversity of New York State increases the generalizability of our findings,” the investigators wrote. “Matching of cases and controls allowed for nuanced analysis of other risk factors.”
But the study may have missed some cases of preeclampsia not formally diagnosed, and the timing of infections relative to stroke was unknown, they acknowledged. Additionally, they noted that causality cannot be inferred from the observational study, and therefore the results should be interpreted cautiously.
The investigators reported research support from the National Institutes of Health. They had no other financial disclosures.
A host of factors, some of them preventable or treatable, increase the risk of pregnancy-related stroke among women hospitalized for preeclampsia, according to findings from a case-control study of nearly 800 preeclamptic women in New York.
Women who experienced a stroke were roughly seven times more likely to have severe preeclampsia or eclampsia, and about three to four times more likely to have an infection, a prothrombotic state, a coagulopathy, or chronic hypertension, according to the findings (Stroke. 2017 May 25. doi: 10.1161/STROKEAHA.117.017374).
“Prospective studies are needed to confirm these findings and develop interventions aimed at preventing strokes in this uniquely vulnerable group,” they added.
For the study, the investigators used billing data from the 2003-2012 New York State Department of Health inpatient database to identify women aged 12-55 years admitted with preeclampsia.
They matched each woman who experienced pregnancy-associated stroke with three randomly selected controls of the same age, race/ethnicity, and insurance status. They then compared the groups on a set of predefined risk factors.
Results showed that of 88,857 women admitted for preeclampsia during the study period, 0.2% experienced pregnancy-associated stroke, translating to a cumulative incidence of 222 per 100,000 preeclamptic women, a value more than six times that seen in the general pregnant population, the investigators noted.
The majority of strokes occurred post partum (66.5%), but more than a quarter occurred before delivery (27.9%). The single most common type of stroke was hemorrhagic (46.7%).
The 197 women with preeclampsia who experienced pregnancy-associated stroke had a sharply higher rate of in-hospital mortality (13.2%), compared with the 591 controls (0.2%).
In multivariate analysis, women with preeclampsia experiencing stroke were more likely to have severe preeclampsia or eclampsia (odds ratio, 7.2; 95% confidence interval, 4.6-11.3), or infections at the time of admission (OR, 3.0; 95% CI, 1.6-5.8), predominantly genitourinary infections.
Other risk factors for pregnancy-associated stroke included prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5).
The findings were similar when women were matched by the severity of preeclampsia, when women with eclampsia were excluded, or when women with only postpartum stroke were included.
Heart disease, multiple gestation, and previous pregnancies were not significantly independently associated with the risk of pregnancy-associated stroke.
“The ethnic and regional diversity of New York State increases the generalizability of our findings,” the investigators wrote. “Matching of cases and controls allowed for nuanced analysis of other risk factors.”
But the study may have missed some cases of preeclampsia not formally diagnosed, and the timing of infections relative to stroke was unknown, they acknowledged. Additionally, they noted that causality cannot be inferred from the observational study, and therefore the results should be interpreted cautiously.
The investigators reported research support from the National Institutes of Health. They had no other financial disclosures.
FROM STROKE
Key clinical point:
Major finding: Independent risk factors for pregnancy-associated stroke were severe preeclampsia or eclampsia (OR, 7.2), infections (OR, 3.0), prothrombotic states (OR, 3.5), coagulopathies (OR, 3.1), or chronic hypertension (OR, 3.2).
Data source: A matched, case-control study of 788 women from a New York inpatient database who were hospitalized for preeclampsia.
Disclosures: The investigators reported research support from the National Institutes of Health. They had no other financial disclosures.
Oral HPV infections sharply lower for vaccinated youth
Vaccination against human papillomavirus (HPV) appears to be highly effective at preventing oral infection with oncogenic types of the virus, based on the results of a cohort study of a nationally representative sample of more than 2,600 U.S. young adults.
“HPV-positive oropharynx cancer is the fastest rising cancer among young white men in the United States. Over 90% of these cancers are caused by HPV type 16,” said senior study author Maura L. Gillison, MD, PhD, who conducted the research at Ohio State University, Columbus. “HPV 16 is one of the types covered in currently recommended HPV vaccines that have been shown to be safe and effective in the prevention of anogenital infections and associated cancers.
Results of the study showed that only about a sixth of the young adults surveyed between 2011 and 2014 had received at least one dose of an HPV vaccine. But relative to peers who had not received any doses, these young adults had an 88% lower prevalence of oral infection with HPV types 16, 18, 6, and 11, which are covered by vaccines; in particular, prevalence was 100% lower, with complete absence of these infections, in vaccinated young men, compared with unvaccinated young men, Dr. Gillison said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Analyses further suggested that based on levels of vaccine uptake seen in 2014 in the population, the vaccine was preventing only about 17% of the total of approximately 927,000 preventable oral infections with these virus types in that year.
“Our data indicate that HPV vaccines have tremendous potential to prevent oral infection,” said Dr. Gillison, noting that they are already strongly recommended by numerous health and medical organizations. Unfortunately, at the time of the study, “low vaccine uptake limited the population impact of the vaccine.”
However, there is now “considerable optimism,” she said, because recent data have shown that 60% of girls and 40% of boys younger than 18 have received at least one dose of HPV vaccine, marking a major increase in uptake.
“We can’t say that this is cause effect, the impact of these vaccines on infection, because this isn’t a prospective clinical trial,” she acknowledged. “Nevertheless, we can conclude that HPV vaccination may have additional benefits beyond prevention of anogenital cancers.”
The findings are encouraging in that they suggest it will be possible to avert infection-induced oropharyngeal cancer, according to ASCO President-Elect Bruce E. Johnson, MD, who is also chief clinical research officer at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.
“This certainly shows that in the target population to get vaccination, you can indeed prevent the infection, which is one of the first steps that would eventually potentially lead to cancer,” he said.
In the study, Dr. Gillison and her colleagues analyzed data from 2,627 men and women aged 18-33 years who participated in the National Health and Nutrition Examination Survey in the years 2011-2014. Oral rinses were collected as part of the survey to assess HPV infection.
The results showed that 18% of the young adults overall reported having received at least one dose of HPV vaccine, although receipt was much higher among young women than among young men (29% vs. 7%).
The prevalence of oral infection with HPV types 16/18/6/11 was sharply lower for these vaccinated young adults, compared with unvaccinated peers in the cohort as a whole (0.11% vs. 1.6%; P = .008). In a sex-stratified analysis, the reduction was especially striking among men (0% vs. 2%, P = .007), reported Dr. Gillison, who is now professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.
The vaccinated and unvaccinated groups did not differ significantly with respect to the combined prevalence of oral infection with 33 types of HPV that are not covered by vaccines.
When HPV vaccine uptake in the population in 2014 was considered, estimates suggested that vaccination was preventing only 17% of all vaccine-preventable oral HPV 16/18/6/11 infections in that year (25% in women and 7% in men).
Research on anogenital HPV infection, especially cervical HPV infection, suggests that most individuals will clear the infection on their own naturally, without any intervention, Dr. Gillison said. However, research has failed to identify good predictors of clearance or persistence.
