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Interventions ease cancer-related stress, depression
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
CHICAGO – Clinicians have gotten much better in recent decades at helping patients cope with physical side effects from cancer care, but mental health interventions aimed at easing stress and fear are often absent or, at best, an afterthought.
As three new studies show, however, early psychological interventions can both improve the quality of life for patients with cancer and enhance clinical outcomes.
For example, an online stress management program dubbed STREAM, developed jointly by oncologists and psychologists, was associated with significantly better quality of life and lower levels of distress for patients 2 months after a new cancer diagnosis, compared with controls who had not yet used it, reported Viviane Hess, MD, a medical oncologist at the University Hospital of Basel (Switzerland).
“From randomized controlled trials, we know that cognitive behavioral therapies are effective in mediating distress. However, the majority of cancer patients lack psychological support, due to both barriers on the patients’ side and lack of resources on the providers’ side,” she said at a briefing at the annual meeting of the American Society of Clinical Oncology.
Other studies presented in the briefing show that psychological interventions can significantly reduce patient anxieties about the possibility of cancer recurrence and help relieve depressive symptoms for at least 6 months among patients with advanced cancers.
STREAM
Dr. Hess and her colleagues conducted a prospective, wait-list controlled trial for patients who had started therapy for a newly diagnosed cancer within the past 12 weeks. The patients were randomized to either immediate use of an online psychological intervention or to a delayed start.
The investigators chose a web-based intervention because a majority of patients with cancer already use the Internet for information, and because Internet interventions can overcome barriers of time and distance, with results comparable to those seen with face-to-face interventions, Dr. Hess said.
The intervention consisted of eight weekly sessions based on approaches used in cognitive behavioral therapy, with focus on bodily reactions to stress, cognitive stress reduction, feelings, and social interactions. Each of the eight sessions focused on a single topic. Patients were given written and audio information about each topic and then were asked to perform exercises and complete questionnaires.
For this “minimal contact” intervention, psychologists based in Basel reviewed each patient’s progress weekly and gave written feedback personalized for that patient via a secure online portal.
In all, 129 patients were randomized (65 to the intervention and 64 controls). The majority were women treated with curative intent for early-stage breast cancer. Patients newly diagnosed with lung, ovarian, and gastrointestinal cancers, as well as melanoma and lymphoma, also were included.
Patients in both the active intervention and control groups were assessed at baseline and at 2 months with three quality-of-life measures: the FACIT-F (Functional Assessment of Chronic Illness Therapy Fatigue subscale), DT (Distress Thermometer), and HADS (Hospital Anxiety and Depression Scale).
At 2 months, the mean FACIT-F score for patients in both the intervention and control groups increased, indicating an improved quality of life, but the change was significantly greater for patients in the intervention group (mean 8.59 points vs. controls; P = .0032). There was also a significant decrease in the DT scale from 6 points at baseline to 4 points at 2 months among patients randomized to the intervention, but no change among controls. There were no significant differences in either anxiety or depression between the groups, however.
“Most oncologists, particularly when we’re meeting patients for the first time and starting on curative intent therapy, it is assumed there is a level of distress … but we assume that that level of distress will fall naturally as we start them on therapy,” commented ASCO expert Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study.
“What Dr. Hess is showing is that not only do they have distress, but it’s significant distress,” he said, adding that the study shows that online tools can be effective at providing support, and that the ease of access can help patients who might otherwise never meet with a mental health professional.
Recurrence fears assuaged
In a separate study, investigators from Australia reported results of a randomized phase II trial showing that an intervention called Conquer Fear was effective at lowering fear of recurrence among patients with successfully treated stage I-III breast, colorectal, or melanoma cancers who reported a high level of fear of recurrence.
“Fear of cancer recurrence is associated with poorer quality of life, greater distress, lack of planning for the future, avoidance or excessive use of screening, and greater health care utilization,” said Jane MacNeil Beith, MD, PhD, a medical oncologist at the University of Sydney.
Dr. Beith and her colleagues randomly assigned 222 patients to either the Conquer Fear intervention or relaxation training (control group).
Patients assigned to the control group received five 1-hour individual, face-to-face relaxation sessions over 10 weeks. The sessions included muscle relaxation, meditative relaxation, and visualization and quick relaxation techniques taught by trained study instructors. Patients in each group received instructions for home-based relaxation techniques.
The Conquer Fear intervention is intended to help patients with values clarification, detached mindfulness (focusing on the moment), attention training, meta-cognitive therapy (worry or not worry), and a behavioral contract to ensure appropriate follow-up.
They measured fear of recurrence using the validated 42-item Fear of Cancer Recurrence Inventory (FCRI), which scores fear on a scale of 0-168, with higher scores indicating higher levels of fear, Dr. Beith said.
The mean baseline FCRI scores were 82.7 for patients assigned to the intervention and 85.7 in controls.
Participants in both groups had improvement of all outcomes, but patients in the active intervention group had significantly lower FCRI total scores at the end of the intervention and at 3 and 6 months of follow-up. The severity of fear of recurrence was also lower among patients in the intervention group immediately afterward and at 3 months, but not at 6 months, she reported.
“I applaud Dr. Beith for her trial, particularly because we as oncologists have only about 15 minutes with our patients, and the assessments for our patients, even in follow-up, for the most part concentrate on cancer-related outcomes, because that’s what our patients want to know. They want to know if they’re fine, or they want to know, is their cancer back,” Dr. Dizon commented.
The study demonstrates fear of recurrence is real, but that there are also interventions that can help patients reduce those fears, he said.
CALM
In a third study, Gary Rodin, MD, from the department of supportive care at Princess Margaret Cancer Centre in Toronto, and his colleagues reported that a brief psychological intervention with the acronym CALM (for Managing Cancer and Living Meaningfully) was associated with a “clinically meaningful” reduction in depressive symptoms in patients with advanced cancer.
Patients in CALM receive three to six individual sessions delivered over 3-6 months. The program helps patients cope with symptom management and improve communications with health care providers, understand changes in themselves and their relations with others, find a personal sense of meaning and purpose, and learn to live with thoughts of the future and mortality, Dr. Rodin explained.
In a clinical trial, 52% of the 151 patients randomized to the intervention had clinically important reductions in depressive symptoms at 3 months, compared with 33% of controls assigned to usual care. At 6 months, the respective reductions in depressive symptoms were 64% vs. 35%.
The intervention also was effective at preventing depression among 137 patients without depressive symptoms at baseline. In this group, 13% of patients who received the CALM intervention had depressive symptoms at 3 months, compared with 30% of controls.
In addition, patients who received CALM support at both 3 and 6 months said they were better prepared for the end of life, reported that they had greater opportunity to talk about their concerns for the future, were less frightened, and said they had greater ability to express and manage their feelings. At 6 months these effects were strengthened, and the CALM group also felt more able to understand their cancer experience, deal with changes in relationships as a result of cancer, explore ways of communicating with their health care team and family, and clarify their values and beliefs.
