User login
POP-RT trial supports whole-pelvis radiotherapy for high-risk prostate cancer
Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.
“A lot of effort has gone into trying to answer this question,” he added.
Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.
To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.
The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
Efficacy and toxicity
At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.
Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).
Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).
At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.
The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).
There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
Explaining the results
Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.
“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.
In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.
Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).
“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”
“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
Practice-changing findings
“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”
The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.
“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”
“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”
The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.
SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.
Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.
“A lot of effort has gone into trying to answer this question,” he added.
Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.
To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.
The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
Efficacy and toxicity
At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.
Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).
Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).
At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.
The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).
There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
Explaining the results
Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.
“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.
In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.
Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).
“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”
“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
Practice-changing findings
“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”
The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.
“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”
“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”
The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.
SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.
Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.
“A lot of effort has gone into trying to answer this question,” he added.
Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.
To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.
The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
Efficacy and toxicity
At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.
Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).
Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).
At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.
The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).
There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
Explaining the results
Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.
“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.
In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.
Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).
“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”
“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
Practice-changing findings
“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”
The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.
“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”
“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”
The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.
SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.
FROM ESTRO 2020
COVID-19 vaccines and cancer patients: 4 things to know
Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.
Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.
We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.
Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.
The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.
Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.
The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.
Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.
These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.
Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.
Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.
It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.
A version of this article first appeared on Medscape.com.
Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.
Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.
We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.
Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.
The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.
Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.
The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.
Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.
These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.
Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.
Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.
It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.
A version of this article first appeared on Medscape.com.
Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.
Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.
We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.
Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.
The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.
Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.
The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.
Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.
These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.
Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.
Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.
It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.
A version of this article first appeared on Medscape.com.
FDA OKs first oral hormone therapy for advanced prostate cancer
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.
Relugolix is an oral gonadotropin-releasing hormone antagonist. The new pill form may mean fewer clinic visits for patients, an added benefit during the COVID-19 pandemic, said Richard Pazdur, MD, acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a press statement.
“Today’s approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a health care provider,” he commented.
Relugolix works by preventing the pituitary gland from making luteinizing hormone and follicle-stimulating hormone, thus reducing the amount of testosterone the testicles can make.
In the open-label HERO trial, 930 patients with locally advanced or metastatic prostate cancer were randomly assigned to receive either once-daily oral relugolix or leuprolide injection every 3 months for 48 weeks.
The study met its primary endpoint, demonstrating that castration at 48 weeks was maintained in 96.7% of men receiving relugolix vs. 88.8% for patients receiving leuprolide; castration levels of testosterone had to be reached by day 29 and then sustained through the end of the treatment course.
Relugolix has the “potential to become a new standard for ADT and advanced prostate cancer,” commented study investigator Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, South Carolina, at the 2020 annual meeting of the American Society of Clinical Oncology, where the results were first presented.
They were published simultaneously in The New England Journal of Medicine.
At the ASCO meeting, David R. Wise, MD, PhD, Perlmutter Cancer Center at NYU Langone Health, New York, agreed that the drug could be practice-changing – but claimed that it would be for a subset of patients only, specifically, patients with a significant history of cardiovascular disease who are without gastrointestinal malabsorption.
Notably, in the study, relugolix cut the risk for major adverse cardiovascular events by 54% in comparison with leuprolide, as reported by Medscape Medical News.
According to the FDA, the most common side effects of relugolix include hot flush, increased glucose levels, increased triglyceride levels, musculoskeletal pain, decreased hemoglobin, fatigue, constipation, diarrhea, and increased levels of certain liver enzymes.
Concurrent use of relugolix with drugs that inhibit P-glycoprotein is contraindicated.
Also, health care providers should consider having patients undergo periodic electrocardiographic monitoring as well as periodic monitoring of electrolyte levels. Owing to the drug’s suppression of the pituitary gonadal system, any diagnostic test results of the pituitary gonadotropic and gonadal functions conducted during and after taking relugolix may be affected.
A version of this article first appeared on Medscape.com.
Study shows no link between race and mortality in clear cell RCC
The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.
Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.
New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.
“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.
In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.
A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.
In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
Demographic determinism
In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.
The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.
In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.
“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.
In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”
Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.
He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”
The authors did not disclose funding or conflicts of interest.
SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.
The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.
Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.
New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.
“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.
In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.
A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.
In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
Demographic determinism
In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.
The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.
In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.
“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.
In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”
Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.
He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”
The authors did not disclose funding or conflicts of interest.
SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.
The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.
Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.
New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.
“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.
In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.
A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.
In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
Demographic determinism
In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.
The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.
In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.
“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.
In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”
Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.
He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”
The authors did not disclose funding or conflicts of interest.
SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.
FROM UROLOGY
Four factors may predict better survival with cabozantinib in mRCC
Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.
These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.
“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.
The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.
The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.
The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.
The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.
The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).
Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.
Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).
The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).
Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).
“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.
“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).
“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.
Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.
This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.
SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.
Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.
These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.
“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.
The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.
The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.
The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.
The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.
The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).
Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.
Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).
The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).
Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).
“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.
“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).
“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.
Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.
This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.
SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.
Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.
These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.
“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.
The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.
The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.
The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.
The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.
The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).
Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.
Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).
The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).
Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).
“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.
“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).
“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.
Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.
This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.
SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.
FROM THE EUROPEAN JOURNAL OF CANCER
Focal radiation boost nets better outcomes in prostate cancer
The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“We know that local recurrences most often occur at the location of the primary tumor or the dominant intraprostatic lesion, and we also know that biochemical disease–free survival improves with increasing dose to the whole prostate gland,” said principal investigator Linda G.W. Kerkmeijer, MD, PhD, of Radboud University Medical Center Nijmegen, the Netherlands.
However, “with whole-gland dose escalation, increased toxicity has been observed in both external-beam and brachytherapy trials,” she added.
FLAME trial details
A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.
The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).
In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.
A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.
With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).
The boost also netted significantly better disease-free survival (P < .001).
The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.
The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).
The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
‘A standard option’ and next steps
“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”
“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”
The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.
“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.
Any imbalance in the use and duration of hormonal therapy, given that it can delay the time to prostate-specific antigen failure, could lead to overestimation or underestimation of the benefit of the focal boost, with respect to the primary endpoint of the study, he elaborated. Typical durations of this therapy range from 4 to 6 months for patients with intermediate-risk disease and from 18 to 36 months for patients with high-risk disease.
“So it’s important to know and to adjust not just for hormonal therapy use, but for duration between the two arms, stratified by risk group, in a multivariable regression analysis,” Dr. D’Amico concluded.
The FLAME trial was funded by the Dutch Cancer Society and Stand Up Against Cancer Belgium. Dr. Kerkmeijer and Dr. D’Amico disclosed having no conflicts of interest.
SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.
The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“We know that local recurrences most often occur at the location of the primary tumor or the dominant intraprostatic lesion, and we also know that biochemical disease–free survival improves with increasing dose to the whole prostate gland,” said principal investigator Linda G.W. Kerkmeijer, MD, PhD, of Radboud University Medical Center Nijmegen, the Netherlands.
However, “with whole-gland dose escalation, increased toxicity has been observed in both external-beam and brachytherapy trials,” she added.
FLAME trial details
A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.
The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).
In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.
A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.
With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).
The boost also netted significantly better disease-free survival (P < .001).
The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.
The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).
The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
‘A standard option’ and next steps
“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”
“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”
The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.
“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.
Any imbalance in the use and duration of hormonal therapy, given that it can delay the time to prostate-specific antigen failure, could lead to overestimation or underestimation of the benefit of the focal boost, with respect to the primary endpoint of the study, he elaborated. Typical durations of this therapy range from 4 to 6 months for patients with intermediate-risk disease and from 18 to 36 months for patients with high-risk disease.
“So it’s important to know and to adjust not just for hormonal therapy use, but for duration between the two arms, stratified by risk group, in a multivariable regression analysis,” Dr. D’Amico concluded.
The FLAME trial was funded by the Dutch Cancer Society and Stand Up Against Cancer Belgium. Dr. Kerkmeijer and Dr. D’Amico disclosed having no conflicts of interest.
SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.
The results were reported at the European Society for Radiology and Oncology 2020 Online Congress.
