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Immunocompromised people face highest risk of cutaneous SCC metastasis
However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.
In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.
Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.
“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.
Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.
Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.
“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”
Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.
Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.
“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.
Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.
“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”
No disclosures were disclosed for the authors.
However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.
In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.
Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.
“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.
Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.
Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.
“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”
Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.
Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.
“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.
Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.
“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”
No disclosures were disclosed for the authors.
However, no study has thoroughly evaluated the prognostic factors associated with metastasis until now.
In the Journal of Otolaryngology – Head & Neck Surgery, researchers wrote that immunocompromised individuals, such as solid organ transplant patients, make up 73.3% of all patients with cutaneous SCC who are at risk of metastasis and decreased overall survival.
Led by Alex M. Mlynarek, MD, a specialist in head and neck oncology and microvascular reconstruction at McGill University, Montreal, the finding is based on a systematic literature review of 40 studies involving 8,535 patients.
“The prognostic factors for head and neck cutaneous squamous cell carcinoma that were most consistently reported as significant in the literature are a state of immunosuppression, tumor depth, margins involved, number of lymph nodes affected by carcinoma, parotideal disease, and age,” Dr. Mlynarek and colleagues wrote.
Cutaneous SCC is the second most common nonmelanoma skin cancer with an increase of 263% between 2000 and 2010, shows research from the Mayo Clinic Rochester Epidemiology Project.
Patients in this study with tumors that are 6 mm or greater, or whose tumor invaded fat tissue, were found to have a poor prognosis followed by patients with perineural and lymphovascular invasion and in particular, patients with a poorer grade of cellular differentiation. The number of lymph nodes was significant at 70%, with more than two nodes involved linked to a worse the prognosis, followed by 66.7% for margins involved with carcinoma and 50% for tumor depth.
“The majority of patients with cutaneous SCC undergoes electrodesiccation and curettage, cryosurgery, or Mohs surgery, and have an excellent prognosis,” the authors wrote. “However, there is a subset of patients in which these therapies are unsuccessful and where cutaneous SCC appears to be far more aggressive, often resulting in metastasis and recurrence.”
Age was shown to be a significant factor in 53.3% of the studies, but the extent of its effect on prognosis was questionable.
Sentinel lymph node biopsy is commonly used to stage melanoma and has been used in oral SCC.
“A patient post biopsy with either two major criteria or one major and two minor criteria should be considered as a candidate for sentinel lymph node biopsy,” the authors wrote, adding that the findings were consistent with those for cutaneous SCC generally, not specified to the head and neck.
Limitations of the systematic review include potential selection bias as the majority of the studies were based in Australia and most studies were not specified to cutaneous SCC of the head and neck region.
“Given the low rate of metastasis from head and neck cutaneous SCC lesions, it can be challenging to identify the patients who are at high risk of having metastatic disease,” the authors wrote. “We believe this review could help identify patients that would require a closer follow-up and those that could possibly profit from a sentinel lymph node biopsy.”
No disclosures were disclosed for the authors.
FROM THE JOURNAL OF OTOLARYNGOLOGY – HEAD AND NECK SURGERY
Early mortality falls in advanced ovarian cancer with neoadjuvant chemo
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
FROM JAMA ONCOLOGY
Cancer centers with a high use of neoadjuvant chemotherapy in patients with advanced-stage epithelial ovarian cancer show similar improvements in median overall survival and larger declines in short-term mortality than in centers with low use of this treatment. This is according to a study published in JAMA Oncology, suggesting that neoadjuvant chemotherapy may be a suitable first-line treatment approach for many patients with advanced-stage ovarian cancer.
“There is considerable variation in practice. Some centers administer neoadjuvant chemotherapy to 75% of patients with advanced ovarian cancers, others use the approach very infrequently,” said Alexander Melamed, MD, MPH, of Columbia University, New York.
“I hope that those clinicians who have been worried about the negative impacts of too frequent administration of neoadjuvant chemotherapy may be reassured by this study and may come to use this good treatment more often.”
Research has shown that, compared with primary cytoreductive surgery, the use of neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes in patients with ovarian cancer. While the use of neoadjuvant chemotherapy has increased, many experts continue to recommend upfront surgery as the preferred treatment for these patients.
“In part, these recommendations are based on flawed interpretations of real-world data. Specifically, many observational studies have concluded that upfront surgery results in better survival than neoadjuvant chemotherapy, based on study designs that ignored the fact that patients who receive neoadjuvant chemotherapy in the real word are sicker and have more extensive cancer than those who receive upfront surgery,” Dr. Melamed said.
In this difference-in-differences comparative effectiveness analysis, researchers asked if the difference in adoption of neoadjuvant chemotherapy by U.S. cancer centers for advanced-stage epithelial ovarian cancer was associated with differences in median overall survival and 1-year all-cause mortality.
“By assessing how this divergence in practice impacted patient outcomes we were able to infer how frequent use of neoadjuvant impacts survival in ovarian cancer patients. This study design allowed us to sidestep the problem of selection bias that has plagued many other observational studies in this space,” Dr. Melamed explained.
This observational study included 39,299 women with stage IIIC and IV epithelial ovarian cancer, diagnosed between 2004 and 2015 who were followed to the end of 2018, and treated at one of 664 cancer programs. Patients treated in programs that increased neoadjuvant chemotherapy administration had greater improvements in 1-year mortality (difference-in-differences, −2.1%; 95% confidence interval, −3.7 to −0.5) and equivalent gains in median overall survival (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7 months), compared with those treated in programs that used the treatment infrequently.