“The intervention addresses both the practical problems that people face, and there are many – How do I manage my pain? My symptoms? – but also the profound problems and issues that people face – What is the meaning of my life? – when having a terminal diagnosis, for instance,” he said.
The investigators are currently establishing a global network to train health professionals in the delivery of CALM, and to evaluate the program’s effectiveness in different clinical settings and cultures, he said.
The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
AT ASCO 2017
Key clinical point: Oncologists and patients may focus on only the clinical aspects of care while overlooking cancer-associated distress, anxiety, or fear.
Major finding: Each of three psychological interventions was effective at reducing mental health symptoms in patients with cancer.
Data source: Randomized trials of interventions aimed at relieving mental health symptoms associated with a new cancer diagnoses, fear of cancer recurrence, and advanced or metastatic disease.
Disclosures: The STREAM study was institutionally supported. Dr. Hess disclosed travel and accommodations from CSL Behring. The Conquer Fear study was funded by Cancer Australia, beyondBlue, and the Australian National Breast Cancer Foundation. Dr. Beith reported no relevant disclosures. The CALM study was supported by the Canadian Institute of Health Research. Dr. Rodin reported no relevant disclosures.
Single-dose RT suffices for treatment of spinal cord compression due to mets
CHICAGO – A single dose of radiation therapy appears to work as well as multiple doses given over a week for treating spinal cord compression due to metastatic cancer, according to findings of the SCORAD III trial reported at the annual meeting of the American Society of Clinical Oncology.
“There is no standard radiotherapy schedule,” first author Peter Hoskin, MD, FCRP, FRCR, an oncologist at the Mount Vernon Cancer Centre in Middlesex, England, noted in a press briefing. “A range of radiation doses are used internationally, from single doses of 8 to 10 Gy ranging up to 4 weeks of treatment delivering 40 Gy.”
The noninferiority phase III trial enrolled nearly 700 patients in the United Kingdom and Australia with spinal cord compression due to metastases, the majority of whom were able to walk at baseline. They were randomized evenly to receive either 8 Gy of radiation in a single fraction or 20 Gy split into five fractions given over consecutive days.
Results showed that at 8 weeks, more than two-thirds of patients in each group were able to walk, the trial’s primary endpoint. The lower bound of the confidence interval for the difference between groups fell just outside the trial’s margin for noninferiority.
Additionally, the two groups were statistically indistinguishable with respect to median overall survival, bowel and bladder function, and the rate of grade 3 or 4 toxicity.
“A single dose of 8 Gy is as effective as 20 Gy in five fractions for a range of clinically relevant endpoints, particularly ambulatory status, both at 8 weeks and indeed at all time points between 1 week and 12 weeks,” Dr. Hoskin summarized. The trial also underscores the importance of early diagnosis, as the majority of patients who were ambulatory initially remained so with radiation therapy, regardless of dosing schedule.
“A single dose of radiotherapy in our minds is now recommended in this setting. It has major advantages for these patients,” he maintained. “An important thing to realize is that these patients had a very short survival; median survival in this study was only 13 weeks. A single dose has enormous advantages in those patients with short survival times, and of course, it is increasingly cost effective.”
Findings in context
The trial population was not fully representative of all patients with spinal cord compression due to metastases, with underrepresentation of some cancers, such as breast cancer, and the modest survival, Dr. Hoskin acknowledged.
Some patients on the trial have survived for many months and even years, he noted. “We have looked at patients at longer times, although it was not in the protocol, and there was no obvious difference [in outcomes]. But there is some evidence to suggest that for the longer-surviving patients, a more prolonged fractionation may be appropriate, although clearly that needs to be investigated properly in a formal randomized trial.”
“This is the first study that really shows equal outcomes in terms of meaningful benefits for patients with a single dose of radiotherapy versus a much longer course, allowing patients to spend more time with their families, more time doing the things they want to do,” commented ASCO Expert Joshua A. Jones, MD, MA, of the Hospital of the University of Pennsylvania in Philadelphia.
“We still have work to do to figure out for patients who have longer than this average survival of 3 months what is the most appropriate regimen,” he agreed. “But for many patients, this is going to provide tremendous benefit with the idea that sometimes, less really is more.”
Study details
SCORAD III, which was funded by Cancer Research UK, enrolled 688 patients with metastatic prostate (44%), lung (18%), breast (11%), and gastrointestinal (11%) cancers.
At baseline, 66% were able to walk without or with an aid (ambulatory status 1 or 2), whereas the rest were unable to walk but still had some limb power (ambulatory status 3) or had flaccid paraplegia (ambulatory status 4).
At 8 weeks, the proportion of patients with ambulatory status 1 or 2 was 69.5% in the group who received the 8-Gy single-dose radiation therapy and 73.3% in the group who received the 20-Gy multidose radiation therapy, for a risk difference of –3.78%, reported Dr. Hoskin.
The 90% confidence interval for the difference between groups of –11.85% to 4.28% slightly exceeded the trial’s predefined 11% margin for noninferiority.
Among patients having ambulatory status 1 or 2 at baseline, the proportion maintaining that status at 8 weeks was 62.20% with the single dose and 63.07% with multiple doses. Median overall survival was 12.4 weeks and 13.7 weeks, respectively, a nonsignificant difference.
Patients in the single-dose and multidose groups had similar rates of grade 3 or 4 toxicity (20.6% vs. 20.4%), but the former had a lower rate of grade 1 or 2 toxicity (51.0% vs. 56.9%).
CHICAGO – A single dose of radiation therapy appears to work as well as multiple doses given over a week for treating spinal cord compression due to metastatic cancer, according to findings of the SCORAD III trial reported at the annual meeting of the American Society of Clinical Oncology.
“There is no standard radiotherapy schedule,” first author Peter Hoskin, MD, FCRP, FRCR, an oncologist at the Mount Vernon Cancer Centre in Middlesex, England, noted in a press briefing. “A range of radiation doses are used internationally, from single doses of 8 to 10 Gy ranging up to 4 weeks of treatment delivering 40 Gy.”
The noninferiority phase III trial enrolled nearly 700 patients in the United Kingdom and Australia with spinal cord compression due to metastases, the majority of whom were able to walk at baseline. They were randomized evenly to receive either 8 Gy of radiation in a single fraction or 20 Gy split into five fractions given over consecutive days.
Results showed that at 8 weeks, more than two-thirds of patients in each group were able to walk, the trial’s primary endpoint. The lower bound of the confidence interval for the difference between groups fell just outside the trial’s margin for noninferiority.
Additionally, the two groups were statistically indistinguishable with respect to median overall survival, bowel and bladder function, and the rate of grade 3 or 4 toxicity.
“A single dose of 8 Gy is as effective as 20 Gy in five fractions for a range of clinically relevant endpoints, particularly ambulatory status, both at 8 weeks and indeed at all time points between 1 week and 12 weeks,” Dr. Hoskin summarized. The trial also underscores the importance of early diagnosis, as the majority of patients who were ambulatory initially remained so with radiation therapy, regardless of dosing schedule.