“That’s why there is the current recommendation for universal vaccination of young boys and girls, because we don’t know how to distinguish someone who, like the overwhelming majority of individuals, is going to clear their infection with their own immune system, versus those who don’t have that capability and could progress to cancer,” she said.
Dr. Gillison disclosed that she has a consulting or advisory role with GlaxoSmithKline, Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, and Celgene, and that she receives research funding (institutional) from Bristol-Myers Squibb, Kyowa Hakko Kirin, AstraZeneca, and Merck.
Vaccination against human papillomavirus (HPV) appears to be highly effective at preventing oral infection with oncogenic types of the virus, based on the results of a cohort study of a nationally representative sample of more than 2,600 U.S. young adults.
“HPV-positive oropharynx cancer is the fastest rising cancer among young white men in the United States. Over 90% of these cancers are caused by HPV type 16,” said senior study author Maura L. Gillison, MD, PhD, who conducted the research at Ohio State University, Columbus. “HPV 16 is one of the types covered in currently recommended HPV vaccines that have been shown to be safe and effective in the prevention of anogenital infections and associated cancers.
Results of the study showed that only about a sixth of the young adults surveyed between 2011 and 2014 had received at least one dose of an HPV vaccine. But relative to peers who had not received any doses, these young adults had an 88% lower prevalence of oral infection with HPV types 16, 18, 6, and 11, which are covered by vaccines; in particular, prevalence was 100% lower, with complete absence of these infections, in vaccinated young men, compared with unvaccinated young men, Dr. Gillison said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Analyses further suggested that based on levels of vaccine uptake seen in 2014 in the population, the vaccine was preventing only about 17% of the total of approximately 927,000 preventable oral infections with these virus types in that year.
“Our data indicate that HPV vaccines have tremendous potential to prevent oral infection,” said Dr. Gillison, noting that they are already strongly recommended by numerous health and medical organizations. Unfortunately, at the time of the study, “low vaccine uptake limited the population impact of the vaccine.”
However, there is now “considerable optimism,” she said, because recent data have shown that 60% of girls and 40% of boys younger than 18 have received at least one dose of HPV vaccine, marking a major increase in uptake.
“We can’t say that this is cause effect, the impact of these vaccines on infection, because this isn’t a prospective clinical trial,” she acknowledged. “Nevertheless, we can conclude that HPV vaccination may have additional benefits beyond prevention of anogenital cancers.”
The findings are encouraging in that they suggest it will be possible to avert infection-induced oropharyngeal cancer, according to ASCO President-Elect Bruce E. Johnson, MD, who is also chief clinical research officer at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.
“This certainly shows that in the target population to get vaccination, you can indeed prevent the infection, which is one of the first steps that would eventually potentially lead to cancer,” he said.
In the study, Dr. Gillison and her colleagues analyzed data from 2,627 men and women aged 18-33 years who participated in the National Health and Nutrition Examination Survey in the years 2011-2014. Oral rinses were collected as part of the survey to assess HPV infection.
The results showed that 18% of the young adults overall reported having received at least one dose of HPV vaccine, although receipt was much higher among young women than among young men (29% vs. 7%).
The prevalence of oral infection with HPV types 16/18/6/11 was sharply lower for these vaccinated young adults, compared with unvaccinated peers in the cohort as a whole (0.11% vs. 1.6%; P = .008). In a sex-stratified analysis, the reduction was especially striking among men (0% vs. 2%, P = .007), reported Dr. Gillison, who is now professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.
The vaccinated and unvaccinated groups did not differ significantly with respect to the combined prevalence of oral infection with 33 types of HPV that are not covered by vaccines.
When HPV vaccine uptake in the population in 2014 was considered, estimates suggested that vaccination was preventing only 17% of all vaccine-preventable oral HPV 16/18/6/11 infections in that year (25% in women and 7% in men).
Research on anogenital HPV infection, especially cervical HPV infection, suggests that most individuals will clear the infection on their own naturally, without any intervention, Dr. Gillison said. However, research has failed to identify good predictors of clearance or persistence.
“That’s why there is the current recommendation for universal vaccination of young boys and girls, because we don’t know how to distinguish someone who, like the overwhelming majority of individuals, is going to clear their infection with their own immune system, versus those who don’t have that capability and could progress to cancer,” she said.
Dr. Gillison disclosed that she has a consulting or advisory role with GlaxoSmithKline, Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, and Celgene, and that she receives research funding (institutional) from Bristol-Myers Squibb, Kyowa Hakko Kirin, AstraZeneca, and Merck.
Vaccination against human papillomavirus (HPV) appears to be highly effective at preventing oral infection with oncogenic types of the virus, based on the results of a cohort study of a nationally representative sample of more than 2,600 U.S. young adults.
“HPV-positive oropharynx cancer is the fastest rising cancer among young white men in the United States. Over 90% of these cancers are caused by HPV type 16,” said senior study author Maura L. Gillison, MD, PhD, who conducted the research at Ohio State University, Columbus. “HPV 16 is one of the types covered in currently recommended HPV vaccines that have been shown to be safe and effective in the prevention of anogenital infections and associated cancers.
Results of the study showed that only about a sixth of the young adults surveyed between 2011 and 2014 had received at least one dose of an HPV vaccine. But relative to peers who had not received any doses, these young adults had an 88% lower prevalence of oral infection with HPV types 16, 18, 6, and 11, which are covered by vaccines; in particular, prevalence was 100% lower, with complete absence of these infections, in vaccinated young men, compared with unvaccinated young men, Dr. Gillison said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Analyses further suggested that based on levels of vaccine uptake seen in 2014 in the population, the vaccine was preventing only about 17% of the total of approximately 927,000 preventable oral infections with these virus types in that year.
“Our data indicate that HPV vaccines have tremendous potential to prevent oral infection,” said Dr. Gillison, noting that they are already strongly recommended by numerous health and medical organizations. Unfortunately, at the time of the study, “low vaccine uptake limited the population impact of the vaccine.”
However, there is now “considerable optimism,” she said, because recent data have shown that 60% of girls and 40% of boys younger than 18 have received at least one dose of HPV vaccine, marking a major increase in uptake.
“We can’t say that this is cause effect, the impact of these vaccines on infection, because this isn’t a prospective clinical trial,” she acknowledged. “Nevertheless, we can conclude that HPV vaccination may have additional benefits beyond prevention of anogenital cancers.”
The findings are encouraging in that they suggest it will be possible to avert infection-induced oropharyngeal cancer, according to ASCO President-Elect Bruce E. Johnson, MD, who is also chief clinical research officer at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.
“This certainly shows that in the target population to get vaccination, you can indeed prevent the infection, which is one of the first steps that would eventually potentially lead to cancer,” he said.
In the study, Dr. Gillison and her colleagues analyzed data from 2,627 men and women aged 18-33 years who participated in the National Health and Nutrition Examination Survey in the years 2011-2014. Oral rinses were collected as part of the survey to assess HPV infection.
The results showed that 18% of the young adults overall reported having received at least one dose of HPV vaccine, although receipt was much higher among young women than among young men (29% vs. 7%).
The prevalence of oral infection with HPV types 16/18/6/11 was sharply lower for these vaccinated young adults, compared with unvaccinated peers in the cohort as a whole (0.11% vs. 1.6%; P = .008). In a sex-stratified analysis, the reduction was especially striking among men (0% vs. 2%, P = .007), reported Dr. Gillison, who is now professor of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.