“For a long time, experts have suggested that the apparent discordance between randomized controlled trials and real-world studies that compare neoadjuvant chemotherapy to upfront surgery for ovarian cancer might mean that the randomized trials are not applicable to real-world practice. What is significant about our findings, is that, when more appropriate study methods are used to analyze the real-world data, the apparent contradiction between real-world and randomized studies is resolved.
“We found that, just as one would guess based on the findings of randomized trials, patients treated in the centers that increased the use of neoadjuvant chemotherapy did not have any decrement in long-term survival, but that short-term mortality did improve more in these centers than in centers that administered neoadjuvant chemotherapy rarely,” she said.
Dr. Melamed said that the findings should “spur a reappraisal” of what clinicians consider the default treatment for women with stage IIIC and IV ovarian cancer.
Taken together with randomized controlled trials, “the evidence may be at a point where it is now time to consider neoadjuvant chemotherapy as the default approach to patients with bulky carcinomatosis, and that primary surgery may be a reasonable alternative for a select group of healthy, young patients with low-volume metastasis.
“Other factors like the route of adjuvant chemotherapy may also need to be considered. However, I believe the belief that aggressive primary debulking is beneficial for most women with advanced ovarian cancer is outdated,” Dr. Melamed said.
No relevant conflicts of interest were reported for this research.
Donafenib shows potential as first-line treatment of advanced hepatocellular carcinoma
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
“An improvement in the pharmacotherapy of advanced HCC remains a clinical need,” wrote Feng Bi, MD, of Sichuan University, in Chengdu, China, and colleagues.
Liver cancer is one of the most common cancers worldwide, with HCC representing 90% of liver malignancies. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth leading cause of cancer deaths in the United States. Most patients are diagnosed at the advanced stage with a median survival of 6-8 months. Sorafenib, the standard first-line therapy for advanced HCC, has demonstrated the median OS of 10.7 to 14.7 months. No other monotherapy has shown a significant improvement in OS, compared with sorafenib. Donafenib has shown favorable efficacy and safety in phase 1 studies.
This phase 2-3 trial evaluated the efficacy and safety of first-line donafenib, compared with sorafenib, in 668 Chinese patients with advanced HCC. Patients were randomly assigned to receive twice-daily oral donafenib 0.2 g or sorafenib 0.4 g until intolerable toxicity or disease progression. The primary end point was OS, tested for noninferiority and superiority.
Compared with sorafenib, donafenib significantly prolonged OS, 10.3 and 12.1 months, respectively, (hazard ratio, 95% confidence interval, 0.699-0.988; 0.83; P = .0245), and the superiority criteria for OS were met. Donafenib also presented improved safety and tolerability. Common drug-related adverse events, such as hand-foot skin reactions and diarrhea, and drug-related grade 3 or higher adverse events, occurred in fewer patients receiving donafenib than sorafenib, (38% vs. 50%; P = .0018). The authors noted that this lower frequency in adverse events with donafenib “contributed to improved patient adherence and decreased levels of drug interruption and discontinuation.”
Donafenib is a novel, oral, small-molecule, multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis by inhibiting vascular endothelial growth factor receptors and platelet-derived growth factor receptors, and Raf kinases. It is a derivative of sorafenib and in June 2021, it was approved in China as a treatment for unresectable hepatocellular carcinoma for patients who have not received systemic treatment. It is not yet available in the United States.
“This pivotal head-to-head comparison study is the first to demonstrate noninferiority and superiority of a monotherapy, donafenib, with statistically significant extension in OS over sorafenib for first-line treatment of advanced HCC,” the authors wrote. “Compared with international trials, patients in this study presented with more severe baseline disease states, further emphasizing the positive response observed with donafenib.”
Another study, published in the same issue of the Journal of Clinical Oncology, compared tremelimumab and durvalumab as monotherapies and in combination for patients with unresectable HCC, found that use a single priming dose of tremelimumab combined with durvalumab showed the best benefit-risk profile.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Neuroimaging may predict cognitive decline after chemotherapy for breast cancer
“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.
Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.
In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.
The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.
A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.
Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.
The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.
No potential conflicts of interest were reported.
“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.
Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.
In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.
The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.
A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.
Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.
The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.
No potential conflicts of interest were reported.
“Cognitive decline is frequently observed after chemotherapy,” according to Michiel B. de Ruiter, PhD, a research scientist with the Netherlands Cancer Institute in Amsterdam. He specializes in cognitive neuroscience and was the lead author of a study published online Sept. 30, 2021, in the Journal of Clinical Oncology. Dr. de Ruiter and colleagues found that fractional anisotropy may demonstrate a low brain white-matter reserve which could be a risk factor for cognitive decline after chemotherapy for breast cancer treatment.
Cognitive decline after chemotherapy has been reported in 20%-40% of patients with cancer affecting quality of life and daily living skills. Studies have suggested that genetic makeup, advanced age, fatigue, and premorbid intelligence quotient are risk factors for chemotherapy-associated cognitive decline. Changes in the microstructure of brain white matter, known as brain reserve, have been reported after exposure to chemotherapy, but its link to cognitive decline is understudied. Several studies outside of oncology have used MRI to derive fractional anisotropy as a measure for brain reserve.
In the new JCO study, researchers examined fractional anisotropy, as measured by MRI, before chemotherapy. The analysis included 49 patients who underwent neuropsychological tests before treatment with anthracycline-based chemotherapy, then again at 6 months and 2 years after chemotherapy.
The results were compared with those of patients with breast cancer who did not receive systemic therapy and then with a control group consisting of patients without cancer.