“We know that local recurrences most often occur at the location of the primary tumor or the dominant intraprostatic lesion, and we also know that biochemical disease–free survival improves with increasing dose to the whole prostate gland,” said principal investigator Linda G.W. Kerkmeijer, MD, PhD, of Radboud University Medical Center Nijmegen, the Netherlands.
However, “with whole-gland dose escalation, increased toxicity has been observed in both external-beam and brachytherapy trials,” she added.
FLAME trial details
A total of 571 patients took part in the FLAME trial, which is a collaboration of UMC Utrecht, the Netherlands Cancer Institute, University Hospitals Leuven, and Radboudumc.
The patients were randomized evenly to standard radiation therapy alone (77 Gy to the whole prostate in 35 fractions of 2.2 Gy) or with an integrated boost to the macroscopically visible tumor on multiparametric MRI (to reach a total dose of up to 95 Gy in 35 fractions of 2.7 Gy).
In treatment planning, the organs-at-risk constraints were prioritized over the focal boost dose, Dr. Kerkmeijer pointed out.
A majority of patients (84%) had high-risk disease, and two-thirds received hormonal therapy (usually in the adjuvant setting) with equal distribution across study arms, she reported.
With a median follow-up of 72 months, the 5-year rate of biochemical disease–free survival, the trial’s primary endpoint, was superior with the addition of the focal boost as compared with standard radiation therapy alone (92% vs. 85%; P < .001).
The boost also netted significantly better disease-free survival (P < .001).
The arms were similar on distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), and overall survival (P = .50), although longer follow-up is needed to fully assess these outcomes, Dr. Kerkmeijer noted.
The boost and standard therapy arms had much the same late grade 3 or higher genitourinary toxicity (5.6% vs. 3.5%; P = .22) and late grade 3 or higher gastrointestinal toxicity (1.4% vs. 1.4%; P = .99).
The arms were essentially identical on long-term patient-reported urinary symptoms, bowel symptoms, sexual activity, and sexual function, as measured with the EORTC QLQ-PR25 tool and detailed in a companion presentation (abstract OC-0315).
‘A standard option’ and next steps
“FLAME is the first phase 3 randomized controlled trial to show that focal boosting works and that biochemical recurrence was reduced at 5 years,” Dr. Kerkmeijer said. “We propose that the FLAME scheme can be considered as a standard option for patients with intermediate- but especially high-risk prostate cancer.”
“For patients, biochemical recurrence may have impact, as this causes additional follow-up and diagnostic exams, potential anxiety, and potential side effects of subsequent treatments,” she added. “Biochemical recurrences were reduced by almost half and at no additional cost and no additional toxicity by this FLAME isotoxic approach and by using conventional radiotherapy techniques.”
The next step is pairing the boost with ultra-hypofractionation, which requires highly accurate targeting, Dr. Kerkmeijer said. In fact, favorable early toxicity results of the subsequent Hypo-FLAME trial, which tested this strategy, were also reported at the congress (abstract OC-0209), and a trial taking the strategy even further, Hypo-FLAME 2.0, is ongoing.
“The FLAME trial’s results are probably true but may have been impacted by the use of hormonal therapy,” Anthony V. D’Amico, MD, PhD, of the Dana Farber Cancer Institute and Harvard Medical School, Boston, said in an interview.
Any imbalance in the use and duration of hormonal therapy, given that it can delay the time to prostate-specific antigen failure, could lead to overestimation or underestimation of the benefit of the focal boost, with respect to the primary endpoint of the study, he elaborated. Typical durations of this therapy range from 4 to 6 months for patients with intermediate-risk disease and from 18 to 36 months for patients with high-risk disease.
“So it’s important to know and to adjust not just for hormonal therapy use, but for duration between the two arms, stratified by risk group, in a multivariable regression analysis,” Dr. D’Amico concluded.
The FLAME trial was funded by the Dutch Cancer Society and Stand Up Against Cancer Belgium. Dr. Kerkmeijer and Dr. D’Amico disclosed having no conflicts of interest.
SOURCE: De Boer HCJ et al. ESTRO 2020. Abstract OC-0612.
FROM ESTRO 2020
NHS England starts pilot trial of blood test for many cancers
“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.
The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”
However, some clinicians have expressed concerns over the potential for false-positive results with the test.
Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.
It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.
The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”
The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.
Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
Improving early detection rates
The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.
The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.
A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.
The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.
The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.
“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.
“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.
Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.
“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.
However, some clinicians raised potential concerns.
Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”
Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”
Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”
No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.
The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”
However, some clinicians have expressed concerns over the potential for false-positive results with the test.
Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.
It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.
The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”
The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.
Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
Improving early detection rates
The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.
The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.
A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.
The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.
The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.
“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.
“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.
Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.
“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.
However, some clinicians raised potential concerns.
Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”
Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”
Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”
No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.
The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”
However, some clinicians have expressed concerns over the potential for false-positive results with the test.
Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.
It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.
The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”
The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.
Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
Improving early detection rates
The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.
The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.
A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.
The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.
The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.
“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.
“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.
Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.
“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.
However, some clinicians raised potential concerns.
Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”
Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”
Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”
No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Cancer rates on the rise in adolescents and young adults
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.
There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.
Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.
The report was published online December 1 in JAMA Network Open.
“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.
“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.
The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.
The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.
It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.
“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.
Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.
The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.
Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).
Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).
Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.
Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.
Higher rates of melanoma could be related to tanning bed use.
Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.
Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.
Almost 80% of the patients were White; 10.3% were Black.
The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Fear of recurrence highly prevalent in RCC survivors
About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.
Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.
The results were published in JCO Oncology Practice.
The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.
More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.
A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.
More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
Results: FCR persists in RCC
Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.
“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.
“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”
The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.
However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.
Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
Interventions and support
Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.
“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”
“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”
Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.
“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said.
Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.
“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”
Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.
“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.
The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.
SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.
About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.
Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.
The results were published in JCO Oncology Practice.
The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.
More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.
A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.
More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
Results: FCR persists in RCC
Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.
“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.
“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”
The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.
However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.
Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
Interventions and support
Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.
“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”
“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”
Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.
“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said.
Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.
“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”
Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.
“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.
The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.
SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.
About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.
Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.
The results were published in JCO Oncology Practice.
The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.
More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.
A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.
More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
Results: FCR persists in RCC
Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.
“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.
“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”
The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.
However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.
Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
Interventions and support
Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.
“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”
“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”
Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.
“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said.
Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.
“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”
Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.
“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.
The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.
SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.
FROM JCO ONCOLOGY PRACTICE
FDA approves first agent for PSMA-PET imaging in prostate cancer
A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.
The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.
This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.
Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
Institutional use only
Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).
The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.
“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”
Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).
A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.
The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
Trial results with PSMA-PET/CT
“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.
Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.
He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.
“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.
“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.
The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
Trial results with Ga 68 PSMA-11
The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.
The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.
“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.
“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”
The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.
About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.
“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.
“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.
The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.
The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.
A version of this article originally appeared on Medscape.com.
A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.
The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.
This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.
Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
Institutional use only
Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).
The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.
“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”
Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).
A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.
The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
Trial results with PSMA-PET/CT
“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.
Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.
He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.
“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.
“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.
The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
Trial results with Ga 68 PSMA-11
The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.
The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.
“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.
“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”
The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.
About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.
“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.
“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.
The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.
The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.
A version of this article originally appeared on Medscape.com.
A radioactive diagnostic agent has been approved by the U.S. Food and Drug Administration for use in patients with prostate cancer, but only for those treated at two institutions in California.
The product, Gallium 68 PSMA-11 (Ga 68 PSMA-11), is the first agent approved specifically for use in positron-emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)–positive lesions in men with prostate cancer, the FDA noted.
This imaging approach can “detect whether or not the cancer has spread to other parts of the body,” commented Alex Gorovets, MD, acting deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research.
Ga 68 PSMA-11 is indicated for use in patients with suspected prostate cancer metastasis whose conditions are potentially curable by surgery or radiotherapy and in patients with suspected prostate cancer recurrence, as determined on the basis of elevated serum prostate-specific antigen (PSA) levels.
Institutional use only
Ga 68 PSMA-11 has been approved for institutional use at the University of California, Los Angeles and the University of California, San Francisco under an academic new drug application (NDA).
The FDA approval was based partly on a clinical trial conducted by the UCSF and UCLA research teams on the effectiveness of PSMA-PET.