The vaccinated and unvaccinated groups did not differ significantly with respect to the combined prevalence of oral infection with 33 types of HPV that are not covered by vaccines.
When HPV vaccine uptake in the population in 2014 was considered, estimates suggested that vaccination was preventing only 17% of all vaccine-preventable oral HPV 16/18/6/11 infections in that year (25% in women and 7% in men).
Research on anogenital HPV infection, especially cervical HPV infection, suggests that most individuals will clear the infection on their own naturally, without any intervention, Dr. Gillison said. However, research has failed to identify good predictors of clearance or persistence.
“That’s why there is the current recommendation for universal vaccination of young boys and girls, because we don’t know how to distinguish someone who, like the overwhelming majority of individuals, is going to clear their infection with their own immune system, versus those who don’t have that capability and could progress to cancer,” she said.
Dr. Gillison disclosed that she has a consulting or advisory role with GlaxoSmithKline, Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, and Celgene, and that she receives research funding (institutional) from Bristol-Myers Squibb, Kyowa Hakko Kirin, AstraZeneca, and Merck.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with unvaccinated peers, young adults who had received at least one dose of HPV vaccine had an 88% lower prevalence of oral infection with HPV types 16/18/6/11.
Data source: A cross-sectional cohort study of 2,627 men and women aged 18-33 years who participated in the National Health and Nutrition Examination Survey during 2011-2014.
Disclosures: Dr. Gillison disclosed that she has a consulting or advisory role with GlaxoSmithKline, Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, and Celgene, and that she receives research funding (institutional) from Bristol-Myers Squibb, Kyowa Hakko Kirin, AstraZeneca, and Merck.
Healthy lifestyle, tree nuts may protect against colon cancer recurrence
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with counterparts who have the least healthy lifestyle, patients with the healthiest lifestyle were 42%-51% less likely to die. Relative to peers who never ate nuts, patients who ate nuts at least twice a week had a 42% lower risk of disease-free survival events and a 57% lower risk of death.
Data source: A pair of prospective cohort studies among 992 patients and 826 patients with resected stage III colon cancer given adjuvant chemotherapy in a clinical trial (CALGB 89803).
Disclosures: Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Gefitinib bests chemo as adjuvant therapy for early EGFR-mutant NSCLC
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
The targeted agent gefitinib is superior to the standard of care chemotherapy for treating resected early non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, finds the phase III randomized Chinese ADJUVANT trial.
Gefitinib, an oral tyrosine kinase inhibitor that targets the EGFR kinase among others, is already approved by the Food and Drug Administration for treatment of locally advanced or metastatic disease having mutations in the gene for this receptor.
Trial results reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology showed that compared with vinorelbine and cisplatin combination chemotherapy, 2 years of gefitinib prolonged the time to recurrence or death by more than 10 months, reducing risk of these events by a significant 40%. Gefitinib also was better tolerated: The rate of grade 3 or worse adverse events with the targeted agent was one-fourth that seen with the chemotherapy.
“Targeted therapy can delay recurrence of intermediate-stage lung cancer after surgery. Two-year treatment duration of gefitinib is efficacious and tolerated well,” said lead study author Yi-Long Wu, MD, director of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. “Adjuvant gefitinib should be considered as an important option for stage II to IIIA lung cancer patients with an activating EGFR mutation.”
Clinical implications
The improved disease-free survival seen with gefitinib in ADJUVANT is “encouraging,” according to ASCO President-Elect Bruce E. Johnson, MD, chief clinical research officer and an Institute Physician at the Dana-Farber Cancer Institute in Boston.
Longer follow-up will be needed to obtain a full picture as the horizon for events in the adjuvant setting is more on the order of years, and the disease-free survival curves began converging over time, he noted. “We will ultimately be interested in seeing whether this actually prolongs survival in a longer follow-up study, which Dr. Wu’s group is planning to do.
“I haven’t changed my approach yet for the patients with EGFR-mutant lung cancer,” Dr. Johnson concluded. “But I will be following this [trial] very closely to see what happens to the survival.”
The new data from ADJUVANT will likely have several effects on the clinical management of NSCLC, according to presscast moderator and ASCO Chief Medical Officer Richard L. Schilsky, MD.
“I suspect that many doctors will begin testing these lung cancer tumors right after surgery, to see if they actually have an EGFR mutation. That is not currently standard of care in the U.S.; typically the testing doesn’t take place until the cancer recurs or becomes metastatic,” he said. “So that way, doctors and patients will know whether or not treatment with an EGFR inhibitor is even an option.
“If it is an option, then many factors will likely come into play, and most importantly we will be waiting for the survival data,” said Dr. Schilsky, professor emeritus at the University of Chicago. Another consideration is that the trial compared 12 weeks of chemotherapy with 2 years of continuous gefitinib therapy, the latter of which requires a long-term commitment to adherence by patients and carries much greater cost.
“At the end of the day, I think that once the survival data is known in particular, doctors and patients are going to have to have very thoughtful discussions about what is the magnitude of the survival benefit; what is the burden on the patient to take either cytotoxic chemotherapy for 12 weeks or 2 years of an oral treatment, which, while it is less toxic, is not without toxicity; and what’s the financial burden of that treatment choice going to be for the patient,” he concluded.
Study details
Eligibility for the ADJUVANT trial required completely resected pathological stage II-IIIA (N1-N2) NSCLC with an EGFR-activating mutation. In all, 220 patients were randomized evenly to receive gefitinib (Iressa) once daily for 24 months or vinorelbine plus cisplatin every 3 weeks for 4 cycles.
Results showed that median disease-free survival – the trial’s primary endpoint—was 28.7 months with gefitinib compared with 18.0 months with chemotherapy (hazard ratio, 0.60; P = .005), Dr. Wu reported in the presscast. Corresponding 3-year disease-free survival rates were 34% and 27%.
The rate of grade 3 or worse adverse events was 12.3% in the gefitinib group, compared with 48.3% in the chemotherapy group. Most types of events were less common with the tyrosine kinase inhibitor, with the exception of rash, diarrhea, and elevation of liver enzymes.
Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Patients in the gefitinib group had a sharply reduced risk of recurrence or death relative to peers in the vinorelbine-cisplatin group (hazard ratio, 0.60; P = .005).
Data source: ADJUVANT, a phase III randomized controlled study of 220 patients with completely resected EGFR-mutant pathological stage II-IIIA (N1-N2) NSCLC.
Disclosures: Dr. Wu disclosed ties with AstraZeneca, Roche, Merck, Boehringer Ingelheim; Lilly, Pierre Fabre, Pfizer, and Sanofi. The Chinese Thoracic Oncology Group and AstraZeneca Chin funded the trial.
BILCAP: adjuvant capecitabine boosts overall survival of biliary tract cancers
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.
“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD, professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.
“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.
The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD, clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”
Study coauthor John A. Bridgewater, PhD, a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.
“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.
Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”
The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.
At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.
“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”
Study details
Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).
With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).
In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).
Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.
“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.
“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.
Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with observation, capecitabine prolonged median overall survival by 15 months in the intention-to-treat population (P = .097) and by 17 months in the per-protocol population (P = .028).