A low fractional anisotropy score suggested cognitive decline more than 3 years after receiving chemotherapy treatment. The finding was independent of age, premorbid intelligence quotient, baseline fatigue and baseline cognitive complaints. And, having low premorbid intelligence quotient was an independent risk factor for chemotherapy-associated cognitive decline, which the authors said is in line with previous findings.
Fractional anisotropy did not predict cognitive decline in patients who did not receive systemic therapy, as well as patients in the control group.
The findings could possibly lead to the development a pretreatment assessment to screen for patients who may at risk for cognitive decline, the authors wrote. “Clinically validated assessments of white-matter reserve as assessed with an MRI scan may be part of a pretreatment screening. This could also aid in early identification of cognitive decline after chemotherapy, allowing targeted and early interventions to improve cognitive problems,” such as psychoeducation and cognitive rehabilitation.
No potential conflicts of interest were reported.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Priming tremelimumab dose regimen shows promising benefit-risk profile in HCC
The novel regimen featuring a single, priming dose of tremelimumab “displayed the most encouraging benefit-risk profile,” wrote Robin Kate Kelley, MD, of the University of California, San Francisco, and colleagues in the Journal of Clinical Oncology. “These findings suggest that a single dose of tremelimumab may be sufficient to activate the tumor-fighting potential of the immune system.”
The incidence of HCC has been increasing worldwide over the last 20 years. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth-leading cause of cancer deaths in the United States. The 1-year survival rates in patients with HCC are less than 50%.
Atezolizumab plus bevacizumab gained regulatory approval in 2020 for the treatment of unresectable HCC. Several other immunotherapy-containing regimens are being evaluated, including immune checkpoint inhibitors combined with antiangiogenic agents. Immune checkpoint inhibitors – programmed death–ligand 1 and cytotoxic T-lymphocyte–associated antigen-4 – have shown promise in unresectable HCC, but they are insufficient as single agents and anti–CTLA-4 can be accompanied by challenging toxicities.
In this phase 1/2 study, researchers evaluated tremelimumab (anti–CTLA-4) and durvalumab (anti–PD-L1) as monotherapies and in combination, including a regimen featuring a single, priming dose of tremelimumab and durvalumab followed by durvalumab every 4 weeks. A total of 332 patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive one of the four regimens. The primary endpoint was safety.
While the priming doses regimen showed the best benefit-risk profile, all regimens were found to be tolerable and clinically active.
Specifically, in patients on the priming dose, durvalumab, tremelimumab and combination regimes, grade 3 or higher treatment-related adverse events occurred in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. For secondary endpoints, objective response rates were 24.0%, 10.6%, 7.2%, and 9.5%, respectively. The median overall survival was 18.7, 13.6, 15.1, and 11.3 months, respectively.
The priming dose regimen stimulated CD8+ T-cell production, which the authors suggested enhanced response and efficacy.
This novel regimen “may offer distinct differentiating features beyond demonstration of durable objective responses and promising overall survival, including a favorable safety profile with a relatively low steroid requirement, rare [antidrug antibody] formation, and a single, priming dose of tremelimumab followed by monthly durvalumab administration schedule,” the authors wrote. “Moreover, the absence of an antiangiogenic partner allows for treatment of patients who are contraindicated for antiangiogenics because of bleeding risks or comorbidities like cardiovascular disease.”
Another study, recently published in the Journal of Clinical Oncology, showed that donafenib was superior to sorafenib in improving overall survival, along with improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.
The tremelimumab/durvalumab study was funded by AstraZeneca.
The novel regimen featuring a single, priming dose of tremelimumab “displayed the most encouraging benefit-risk profile,” wrote Robin Kate Kelley, MD, of the University of California, San Francisco, and colleagues in the Journal of Clinical Oncology. “These findings suggest that a single dose of tremelimumab may be sufficient to activate the tumor-fighting potential of the immune system.”
The incidence of HCC has been increasing worldwide over the last 20 years. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth-leading cause of cancer deaths in the United States. The 1-year survival rates in patients with HCC are less than 50%.
Atezolizumab plus bevacizumab gained regulatory approval in 2020 for the treatment of unresectable HCC. Several other immunotherapy-containing regimens are being evaluated, including immune checkpoint inhibitors combined with antiangiogenic agents. Immune checkpoint inhibitors – programmed death–ligand 1 and cytotoxic T-lymphocyte–associated antigen-4 – have shown promise in unresectable HCC, but they are insufficient as single agents and anti–CTLA-4 can be accompanied by challenging toxicities.
In this phase 1/2 study, researchers evaluated tremelimumab (anti–CTLA-4) and durvalumab (anti–PD-L1) as monotherapies and in combination, including a regimen featuring a single, priming dose of tremelimumab and durvalumab followed by durvalumab every 4 weeks. A total of 332 patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive one of the four regimens. The primary endpoint was safety.
While the priming doses regimen showed the best benefit-risk profile, all regimens were found to be tolerable and clinically active.
Specifically, in patients on the priming dose, durvalumab, tremelimumab and combination regimes, grade 3 or higher treatment-related adverse events occurred in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. For secondary endpoints, objective response rates were 24.0%, 10.6%, 7.2%, and 9.5%, respectively. The median overall survival was 18.7, 13.6, 15.1, and 11.3 months, respectively.
The priming dose regimen stimulated CD8+ T-cell production, which the authors suggested enhanced response and efficacy.
This novel regimen “may offer distinct differentiating features beyond demonstration of durable objective responses and promising overall survival, including a favorable safety profile with a relatively low steroid requirement, rare [antidrug antibody] formation, and a single, priming dose of tremelimumab followed by monthly durvalumab administration schedule,” the authors wrote. “Moreover, the absence of an antiangiogenic partner allows for treatment of patients who are contraindicated for antiangiogenics because of bleeding risks or comorbidities like cardiovascular disease.”