“It is rare for academic institutions to obtain FDA approval of a drug, and this unique collaboration has led to what is one of the first coapprovals of a drug at two institutions,” said Thomas Hope, MD, an associate professor at UCSF. “We hope that this first step will lead to a more widespread availability of this imaging test to men with prostate cancer throughout the country.”
Ga 68 PSMA-11 was developed outside the United States at the University of Heidelberg (Germany).
A commercial NDA from Telix Pharmaceuticals for TL591-CDx, a radiopharmaceutical cold kit for the preparation of Ga 68 PSMA-11 injection, is under consideration by the FDA.
The agency noted that two other PET diagnostic agents – fluciclovine F18 and choline C11 – are approved for prostate cancer imaging. However, they are only approved for use in patients with suspected cancer recurrence.
Trial results with PSMA-PET/CT
“PSMA-PET/CT is a novel molecular and functional imaging modality specific for prostate cancer cells that has good sensitivity and outstanding specificity in detecting metastasis,” commented T. Martin Ma, MD, PhD, of UCLA.
Dr. Ma presented a U.S. study on the technique at the recent annual meeting of the American Society for Radiation Oncology. That study showed that PSMA-PET/CT led to nodal upstaging in 19.7% of patients and metastasis upstaging in 9.4%.
He said these results were similar to those from the Australian proPSMA trial, which was published in The Lancet earlier this year. That trial found PSMA-PET/CT to be superior to conventional imaging with CT and bone scanning for primary staging of high-risk prostate cancer.
“These findings carry significant clinical implications and can affect treatment decision-making,” Dr. Ma commented.
“PSMA-PET has been a real game changer in high-risk prostate cancer and has implications in the various stages of prostate cancer management from diagnosis and staging to theranostics,” said Renu Eapen, MBBS, of Peter MacCallum Cancer Center, Melbourne, who was not involved in either study.
“PSMA-PET/CT has challenged conventional imaging in staging before curative-intent surgery or radiotherapy,” Dr. Eapen added.
The accuracy of PSMA-PET/CT was 27% higher than that of conventional imaging in the proPSMA trial, she noted in an interview last month. This superior accuracy can ultimately affect management. The imaging has additional benefits of lower radiation dose as well as reproducibility with high reporter agreement, potentially making it a “one-stop-shop” scan.
Trial results with Ga 68 PSMA-11
The safety and efficacy of Ga 68 PSMA-11 were evaluated in two prospective clinical trials with a total of 960 men with prostate cancer, each of whom received one injection of the product.
The first trial involved 325 patients with biopsy-proven prostate cancer who underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11.
“These patients were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis. Among the patients who proceeded to surgery, those with positive readings in the pelvic lymph nodes on Ga 68 PSMA-11 PET had a clinically important rate of metastatic cancer confirmed by surgical pathology,” the FDA noted.
“The availability of this information prior to treatment is expected to have important implications for patient care,” the FDA commented. “For example, it may spare certain patients from undergoing unnecessary surgery.”
The second trial enrolled 635 patients with rising serum PSA levels after initial prostate surgery or radiotherapy. All patients received a single Ga 68 PSMA-11 PET/CT scan or PET/MRI scan.
About three-quarters of patients (74%) had at least one positive lesion detected by Ga 68 PSMA-11 PET in at least one region – bone, prostate bed, pelvic lymph node, or extra-pelvic soft tissue.
“In patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, local recurrence or metastasis of prostate cancer was confirmed in an estimated 91% of cases,” the FDA noted.
“Thus, the second trial demonstrated that Ga 68 PSMA-11 PET can detect sites of disease in patients with biochemical evidence of recurrent prostate cancer, thereby providing important information that may impact the approach to therapy,” the agency added.
The FDA also noted that no serious adverse reactions were attributed to Ga 68 PSMA-11. The most common adverse reactions were nausea, diarrhea, and dizziness.
The FDA said there is a risk for misdiagnosis because Ga 68 PSMA-11 binding may occur in other types of cancer, and certain nonmalignant processes may lead to errors in interpreting images. In addition, there are radiation risks because Ga 68 PSMA-11 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk for cancer.
A version of this article originally appeared on Medscape.com.