“A single dose of radiotherapy in our minds is now recommended in this setting. It has major advantages for these patients,” he maintained. “An important thing to realize is that these patients had a very short survival; median survival in this study was only 13 weeks. A single dose has enormous advantages in those patients with short survival times, and of course, it is increasingly cost effective.”
Findings in context
The trial population was not fully representative of all patients with spinal cord compression due to metastases, with underrepresentation of some cancers, such as breast cancer, and the modest survival, Dr. Hoskin acknowledged.
Some patients on the trial have survived for many months and even years, he noted. “We have looked at patients at longer times, although it was not in the protocol, and there was no obvious difference [in outcomes]. But there is some evidence to suggest that for the longer-surviving patients, a more prolonged fractionation may be appropriate, although clearly that needs to be investigated properly in a formal randomized trial.”
“This is the first study that really shows equal outcomes in terms of meaningful benefits for patients with a single dose of radiotherapy versus a much longer course, allowing patients to spend more time with their families, more time doing the things they want to do,” commented ASCO Expert Joshua A. Jones, MD, MA, of the Hospital of the University of Pennsylvania in Philadelphia.
“We still have work to do to figure out for patients who have longer than this average survival of 3 months what is the most appropriate regimen,” he agreed. “But for many patients, this is going to provide tremendous benefit with the idea that sometimes, less really is more.”
Study details
SCORAD III, which was funded by Cancer Research UK, enrolled 688 patients with metastatic prostate (44%), lung (18%), breast (11%), and gastrointestinal (11%) cancers.
At baseline, 66% were able to walk without or with an aid (ambulatory status 1 or 2), whereas the rest were unable to walk but still had some limb power (ambulatory status 3) or had flaccid paraplegia (ambulatory status 4).
At 8 weeks, the proportion of patients with ambulatory status 1 or 2 was 69.5% in the group who received the 8-Gy single-dose radiation therapy and 73.3% in the group who received the 20-Gy multidose radiation therapy, for a risk difference of –3.78%, reported Dr. Hoskin.
The 90% confidence interval for the difference between groups of –11.85% to 4.28% slightly exceeded the trial’s predefined 11% margin for noninferiority.
Among patients having ambulatory status 1 or 2 at baseline, the proportion maintaining that status at 8 weeks was 62.20% with the single dose and 63.07% with multiple doses. Median overall survival was 12.4 weeks and 13.7 weeks, respectively, a nonsignificant difference.
Patients in the single-dose and multidose groups had similar rates of grade 3 or 4 toxicity (20.6% vs. 20.4%), but the former had a lower rate of grade 1 or 2 toxicity (51.0% vs. 56.9%).
CHICAGO – A single dose of radiation therapy appears to work as well as multiple doses given over a week for treating spinal cord compression due to metastatic cancer, according to findings of the SCORAD III trial reported at the annual meeting of the American Society of Clinical Oncology.
“There is no standard radiotherapy schedule,” first author Peter Hoskin, MD, FCRP, FRCR, an oncologist at the Mount Vernon Cancer Centre in Middlesex, England, noted in a press briefing. “A range of radiation doses are used internationally, from single doses of 8 to 10 Gy ranging up to 4 weeks of treatment delivering 40 Gy.”
The noninferiority phase III trial enrolled nearly 700 patients in the United Kingdom and Australia with spinal cord compression due to metastases, the majority of whom were able to walk at baseline. They were randomized evenly to receive either 8 Gy of radiation in a single fraction or 20 Gy split into five fractions given over consecutive days.
Results showed that at 8 weeks, more than two-thirds of patients in each group were able to walk, the trial’s primary endpoint. The lower bound of the confidence interval for the difference between groups fell just outside the trial’s margin for noninferiority.
Additionally, the two groups were statistically indistinguishable with respect to median overall survival, bowel and bladder function, and the rate of grade 3 or 4 toxicity.
“A single dose of 8 Gy is as effective as 20 Gy in five fractions for a range of clinically relevant endpoints, particularly ambulatory status, both at 8 weeks and indeed at all time points between 1 week and 12 weeks,” Dr. Hoskin summarized. The trial also underscores the importance of early diagnosis, as the majority of patients who were ambulatory initially remained so with radiation therapy, regardless of dosing schedule.
“A single dose of radiotherapy in our minds is now recommended in this setting. It has major advantages for these patients,” he maintained. “An important thing to realize is that these patients had a very short survival; median survival in this study was only 13 weeks. A single dose has enormous advantages in those patients with short survival times, and of course, it is increasingly cost effective.”
Findings in context
The trial population was not fully representative of all patients with spinal cord compression due to metastases, with underrepresentation of some cancers, such as breast cancer, and the modest survival, Dr. Hoskin acknowledged.
Some patients on the trial have survived for many months and even years, he noted. “We have looked at patients at longer times, although it was not in the protocol, and there was no obvious difference [in outcomes]. But there is some evidence to suggest that for the longer-surviving patients, a more prolonged fractionation may be appropriate, although clearly that needs to be investigated properly in a formal randomized trial.”
“This is the first study that really shows equal outcomes in terms of meaningful benefits for patients with a single dose of radiotherapy versus a much longer course, allowing patients to spend more time with their families, more time doing the things they want to do,” commented ASCO Expert Joshua A. Jones, MD, MA, of the Hospital of the University of Pennsylvania in Philadelphia.
“We still have work to do to figure out for patients who have longer than this average survival of 3 months what is the most appropriate regimen,” he agreed. “But for many patients, this is going to provide tremendous benefit with the idea that sometimes, less really is more.”
Study details
SCORAD III, which was funded by Cancer Research UK, enrolled 688 patients with metastatic prostate (44%), lung (18%), breast (11%), and gastrointestinal (11%) cancers.
At baseline, 66% were able to walk without or with an aid (ambulatory status 1 or 2), whereas the rest were unable to walk but still had some limb power (ambulatory status 3) or had flaccid paraplegia (ambulatory status 4).
At 8 weeks, the proportion of patients with ambulatory status 1 or 2 was 69.5% in the group who received the 8-Gy single-dose radiation therapy and 73.3% in the group who received the 20-Gy multidose radiation therapy, for a risk difference of –3.78%, reported Dr. Hoskin.
The 90% confidence interval for the difference between groups of –11.85% to 4.28% slightly exceeded the trial’s predefined 11% margin for noninferiority.
Among patients having ambulatory status 1 or 2 at baseline, the proportion maintaining that status at 8 weeks was 62.20% with the single dose and 63.07% with multiple doses. Median overall survival was 12.4 weeks and 13.7 weeks, respectively, a nonsignificant difference.
Patients in the single-dose and multidose groups had similar rates of grade 3 or 4 toxicity (20.6% vs. 20.4%), but the former had a lower rate of grade 1 or 2 toxicity (51.0% vs. 56.9%).
At ASCO 2017
Key clinical point:
Major finding: At 8 weeks, the proportion of patients able to walk was 69.5% with 8 Gy given in a single dose and 73.3% with 20 Gy given in five doses.
Data source: A randomized phase III noninferiority trial among 688 patients with spinal cord compression due to metastatic cancer (SCORAD III trial).
Disclosures: Dr. Hoskin disclosed that he receives research funding (institutional) from Varian Medical Systems. The trial was funded by Cancer Research UK.
Severe health conditions decline in childhood cancer survivors
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have steadily declined, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study, funded by the National Institutes of Health.
For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: hazard ratio, 0.84 [95% confidence interval, 0.80-0.89]), Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, reported at a press conference at the annual meeting of the American Society of Clinical Oncology.
The association with diagnosis decade was attenuated (HR, 0.92 [95% CI, 0.85-1.00]) when detailed treatment data were included in the model, indicating that treatment reductions mediated risk.
Changes in childhood cancer treatment protocols to reduce the intensity of therapy – along with improved screening and early detection – have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity, Dr. Gibson said.
As the data address children diagnosed over 15 years ago, it is likely that improvements since then in determining patient risk and targeting therapy might result in further incremental improvements, he said in an interview.
By cancer type, severe health problems by 15 years after diagnosis decreased from 13% to 5% among survivors of Wilms’ tumor, from 18% to 11% among survivors of Hodgkin lymphoma, from 15% to 9% among survivors of astrocytoma, from 10% to 6% among survivors of non-Hodgkin lymphoma, and from 9% to 7% among survivors of acute lymphoblastic leukemia. The conclusions are based on the incidence of severe, disabling/life-threatening, or fatal chronic health conditions (Common Terminology Criteria for Adverse Events, grades 3-5) among 5-year survivors diagnosed prior to age 21 years from 1970 through 1999.
Adjusted for sex and attained age, significant reduction in risk over time was found among survivors of Wilms tumor (HR, 0.57 [95% CI, 0.46-0.70]), Hodgkin lymphoma (HR, 0.75 [95% CI, 0.65-0.85]), astrocytoma (HR, 0.77 [95% CI, 0.64-0.92]), non-Hodgkin lymphoma (HR, 0.79 [95% CI, 0.63-0.99]), and acute lymphoblastic leukemia (HR, 0.86 [95% CI, 0.76-0.98]).
The decreases in serious health conditions were largely driven by a reduced incidence of endocrine conditions (1970s: 4.0% vs. 1990s: 1.6%; HR, 0.66 [95% CI, 0.59-0.73]) and subsequent malignant neoplasms (1970s: 2.4% vs. 1990s: 1.6%; HR, 0.85 [95% CI, 0.76-0.96]).
Gastrointestinal (HR, 0.80 [95% CI, 0.66-0.97]) and neurological conditions (HR, 0.77 [95% CI, 0.65-0.91]) also were reduced, but cardiac and pulmonary conditions were not. Changes in childhood cancer treatment protocols have not only extended lifespan for many survivors, but also have reduced the incidence of serious chronic morbidity in this population, Dr. Gibson concluded.
[email protected]
On Twitter @maryjodales
AT ASCO 2017
Key clinical point:
Major finding: For all childhood cancer survivors, the 15-year cumulative incidence of severe health conditions decreased from 12.7% in those diagnosed in the 1970s, to 10.1% in the 1980s, and to 8.8% among those diagnosed in the 1990s (per 10 years: HR, 0.84 [95% CI, 0.80-0.89]).
Data source: An analysis of 23,600 participants in the Childhood Cancer Survivor Study.
Disclosures: The study was funded by the National Institutes of Health.
VIDEO: Single dose of RT suffices, but will radiation oncologists adopt the strategy?
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The randomized SCORAD III trial shows that a single 8-Gy dose of radiation therapy has efficacy similar to that of a 20-Gy dose given over the course of a week for treating metastatic spinal cord compression in patients with modest survival, first author Peter Hoskin, MD, FCRP, FRCR, said in a video interview at the annual meeting of the American Society of Clinical Oncology. But will radiation oncologists adopt this new strategy?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
VIDEO: Helping cancer patients cope with psychological side effects
CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.
Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.
Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.
Dr. Dizon reported having no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.
Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.
Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.
Dr. Dizon reported having no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Oncologists are highly skilled at minimizing side effects associated with toxic but curative therapies, but are less adept at helping patients cope with the distress, anxiety, fear, and other emotions associated with cancer.
Three studies presented at the annual meeting of the American Society of Clinical Oncology detail randomized, controlled trials of psychological interventions aimed at helping patients cope with a new cancer diagnosis, reduce fears of a recurrence, and come to grips with the realities of advanced disease, including fears of death or disability.
Don S. Dizon, MD, from the Massachusetts General Hospital Cancer Center, Boston, discusses the social and financial barriers that cancer patients face when they experience distress, and the difficulties that providers face with limited time and financial resources to help patients cope in this video interview.
Dr. Dizon reported having no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASCO 2017
VIDEO: Childhood cancer survivors living longer with fewer severe health problems
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.
Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.
Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @maryjodales
CHICAGO – Severe health problems occurring 5 or more years after diagnosis of a childhood cancer have been steadily declining, based on an analysis of 23,600 participants in the Childhood Cancer Survivor Study (CCSS), funded by the National Institutes of Health.
Watch our video interview with lead author Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital, Memphis, who reported the data at a press conference at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @maryjodales
AT ASCO 2017
FDA panel backs licensure for epoetin alfa biosimilar
A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.
Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.
“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.
The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.
Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”
“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.
For one member, however, the concerns were enough for a “no” vote.
“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.
“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.
To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.
Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.
The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.
The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.
Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.
Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”
The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.
In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”
The advisory committee members were screened and found to have no relevant conflicts of interest.
A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.
Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.
“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.
The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.
Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”
“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.
For one member, however, the concerns were enough for a “no” vote.
“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.
“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.
To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.
Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.
The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.
The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.
Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.
Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”
The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.
In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”
The advisory committee members were screened and found to have no relevant conflicts of interest.
A Food and Drug Administration advisory committee voted overwhelmingly in support of licensure for Epoetin Hospira as a biosimilar product to epoetin alfa (Epogen/Procrit) for all approved Epogen/Procrit indications.
Most committee members who voted “yes” said they were hesitant to do so, however, because of safety concerns, particularly in HIV and oncology patients.
“I voted yes. I came in with concerns about the HIV and oncology patients. However, I do believe ... after hearing the justification, that it meets the [FDA regulatory guideline],” said temporary voting member and patient representative Karen E. Arscott, DO, of the Commonwealth Medical College, Scranton, Penn. “I would like to see extensive follow-up in these two population groups,” she said.
The concerns about HIV and oncology patients are related to the potential for immunogenicity-related events. Some members noted that the study populations were likely too small to detect these rare events.
Scott A. Waldman, MD, of Thomas Jefferson University, Philadelphia, also a temporary member, said he voted “yes” because there was “no substantial difference analytically, biologically, or clinically in what was tested.”
“I think the residual uncertainty of immunogenicity and hypersensitivity and the extrapolation across different patient populations will emerge in postmarketing surveillance. I think that’s when we’ll get the clearest picture of whether there really is any uncertainty in how these drugs perform,” he said.
For one member, however, the concerns were enough for a “no” vote.
“The analytical, clinical, and preclinical data support biosimilarity, and I strongly support approval for indications 1 and 4 based on the clinical data ... but I have residual concerns about lack of data, immunogenicity, basic safety data in patients with HIV and cancer and, for that reason, voted no for the broader indication,” said Thomas S. Uldrick, MD, of the HIV & AIDS Malignancy Branch at the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
Gregory J. Riely, MD, of Memorial Sloan-Kettering Cancer Center in New York expressed similar concerns but said he found the data compelling.
“I understand the concerns around immunogenicity for HIV and cancer patients. I was somewhat reassured by the nonclinical data showing an absence of increased immunogenicity for this biosimilar,” he said.
To support its BLA for Epoetin Hospira, Hospira submitted data from four studies comparing it with the U.S.-licensed Epogen/Procrit and presented an analytical biosimilarity assessment and a nonclinical, clinical pharmacology and clinical biosimilarity assessment. The FDA analysis of the data considered chemistry, manufacturing, and controls, as well as pharmacology/toxicology, immunogenicity, clinical pharmacology, and clinical efficacy and safety.
Sumant Ramachandra, MD, of Pfizer Essential Health noted that the company is not currently seeking an interchangeability designation and that, while this is the first application for a biosimilar product to Amgen’s Epogen/Procrit product, which was approved in 1989, a “highly related epoetin product” from Pfizer (Retacrit) has been available in Europe for 9 years, with more than 363,000 patient years of treatment administered.
The demonstration of biosimilarity in the Epoetin Hospira data presented to the FDA, coupled with well-characterized nature of the reference product, “together support extrapolation across all conditions of use for the reference product,” he said, noting that the data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.
The FDA assessment of the data led to a similar conclusion that no clinically significant differences were found between the biosimilar and reference product.
Among other concerns expressed by advisory committee members and/or the public were in regard to the extrapolation of data from patients with chronic kidney disease on hemodialysis to other indications (although this is considered acceptable, according to FDA regulations) and to populations that weren’t studied and about the possibility that Epoetin Hospira would be forced on patients inappropriately, despite the fact that Hospira is not seeking an interchangeability designation. Patients and others speaking on behalf of various patient groups and advocacy organizations called for safeguards against such inappropriate substitution.
Acting committee chair, Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Clinic, Ohio, said he voted “yes” because the product met all regulatory requirements but agreed that the “need for vigilance is exceedingly important not only for this drug but for all drugs in this circumstance.”
The FDA, which usually follows the recommendations of its advisory committees, will now consider the BLA for Epoetin Hospira.
In a statement released after the vote, Diem Nguyen, Pfizer Essential Health global president, Americas, said the committee’s recommendation for approval “reinforces the potential value of biosimilars in expanding access to additional high-quality treatment options for the patients in the U.S. who need them.”
The advisory committee members were screened and found to have no relevant conflicts of interest.
Key clinical point:
Major finding: The data demonstrate that the mechanism of action for both the biosimilar and reference product is the same, and that the immunogenicity profiles are consistent.
Data source: An FDA advisory committee review of epoetin alfa biosimilar Epoetin Hospira.
Disclosures: The advisory committee members were screened and found to have no relevant conflicts of interest.
Fighting in a passive manner active against Clostridium difficile
Infections resulting from Clostridium difficile are a major clinical challenge. In hematology and oncology, the widespread use of broad-spectrum antibiotics is essential for patients with profound neutropenia and infectious complications, which are a high-risk factor for C. difficile enteritis.
C. difficile enteritis occurs in 5%-20% of cancer patients.1 With standard of care antibiotics, oral metronidazole or oral vancomycin, high C. difficile cure rates are possible, but up to 25% of these infections recur. Recently, oral fidaxomicin was approved for treatment of C. difficile enteritis and was associated with high cure rates and, more importantly, with significantly lower recurrence rates.2
Bezlotoxumab, a fully humanized monoclonal antibody against C. difficile toxin B, has been shown by x-ray crystallography to neutralize toxin B by blocking its ability to bind to host cells.7 Most recently, this new therapeutic approach was investigated in humans.8
Wilcox et al. used pooled data of 2655 adults treated in two double-blind, randomized, placebo-controlled phase III clinical trials (MODIFY I and MODIFY II) for primary or recurrent C. difficile enteritis. This industry-sponsored trial was conducted at 322 sites in 30 countries.
In one treatment group, patients received a single infusion of bezlotoxumab (781 patients) or placebo (773 patients) and one of the three oral standard-of-care C. difficile antibiotics. Importantly, the primary end point of this trial was recurrent infection within 12 weeks. About 28% of the patients in both the bezlotoxumab group and the placebo group previously had at least one episode of C. difficile enteritis. About 20% of the patients in both groups were immunocompromised.
Pooled data showed that recurrent infection was significantly lower (P less than 0.001) in the bezlotoxumab group (17%), compared with the placebo group (27%). The difference in recurrence rate (25% vs. 41%) was even more pronounced in patients with one or more episodes of recurrent C. difficile enteritis in the past 6 months. Furthermore, a benefit for bezlotoxumab was seen in immunocompromised patients, whose recurrence rates were 15% with bezlotoxumab, vs. 28% with placebo. After the 12 weeks of follow-up, the absolute difference in the Kaplan-Meier rates of recurrent infection was 13% (absolute rate, 21% in bezlotoxumab group vs. 34% in placebo group; P less than 0.001).
The results indicate that bezlotoxumab, which was approved in 2016 by the U.S. Food and Drug Administration, might improve the outcome of patients with C. difficile enteritis. However, bezlotoxumab is not a “magic bullet.” The number needed to treat to prevent one episode of C. difficile enteritis is 10.
It is conceivable that bezlotoxumab may find its role in high-risk patients – those older than 65 years or patients with recurrent C. difficile enteritis – since the number needed to treat is only 6 in these subgroups.8
This new agent could be an important treatment option for our high-risk patients in hematology. However, more studies concerning costs and real-life efficacy are needed.
The new approach of passive immunization for prevention of recurrent C. difficile enteritis shows the importance and the role of toxin B – not only the bacterium per se – in pathogenesis and virulence of C. difficile. This could mean that we have to renew our view on the role of antibiotics against C. difficile. However, in contrast, bezlotoxumab does not affect the efficacy of standard of care antibiotics since the initial cure rates were 80% for both the antibody and the placebo groups.8 Toxin B levels are not detectable in stool samples between days 4 and 10 of standard of care antibiotic treatment. Afterward, however, they increase again.9 Most of the patients had received bezlotoxumab 3 or more days after they began standard-of-care antibiotic treatment – in the time period when toxin B is undetectable in stool – which underlines the importance of toxin B in the pathogenesis of recurrent C. difficile enteritis.8
In summary, the introduction of bezlotoxumab in clinical care gives new and important insights and solutions not only for treatment options but also for our understanding of C. difficile pathogenesis.
Dr. Schalk is consultant of internal medicine at the department of hematology and oncology, Magdeburg University Hospital, Germany, with clinical and research focus on infectious diseases in hematology and oncology.
Dr. Fischer is professor of internal medicine, hematology and oncology, at the Otto-von-Guericke University Hospital Magdeburg, Germany. He is head of the department of hematology and oncology and a clinical/molecular researcher in myeloid neoplasms. He is a member of the editorial advisory board of Hematology News.
Contact Dr. Schalk at [email protected].
References
1. Vehreschild, MJ et al. Diagnosis and management of gastrointestinal complications in adult cancer patients: Wvidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Oncol. 2013;24:1189-202
2. Cornely, OA. Current and emerging management options for Clostridium difficile infection: What is the role of fidaxomicin? Clin Microbiol Infect. 2012;18(Suppl 6):28-35.
3. Bartlett, JG et al. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298(10):531-4.
4. Lyras, D et al. Toxin B is essential for virulence of Clostridium difficile. Nature. 2009;458:1176-9.
5. Reineke, J et al. Autocatalytic cleavage of Clostridium difficile toxin B. Nature. 2007;446:415-9.
6. Leav, BA et al. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010;28:965-9.
7. Orth, P et al. Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J Biol Chem. 2014;289:18008-21.
8. Wilcox, MH et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-17.
9. Louie, TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;5(Suppl 2):S132-42.
Infections resulting from Clostridium difficile are a major clinical challenge. In hematology and oncology, the widespread use of broad-spectrum antibiotics is essential for patients with profound neutropenia and infectious complications, which are a high-risk factor for C. difficile enteritis.
C. difficile enteritis occurs in 5%-20% of cancer patients.1 With standard of care antibiotics, oral metronidazole or oral vancomycin, high C. difficile cure rates are possible, but up to 25% of these infections recur. Recently, oral fidaxomicin was approved for treatment of C. difficile enteritis and was associated with high cure rates and, more importantly, with significantly lower recurrence rates.2
Bezlotoxumab, a fully humanized monoclonal antibody against C. difficile toxin B, has been shown by x-ray crystallography to neutralize toxin B by blocking its ability to bind to host cells.7 Most recently, this new therapeutic approach was investigated in humans.8
Wilcox et al. used pooled data of 2655 adults treated in two double-blind, randomized, placebo-controlled phase III clinical trials (MODIFY I and MODIFY II) for primary or recurrent C. difficile enteritis. This industry-sponsored trial was conducted at 322 sites in 30 countries.
In one treatment group, patients received a single infusion of bezlotoxumab (781 patients) or placebo (773 patients) and one of the three oral standard-of-care C. difficile antibiotics. Importantly, the primary end point of this trial was recurrent infection within 12 weeks. About 28% of the patients in both the bezlotoxumab group and the placebo group previously had at least one episode of C. difficile enteritis. About 20% of the patients in both groups were immunocompromised.
Pooled data showed that recurrent infection was significantly lower (P less than 0.001) in the bezlotoxumab group (17%), compared with the placebo group (27%). The difference in recurrence rate (25% vs. 41%) was even more pronounced in patients with one or more episodes of recurrent C. difficile enteritis in the past 6 months. Furthermore, a benefit for bezlotoxumab was seen in immunocompromised patients, whose recurrence rates were 15% with bezlotoxumab, vs. 28% with placebo. After the 12 weeks of follow-up, the absolute difference in the Kaplan-Meier rates of recurrent infection was 13% (absolute rate, 21% in bezlotoxumab group vs. 34% in placebo group; P less than 0.001).
The results indicate that bezlotoxumab, which was approved in 2016 by the U.S. Food and Drug Administration, might improve the outcome of patients with C. difficile enteritis. However, bezlotoxumab is not a “magic bullet.” The number needed to treat to prevent one episode of C. difficile enteritis is 10.
It is conceivable that bezlotoxumab may find its role in high-risk patients – those older than 65 years or patients with recurrent C. difficile enteritis – since the number needed to treat is only 6 in these subgroups.8
This new agent could be an important treatment option for our high-risk patients in hematology. However, more studies concerning costs and real-life efficacy are needed.
The new approach of passive immunization for prevention of recurrent C. difficile enteritis shows the importance and the role of toxin B – not only the bacterium per se – in pathogenesis and virulence of C. difficile. This could mean that we have to renew our view on the role of antibiotics against C. difficile. However, in contrast, bezlotoxumab does not affect the efficacy of standard of care antibiotics since the initial cure rates were 80% for both the antibody and the placebo groups.8 Toxin B levels are not detectable in stool samples between days 4 and 10 of standard of care antibiotic treatment. Afterward, however, they increase again.9 Most of the patients had received bezlotoxumab 3 or more days after they began standard-of-care antibiotic treatment – in the time period when toxin B is undetectable in stool – which underlines the importance of toxin B in the pathogenesis of recurrent C. difficile enteritis.8
In summary, the introduction of bezlotoxumab in clinical care gives new and important insights and solutions not only for treatment options but also for our understanding of C. difficile pathogenesis.
Dr. Schalk is consultant of internal medicine at the department of hematology and oncology, Magdeburg University Hospital, Germany, with clinical and research focus on infectious diseases in hematology and oncology.
Dr. Fischer is professor of internal medicine, hematology and oncology, at the Otto-von-Guericke University Hospital Magdeburg, Germany. He is head of the department of hematology and oncology and a clinical/molecular researcher in myeloid neoplasms. He is a member of the editorial advisory board of Hematology News.
Contact Dr. Schalk at [email protected].
References
1. Vehreschild, MJ et al. Diagnosis and management of gastrointestinal complications in adult cancer patients: Wvidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Oncol. 2013;24:1189-202
2. Cornely, OA. Current and emerging management options for Clostridium difficile infection: What is the role of fidaxomicin? Clin Microbiol Infect. 2012;18(Suppl 6):28-35.
3. Bartlett, JG et al. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298(10):531-4.
4. Lyras, D et al. Toxin B is essential for virulence of Clostridium difficile. Nature. 2009;458:1176-9.
5. Reineke, J et al. Autocatalytic cleavage of Clostridium difficile toxin B. Nature. 2007;446:415-9.
6. Leav, BA et al. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010;28:965-9.
7. Orth, P et al. Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J Biol Chem. 2014;289:18008-21.
8. Wilcox, MH et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-17.
9. Louie, TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;5(Suppl 2):S132-42.
Infections resulting from Clostridium difficile are a major clinical challenge. In hematology and oncology, the widespread use of broad-spectrum antibiotics is essential for patients with profound neutropenia and infectious complications, which are a high-risk factor for C. difficile enteritis.
C. difficile enteritis occurs in 5%-20% of cancer patients.1 With standard of care antibiotics, oral metronidazole or oral vancomycin, high C. difficile cure rates are possible, but up to 25% of these infections recur. Recently, oral fidaxomicin was approved for treatment of C. difficile enteritis and was associated with high cure rates and, more importantly, with significantly lower recurrence rates.2
Bezlotoxumab, a fully humanized monoclonal antibody against C. difficile toxin B, has been shown by x-ray crystallography to neutralize toxin B by blocking its ability to bind to host cells.7 Most recently, this new therapeutic approach was investigated in humans.8
Wilcox et al. used pooled data of 2655 adults treated in two double-blind, randomized, placebo-controlled phase III clinical trials (MODIFY I and MODIFY II) for primary or recurrent C. difficile enteritis. This industry-sponsored trial was conducted at 322 sites in 30 countries.
In one treatment group, patients received a single infusion of bezlotoxumab (781 patients) or placebo (773 patients) and one of the three oral standard-of-care C. difficile antibiotics. Importantly, the primary end point of this trial was recurrent infection within 12 weeks. About 28% of the patients in both the bezlotoxumab group and the placebo group previously had at least one episode of C. difficile enteritis. About 20% of the patients in both groups were immunocompromised.
Pooled data showed that recurrent infection was significantly lower (P less than 0.001) in the bezlotoxumab group (17%), compared with the placebo group (27%). The difference in recurrence rate (25% vs. 41%) was even more pronounced in patients with one or more episodes of recurrent C. difficile enteritis in the past 6 months. Furthermore, a benefit for bezlotoxumab was seen in immunocompromised patients, whose recurrence rates were 15% with bezlotoxumab, vs. 28% with placebo. After the 12 weeks of follow-up, the absolute difference in the Kaplan-Meier rates of recurrent infection was 13% (absolute rate, 21% in bezlotoxumab group vs. 34% in placebo group; P less than 0.001).
The results indicate that bezlotoxumab, which was approved in 2016 by the U.S. Food and Drug Administration, might improve the outcome of patients with C. difficile enteritis. However, bezlotoxumab is not a “magic bullet.” The number needed to treat to prevent one episode of C. difficile enteritis is 10.
It is conceivable that bezlotoxumab may find its role in high-risk patients – those older than 65 years or patients with recurrent C. difficile enteritis – since the number needed to treat is only 6 in these subgroups.8
This new agent could be an important treatment option for our high-risk patients in hematology. However, more studies concerning costs and real-life efficacy are needed.
The new approach of passive immunization for prevention of recurrent C. difficile enteritis shows the importance and the role of toxin B – not only the bacterium per se – in pathogenesis and virulence of C. difficile. This could mean that we have to renew our view on the role of antibiotics against C. difficile. However, in contrast, bezlotoxumab does not affect the efficacy of standard of care antibiotics since the initial cure rates were 80% for both the antibody and the placebo groups.8 Toxin B levels are not detectable in stool samples between days 4 and 10 of standard of care antibiotic treatment. Afterward, however, they increase again.9 Most of the patients had received bezlotoxumab 3 or more days after they began standard-of-care antibiotic treatment – in the time period when toxin B is undetectable in stool – which underlines the importance of toxin B in the pathogenesis of recurrent C. difficile enteritis.8
In summary, the introduction of bezlotoxumab in clinical care gives new and important insights and solutions not only for treatment options but also for our understanding of C. difficile pathogenesis.
Dr. Schalk is consultant of internal medicine at the department of hematology and oncology, Magdeburg University Hospital, Germany, with clinical and research focus on infectious diseases in hematology and oncology.
Dr. Fischer is professor of internal medicine, hematology and oncology, at the Otto-von-Guericke University Hospital Magdeburg, Germany. He is head of the department of hematology and oncology and a clinical/molecular researcher in myeloid neoplasms. He is a member of the editorial advisory board of Hematology News.
Contact Dr. Schalk at [email protected].
References
1. Vehreschild, MJ et al. Diagnosis and management of gastrointestinal complications in adult cancer patients: Wvidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Oncol. 2013;24:1189-202
2. Cornely, OA. Current and emerging management options for Clostridium difficile infection: What is the role of fidaxomicin? Clin Microbiol Infect. 2012;18(Suppl 6):28-35.
3. Bartlett, JG et al. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298(10):531-4.
4. Lyras, D et al. Toxin B is essential for virulence of Clostridium difficile. Nature. 2009;458:1176-9.
5. Reineke, J et al. Autocatalytic cleavage of Clostridium difficile toxin B. Nature. 2007;446:415-9.
6. Leav, BA et al. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010;28:965-9.
7. Orth, P et al. Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J Biol Chem. 2014;289:18008-21.
8. Wilcox, MH et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305-17.
9. Louie, TJ et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;5(Suppl 2):S132-42.
Skin cancer risk similar for liver and kidney transplant recipients
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
SYDNEY – The risk of developing nonmelanoma skin cancer among liver transplant recipients is similar to that among kidney transplant recipients, but the former tend to have more skin cancer risk factors at baseline, according to a longitudinal cohort study reported at the annual meeting of the Australasian College of Dermatologists.
Liver transplant recipients have been thought to be at a lower risk of developing nonmelanoma skin cancers than are other solid organ transplant recipients, said Ludi Ge, MD, of the department of dermatology at the University of Sydney and Royal Prince Alfred Hospital, Sydney. However, data from a longitudinal cohort study of 230 kidney or liver transplant patients suggest the risk of nonmelanoma skin cancer is similar – if not greater – among liver transplant recipients, compared with kidney transplant recipients.
Over a 5-year period, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, representing a 78% greater risk among liver transplant recipients. However, Dr. Ge said the confidence intervals were wide, and the difference lost statistical significance in the multivariate analysis.
The researchers also noted that the liver transplant recipients in the study tended to be older at baseline, with a history of more sun exposure and more previous skin cancers, and were more likely to have a high risk skin type that sunburns easily.
In an interview, Dr. Ge said the findings had implications for the screening and follow-up of liver transplant recipients.
“Previously, we always thought that liver transplant recipients were at lower risk, and, possibly, they’re not screened as much so not followed up as much,” she said. “I think they really should be thought ... as high risk as renal transplant patients and the heart and lung transplant patients.”
The study showed that, while the renal transplant patients developed fewer skin cancers, they developed 1.9 lesions per year on average, compared with liver transplant patients, who developed 1.4 lesions per year.
The majority of skin cancers in both groups were squamous cell carcinomas and basal cell carcinomas, with a small number of keratoacanthomas. There was a similar ratio of squamous cell carcinomas to basal cell carcinomas between the two groups of transplant recipients – 1.7:1 in renal transplant recipients and 1.6:1 in liver recipients – which differed from the previously reported ratios of about 3:1, Dr. Ge said at the meeting.
She noted that this may have been because not every squamous cell carcinoma in situ was biopsied because of the sheer number of tumors, so many were treated empirically and, therefore, not entered into the clinic database.
Dr. Ge also pointed out that the evidence for the 3:1 ratio was around 10 years old.
“I think there’s been quite a change in the immunosuppressants that are used by transplant physicians, so, more and more, we’re seeing the use of sirolimus and everolimus, which are antiangiogenic,” she said.
Dr. Ge also strongly recommended that dermatology clinics specifically manage organ transplant recipients and commented that this could revolutionize the management of these patients, who tend to get lost to follow-up in standard dermatology clinics. “They’re very difficult to look after, they develop innumerable skin cancers that can result in death, and you need to intervene quite early,” she said in the interview.
No conflicts of interest were declared.
AT ACDASM 2017
Key clinical point: Liver transplant recipients should be screened and followed for the development of nonmelanoma skin cancers as closely as are kidney transplant recipients.
Major finding: Over 5 years, 47% of liver transplant recipients developed at least one nonmelanoma skin cancer, compared with 33% of renal transplant recipients, a difference that was not statistically significant after a multivariate analysis was done.
Data source: A longitudinal cohort study of 230 kidney or liver transplant recipients attending a dermatology clinic affiliated with an organ transplant unit.
Disclosures: No conflicts of interest were disclosed.
Healthy lifestyle, tree nuts may protect against colon cancer recurrence
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
Oncologists whose patients with treated early colon cancer ask what they can do to prevent it from coming back can now more strongly endorse lifestyle modification, based on findings from a pair of cohort studies reported at a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Both studies were conducted among more than 800 patients with stage III colon cancer participating in a nationwide randomized adjuvant chemotherapy trial who completed comprehensive lifestyle questionnaires.
Data for the studies were collected prospectively, noted ASCO President Daniel F. Hayes, MD. “So, that takes a lot of the biases out of the classic retrospective observational studies where patients are asked, ‘Do you remember what you did several years ago?’ Most of us would not. In this case, it was in real time, so it makes these findings even more compelling, in my opinion.
“We can now present optimism to patients with early-stage colon cancer,” Dr. Hayes added. “The odds of surviving colon cancer if it is not metastatic are quite high these days, thanks to lots of hard work and a number of trials done over the last 30 years showing that adequate surgery and adjuvant chemotherapy improve survival.”
Therefore, patients today have even more reason to make a commitment to a healthy lifestyle, which may further improve their outcomes, in addition to its other benefits, he commented.
At the same time, the studies’ findings should not be used to justify skipping good standard of care treatment for early colon cancer, stressed Dr. Hayes, who is also clinical director of the breast oncology program and Stuart B. Padnos Professor in breast cancer research at the University of Michigan in Ann Arbor.
“Nobody wants to undergo chemotherapy. We understand that,” Dr. Hayes said. “But chemotherapy clearly saves lives, so people should not interpret these two abstracts as suggesting that, if you live a healthy lifestyle and if you eat tree nuts, you don’t need to take the chemotherapy that your oncologist would recommend. That’s a very dangerous interpretation, and it’s not what we’re trying to get across. It’s that healthy people live healthier.”
In the first study, Erin Van Blarigan, ScD, assistant professor of epidemiology and biostatistics, University of California, San Francisco, and her colleagues assessed adherence to the American Cancer Society’s Nutrition and Physical Activity Guidelines for Cancer Survivors among 992 patients with stage III colon cancer who enrolled in the Cancer and Leukemia Group B (CALGB) 89803 adjuvant chemotherapy trial within 8 weeks of cancer resection.
“The guidelines are based on published scientific studies, but it’s not actually known if patients who follow the guidelines after diagnosis live longer,” she explained in the presscast.
All patients completed a validated lifestyle questionnaire during and 6 months after completing chemotherapy. Responses were used to assign patients points reflecting guideline adherence on body weight; regular physical activity; a dietary pattern high in vegetables, fruits, and whole grains, and low in red meat and processed meat; and alcohol intake (not specifically included in the guidelines but described in the text).
When lifestyle scores were calculated without consideration of alcohol intake, 26% of patients had a score of 0-1, corresponding to the least healthy lifestyle, while 9% had a score of 5-6, corresponding to the most healthy lifestyle, Dr. Van Blarigan reported.
Risks of both disease-free and overall survival events fell significantly with increasing score (P = .01). Compared with peers who scored 0-1, patients who scored 5-6 had a 42% lower risk of death.
When lifestyle scores were calculated with consideration of alcohol intake, 19% of patients had a score of 0-2, while 16% had a score of 6-8.
Here, too, risks of both disease-free and overall survival events fell significantly with increasing score (P = .002). Compared with peers who scored 0-2, patients who scored 6-8 had a 51% lower risk of death.
“Colon cancer patients who had a healthy body weight, engaged in regular physical activity of approximately 1 hour 5 days a week, and ate a diet rich in a variety of vegetables and fruit – choosing whole grains over refined ones, avoiding red and processed meats, and drinking small to moderate amounts of alcohol – had longer disease-free and overall survival, compared with patients who did not engage in these behaviors,” summarized Dr. Van Blarigan.
The mechanism by which low to moderate alcohol intake, compared with none, may be protective is unclear, but the pattern is consistent with that seen for other diseases, she said.
“There has been some literature in cardiovascular disease about changes in insulin and inflammation and elasticity of blood vessels and things like that,” Dr. Van Blarigan noted. “So, I think that’s something to explore further for colon cancer.”
In the second study, Temidayo Fadelu, MD, a clinical fellow in medicine at the Dana-Farber Cancer Institute in Boston, and his colleagues assessed nut intake among 826 patients enrolled in the same trial. They used questionnaires completed 6 months after the end of chemotherapy, which asked about consumption of tree nuts, peanuts, and peanut butter.
“States of energy excess are associated with an increased risk of colon cancer death and recurrence … and one mechanism is thought to maybe be hyperinsulinemia,” he commented in the presscast. Research has found nut consumption to be associated with lower incidences of type 2 diabetes, metabolic syndrome, and insulin resistance.
Study results showed that the adjusted risks of both disease-free survival and overall survival events fell with increasing frequency of total nut consumption. Patients eating nuts at least twice weekly (19% of the cohort) had a 42% lower adjusted risk of disease-free survival events and a 57% lower adjusted risk of death, relative to counterparts who never ate nuts.
“We don’t really know what the underlying biologic mechanism is for this association, but we hypothesize that it’s perhaps due to the influence of nuts on insulin resistance,” Dr. Fadelu said, noting that they contain fatty acids, fiber, and flavonoids and that insulin levels rise to a lesser degree after eating nuts than after eating foods such as simple sugars. “There need to be further studies to really evaluate this hypothesis,” he added.
“We did a secondary analysis, and we observed that the association described was limited to tree nuts; the association was not seen with peanuts or peanut butter intake,” noted Dr. Fadelu, who reported that he had no disclosures. “Peanuts are technically legumes, and this difference may perhaps be due to the different biochemical composition between peanuts and tree nuts.”
Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.
FROM THE 2017 ASCO ANNUAL MEETING
Key clinical point:
Major finding: Compared with counterparts who have the least healthy lifestyle, patients with the healthiest lifestyle were 42%-51% less likely to die. Relative to peers who never ate nuts, patients who ate nuts at least twice a week had a 42% lower risk of disease-free survival events and a 57% lower risk of death.
Data source: A pair of prospective cohort studies among 992 patients and 826 patients with resected stage III colon cancer given adjuvant chemotherapy in a clinical trial (CALGB 89803).
Disclosures: Dr. Van Blarigan reported that she had no disclosures. Dr. Fadelu reported that he had no disclosures.