Another study, recently published in the Journal of Clinical Oncology, showed that donafenib was superior to sorafenib in improving overall survival, along with improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.
The tremelimumab/durvalumab study was funded by AstraZeneca.
The novel regimen featuring a single, priming dose of tremelimumab “displayed the most encouraging benefit-risk profile,” wrote Robin Kate Kelley, MD, of the University of California, San Francisco, and colleagues in the Journal of Clinical Oncology. “These findings suggest that a single dose of tremelimumab may be sufficient to activate the tumor-fighting potential of the immune system.”
The incidence of HCC has been increasing worldwide over the last 20 years. HCC most commonly occurs in people with liver disease, particularly in those with chronic hepatitis B and C and although rare, HCC is the ninth-leading cause of cancer deaths in the United States. The 1-year survival rates in patients with HCC are less than 50%.
Atezolizumab plus bevacizumab gained regulatory approval in 2020 for the treatment of unresectable HCC. Several other immunotherapy-containing regimens are being evaluated, including immune checkpoint inhibitors combined with antiangiogenic agents. Immune checkpoint inhibitors – programmed death–ligand 1 and cytotoxic T-lymphocyte–associated antigen-4 – have shown promise in unresectable HCC, but they are insufficient as single agents and anti–CTLA-4 can be accompanied by challenging toxicities.
In this phase 1/2 study, researchers evaluated tremelimumab (anti–CTLA-4) and durvalumab (anti–PD-L1) as monotherapies and in combination, including a regimen featuring a single, priming dose of tremelimumab and durvalumab followed by durvalumab every 4 weeks. A total of 332 patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive one of the four regimens. The primary endpoint was safety.
While the priming doses regimen showed the best benefit-risk profile, all regimens were found to be tolerable and clinically active.
Specifically, in patients on the priming dose, durvalumab, tremelimumab and combination regimes, grade 3 or higher treatment-related adverse events occurred in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. For secondary endpoints, objective response rates were 24.0%, 10.6%, 7.2%, and 9.5%, respectively. The median overall survival was 18.7, 13.6, 15.1, and 11.3 months, respectively.
The priming dose regimen stimulated CD8+ T-cell production, which the authors suggested enhanced response and efficacy.
This novel regimen “may offer distinct differentiating features beyond demonstration of durable objective responses and promising overall survival, including a favorable safety profile with a relatively low steroid requirement, rare [antidrug antibody] formation, and a single, priming dose of tremelimumab followed by monthly durvalumab administration schedule,” the authors wrote. “Moreover, the absence of an antiangiogenic partner allows for treatment of patients who are contraindicated for antiangiogenics because of bleeding risks or comorbidities like cardiovascular disease.”
Another study, recently published in the Journal of Clinical Oncology, showed that donafenib was superior to sorafenib in improving overall survival, along with improved safety and tolerability, rendering it a potential first-line monotherapy for patients with advanced HCC.
The tremelimumab/durvalumab study was funded by AstraZeneca.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Watchful waiting sometimes best for asymptomatic basal cell carcinoma
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
“Patient preferences, treatment goals, and the option for proceeding with a watchful waiting approach should be discussed as part of personalized shared decision-making,” wrote Marieke van Winden, MD, MSc, of Radboud University Medical Center in Nijmegen, the Netherlands, and colleagues. “In patients with a limited life expectancy and asymptomatic low-risk tumors, the time to benefit from treatment might exceed life expectancy, and watchful waiting should be discussed as a potentially appropriate approach.”
As little research has been undertaken on watchful waiting in patients with BCC, the expected tumor growth, progression and the chance of developing symptoms while taking this approach are poorly understood. Patients with limited life expectancy might not live long enough to develop BCC symptoms and may benefit more from watchful waiting than active treatment, authors of the study wrote.
This observational cohort study evaluated the reasons for watchful waiting, along with the natural course of 280 BCCs in 89 patients (53% men, median age 83 years) who chose this approach. Patients had one or more untreated BCCs for at least 3 months and the median follow-up was 9 months. The researchers also looked at the reasons for initiating later treatment.
Patient-related factors, including limited life expectancy, comorbidity prioritizations, and frailty, were the most important reasons to choose watchful waiting in 83% of patients, followed by tumor-related factors in 55% of patients. Of the tumors, 47% increased in size. The estimated tumor diameter increase in 1 year was 4.46 mm for infiltrative/micronodular BCCs and 1.06 mm for nodular, superficial, or clinical BCCs. Tumor growth was not associated with initial tumor size and location.
The most common reasons to initiate active treatment were tumor burden, resolved reasons for watchful waiting, and reevaluation of patient-related factors.
“All patients should be followed up regularly to determine whether a watchful waiting approach is still suited and if patients still prefer watchful waiting to reconsider the consequences of refraining from treatment,” the authors wrote.
In an accompanying editorial, Mackenzie R. Wehner, MD, MPhil, of the University of Texas MD Anderson Cancer Center in Houston, said that, while the observational and retrospective design was a limitation of the study, this allowed the authors to observe patients avoiding or delaying treatment for BCC in real clinical practice.
The study “shows that few patients developed new symptoms, and few patients who decided to treat after a delay had more invasive interventions than originally anticipated, an encouraging result as we continue to study the option and hone the details of active surveillance in BCC,” Dr. Wehner wrote. “It is important to note that the authors did not perform actual active surveillance. This study did not prospectively enroll patients and see them in follow-up at set times, nor did it have prespecified end points for recommending treatment.”