Data source: BILCAP, a phase III randomized controlled trial among 447 patients who had undergone complete resection of biliary tract cancers.
Disclosures: Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.
More early-stage cancer diagnosis since ACA implementation
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
Implementation of the Affordable Care Act (ACA) has been associated with a shift toward earlier stage at diagnosis for common screenable cancers, finds an analysis of nearly 273,000 patients reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“Extensive evidence has shown that people without insurance are more likely to be diagnosed at later stage, especially for the cancers that can be detected earlier through screening or symptoms,” said lead study author Xuesong Han, PhD, strategic director of health policy and health care delivery research at the American Cancer Society in Atlanta. “In 2014, two major components of the Affordable Care Act – Medicaid expansion and marketplace exchange – were implemented. As a result, insurance coverage has substantially increased for nonelderly Americans.”
Study findings showed that, for four of five screenable cancers – breast and cervical cancer in women and lung and colorectal cancer in both sexes combined – the proportion of cancers that were stage I at diagnosis, and hence most curable, increased by an absolute 1% or so after the ACA was implemented. Prostate cancer was the outlier: the value for this malignancy decreased by 1%.
“The increases for the first four cancers were consistent with our hypothesis, with more people gaining insurance and access to screening services or access to physicians to detect early symptoms,” Dr. Han summarized. “But what about prostate cancer? We think [that pattern] may reflect the recent USPSTF recommendations against routine prostate cancer screening.”
“We think that this is an important study,” commented ASCO president-elect Bruce E. Johnson, MD, who is also chief clinical research officer and an institute physician at the Dana-Farber Cancer Institute in Boston. “Obviously, the changes are not enormous; they are not dramatic. But … because the uptake of screening is relatively slow, this is certainly consistent with the idea that, by doing additional screening, you can potentially find more stage I patients, and, the earlier the stage, the more likely one is to be cured.”
“The other important thing is that ASCO strongly supports the relative ease of access to screening capabilities, and that’s one of the characteristics of the Affordable Care Act, that most of the cancer screening is covered,” he further stated. “Whatever form our health care takes over the next several years, we advocate for patients to have early access to screening, which can identify cancers at an earlier stage in their more curable forms.”
Study details
For the study, the investigators used the National Cancer Database – which captures 70% of newly diagnosed cases in the United States – to identify patients younger than 65 who were eligible for cancer screening and who received a diagnosis of any of the five screenable cancers in 2013 or 2014. They compared stage distribution before ACA implementation (first nine months of 2013) and afterward (last nine months of 2014).
Analyses were based on data from 121,402 female breast cancer patients aged 40-64 years, 39,418 colorectal cancer patients aged 50-64 years, 11,190 cervical cancer patients aged 21-64 years, 59,210 prostate cancer patients aged 50-64 years, and 41,436 lung cancer patients aged 55-64 years.
Results showed that the proportion of cancers that were stage I at diagnosis increased after ACA implementation from 47.8% to 48.9% for breast cancer (adjusted prevalence ratio, 1.02) and from 47.3% to 48.8% for cervical cancer (APR, 1.02) in women, and from 16.6% to 17.7% for lung cancer (APR, 1.07) and from 22.8% to 23.7% for colorectal cancer (APR, 1.04) in men and women combined, Dr. Han reported.
Prostate cancer was the exception, with the proportion of cases that were stage I at diagnosis falling from 18.5% to 17.2% (APR, 0.93).
In a stratified analysis, the significant downshift in lung and colorectal cancer stage were seen only in states that had actually adopted the Medicaid expansion component of the ACA, which covers low-income individuals, according to Dr. Han. The downshift in female breast cancer stage and upshift in prostate cancer stage occurred regardless of whether states had done so.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: The proportion of cancers that were stage I when diagnosed increased by about 1% after ACA implementation for breast, cervical, lung, and colorectal cancer, while it decreased by 1% for prostate cancer.
Data source: A cohort study of 272,656 patients with these five cancers from the National Cancer Database.
Disclosures: Dr. Han reported that she had no disclosures.
Oncology treatment errors: Emerging data shed light on risk factors, prevention
ORLANDO – Accumulating evidence is helping researchers better understand why errors occur during the delivery of cancer treatment and how to prevent them. Findings from a trio of studies were reported at a symposium on quality care sponsored by the American Society of Clinical Oncology.
Identifying causes of incidents in radiation therapy
In the first study, Greg D. Judy, MD, a radiation oncology resident at the University of North Carolina at Chapel Hill, and his colleagues retrospectively reviewed records in their institution’s reporting system, called Good Catch, to identify near-miss incidents (ones that didn’t reach the patient) and safety incidents (ones that did) among patients undergoing radiation therapy from October 2014 through April 2016.
Multivariate analysis showed that patients had a significantly higher risk of near-miss or safety incidents if they had stage T2 disease (odds ratio, 3.3), were being treated for cancer involving the head and neck (5.2), or were receiving image-guided intensity-modulated radiation therapy (3.0) or daily imaging as part of their treatment (7.0), Dr. Judy reported.
“Head and neck site and image-guided IMRT [intensity-modulated radiation therapy] are complex entities: They have multiple steps in both the planning and delivery phase,” he said. “Daily imaging as well. It’s a much more complex process to do daily imaging for setup verification than it is to do once-a-week or even once-every-2-weeks setup verification.”
On the other hand, it was unclear why T2 stage was a risk factor. “We kind of hypothesized that it might be more of the disease site that really drives this, as you can have HPV-positive oropharyngeal cancer which usually has lower T stages and more advanced nodal stages, but even then, that’s a head and neck site and we usually use image-guided IMRT, which are both very complex entities,” he said. The most common root causes for the incidents were issues related to documentation and scheduling (29% each), followed by issues related to communication (22%), technical treatment planning (14%), and technical treatment delivery (6%).
Incidents having a communication root cause were more likely than were others to affect patients (P less than .001), and those having a technical treatment delivery root cause were more likely to have higher severity (P = .005).
“Like some other studies, we found really the key factor was the complexity of the treatment plan and complexity of the overall process that is the real driving factor. This is important to understand because it promotes the idea of developing a more dedicated and robust QA system for complex cases,” said Dr. Judy. “It also highlights the importance of a strong reporting system to support a safety culture, as well as promote the continuous learning improvements within a department.”
The national Radiation Oncology Incident Learning System (RO-ILS) has been developed by the American Society for Radiation Oncology (ASTRO). “This is gaining membership very rapidly, and it’s good because it facilitates cooperative research and also safety standards for our field,” he maintained.
“I’ll argue that they did that for a variety of reasons,” he elaborated. “Strong and effective leadership by Dr. Larry Marks, who’s really created a departmental culture of safety in which people can feel free to speak up. They have this wonderful Good Catch program in place. And they have these simulation review huddles ... where people feel free to talk about what happened yesterday or today that may be relevant moving forward.”
As for the national RO-ILS initiative, “I would look out to the audience and say, why is it that we don’t have such a program in medical oncology?” Dr. Jacobson said. “It’s probably time for us to do this,” he maintained.
Reducing chemotherapy errors in pediatric oncology
In the second study, Brian D. Weiss, MD, associate director of safety and compliance at Cincinnati Children’s Hospital Medical Center, and his colleagues studied the impact of a safety initiative to prevent chemotherapy errors at their large urban pediatric academic center (J Clin Oncol 35, 2017 [suppl 8S; abstract 37]).
“Pediatric chemotherapy protocols are different from adult protocols. We dose based on age or weight or body surface area, and that can change within a protocol. You have to do adjustments every time they gain weight or grow some, which is different than for adult protocols,” he explained. “We have parents administering chemo at home. And the protocols most patients are on are very complicated, but there is no standardized format, so it makes crucial information for dose adjustments difficult to find.”
The team successively implemented about half a dozen interventions, such as dedicated chemotherapy safety zones where staff were not to be disturbed while checking orders and ear protectors as a visual deterrent to interruptions; a new chemotherapy registered nurse role with a detailed list of responsibilities; an event-reporting system to supplement the center’s error-reporting system and capture events not reaching the patient (near-miss events); and a daily chemotherapy huddle to discuss errors in a nonpunitive setting and review upcoming chemotherapy for readiness.
In the 6 years after the start of the initiative, 105,187 chemotherapy doses were administered at the center and 998 errors occurred, including 250 errors that reached the patient, according to results reported at the symposium and recently published (J Oncol Pract. 2017 April;13:e329-e336).
At the 22-month mark, the rate of chemotherapy errors reaching the patient had fallen from 3.8 in 1,000 doses at baseline to 1.9 in 1,000 doses. The reduction has since persisted for more than 4 years and translates to an estimated 155 fewer predicted errors reaching the patient because of the initiative.
“The errors that reached the patient were more often administration and dispensing errors,” Dr. Weiss said. “About two-thirds of those errors that didn’t reach the patient – because they got caught by the pharmacists and the nurses – were prescription errors.
“Our chemotherapy huddle has certainly increased our reporting of errors. We also now use it for patients on clinical trials ... any patient getting PK [pharmacokinetics] or PD [pharmacodynamics] sampled within the next 24 hours is reviewed at that meeting. And our missed samples have gone down significantly,” he noted. “It’s allowed us to manage our bed space better because now everybody knows who’s definitely coming in the next day and who’s maybe coming in the next day.”
“We are a large urban academic pediatric medical center. Some of these things may seem difficult to translate [to smaller facilities], but I’m not sure they are,” concluded Dr. Weiss.
Dr. Jacobson, the discussant, noted that the initiative was in keeping with this health system’s longstanding “obsessive” focus on patient safety and commended its rigorousness in, for example, setting clear goals, focusing on key drivers [processes] needed for change, and selecting a good outcome metric.
“This is very successful project,” he said. The success can be attributed to “strong and effective organization and leadership, building a culture of safety at Cincinnati Children’s Hospital, and an important predefined measurement program and methodology.”
Building chemotherapy regimens more accurately
In the third study, a team led by Andrea Crespo, BSc, BScPhm, BCOP, an oncology pharmacist and member of the Systemic Treatment Team at Cancer Care Ontario, Toronto, studied errors introduced when chemotherapy regimens were moved from publications into orders used by centers in the province (J Clin Oncol. 35, 2017 [suppl 8S; abstract 51]).
Nearly all outpatient intravenous systemic treatment visits in Ontario are supported by a Systemic Treatment Computerized Prescriber Order Entry (ST-CPOE) system, she noted. Such systems can reduce error rates but are not foolproof.
She and her colleagues asked all Ontario treatment centers to review their active chemotherapy regimens. Data were analyzed to determine whether the regimens were built as intended with respect to their component drugs and doses, leading to identification of any unintentional discrepancies with the original regimen.
A total of 33 centers performed the review, and the median number of regimens reviewed was 375 per center, Ms. Crespo reported.
Unintentional discrepancies in regimens were found at 27% of centers. The total number reported was 369 discrepancies, with a range from 2 to 198 per center.
All of the nine centers where discrepancies were found participated in the provincial ST-CPOE system, and most had for at least 20 years. Furthermore, eight of them used a team of at least two pharmacists and one oncologist to build their regimens. “So you can see that discrepancies occurred despite a fairly rigorous regimen-build process and many years of experience with the system,” she said.
Of the 369 total discrepancies, 41% were related to alignment with the Systemic Treatment Quality-Based Program regimen, and 32% were regimens flagged to be inactivated because of outdated information, new standards, or lack of use.
A detailed analysis of the remaining 27%, or 101 unintentional discrepancies, showed that the majority were due to missing information (35.6%) or missing drugs (13.9%), incorrect doses (10.9%), and incorrect or missing schedules (10.9%). Potential to cause harm was mild for 55%, moderate for 28%, and none for 17%.
“Corrective action has been taken to address the discrepancies identified,” said Ms. Crespo.
Only 6% of the 33 centers reported having an established regimen review and maintenance process in place before the study, but all now have such a process. In addition, some centers that did not find any regimen discrepancies nonetheless reported adding quality improvement activities, such as changes in the ways regimens were built and documented, and revising regimen names to facilitate accurate selection.
In discussing the study, Dr. Jacobson noted the low proportion of centers having an established process at baseline to ensure appropriate regimen maintenance and updates. “You might want to think to yourselves, the medical oncologists in the group, whether your center has such a process in place,” he proposed.
It is not yet known whether the project has met its goal of improving the quality and accuracy of oncology regimens in Ontario, he maintained. “We are going to have to invite [Ms. Crespo] back in a year or two to see whether that turns out to be true.” On the other hand, “clearly what they have achieved was the ability to measure the variance between what was intended and what was actually built.”
Chief among the reasons for success, again, “was a strong and effective leadership and organizational structure, not at the department level or hospital level, but across the entire province through Cancer Care Ontario,” Dr. Jacobson said. “It’s clear that they have a focus on quality and patient safety, and this measurement program that they have put in place turned out to be useful.”
Dr. Judy, Dr. Weiss, and Ms. Crespo disclosed that they had no relevant conflicts of interest.
ORLANDO – Accumulating evidence is helping researchers better understand why errors occur during the delivery of cancer treatment and how to prevent them. Findings from a trio of studies were reported at a symposium on quality care sponsored by the American Society of Clinical Oncology.
Identifying causes of incidents in radiation therapy
In the first study, Greg D. Judy, MD, a radiation oncology resident at the University of North Carolina at Chapel Hill, and his colleagues retrospectively reviewed records in their institution’s reporting system, called Good Catch, to identify near-miss incidents (ones that didn’t reach the patient) and safety incidents (ones that did) among patients undergoing radiation therapy from October 2014 through April 2016.
Multivariate analysis showed that patients had a significantly higher risk of near-miss or safety incidents if they had stage T2 disease (odds ratio, 3.3), were being treated for cancer involving the head and neck (5.2), or were receiving image-guided intensity-modulated radiation therapy (3.0) or daily imaging as part of their treatment (7.0), Dr. Judy reported.
“Head and neck site and image-guided IMRT [intensity-modulated radiation therapy] are complex entities: They have multiple steps in both the planning and delivery phase,” he said. “Daily imaging as well. It’s a much more complex process to do daily imaging for setup verification than it is to do once-a-week or even once-every-2-weeks setup verification.”
On the other hand, it was unclear why T2 stage was a risk factor. “We kind of hypothesized that it might be more of the disease site that really drives this, as you can have HPV-positive oropharyngeal cancer which usually has lower T stages and more advanced nodal stages, but even then, that’s a head and neck site and we usually use image-guided IMRT, which are both very complex entities,” he said. The most common root causes for the incidents were issues related to documentation and scheduling (29% each), followed by issues related to communication (22%), technical treatment planning (14%), and technical treatment delivery (6%).
Incidents having a communication root cause were more likely than were others to affect patients (P less than .001), and those having a technical treatment delivery root cause were more likely to have higher severity (P = .005).
“Like some other studies, we found really the key factor was the complexity of the treatment plan and complexity of the overall process that is the real driving factor. This is important to understand because it promotes the idea of developing a more dedicated and robust QA system for complex cases,” said Dr. Judy. “It also highlights the importance of a strong reporting system to support a safety culture, as well as promote the continuous learning improvements within a department.”
The national Radiation Oncology Incident Learning System (RO-ILS) has been developed by the American Society for Radiation Oncology (ASTRO). “This is gaining membership very rapidly, and it’s good because it facilitates cooperative research and also safety standards for our field,” he maintained.
“I’ll argue that they did that for a variety of reasons,” he elaborated. “Strong and effective leadership by Dr. Larry Marks, who’s really created a departmental culture of safety in which people can feel free to speak up. They have this wonderful Good Catch program in place. And they have these simulation review huddles ... where people feel free to talk about what happened yesterday or today that may be relevant moving forward.”
As for the national RO-ILS initiative, “I would look out to the audience and say, why is it that we don’t have such a program in medical oncology?” Dr. Jacobson said. “It’s probably time for us to do this,” he maintained.
Reducing chemotherapy errors in pediatric oncology
In the second study, Brian D. Weiss, MD, associate director of safety and compliance at Cincinnati Children’s Hospital Medical Center, and his colleagues studied the impact of a safety initiative to prevent chemotherapy errors at their large urban pediatric academic center (J Clin Oncol 35, 2017 [suppl 8S; abstract 37]).
“Pediatric chemotherapy protocols are different from adult protocols. We dose based on age or weight or body surface area, and that can change within a protocol. You have to do adjustments every time they gain weight or grow some, which is different than for adult protocols,” he explained. “We have parents administering chemo at home. And the protocols most patients are on are very complicated, but there is no standardized format, so it makes crucial information for dose adjustments difficult to find.”
The team successively implemented about half a dozen interventions, such as dedicated chemotherapy safety zones where staff were not to be disturbed while checking orders and ear protectors as a visual deterrent to interruptions; a new chemotherapy registered nurse role with a detailed list of responsibilities; an event-reporting system to supplement the center’s error-reporting system and capture events not reaching the patient (near-miss events); and a daily chemotherapy huddle to discuss errors in a nonpunitive setting and review upcoming chemotherapy for readiness.
In the 6 years after the start of the initiative, 105,187 chemotherapy doses were administered at the center and 998 errors occurred, including 250 errors that reached the patient, according to results reported at the symposium and recently published (J Oncol Pract. 2017 April;13:e329-e336).
At the 22-month mark, the rate of chemotherapy errors reaching the patient had fallen from 3.8 in 1,000 doses at baseline to 1.9 in 1,000 doses. The reduction has since persisted for more than 4 years and translates to an estimated 155 fewer predicted errors reaching the patient because of the initiative.
“The errors that reached the patient were more often administration and dispensing errors,” Dr. Weiss said. “About two-thirds of those errors that didn’t reach the patient – because they got caught by the pharmacists and the nurses – were prescription errors.
“Our chemotherapy huddle has certainly increased our reporting of errors. We also now use it for patients on clinical trials ... any patient getting PK [pharmacokinetics] or PD [pharmacodynamics] sampled within the next 24 hours is reviewed at that meeting. And our missed samples have gone down significantly,” he noted. “It’s allowed us to manage our bed space better because now everybody knows who’s definitely coming in the next day and who’s maybe coming in the next day.”
“We are a large urban academic pediatric medical center. Some of these things may seem difficult to translate [to smaller facilities], but I’m not sure they are,” concluded Dr. Weiss.
Dr. Jacobson, the discussant, noted that the initiative was in keeping with this health system’s longstanding “obsessive” focus on patient safety and commended its rigorousness in, for example, setting clear goals, focusing on key drivers [processes] needed for change, and selecting a good outcome metric.
“This is very successful project,” he said. The success can be attributed to “strong and effective organization and leadership, building a culture of safety at Cincinnati Children’s Hospital, and an important predefined measurement program and methodology.”
Building chemotherapy regimens more accurately
In the third study, a team led by Andrea Crespo, BSc, BScPhm, BCOP, an oncology pharmacist and member of the Systemic Treatment Team at Cancer Care Ontario, Toronto, studied errors introduced when chemotherapy regimens were moved from publications into orders used by centers in the province (J Clin Oncol. 35, 2017 [suppl 8S; abstract 51]).
Nearly all outpatient intravenous systemic treatment visits in Ontario are supported by a Systemic Treatment Computerized Prescriber Order Entry (ST-CPOE) system, she noted. Such systems can reduce error rates but are not foolproof.
She and her colleagues asked all Ontario treatment centers to review their active chemotherapy regimens. Data were analyzed to determine whether the regimens were built as intended with respect to their component drugs and doses, leading to identification of any unintentional discrepancies with the original regimen.
A total of 33 centers performed the review, and the median number of regimens reviewed was 375 per center, Ms. Crespo reported.
Unintentional discrepancies in regimens were found at 27% of centers. The total number reported was 369 discrepancies, with a range from 2 to 198 per center.
All of the nine centers where discrepancies were found participated in the provincial ST-CPOE system, and most had for at least 20 years. Furthermore, eight of them used a team of at least two pharmacists and one oncologist to build their regimens. “So you can see that discrepancies occurred despite a fairly rigorous regimen-build process and many years of experience with the system,” she said.
Of the 369 total discrepancies, 41% were related to alignment with the Systemic Treatment Quality-Based Program regimen, and 32% were regimens flagged to be inactivated because of outdated information, new standards, or lack of use.
A detailed analysis of the remaining 27%, or 101 unintentional discrepancies, showed that the majority were due to missing information (35.6%) or missing drugs (13.9%), incorrect doses (10.9%), and incorrect or missing schedules (10.9%). Potential to cause harm was mild for 55%, moderate for 28%, and none for 17%.
“Corrective action has been taken to address the discrepancies identified,” said Ms. Crespo.
Only 6% of the 33 centers reported having an established regimen review and maintenance process in place before the study, but all now have such a process. In addition, some centers that did not find any regimen discrepancies nonetheless reported adding quality improvement activities, such as changes in the ways regimens were built and documented, and revising regimen names to facilitate accurate selection.
In discussing the study, Dr. Jacobson noted the low proportion of centers having an established process at baseline to ensure appropriate regimen maintenance and updates. “You might want to think to yourselves, the medical oncologists in the group, whether your center has such a process in place,” he proposed.
It is not yet known whether the project has met its goal of improving the quality and accuracy of oncology regimens in Ontario, he maintained. “We are going to have to invite [Ms. Crespo] back in a year or two to see whether that turns out to be true.” On the other hand, “clearly what they have achieved was the ability to measure the variance between what was intended and what was actually built.”
Chief among the reasons for success, again, “was a strong and effective leadership and organizational structure, not at the department level or hospital level, but across the entire province through Cancer Care Ontario,” Dr. Jacobson said. “It’s clear that they have a focus on quality and patient safety, and this measurement program that they have put in place turned out to be useful.”
Dr. Judy, Dr. Weiss, and Ms. Crespo disclosed that they had no relevant conflicts of interest.
ORLANDO – Accumulating evidence is helping researchers better understand why errors occur during the delivery of cancer treatment and how to prevent them. Findings from a trio of studies were reported at a symposium on quality care sponsored by the American Society of Clinical Oncology.
Identifying causes of incidents in radiation therapy
In the first study, Greg D. Judy, MD, a radiation oncology resident at the University of North Carolina at Chapel Hill, and his colleagues retrospectively reviewed records in their institution’s reporting system, called Good Catch, to identify near-miss incidents (ones that didn’t reach the patient) and safety incidents (ones that did) among patients undergoing radiation therapy from October 2014 through April 2016.
Multivariate analysis showed that patients had a significantly higher risk of near-miss or safety incidents if they had stage T2 disease (odds ratio, 3.3), were being treated for cancer involving the head and neck (5.2), or were receiving image-guided intensity-modulated radiation therapy (3.0) or daily imaging as part of their treatment (7.0), Dr. Judy reported.
“Head and neck site and image-guided IMRT [intensity-modulated radiation therapy] are complex entities: They have multiple steps in both the planning and delivery phase,” he said. “Daily imaging as well. It’s a much more complex process to do daily imaging for setup verification than it is to do once-a-week or even once-every-2-weeks setup verification.”
On the other hand, it was unclear why T2 stage was a risk factor. “We kind of hypothesized that it might be more of the disease site that really drives this, as you can have HPV-positive oropharyngeal cancer which usually has lower T stages and more advanced nodal stages, but even then, that’s a head and neck site and we usually use image-guided IMRT, which are both very complex entities,” he said. The most common root causes for the incidents were issues related to documentation and scheduling (29% each), followed by issues related to communication (22%), technical treatment planning (14%), and technical treatment delivery (6%).
Incidents having a communication root cause were more likely than were others to affect patients (P less than .001), and those having a technical treatment delivery root cause were more likely to have higher severity (P = .005).
“Like some other studies, we found really the key factor was the complexity of the treatment plan and complexity of the overall process that is the real driving factor. This is important to understand because it promotes the idea of developing a more dedicated and robust QA system for complex cases,” said Dr. Judy. “It also highlights the importance of a strong reporting system to support a safety culture, as well as promote the continuous learning improvements within a department.”
The national Radiation Oncology Incident Learning System (RO-ILS) has been developed by the American Society for Radiation Oncology (ASTRO). “This is gaining membership very rapidly, and it’s good because it facilitates cooperative research and also safety standards for our field,” he maintained.
“I’ll argue that they did that for a variety of reasons,” he elaborated. “Strong and effective leadership by Dr. Larry Marks, who’s really created a departmental culture of safety in which people can feel free to speak up. They have this wonderful Good Catch program in place. And they have these simulation review huddles ... where people feel free to talk about what happened yesterday or today that may be relevant moving forward.”
As for the national RO-ILS initiative, “I would look out to the audience and say, why is it that we don’t have such a program in medical oncology?” Dr. Jacobson said. “It’s probably time for us to do this,” he maintained.
Reducing chemotherapy errors in pediatric oncology
In the second study, Brian D. Weiss, MD, associate director of safety and compliance at Cincinnati Children’s Hospital Medical Center, and his colleagues studied the impact of a safety initiative to prevent chemotherapy errors at their large urban pediatric academic center (J Clin Oncol 35, 2017 [suppl 8S; abstract 37]).
“Pediatric chemotherapy protocols are different from adult protocols. We dose based on age or weight or body surface area, and that can change within a protocol. You have to do adjustments every time they gain weight or grow some, which is different than for adult protocols,” he explained. “We have parents administering chemo at home. And the protocols most patients are on are very complicated, but there is no standardized format, so it makes crucial information for dose adjustments difficult to find.”
The team successively implemented about half a dozen interventions, such as dedicated chemotherapy safety zones where staff were not to be disturbed while checking orders and ear protectors as a visual deterrent to interruptions; a new chemotherapy registered nurse role with a detailed list of responsibilities; an event-reporting system to supplement the center’s error-reporting system and capture events not reaching the patient (near-miss events); and a daily chemotherapy huddle to discuss errors in a nonpunitive setting and review upcoming chemotherapy for readiness.
In the 6 years after the start of the initiative, 105,187 chemotherapy doses were administered at the center and 998 errors occurred, including 250 errors that reached the patient, according to results reported at the symposium and recently published (J Oncol Pract. 2017 April;13:e329-e336).
At the 22-month mark, the rate of chemotherapy errors reaching the patient had fallen from 3.8 in 1,000 doses at baseline to 1.9 in 1,000 doses. The reduction has since persisted for more than 4 years and translates to an estimated 155 fewer predicted errors reaching the patient because of the initiative.
“The errors that reached the patient were more often administration and dispensing errors,” Dr. Weiss said. “About two-thirds of those errors that didn’t reach the patient – because they got caught by the pharmacists and the nurses – were prescription errors.
“Our chemotherapy huddle has certainly increased our reporting of errors. We also now use it for patients on clinical trials ... any patient getting PK [pharmacokinetics] or PD [pharmacodynamics] sampled within the next 24 hours is reviewed at that meeting. And our missed samples have gone down significantly,” he noted. “It’s allowed us to manage our bed space better because now everybody knows who’s definitely coming in the next day and who’s maybe coming in the next day.”
“We are a large urban academic pediatric medical center. Some of these things may seem difficult to translate [to smaller facilities], but I’m not sure they are,” concluded Dr. Weiss.
Dr. Jacobson, the discussant, noted that the initiative was in keeping with this health system’s longstanding “obsessive” focus on patient safety and commended its rigorousness in, for example, setting clear goals, focusing on key drivers [processes] needed for change, and selecting a good outcome metric.
“This is very successful project,” he said. The success can be attributed to “strong and effective organization and leadership, building a culture of safety at Cincinnati Children’s Hospital, and an important predefined measurement program and methodology.”
Building chemotherapy regimens more accurately
In the third study, a team led by Andrea Crespo, BSc, BScPhm, BCOP, an oncology pharmacist and member of the Systemic Treatment Team at Cancer Care Ontario, Toronto, studied errors introduced when chemotherapy regimens were moved from publications into orders used by centers in the province (J Clin Oncol. 35, 2017 [suppl 8S; abstract 51]).
Nearly all outpatient intravenous systemic treatment visits in Ontario are supported by a Systemic Treatment Computerized Prescriber Order Entry (ST-CPOE) system, she noted. Such systems can reduce error rates but are not foolproof.
She and her colleagues asked all Ontario treatment centers to review their active chemotherapy regimens. Data were analyzed to determine whether the regimens were built as intended with respect to their component drugs and doses, leading to identification of any unintentional discrepancies with the original regimen.
A total of 33 centers performed the review, and the median number of regimens reviewed was 375 per center, Ms. Crespo reported.
Unintentional discrepancies in regimens were found at 27% of centers. The total number reported was 369 discrepancies, with a range from 2 to 198 per center.
All of the nine centers where discrepancies were found participated in the provincial ST-CPOE system, and most had for at least 20 years. Furthermore, eight of them used a team of at least two pharmacists and one oncologist to build their regimens. “So you can see that discrepancies occurred despite a fairly rigorous regimen-build process and many years of experience with the system,” she said.
Of the 369 total discrepancies, 41% were related to alignment with the Systemic Treatment Quality-Based Program regimen, and 32% were regimens flagged to be inactivated because of outdated information, new standards, or lack of use.
A detailed analysis of the remaining 27%, or 101 unintentional discrepancies, showed that the majority were due to missing information (35.6%) or missing drugs (13.9%), incorrect doses (10.9%), and incorrect or missing schedules (10.9%). Potential to cause harm was mild for 55%, moderate for 28%, and none for 17%.
“Corrective action has been taken to address the discrepancies identified,” said Ms. Crespo.
Only 6% of the 33 centers reported having an established regimen review and maintenance process in place before the study, but all now have such a process. In addition, some centers that did not find any regimen discrepancies nonetheless reported adding quality improvement activities, such as changes in the ways regimens were built and documented, and revising regimen names to facilitate accurate selection.
In discussing the study, Dr. Jacobson noted the low proportion of centers having an established process at baseline to ensure appropriate regimen maintenance and updates. “You might want to think to yourselves, the medical oncologists in the group, whether your center has such a process in place,” he proposed.
It is not yet known whether the project has met its goal of improving the quality and accuracy of oncology regimens in Ontario, he maintained. “We are going to have to invite [Ms. Crespo] back in a year or two to see whether that turns out to be true.” On the other hand, “clearly what they have achieved was the ability to measure the variance between what was intended and what was actually built.”
Chief among the reasons for success, again, “was a strong and effective leadership and organizational structure, not at the department level or hospital level, but across the entire province through Cancer Care Ontario,” Dr. Jacobson said. “It’s clear that they have a focus on quality and patient safety, and this measurement program that they have put in place turned out to be useful.”
Dr. Judy, Dr. Weiss, and Ms. Crespo disclosed that they had no relevant conflicts of interest.
AT THE QUALITY CARE SYMPOSIUM
Key clinical point:
Major finding: Risk factors for radiation therapy near-miss and safety incidents were T2 stage, H&N site, and more complex techniques (odds ratios, 3.0-7.0). A quality improvement initiative halved the rate of chemotherapy errors reaching the patient from 3.8 to 1.9 per 1,000 doses. Twenty-seven percent of centers found unintentional discrepancies in their chemotherapy regimens, 83% with potential to cause harm.
Data source: A retrospective case-control study of 400 patients receiving radiation therapy, a longitudinal cohort study of a quality improvement initiative at an urban pediatric academic medical center involving administration of 105,187 chemotherapy doses, and a cohort study of 33 Ontario treatment centers that reviewed a median of 375 chemotherapy regimens.
Disclosures: Dr. Judy, Dr. Weiss, and Ms. Crespo disclosed that they had no relevant conflicts of interest.
Ibrutinib monotherapy data in previously treated MZL is available
Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.
Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.
“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”
“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”
In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.
The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy
After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.
The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.
“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.
Dr. Noy disclosed that she has received research funding from Pharmacyclics.
Putting these results into context, the efficacy of ibrutinib seems similar to that of other single agents evaluated in patients with relapsed marginal zone lymphoma, including other agents that target molecules downstream of the B-cell receptor.
The observed response rate is “modest” compared with that seen when the drug is used to treat other conditions for which it is approved, he notes. Therefore, additional correlative studies to identify biomarkers predicting benefit in marginal zone lymphoma would have been helpful.
Nonetheless, the study team should be congratulated, as the trial demonstrates the ability to investigate rare disease subtypes in multicenter collaborations. The results justify ibrutinib as the first FDA-approved therapy for this disease and form the basis for subsequent trials that combine ibrutinib with anti-CD20 monoclonal antibodies and other targeted agents.
Paul M. Barr, MD, of the Wilmot Cancer Institute at the University of Rochester in New York made his remarks in an accompanying editorial (Blood. 2017;129:2207-08). Dr. Barr disclosed that he has consulted for and received research funding from Pharmacyclics and AbbVie.
Putting these results into context, the efficacy of ibrutinib seems similar to that of other single agents evaluated in patients with relapsed marginal zone lymphoma, including other agents that target molecules downstream of the B-cell receptor.
The observed response rate is “modest” compared with that seen when the drug is used to treat other conditions for which it is approved, he notes. Therefore, additional correlative studies to identify biomarkers predicting benefit in marginal zone lymphoma would have been helpful.
Nonetheless, the study team should be congratulated, as the trial demonstrates the ability to investigate rare disease subtypes in multicenter collaborations. The results justify ibrutinib as the first FDA-approved therapy for this disease and form the basis for subsequent trials that combine ibrutinib with anti-CD20 monoclonal antibodies and other targeted agents.
Paul M. Barr, MD, of the Wilmot Cancer Institute at the University of Rochester in New York made his remarks in an accompanying editorial (Blood. 2017;129:2207-08). Dr. Barr disclosed that he has consulted for and received research funding from Pharmacyclics and AbbVie.
Putting these results into context, the efficacy of ibrutinib seems similar to that of other single agents evaluated in patients with relapsed marginal zone lymphoma, including other agents that target molecules downstream of the B-cell receptor.
The observed response rate is “modest” compared with that seen when the drug is used to treat other conditions for which it is approved, he notes. Therefore, additional correlative studies to identify biomarkers predicting benefit in marginal zone lymphoma would have been helpful.
Nonetheless, the study team should be congratulated, as the trial demonstrates the ability to investigate rare disease subtypes in multicenter collaborations. The results justify ibrutinib as the first FDA-approved therapy for this disease and form the basis for subsequent trials that combine ibrutinib with anti-CD20 monoclonal antibodies and other targeted agents.
Paul M. Barr, MD, of the Wilmot Cancer Institute at the University of Rochester in New York made his remarks in an accompanying editorial (Blood. 2017;129:2207-08). Dr. Barr disclosed that he has consulted for and received research funding from Pharmacyclics and AbbVie.
Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.
Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.
“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”
“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”
In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.
The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy
After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.
The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.
“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.
Dr. Noy disclosed that she has received research funding from Pharmacyclics.
Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.
Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study (Blood. 2017;129:2224-32). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.
“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD, a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”
“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”
In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.
The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy
After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.
The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.
“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.
Dr. Noy disclosed that she has received research funding from Pharmacyclics.
Key clinical point:
Major finding: The overall response rate was 48%, and the drug was well tolerated.
Data source: A multicenter, open-label phase II trial of ibrutinib in 63 patients with previously treated marginal zone lymphoma.
Disclosures: Dr. Noy disclosed that she has received research funding from Pharmacyclics. The trial was funded by Pharmacyclics, an AbbVie Company.