“Before evidence-based active surveillance in BCC can become a viable option, prospective studies of active surveillance, with specified follow-up times and clear outcome measures, are needed,” Dr. Wehner wrote.
Dr. van Winden did not report any conflicts of interest.
FROM JAMA DERMATOLOGY
Gluten-free diet may reduce cancer risk in celiac disease
Overall cancer risk is slightly increased in patients older than 40 years within their first year of a celiac disease diagnosis, but the risk drops within a year of diagnosis, shows a Swedish study of 47,000 people with celiac disease.
“Celiac disease is associated with an increased risk of types of cancer, and we believe that this is due to the longstanding inflammation that is induced by gluten,” said first author Benjamin Lebwohl, MD, director of clinical research at the Columbia University Celiac Disease Center in New York.
Writing in Clinical Gastroenterology and Hepatology, the authors explained that most studies investigating cancer risk in patients with celiac disease were done before both the widespread use of serologic testing for celiac disease and access to gluten-free food was widely available. Earlier studies linked celiac disease to gastrointestinal malignancies, such as small intestinal adenocarcinoma, and lymphomas.
A prior analysis of this Swedish cohort found that the risk of small intestinal adenocarcinoma, while low, continued for up to 10 years after diagnosis with celiac disease. In the study, which was published in Gastroenterology, the authors found the risks of small-bowel adenocarcinoma and adenomas were significantly increased in people with celiac disease, compared with those without this disease.
“We have known from prior studies that people with celiac disease are at increased risk of developing certain cancers, but there has been limited study of this risk in celiac disease in the 21st century, where there is increased recognition (leading to more prompt diagnosis) and increased access to gluten-free food options (which may allow for more effective treatment),” said Dr. Lebwohl, who is also the director of quality improvement in the division of digestive and liver diseases at Columbia University. “We aimed to determine whether there is still an increased risk of cancer in this modern era, and we found that there still is an increased risk, but this increase is small and that it diminishes beyond the first year after the diagnosis of celiac disease.”
This nationwide cohort study in Sweden included 47,241 patients with celiac disease (62% female; mean age, 24 years), of which 64% were diagnosed since 2000. Each patient was age and sex matched to up to five controls. After a median follow-up of 11.5 years, a 1.11-fold increased risk of cancer overall was found in patients with celiac disease, compared with controls. The respective incidences of cancer were 6.5 and 5.7 per 1,000 person-years, and most of the excess risk was caused by gastrointestinal and hematologic cancer.
The overall risk of cancer was increased in the first year after celiac disease diagnosis (HR, 2.47; 95% CI, 2.22-2.74) but not afterwards (HR, 1.01; 95% CI, 0.97-1.05).
“It appears that the increased risk of cancer in people with celiac disease decreased over time, and this may be related to the beneficial effect of the gluten-free diet in the long term,” Dr. Lebwohl said.
The authors suggest that cancer risk, followed by a decline to no risk, may alternatively be due to the increased monitoring and medical examinations among patients with celiac disease. Also, symptoms of cancer, such as weight loss, may lead to broad testing that identifies celiac disease, the authors wrote.
For cancer subtypes, the strongest association between celiac disease and cancer was found for hematologic, lymphoproliferative and gastrointestinal cancers. Among gastrointestinal cancer subtypes, elevated risks were found for hepatobiliary and pancreatic cancer, but not for gastric or colorectal cancer. The cancer risk in celiac disease decreased in breast and lung cancer, which the authors suggested may be attributed to lower body mass index and smoking rates, respectively, observed in individuals with celiac disease.
Certain cancer types persist after 1 year
Although there was no overall cancer risk for more than 1 year after celiac disease diagnosis, the risks of hematologic and lymphoproliferative cancers persisted. While the increased risk of gastrointestinal cancers collectively was no longer significant beyond 1 year after celiac disease diagnosis, the risk persisted for hepatobiliary and pancreatic cancer.
“We found that the risk of gastrointestinal cancers is increased in people with celiac disease, compared to the general population, but these risks vary according to the cancer type,” Dr. Lebwohl said. “For instance, the risk of pancreatic cancer is increased in people with celiac disease, compared to the general population, while the risk of colon cancer in people with celiac disease is not increased, compared to the general population.
“But pancreatic cancer is far less common than colon cancer. We found that pancreatic cancer occurs in 1 in 5,000 people with celiac disease per year, whereas colorectal cancer occurred in 1 in 1,400 people per year. Taken all together, the risk of any gastrointestinal cancer was around 1 in 700 per year among people with celiac disease,” Dr. Lebwohl said.
The overall cancer risk was highest in patients diagnosed with celiac disease after age 60 and was not increased in those diagnosed with celiac disease before age 40. The authors noted that, in recent years, there has been a pronounced increase in the diagnosis of celiac disease in people aged over 60, an age group with a higher risk of developing severe outcomes related to refractory celiac disease. The cancer risk was similar among patients diagnosed with celiac disease before or after 2000.
Since this is an observational study, causality cannot be proven, and the authors suggested that the findings may not be applicable to settings outside of the relatively homogeneous ethnic population of Sweden.
Carol E. Semrad, MD, professor of medicine and director of clinical research in the Celiac Center at the University of Chicago Medicine, said: “This is an observational study and therefore cannot answer whether celiac disease is the cause of cancer or merely an association.” She added that “it is unknown why the risk for some cancers is higher in celiac disease.
“This paper argues against delayed diagnosis and low detection rate to explain the increase in cancer risk as those diagnosed with celiac disease prior to 2000 had the same cancer risk as those diagnosed after 2000 when diagnostic testing, earlier diagnosis, and access to a gluten-free diet were better,” Dr. Semrad said.
Link to mortality data
The authors said increased cancer risk being restricted to the first year of diagnosis is consistent with prior celiac disease studies of morbidity and mortality.
A study published in 2019 in United European Gastroenterology looked at mortality risk in 602 patients with celiac disease from Lothian, Scotland, identified between 1979 and 1983 and followed up from 1970 to 2016. All-cause mortality was 43% higher than in the general population, mainly from hematologic malignancies, and this risk was greatest during the first few years of diagnosis.
An analysis of cause-specific mortality in the Swedish cohort, published in 2020 in JAMA, found that celiac disease was associated with a small but statistically significant increased mortality risk. After a median follow-up of 12.5 years of 49,829 patients with celiac disease, the mortality rate was 9.7 and 8.6 deaths per 1000 person-years, compared with the general population, respectively. Individuals with celiac disease were at increased risk of death from cancer, cardiovascular disease and respiratory disease. The overall mortality risk was greatest in the first year after diagnosis with celiac disease, after which the risk diminished with the establishment of the gluten-free diet but remained modestly elevated in the long term.
However, a Finnish population-based study, published in the American Journal of Gastroenterology, found no increase in overall mortality in patients with celiac disease. The study included 12,803 adults diagnosed with celiac disease between 2005 and 2014. Participants were followed for an average of 7.7 years and mortality from all malignancies, gastrointestinal tract malignancies or cardiovascular diseases were not increased among patients with celiac disease, compared with the general population. Mortality from lymphoproliferative diseases was increased in patients with celiac disease but was lower than previously reported.
Dr. Lebwohl and colleagues noted that the incidences of cancer types vary by the age and geographical region of the study population, as does the diagnosis of celiac disease, which may explain why increased risk for cancer or cancer related-mortality in patients with celiac disease has not always been reported.
Dr Ludvigsson coordinates a study on behalf of the Swedish IBD quality register. This study has received funding from Janssen. The remaining authors disclosed no conflicts.
Overall cancer risk is slightly increased in patients older than 40 years within their first year of a celiac disease diagnosis, but the risk drops within a year of diagnosis, shows a Swedish study of 47,000 people with celiac disease.
“Celiac disease is associated with an increased risk of types of cancer, and we believe that this is due to the longstanding inflammation that is induced by gluten,” said first author Benjamin Lebwohl, MD, director of clinical research at the Columbia University Celiac Disease Center in New York.
Writing in Clinical Gastroenterology and Hepatology, the authors explained that most studies investigating cancer risk in patients with celiac disease were done before both the widespread use of serologic testing for celiac disease and access to gluten-free food was widely available. Earlier studies linked celiac disease to gastrointestinal malignancies, such as small intestinal adenocarcinoma, and lymphomas.
A prior analysis of this Swedish cohort found that the risk of small intestinal adenocarcinoma, while low, continued for up to 10 years after diagnosis with celiac disease. In the study, which was published in Gastroenterology, the authors found the risks of small-bowel adenocarcinoma and adenomas were significantly increased in people with celiac disease, compared with those without this disease.
“We have known from prior studies that people with celiac disease are at increased risk of developing certain cancers, but there has been limited study of this risk in celiac disease in the 21st century, where there is increased recognition (leading to more prompt diagnosis) and increased access to gluten-free food options (which may allow for more effective treatment),” said Dr. Lebwohl, who is also the director of quality improvement in the division of digestive and liver diseases at Columbia University. “We aimed to determine whether there is still an increased risk of cancer in this modern era, and we found that there still is an increased risk, but this increase is small and that it diminishes beyond the first year after the diagnosis of celiac disease.”
This nationwide cohort study in Sweden included 47,241 patients with celiac disease (62% female; mean age, 24 years), of which 64% were diagnosed since 2000. Each patient was age and sex matched to up to five controls. After a median follow-up of 11.5 years, a 1.11-fold increased risk of cancer overall was found in patients with celiac disease, compared with controls. The respective incidences of cancer were 6.5 and 5.7 per 1,000 person-years, and most of the excess risk was caused by gastrointestinal and hematologic cancer.
The overall risk of cancer was increased in the first year after celiac disease diagnosis (HR, 2.47; 95% CI, 2.22-2.74) but not afterwards (HR, 1.01; 95% CI, 0.97-1.05).
“It appears that the increased risk of cancer in people with celiac disease decreased over time, and this may be related to the beneficial effect of the gluten-free diet in the long term,” Dr. Lebwohl said.
The authors suggest that cancer risk, followed by a decline to no risk, may alternatively be due to the increased monitoring and medical examinations among patients with celiac disease. Also, symptoms of cancer, such as weight loss, may lead to broad testing that identifies celiac disease, the authors wrote.
For cancer subtypes, the strongest association between celiac disease and cancer was found for hematologic, lymphoproliferative and gastrointestinal cancers. Among gastrointestinal cancer subtypes, elevated risks were found for hepatobiliary and pancreatic cancer, but not for gastric or colorectal cancer. The cancer risk in celiac disease decreased in breast and lung cancer, which the authors suggested may be attributed to lower body mass index and smoking rates, respectively, observed in individuals with celiac disease.
Certain cancer types persist after 1 year
Although there was no overall cancer risk for more than 1 year after celiac disease diagnosis, the risks of hematologic and lymphoproliferative cancers persisted. While the increased risk of gastrointestinal cancers collectively was no longer significant beyond 1 year after celiac disease diagnosis, the risk persisted for hepatobiliary and pancreatic cancer.
“We found that the risk of gastrointestinal cancers is increased in people with celiac disease, compared to the general population, but these risks vary according to the cancer type,” Dr. Lebwohl said. “For instance, the risk of pancreatic cancer is increased in people with celiac disease, compared to the general population, while the risk of colon cancer in people with celiac disease is not increased, compared to the general population.
“But pancreatic cancer is far less common than colon cancer. We found that pancreatic cancer occurs in 1 in 5,000 people with celiac disease per year, whereas colorectal cancer occurred in 1 in 1,400 people per year. Taken all together, the risk of any gastrointestinal cancer was around 1 in 700 per year among people with celiac disease,” Dr. Lebwohl said.
The overall cancer risk was highest in patients diagnosed with celiac disease after age 60 and was not increased in those diagnosed with celiac disease before age 40. The authors noted that, in recent years, there has been a pronounced increase in the diagnosis of celiac disease in people aged over 60, an age group with a higher risk of developing severe outcomes related to refractory celiac disease. The cancer risk was similar among patients diagnosed with celiac disease before or after 2000.
Since this is an observational study, causality cannot be proven, and the authors suggested that the findings may not be applicable to settings outside of the relatively homogeneous ethnic population of Sweden.
Carol E. Semrad, MD, professor of medicine and director of clinical research in the Celiac Center at the University of Chicago Medicine, said: “This is an observational study and therefore cannot answer whether celiac disease is the cause of cancer or merely an association.” She added that “it is unknown why the risk for some cancers is higher in celiac disease.
“This paper argues against delayed diagnosis and low detection rate to explain the increase in cancer risk as those diagnosed with celiac disease prior to 2000 had the same cancer risk as those diagnosed after 2000 when diagnostic testing, earlier diagnosis, and access to a gluten-free diet were better,” Dr. Semrad said.
Link to mortality data
The authors said increased cancer risk being restricted to the first year of diagnosis is consistent with prior celiac disease studies of morbidity and mortality.
A study published in 2019 in United European Gastroenterology looked at mortality risk in 602 patients with celiac disease from Lothian, Scotland, identified between 1979 and 1983 and followed up from 1970 to 2016. All-cause mortality was 43% higher than in the general population, mainly from hematologic malignancies, and this risk was greatest during the first few years of diagnosis.
An analysis of cause-specific mortality in the Swedish cohort, published in 2020 in JAMA, found that celiac disease was associated with a small but statistically significant increased mortality risk. After a median follow-up of 12.5 years of 49,829 patients with celiac disease, the mortality rate was 9.7 and 8.6 deaths per 1000 person-years, compared with the general population, respectively. Individuals with celiac disease were at increased risk of death from cancer, cardiovascular disease and respiratory disease. The overall mortality risk was greatest in the first year after diagnosis with celiac disease, after which the risk diminished with the establishment of the gluten-free diet but remained modestly elevated in the long term.
However, a Finnish population-based study, published in the American Journal of Gastroenterology, found no increase in overall mortality in patients with celiac disease. The study included 12,803 adults diagnosed with celiac disease between 2005 and 2014. Participants were followed for an average of 7.7 years and mortality from all malignancies, gastrointestinal tract malignancies or cardiovascular diseases were not increased among patients with celiac disease, compared with the general population. Mortality from lymphoproliferative diseases was increased in patients with celiac disease but was lower than previously reported.
Dr. Lebwohl and colleagues noted that the incidences of cancer types vary by the age and geographical region of the study population, as does the diagnosis of celiac disease, which may explain why increased risk for cancer or cancer related-mortality in patients with celiac disease has not always been reported.
Dr Ludvigsson coordinates a study on behalf of the Swedish IBD quality register. This study has received funding from Janssen. The remaining authors disclosed no conflicts.
Overall cancer risk is slightly increased in patients older than 40 years within their first year of a celiac disease diagnosis, but the risk drops within a year of diagnosis, shows a Swedish study of 47,000 people with celiac disease.
“Celiac disease is associated with an increased risk of types of cancer, and we believe that this is due to the longstanding inflammation that is induced by gluten,” said first author Benjamin Lebwohl, MD, director of clinical research at the Columbia University Celiac Disease Center in New York.
Writing in Clinical Gastroenterology and Hepatology, the authors explained that most studies investigating cancer risk in patients with celiac disease were done before both the widespread use of serologic testing for celiac disease and access to gluten-free food was widely available. Earlier studies linked celiac disease to gastrointestinal malignancies, such as small intestinal adenocarcinoma, and lymphomas.
A prior analysis of this Swedish cohort found that the risk of small intestinal adenocarcinoma, while low, continued for up to 10 years after diagnosis with celiac disease. In the study, which was published in Gastroenterology, the authors found the risks of small-bowel adenocarcinoma and adenomas were significantly increased in people with celiac disease, compared with those without this disease.
“We have known from prior studies that people with celiac disease are at increased risk of developing certain cancers, but there has been limited study of this risk in celiac disease in the 21st century, where there is increased recognition (leading to more prompt diagnosis) and increased access to gluten-free food options (which may allow for more effective treatment),” said Dr. Lebwohl, who is also the director of quality improvement in the division of digestive and liver diseases at Columbia University. “We aimed to determine whether there is still an increased risk of cancer in this modern era, and we found that there still is an increased risk, but this increase is small and that it diminishes beyond the first year after the diagnosis of celiac disease.”
This nationwide cohort study in Sweden included 47,241 patients with celiac disease (62% female; mean age, 24 years), of which 64% were diagnosed since 2000. Each patient was age and sex matched to up to five controls. After a median follow-up of 11.5 years, a 1.11-fold increased risk of cancer overall was found in patients with celiac disease, compared with controls. The respective incidences of cancer were 6.5 and 5.7 per 1,000 person-years, and most of the excess risk was caused by gastrointestinal and hematologic cancer.
The overall risk of cancer was increased in the first year after celiac disease diagnosis (HR, 2.47; 95% CI, 2.22-2.74) but not afterwards (HR, 1.01; 95% CI, 0.97-1.05).
“It appears that the increased risk of cancer in people with celiac disease decreased over time, and this may be related to the beneficial effect of the gluten-free diet in the long term,” Dr. Lebwohl said.
The authors suggest that cancer risk, followed by a decline to no risk, may alternatively be due to the increased monitoring and medical examinations among patients with celiac disease. Also, symptoms of cancer, such as weight loss, may lead to broad testing that identifies celiac disease, the authors wrote.
For cancer subtypes, the strongest association between celiac disease and cancer was found for hematologic, lymphoproliferative and gastrointestinal cancers. Among gastrointestinal cancer subtypes, elevated risks were found for hepatobiliary and pancreatic cancer, but not for gastric or colorectal cancer. The cancer risk in celiac disease decreased in breast and lung cancer, which the authors suggested may be attributed to lower body mass index and smoking rates, respectively, observed in individuals with celiac disease.
Certain cancer types persist after 1 year
Although there was no overall cancer risk for more than 1 year after celiac disease diagnosis, the risks of hematologic and lymphoproliferative cancers persisted. While the increased risk of gastrointestinal cancers collectively was no longer significant beyond 1 year after celiac disease diagnosis, the risk persisted for hepatobiliary and pancreatic cancer.
“We found that the risk of gastrointestinal cancers is increased in people with celiac disease, compared to the general population, but these risks vary according to the cancer type,” Dr. Lebwohl said. “For instance, the risk of pancreatic cancer is increased in people with celiac disease, compared to the general population, while the risk of colon cancer in people with celiac disease is not increased, compared to the general population.
“But pancreatic cancer is far less common than colon cancer. We found that pancreatic cancer occurs in 1 in 5,000 people with celiac disease per year, whereas colorectal cancer occurred in 1 in 1,400 people per year. Taken all together, the risk of any gastrointestinal cancer was around 1 in 700 per year among people with celiac disease,” Dr. Lebwohl said.
The overall cancer risk was highest in patients diagnosed with celiac disease after age 60 and was not increased in those diagnosed with celiac disease before age 40. The authors noted that, in recent years, there has been a pronounced increase in the diagnosis of celiac disease in people aged over 60, an age group with a higher risk of developing severe outcomes related to refractory celiac disease. The cancer risk was similar among patients diagnosed with celiac disease before or after 2000.
Since this is an observational study, causality cannot be proven, and the authors suggested that the findings may not be applicable to settings outside of the relatively homogeneous ethnic population of Sweden.
Carol E. Semrad, MD, professor of medicine and director of clinical research in the Celiac Center at the University of Chicago Medicine, said: “This is an observational study and therefore cannot answer whether celiac disease is the cause of cancer or merely an association.” She added that “it is unknown why the risk for some cancers is higher in celiac disease.
“This paper argues against delayed diagnosis and low detection rate to explain the increase in cancer risk as those diagnosed with celiac disease prior to 2000 had the same cancer risk as those diagnosed after 2000 when diagnostic testing, earlier diagnosis, and access to a gluten-free diet were better,” Dr. Semrad said.
Link to mortality data
The authors said increased cancer risk being restricted to the first year of diagnosis is consistent with prior celiac disease studies of morbidity and mortality.
A study published in 2019 in United European Gastroenterology looked at mortality risk in 602 patients with celiac disease from Lothian, Scotland, identified between 1979 and 1983 and followed up from 1970 to 2016. All-cause mortality was 43% higher than in the general population, mainly from hematologic malignancies, and this risk was greatest during the first few years of diagnosis.
An analysis of cause-specific mortality in the Swedish cohort, published in 2020 in JAMA, found that celiac disease was associated with a small but statistically significant increased mortality risk. After a median follow-up of 12.5 years of 49,829 patients with celiac disease, the mortality rate was 9.7 and 8.6 deaths per 1000 person-years, compared with the general population, respectively. Individuals with celiac disease were at increased risk of death from cancer, cardiovascular disease and respiratory disease. The overall mortality risk was greatest in the first year after diagnosis with celiac disease, after which the risk diminished with the establishment of the gluten-free diet but remained modestly elevated in the long term.
However, a Finnish population-based study, published in the American Journal of Gastroenterology, found no increase in overall mortality in patients with celiac disease. The study included 12,803 adults diagnosed with celiac disease between 2005 and 2014. Participants were followed for an average of 7.7 years and mortality from all malignancies, gastrointestinal tract malignancies or cardiovascular diseases were not increased among patients with celiac disease, compared with the general population. Mortality from lymphoproliferative diseases was increased in patients with celiac disease but was lower than previously reported.
Dr. Lebwohl and colleagues noted that the incidences of cancer types vary by the age and geographical region of the study population, as does the diagnosis of celiac disease, which may explain why increased risk for cancer or cancer related-mortality in patients with celiac disease has not always been reported.
Dr Ludvigsson coordinates a study on behalf of the Swedish IBD quality register. This study has received funding from Janssen. The remaining authors disclosed no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY