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Can Counseling Add Value to an Exercise Intervention for Improving Quality of Life in Breast Cancer Survivors? A Feasibility Study
Fiona Naumann, PhD
Abstract
Background
Improved survivorship has led to increased recognition of the need to manage the side effects of cancer and its treatment. Exercise and psychological interventions benefit survivors; however, it is unknown if additional benefits can be gained by combining these two modalities.
Objective
Our purpose was to examine the feasibility of delivering an exercise and counseling intervention to 43 breast cancer survivors, to determine if counseling can add value to an exercise intervention for improving quality of life (QOL) in terms of physical and psychological function.
Methods
We compared exercise only (Ex), counseling only (C), exercise and counseling (ExC), and usual care (UsC) over an 8 week intervention.
Results
In all, 93% of participants completed the interventions, with no adverse effects documented. There were significant improvements in VO2max as well as upper body and lower body strength in the ExC and Ex groups compared to the C and UsC groups (P < .05). Significant improvements on the Beck Depression Inventory were observed in the ExC and Ex groups, compared with UsC (P < .04), with significant reduction in fatigue for the ExC group, compared with UsC, and no significant differences in QOL change between groups, although the ExC group had significant clinical improvement.
Limitations
Limitations included small subject number and study of only breast cancer survivors.
Conclusions
These preliminary results suggest that a combined exercise and psychological counseling program is both feasible and acceptable for breast cancer survivors and may improve QOL more than would a single-entity intervention.
*For a PDF of the full article, click on the link to the left of this introduction.
Fiona Naumann, PhD
Abstract
Background
Improved survivorship has led to increased recognition of the need to manage the side effects of cancer and its treatment. Exercise and psychological interventions benefit survivors; however, it is unknown if additional benefits can be gained by combining these two modalities.
Objective
Our purpose was to examine the feasibility of delivering an exercise and counseling intervention to 43 breast cancer survivors, to determine if counseling can add value to an exercise intervention for improving quality of life (QOL) in terms of physical and psychological function.
Methods
We compared exercise only (Ex), counseling only (C), exercise and counseling (ExC), and usual care (UsC) over an 8 week intervention.
Results
In all, 93% of participants completed the interventions, with no adverse effects documented. There were significant improvements in VO2max as well as upper body and lower body strength in the ExC and Ex groups compared to the C and UsC groups (P < .05). Significant improvements on the Beck Depression Inventory were observed in the ExC and Ex groups, compared with UsC (P < .04), with significant reduction in fatigue for the ExC group, compared with UsC, and no significant differences in QOL change between groups, although the ExC group had significant clinical improvement.
Limitations
Limitations included small subject number and study of only breast cancer survivors.
Conclusions
These preliminary results suggest that a combined exercise and psychological counseling program is both feasible and acceptable for breast cancer survivors and may improve QOL more than would a single-entity intervention.
*For a PDF of the full article, click on the link to the left of this introduction.
Fiona Naumann, PhD
Abstract
Background
Improved survivorship has led to increased recognition of the need to manage the side effects of cancer and its treatment. Exercise and psychological interventions benefit survivors; however, it is unknown if additional benefits can be gained by combining these two modalities.
Objective
Our purpose was to examine the feasibility of delivering an exercise and counseling intervention to 43 breast cancer survivors, to determine if counseling can add value to an exercise intervention for improving quality of life (QOL) in terms of physical and psychological function.
Methods
We compared exercise only (Ex), counseling only (C), exercise and counseling (ExC), and usual care (UsC) over an 8 week intervention.
Results
In all, 93% of participants completed the interventions, with no adverse effects documented. There were significant improvements in VO2max as well as upper body and lower body strength in the ExC and Ex groups compared to the C and UsC groups (P < .05). Significant improvements on the Beck Depression Inventory were observed in the ExC and Ex groups, compared with UsC (P < .04), with significant reduction in fatigue for the ExC group, compared with UsC, and no significant differences in QOL change between groups, although the ExC group had significant clinical improvement.
Limitations
Limitations included small subject number and study of only breast cancer survivors.
Conclusions
These preliminary results suggest that a combined exercise and psychological counseling program is both feasible and acceptable for breast cancer survivors and may improve QOL more than would a single-entity intervention.
*For a PDF of the full article, click on the link to the left of this introduction.
Integrating Palliative Care in the Intensive Care Unit
Jacob J. Strand, MD
Abstract
The admission of cancer patients into intensive care units (ICUs) is on the rise. These patients are at high risk for physical and psychosocial suffering. Patients and their families often face difficult end-of-life decisions that highlight the importance of effective and empathetic communication. Palliative care teams are uniquely equipped to help care for cancer patients who are admitted to ICUs.
When utilized in the ICU, palliative care has the potential to improve a patient's symptoms, enhance the communication between care teams and families, and improve family-centered decision making. Within the context of this article, we will discuss how palliative care can be integrated into the care of ICU patients and how to enhance family-centered communication; we will also highlight the care of ICU patients at the end of life.
*For a PDF of the full article, click on the link to the left of this introduction.
Jacob J. Strand, MD
Abstract
The admission of cancer patients into intensive care units (ICUs) is on the rise. These patients are at high risk for physical and psychosocial suffering. Patients and their families often face difficult end-of-life decisions that highlight the importance of effective and empathetic communication. Palliative care teams are uniquely equipped to help care for cancer patients who are admitted to ICUs.
When utilized in the ICU, palliative care has the potential to improve a patient's symptoms, enhance the communication between care teams and families, and improve family-centered decision making. Within the context of this article, we will discuss how palliative care can be integrated into the care of ICU patients and how to enhance family-centered communication; we will also highlight the care of ICU patients at the end of life.
*For a PDF of the full article, click on the link to the left of this introduction.
Jacob J. Strand, MD
Abstract
The admission of cancer patients into intensive care units (ICUs) is on the rise. These patients are at high risk for physical and psychosocial suffering. Patients and their families often face difficult end-of-life decisions that highlight the importance of effective and empathetic communication. Palliative care teams are uniquely equipped to help care for cancer patients who are admitted to ICUs.
When utilized in the ICU, palliative care has the potential to improve a patient's symptoms, enhance the communication between care teams and families, and improve family-centered decision making. Within the context of this article, we will discuss how palliative care can be integrated into the care of ICU patients and how to enhance family-centered communication; we will also highlight the care of ICU patients at the end of life.
*For a PDF of the full article, click on the link to the left of this introduction.
Implementing the Exercise Guidelines for Cancer Survivors
Kathleen Y. Wolin, ScD, Anna L. Schwartz, PhD, Charles E. Matthews, PhD, FACSM, Kerry S. Courneya, PhD, Kathryn H. Schmitz, PhD
Abstract
In 2009, the American College of Sports Medicine convened an expert roundtable to issue guidelines on exercise for cancer survivors. This multidisciplinary group evaluated the strength of the evidence for the safety and benefits of exercise as a therapeutic intervention for survivors. The panel concluded that exercise is safe and offers myriad benefits for survivors including improvements in physical function, strength, fatigue, quality of life, and possibly recurrence and survival. Recommendations for situations in which deviations from the US Physical Activity Guidelines for Americans are appropriate were provided. Here, we outline a process for implementing the guidelines in clinical practice and provide recommendations for how the oncology care provider can interface with the exercise and physical therapy community.
*For a PDF of the full article and accompanying commentary by Nicole Stout, click on the links to the left of this introduction.
Kathleen Y. Wolin, ScD, Anna L. Schwartz, PhD, Charles E. Matthews, PhD, FACSM, Kerry S. Courneya, PhD, Kathryn H. Schmitz, PhD
Abstract
In 2009, the American College of Sports Medicine convened an expert roundtable to issue guidelines on exercise for cancer survivors. This multidisciplinary group evaluated the strength of the evidence for the safety and benefits of exercise as a therapeutic intervention for survivors. The panel concluded that exercise is safe and offers myriad benefits for survivors including improvements in physical function, strength, fatigue, quality of life, and possibly recurrence and survival. Recommendations for situations in which deviations from the US Physical Activity Guidelines for Americans are appropriate were provided. Here, we outline a process for implementing the guidelines in clinical practice and provide recommendations for how the oncology care provider can interface with the exercise and physical therapy community.
*For a PDF of the full article and accompanying commentary by Nicole Stout, click on the links to the left of this introduction.
Kathleen Y. Wolin, ScD, Anna L. Schwartz, PhD, Charles E. Matthews, PhD, FACSM, Kerry S. Courneya, PhD, Kathryn H. Schmitz, PhD
Abstract
In 2009, the American College of Sports Medicine convened an expert roundtable to issue guidelines on exercise for cancer survivors. This multidisciplinary group evaluated the strength of the evidence for the safety and benefits of exercise as a therapeutic intervention for survivors. The panel concluded that exercise is safe and offers myriad benefits for survivors including improvements in physical function, strength, fatigue, quality of life, and possibly recurrence and survival. Recommendations for situations in which deviations from the US Physical Activity Guidelines for Americans are appropriate were provided. Here, we outline a process for implementing the guidelines in clinical practice and provide recommendations for how the oncology care provider can interface with the exercise and physical therapy community.
*For a PDF of the full article and accompanying commentary by Nicole Stout, click on the links to the left of this introduction.
Access to specialized treatment by adult Hispanic brain tumor patients: findings from a single-institution retrospective study
Background: The Hispanic population accounts for 15% of the population of the United States, and for as much as 75% in cities throughout California. Racial disparities that are reflected by limited access to health care and worse disease outcomes are well documented for adult Hispanic cancer patients.
Objective: To determine whether there are similar disparities—including delays in accessing surgery, radiation, and oncologic care—for adult Hispanic non English-speaking (HNES) neuro-oncology patients and white English-only–speaking (WES) patients in an academic, tertiary care center with a multidisciplinary neuro-oncology team.
Methods: This retrospective study was conducted at the Chao Family Comprehensive Cancer Center of the University of California, Irvine. All patients who were diagnosed with a primary brain tumor during January 1, 2003, to December 31, 2008, were identified and data were collected on their age, sex, ethnicity, languages spoken, diagnosis, and insurance status. The times from the date of diagnosis to the date of surgery, from the date of surgery to the date of starting radiation (if indicated), and from the date of finishing radiation to the date of starting chemotherapy (if indicated) were also recorded.
Results: Most of the HNES patients (56.4%) had state insurance for the indigent, whereas most of the WES patients (41.8%) had private insurance from a health maintenance organization. Moreover, 12.8% of HNES patients were uninsured, compared with 4.5% of WES patients. There were no significant delays in the time from diagnosis to surgery, but there was a significant delay in access to radiation treatment (P .023). There were no differences on overall survival between the 2 groups of patients.
Limitations: This is a retrospective study of a relatively small number of patients. Larger studies are needed to corroborate these findings
Conclusions: The findings demonstrate that there are disparities in insurance status and access to radiation therapy between HNES and WES neuro-oncology patients.
*To read the the full article, click on the link at the top of this introduction.
Background: The Hispanic population accounts for 15% of the population of the United States, and for as much as 75% in cities throughout California. Racial disparities that are reflected by limited access to health care and worse disease outcomes are well documented for adult Hispanic cancer patients.
Objective: To determine whether there are similar disparities—including delays in accessing surgery, radiation, and oncologic care—for adult Hispanic non English-speaking (HNES) neuro-oncology patients and white English-only–speaking (WES) patients in an academic, tertiary care center with a multidisciplinary neuro-oncology team.
Methods: This retrospective study was conducted at the Chao Family Comprehensive Cancer Center of the University of California, Irvine. All patients who were diagnosed with a primary brain tumor during January 1, 2003, to December 31, 2008, were identified and data were collected on their age, sex, ethnicity, languages spoken, diagnosis, and insurance status. The times from the date of diagnosis to the date of surgery, from the date of surgery to the date of starting radiation (if indicated), and from the date of finishing radiation to the date of starting chemotherapy (if indicated) were also recorded.
Results: Most of the HNES patients (56.4%) had state insurance for the indigent, whereas most of the WES patients (41.8%) had private insurance from a health maintenance organization. Moreover, 12.8% of HNES patients were uninsured, compared with 4.5% of WES patients. There were no significant delays in the time from diagnosis to surgery, but there was a significant delay in access to radiation treatment (P .023). There were no differences on overall survival between the 2 groups of patients.
Limitations: This is a retrospective study of a relatively small number of patients. Larger studies are needed to corroborate these findings
Conclusions: The findings demonstrate that there are disparities in insurance status and access to radiation therapy between HNES and WES neuro-oncology patients.
*To read the the full article, click on the link at the top of this introduction.
Background: The Hispanic population accounts for 15% of the population of the United States, and for as much as 75% in cities throughout California. Racial disparities that are reflected by limited access to health care and worse disease outcomes are well documented for adult Hispanic cancer patients.
Objective: To determine whether there are similar disparities—including delays in accessing surgery, radiation, and oncologic care—for adult Hispanic non English-speaking (HNES) neuro-oncology patients and white English-only–speaking (WES) patients in an academic, tertiary care center with a multidisciplinary neuro-oncology team.
Methods: This retrospective study was conducted at the Chao Family Comprehensive Cancer Center of the University of California, Irvine. All patients who were diagnosed with a primary brain tumor during January 1, 2003, to December 31, 2008, were identified and data were collected on their age, sex, ethnicity, languages spoken, diagnosis, and insurance status. The times from the date of diagnosis to the date of surgery, from the date of surgery to the date of starting radiation (if indicated), and from the date of finishing radiation to the date of starting chemotherapy (if indicated) were also recorded.
Results: Most of the HNES patients (56.4%) had state insurance for the indigent, whereas most of the WES patients (41.8%) had private insurance from a health maintenance organization. Moreover, 12.8% of HNES patients were uninsured, compared with 4.5% of WES patients. There were no significant delays in the time from diagnosis to surgery, but there was a significant delay in access to radiation treatment (P .023). There were no differences on overall survival between the 2 groups of patients.
Limitations: This is a retrospective study of a relatively small number of patients. Larger studies are needed to corroborate these findings
Conclusions: The findings demonstrate that there are disparities in insurance status and access to radiation therapy between HNES and WES neuro-oncology patients.
*To read the the full article, click on the link at the top of this introduction.
Navigating the drug shortages
In November 2010, pharmacists at Georgia Cancer Specialists, a private cancer practice with 27 offices, noticed our first instance of the latest wave of drug shortages. We had tried to place an order for doxorubicin, but our primary wholesaler was not able to fill it. We also discovered that our secondary wholesalers had little or no available doxorubicin, and that some suppliers had increased their prices for the drug to such an extent that it was out of our reach. We began to take inventory of the doxorubicin that we had in all of our offices. At that point, we realized we had a crisis on our hands...
*For a PDF of the full article and accompanying Commentary, click on the links to the left of this introduction.
In November 2010, pharmacists at Georgia Cancer Specialists, a private cancer practice with 27 offices, noticed our first instance of the latest wave of drug shortages. We had tried to place an order for doxorubicin, but our primary wholesaler was not able to fill it. We also discovered that our secondary wholesalers had little or no available doxorubicin, and that some suppliers had increased their prices for the drug to such an extent that it was out of our reach. We began to take inventory of the doxorubicin that we had in all of our offices. At that point, we realized we had a crisis on our hands...
*For a PDF of the full article and accompanying Commentary, click on the links to the left of this introduction.
In November 2010, pharmacists at Georgia Cancer Specialists, a private cancer practice with 27 offices, noticed our first instance of the latest wave of drug shortages. We had tried to place an order for doxorubicin, but our primary wholesaler was not able to fill it. We also discovered that our secondary wholesalers had little or no available doxorubicin, and that some suppliers had increased their prices for the drug to such an extent that it was out of our reach. We began to take inventory of the doxorubicin that we had in all of our offices. At that point, we realized we had a crisis on our hands...
*For a PDF of the full article and accompanying Commentary, click on the links to the left of this introduction.
Intravenous iron in chemotherapy and cancer-related anemia
Recent guidance from the Centers for Medicare and Medicaid Services restricting erythropoiesis-stimulating agents (ESAs) in chemotherapy and cancer-related anemias has resulted in an increase in transfusions. Nine studies, without published contradictory evidence, have shown optimization of the response to ESAs by intravenous (IV) iron when the iron was added to the treatment of chemotherapy-induced anemia. The synergy observed, although greater in iron deficiency, was independent of pretreatment iron parameters. Three studies demonstrated decreased transfusions when IV iron is administered without ESAs. Discordant recommendations regarding IV iron currently exist among the American Society of Hematology/American Society of Clinical Oncology guidelines, the National Comprehensive Cancer Network, and the European Society of Medical Oncology. This discordance is at least partly the result of misconceptions about the clinical nature and incidence of adverse effects with IV iron. Other reasons for this discordance are presented in this review. Based on thousands of studied patients, we conclude that IV iron is safe and probably safer than most physicians realize. Education is needed relating to the interpretation of minor, subclinical infusion reactions that resolve without therapy. IV iron without ESAs may be an effective treatment for chemotherapy-induced anemia and warrants further study. We present evidence supporting the conclusion that baseline serum hepcidin levels may predict responses to IV iron, and we examine the published evidence supporting the conclusion that IV iron should be a standard addition to the management of chemotherapy and cancer-related anemia.
Click on the PDF icon at the top of this introduction to read the full article.
Recent guidance from the Centers for Medicare and Medicaid Services restricting erythropoiesis-stimulating agents (ESAs) in chemotherapy and cancer-related anemias has resulted in an increase in transfusions. Nine studies, without published contradictory evidence, have shown optimization of the response to ESAs by intravenous (IV) iron when the iron was added to the treatment of chemotherapy-induced anemia. The synergy observed, although greater in iron deficiency, was independent of pretreatment iron parameters. Three studies demonstrated decreased transfusions when IV iron is administered without ESAs. Discordant recommendations regarding IV iron currently exist among the American Society of Hematology/American Society of Clinical Oncology guidelines, the National Comprehensive Cancer Network, and the European Society of Medical Oncology. This discordance is at least partly the result of misconceptions about the clinical nature and incidence of adverse effects with IV iron. Other reasons for this discordance are presented in this review. Based on thousands of studied patients, we conclude that IV iron is safe and probably safer than most physicians realize. Education is needed relating to the interpretation of minor, subclinical infusion reactions that resolve without therapy. IV iron without ESAs may be an effective treatment for chemotherapy-induced anemia and warrants further study. We present evidence supporting the conclusion that baseline serum hepcidin levels may predict responses to IV iron, and we examine the published evidence supporting the conclusion that IV iron should be a standard addition to the management of chemotherapy and cancer-related anemia.
Click on the PDF icon at the top of this introduction to read the full article.
Recent guidance from the Centers for Medicare and Medicaid Services restricting erythropoiesis-stimulating agents (ESAs) in chemotherapy and cancer-related anemias has resulted in an increase in transfusions. Nine studies, without published contradictory evidence, have shown optimization of the response to ESAs by intravenous (IV) iron when the iron was added to the treatment of chemotherapy-induced anemia. The synergy observed, although greater in iron deficiency, was independent of pretreatment iron parameters. Three studies demonstrated decreased transfusions when IV iron is administered without ESAs. Discordant recommendations regarding IV iron currently exist among the American Society of Hematology/American Society of Clinical Oncology guidelines, the National Comprehensive Cancer Network, and the European Society of Medical Oncology. This discordance is at least partly the result of misconceptions about the clinical nature and incidence of adverse effects with IV iron. Other reasons for this discordance are presented in this review. Based on thousands of studied patients, we conclude that IV iron is safe and probably safer than most physicians realize. Education is needed relating to the interpretation of minor, subclinical infusion reactions that resolve without therapy. IV iron without ESAs may be an effective treatment for chemotherapy-induced anemia and warrants further study. We present evidence supporting the conclusion that baseline serum hepcidin levels may predict responses to IV iron, and we examine the published evidence supporting the conclusion that IV iron should be a standard addition to the management of chemotherapy and cancer-related anemia.
Click on the PDF icon at the top of this introduction to read the full article.
Acetyl-l-Carnitine Yields Mixed Results for Chemo-Induced Neuropathy
CHICAGO – The impact of acetyl-l-carnitine on chemotherapy-induced peripheral neuropathy may depend largely on the clinical context and patient population, a pair of phase III trials suggests.
Acetyl-l-carnitine (ALC), a natural substance marketed over the counter as a dietary supplement, is popular among cancer patients as a result of preclinical and early-phase data in chemotherapy-related neuropathy and also a study in patients with diabetes-related peripheral neuropathy.
But in a trial among 409 U.S. women receiving adjuvant chemotherapy for breast cancer, those who took ALC not only had no decrease in the development of peripheral neuropathy symptoms relative to peers who were given a placebo, but actually had an increase. And they had a higher rate of serious neuropathy, too.
In contrast, in a trial among more than 200 Chinese patients with various cancers who had peripheral neuropathy from previous chemotherapy, those who took ALC were more likely than those who took a placebo to have an improvement of at least one grade in their neuropathy. They also were more likely to have improvements in fatigue and strength.
Taken together, the two trials, which were reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology, provide yet another cautionary lesson on the complexity of combining conventional and complementary therapies.
"The use of ALC for prevention is not recommended, and I would say, based on [these results], should be cautioned against. It will be interesting to see the carnitine data and to understand, as much as possible, why the trial was negative," commented Debra L. Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., who was invited to discuss the research. "Further studies are needed to really understand if ALC should be used to treat peripheral neuropathy."
ALC for Prevention of Peripheral Neuropathy
In the first trial, Southwest Oncology Group (SWOG) protocol S0715, investigators led by Dr. Dawn L. Hershman randomized women receiving adjuvant taxane chemotherapy for early breast cancer evenly to either oral ALC 1,000 mg three times daily or matching placebo, for 24 weeks.
Compared with their counterparts in the placebo group, women in the ALC group were more likely to have a greater than 5-point adjusted decrease on the neurotoxicity subscale of the Functional Assessment of Cancer Therapy–Taxane (FACT-NTX) instrument at 12 weeks (odds ratio, 1.48; P = .08) and also at 24 weeks (38% vs. 28%; OR, 1.57; P = .05).
This magnitude of worsening is clinically meaningful, maintained Dr. Hershman of Columbia University in New York, "so this is not like a lot of studies where you find a statistically significant difference that’s not clinically meaningful."
In addition, the incidence of grade 3/4 neurotoxicity was 3.8% with ALC, much higher than the 0.5% seen with placebo.
Patients in the ALC group also had scores on the FACT trial outcome index subscale (FACT-TOI), an overall measure of function, that were on average 3.5 points lower (worse) than those among their placebo counterparts (P = .03). There were no significant differences between groups in terms of fatigue and other toxicities.
The investigators have collected biosamples and will be assessing potential biological correlates with peripheral neuropathy outcomes, according to Dr. Hershman.
"We are looking at DNA, oxidative stress, and carnitine levels to better understand the mechanisms of chemotherapy-induced peripheral neuropathy to begin with, because there is not a whole lot known in terms of mechanism," she said. "If we can figure out what makes people worse, then we will maybe be able to figure out how to make people better from a more mechanistic standpoint, because there are very few drugs to treat chemotherapy-induced peripheral neuropathy."
An obvious concern from the trial’s findings is that ALC may somehow potentiate the neurotoxic effects of taxanes. "Based on these data, physicians should be telling patients not to take ALC during adjuvant chemotherapy," Dr. Hershman concluded. "You need to talk to patients. We know from the literature that overwhelmingly large number of patients take supplements during chemotherapy and afterward, many of which have not been tested. It’s important to get that history from patients."
Dr. Barton, the discussant, praised the trial’s rigorous methodology and proposed that there may have been several reasons for the lack of ALC benefit in preventing neuropathy, despite compelling earlier data.
Previous prevention research was done in animals and thus may not translate to humans, she said. And a positive trial for treatment in humans used intravenous administration, which may result in different bioavailability. Finally, "ALC capsules needed to be taken three times a day, and they are rather large, and these patients were, after all, on chemotherapy. They were likely nauseated [and] dyspeptic, and taking what some might call a horse pill three times a day could not have been an easy task. The study did use pill diaries, but we know those aren’t a perfect tool for adherence."
"The great thing is that the study collected blood and they are able to look at carnitine levels," Dr. Barton said. "So if carnitine is up in the group that got acetyl-carnitine and not in the group that got placebo, well, I think that pretty much confirms that this just didn’t work."
ALC for Treatment of Peripheral Neuropathy
In the second trial, protocol ZHAOKE-2007L03540, investigators led by Dr. Yuanjue Sun of the Sixth Affiliated Hospital of Shanghai (China) Jiao Tong University, enrolled 239 patients who had cancer of various types and stages, had completed chemotherapy, and had had at least grade 2 peripheral neuropathy for up to 6 months.
They were randomly assigned to receive either oral ALC at a dose of 3 g/day or matching placebo, for 8 weeks, with outcomes assessed at clinic visits or by telephone.
Analyses showed that compared with their counterparts in the placebo group, patients in the ALC group were more likely to have had an improvement of at least one grade in their neuropathy, both at 8 weeks (51% vs. 24%; P less than .001) and at 12 weeks (58% vs. 40%; P less than .001).
In terms of secondary outcomes, the ALC group was also more likely to have had an improvement in cancer-related fatigue (31% vs. 20%; P = .048), physical strength (29% vs. 13%; P = .02), and electrophysiology in peripheral nerves (75% vs. 58%; P = .02).
The two groups had statistically indistinguishable rates of adverse events (20% vs. 15%) and adverse reactions (6% vs. 5%). The most common events were gastrointestinal ones and skin allergies.
"This is the first time to confirm that ALC has a positive effect to cure chemotherapy-induced peripheral neuropathy in the Chinese population," Dr. Sun commented through a translator.
"I think the very important thing for this trial is, it is a different kind of patient population. Before this, most clinical trials were performed in [whites] or maybe Americans. This is an only-Asian [population]," he noted, and it is possible that there are genetic differences in how ALC is metabolized.
Dr. Barton, the discussant, took a cautionary view, saying that "there are some things to consider before going out and telling patients to consider acetyl-carnitine for their peripheral neuropathy."
It was unclear from the results reported whether the two treatment groups were well balanced and what criteria were used to define improvement for the secondary outcomes, she noted. Additionally, "outcome measures were all provider graded, [and there were] no self-report measures, so it is difficult to understand the impact of treatment on symptoms, particularly from the patient perspective," she noted.
Dr. Hershman, Dr. Sun, and Dr. Barton disclosed no relevant conflicts of interest; the ZHAOKE-2007L03540 trial was sponsored by Lee’s Pharmaceutical Limited.
CHICAGO – The impact of acetyl-l-carnitine on chemotherapy-induced peripheral neuropathy may depend largely on the clinical context and patient population, a pair of phase III trials suggests.
Acetyl-l-carnitine (ALC), a natural substance marketed over the counter as a dietary supplement, is popular among cancer patients as a result of preclinical and early-phase data in chemotherapy-related neuropathy and also a study in patients with diabetes-related peripheral neuropathy.
But in a trial among 409 U.S. women receiving adjuvant chemotherapy for breast cancer, those who took ALC not only had no decrease in the development of peripheral neuropathy symptoms relative to peers who were given a placebo, but actually had an increase. And they had a higher rate of serious neuropathy, too.
In contrast, in a trial among more than 200 Chinese patients with various cancers who had peripheral neuropathy from previous chemotherapy, those who took ALC were more likely than those who took a placebo to have an improvement of at least one grade in their neuropathy. They also were more likely to have improvements in fatigue and strength.
Taken together, the two trials, which were reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology, provide yet another cautionary lesson on the complexity of combining conventional and complementary therapies.
"The use of ALC for prevention is not recommended, and I would say, based on [these results], should be cautioned against. It will be interesting to see the carnitine data and to understand, as much as possible, why the trial was negative," commented Debra L. Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., who was invited to discuss the research. "Further studies are needed to really understand if ALC should be used to treat peripheral neuropathy."
ALC for Prevention of Peripheral Neuropathy
In the first trial, Southwest Oncology Group (SWOG) protocol S0715, investigators led by Dr. Dawn L. Hershman randomized women receiving adjuvant taxane chemotherapy for early breast cancer evenly to either oral ALC 1,000 mg three times daily or matching placebo, for 24 weeks.
Compared with their counterparts in the placebo group, women in the ALC group were more likely to have a greater than 5-point adjusted decrease on the neurotoxicity subscale of the Functional Assessment of Cancer Therapy–Taxane (FACT-NTX) instrument at 12 weeks (odds ratio, 1.48; P = .08) and also at 24 weeks (38% vs. 28%; OR, 1.57; P = .05).
This magnitude of worsening is clinically meaningful, maintained Dr. Hershman of Columbia University in New York, "so this is not like a lot of studies where you find a statistically significant difference that’s not clinically meaningful."
In addition, the incidence of grade 3/4 neurotoxicity was 3.8% with ALC, much higher than the 0.5% seen with placebo.
Patients in the ALC group also had scores on the FACT trial outcome index subscale (FACT-TOI), an overall measure of function, that were on average 3.5 points lower (worse) than those among their placebo counterparts (P = .03). There were no significant differences between groups in terms of fatigue and other toxicities.
The investigators have collected biosamples and will be assessing potential biological correlates with peripheral neuropathy outcomes, according to Dr. Hershman.
"We are looking at DNA, oxidative stress, and carnitine levels to better understand the mechanisms of chemotherapy-induced peripheral neuropathy to begin with, because there is not a whole lot known in terms of mechanism," she said. "If we can figure out what makes people worse, then we will maybe be able to figure out how to make people better from a more mechanistic standpoint, because there are very few drugs to treat chemotherapy-induced peripheral neuropathy."
An obvious concern from the trial’s findings is that ALC may somehow potentiate the neurotoxic effects of taxanes. "Based on these data, physicians should be telling patients not to take ALC during adjuvant chemotherapy," Dr. Hershman concluded. "You need to talk to patients. We know from the literature that overwhelmingly large number of patients take supplements during chemotherapy and afterward, many of which have not been tested. It’s important to get that history from patients."
Dr. Barton, the discussant, praised the trial’s rigorous methodology and proposed that there may have been several reasons for the lack of ALC benefit in preventing neuropathy, despite compelling earlier data.
Previous prevention research was done in animals and thus may not translate to humans, she said. And a positive trial for treatment in humans used intravenous administration, which may result in different bioavailability. Finally, "ALC capsules needed to be taken three times a day, and they are rather large, and these patients were, after all, on chemotherapy. They were likely nauseated [and] dyspeptic, and taking what some might call a horse pill three times a day could not have been an easy task. The study did use pill diaries, but we know those aren’t a perfect tool for adherence."
"The great thing is that the study collected blood and they are able to look at carnitine levels," Dr. Barton said. "So if carnitine is up in the group that got acetyl-carnitine and not in the group that got placebo, well, I think that pretty much confirms that this just didn’t work."
ALC for Treatment of Peripheral Neuropathy
In the second trial, protocol ZHAOKE-2007L03540, investigators led by Dr. Yuanjue Sun of the Sixth Affiliated Hospital of Shanghai (China) Jiao Tong University, enrolled 239 patients who had cancer of various types and stages, had completed chemotherapy, and had had at least grade 2 peripheral neuropathy for up to 6 months.
They were randomly assigned to receive either oral ALC at a dose of 3 g/day or matching placebo, for 8 weeks, with outcomes assessed at clinic visits or by telephone.
Analyses showed that compared with their counterparts in the placebo group, patients in the ALC group were more likely to have had an improvement of at least one grade in their neuropathy, both at 8 weeks (51% vs. 24%; P less than .001) and at 12 weeks (58% vs. 40%; P less than .001).
In terms of secondary outcomes, the ALC group was also more likely to have had an improvement in cancer-related fatigue (31% vs. 20%; P = .048), physical strength (29% vs. 13%; P = .02), and electrophysiology in peripheral nerves (75% vs. 58%; P = .02).
The two groups had statistically indistinguishable rates of adverse events (20% vs. 15%) and adverse reactions (6% vs. 5%). The most common events were gastrointestinal ones and skin allergies.
"This is the first time to confirm that ALC has a positive effect to cure chemotherapy-induced peripheral neuropathy in the Chinese population," Dr. Sun commented through a translator.
"I think the very important thing for this trial is, it is a different kind of patient population. Before this, most clinical trials were performed in [whites] or maybe Americans. This is an only-Asian [population]," he noted, and it is possible that there are genetic differences in how ALC is metabolized.
Dr. Barton, the discussant, took a cautionary view, saying that "there are some things to consider before going out and telling patients to consider acetyl-carnitine for their peripheral neuropathy."
It was unclear from the results reported whether the two treatment groups were well balanced and what criteria were used to define improvement for the secondary outcomes, she noted. Additionally, "outcome measures were all provider graded, [and there were] no self-report measures, so it is difficult to understand the impact of treatment on symptoms, particularly from the patient perspective," she noted.
Dr. Hershman, Dr. Sun, and Dr. Barton disclosed no relevant conflicts of interest; the ZHAOKE-2007L03540 trial was sponsored by Lee’s Pharmaceutical Limited.
CHICAGO – The impact of acetyl-l-carnitine on chemotherapy-induced peripheral neuropathy may depend largely on the clinical context and patient population, a pair of phase III trials suggests.
Acetyl-l-carnitine (ALC), a natural substance marketed over the counter as a dietary supplement, is popular among cancer patients as a result of preclinical and early-phase data in chemotherapy-related neuropathy and also a study in patients with diabetes-related peripheral neuropathy.
But in a trial among 409 U.S. women receiving adjuvant chemotherapy for breast cancer, those who took ALC not only had no decrease in the development of peripheral neuropathy symptoms relative to peers who were given a placebo, but actually had an increase. And they had a higher rate of serious neuropathy, too.
In contrast, in a trial among more than 200 Chinese patients with various cancers who had peripheral neuropathy from previous chemotherapy, those who took ALC were more likely than those who took a placebo to have an improvement of at least one grade in their neuropathy. They also were more likely to have improvements in fatigue and strength.
Taken together, the two trials, which were reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology, provide yet another cautionary lesson on the complexity of combining conventional and complementary therapies.
"The use of ALC for prevention is not recommended, and I would say, based on [these results], should be cautioned against. It will be interesting to see the carnitine data and to understand, as much as possible, why the trial was negative," commented Debra L. Barton, Ph.D., of the Mayo Clinic in Rochester, Minn., who was invited to discuss the research. "Further studies are needed to really understand if ALC should be used to treat peripheral neuropathy."
ALC for Prevention of Peripheral Neuropathy
In the first trial, Southwest Oncology Group (SWOG) protocol S0715, investigators led by Dr. Dawn L. Hershman randomized women receiving adjuvant taxane chemotherapy for early breast cancer evenly to either oral ALC 1,000 mg three times daily or matching placebo, for 24 weeks.
Compared with their counterparts in the placebo group, women in the ALC group were more likely to have a greater than 5-point adjusted decrease on the neurotoxicity subscale of the Functional Assessment of Cancer Therapy–Taxane (FACT-NTX) instrument at 12 weeks (odds ratio, 1.48; P = .08) and also at 24 weeks (38% vs. 28%; OR, 1.57; P = .05).
This magnitude of worsening is clinically meaningful, maintained Dr. Hershman of Columbia University in New York, "so this is not like a lot of studies where you find a statistically significant difference that’s not clinically meaningful."
In addition, the incidence of grade 3/4 neurotoxicity was 3.8% with ALC, much higher than the 0.5% seen with placebo.
Patients in the ALC group also had scores on the FACT trial outcome index subscale (FACT-TOI), an overall measure of function, that were on average 3.5 points lower (worse) than those among their placebo counterparts (P = .03). There were no significant differences between groups in terms of fatigue and other toxicities.
The investigators have collected biosamples and will be assessing potential biological correlates with peripheral neuropathy outcomes, according to Dr. Hershman.
"We are looking at DNA, oxidative stress, and carnitine levels to better understand the mechanisms of chemotherapy-induced peripheral neuropathy to begin with, because there is not a whole lot known in terms of mechanism," she said. "If we can figure out what makes people worse, then we will maybe be able to figure out how to make people better from a more mechanistic standpoint, because there are very few drugs to treat chemotherapy-induced peripheral neuropathy."
An obvious concern from the trial’s findings is that ALC may somehow potentiate the neurotoxic effects of taxanes. "Based on these data, physicians should be telling patients not to take ALC during adjuvant chemotherapy," Dr. Hershman concluded. "You need to talk to patients. We know from the literature that overwhelmingly large number of patients take supplements during chemotherapy and afterward, many of which have not been tested. It’s important to get that history from patients."
Dr. Barton, the discussant, praised the trial’s rigorous methodology and proposed that there may have been several reasons for the lack of ALC benefit in preventing neuropathy, despite compelling earlier data.
Previous prevention research was done in animals and thus may not translate to humans, she said. And a positive trial for treatment in humans used intravenous administration, which may result in different bioavailability. Finally, "ALC capsules needed to be taken three times a day, and they are rather large, and these patients were, after all, on chemotherapy. They were likely nauseated [and] dyspeptic, and taking what some might call a horse pill three times a day could not have been an easy task. The study did use pill diaries, but we know those aren’t a perfect tool for adherence."
"The great thing is that the study collected blood and they are able to look at carnitine levels," Dr. Barton said. "So if carnitine is up in the group that got acetyl-carnitine and not in the group that got placebo, well, I think that pretty much confirms that this just didn’t work."
ALC for Treatment of Peripheral Neuropathy
In the second trial, protocol ZHAOKE-2007L03540, investigators led by Dr. Yuanjue Sun of the Sixth Affiliated Hospital of Shanghai (China) Jiao Tong University, enrolled 239 patients who had cancer of various types and stages, had completed chemotherapy, and had had at least grade 2 peripheral neuropathy for up to 6 months.
They were randomly assigned to receive either oral ALC at a dose of 3 g/day or matching placebo, for 8 weeks, with outcomes assessed at clinic visits or by telephone.
Analyses showed that compared with their counterparts in the placebo group, patients in the ALC group were more likely to have had an improvement of at least one grade in their neuropathy, both at 8 weeks (51% vs. 24%; P less than .001) and at 12 weeks (58% vs. 40%; P less than .001).
In terms of secondary outcomes, the ALC group was also more likely to have had an improvement in cancer-related fatigue (31% vs. 20%; P = .048), physical strength (29% vs. 13%; P = .02), and electrophysiology in peripheral nerves (75% vs. 58%; P = .02).
The two groups had statistically indistinguishable rates of adverse events (20% vs. 15%) and adverse reactions (6% vs. 5%). The most common events were gastrointestinal ones and skin allergies.
"This is the first time to confirm that ALC has a positive effect to cure chemotherapy-induced peripheral neuropathy in the Chinese population," Dr. Sun commented through a translator.
"I think the very important thing for this trial is, it is a different kind of patient population. Before this, most clinical trials were performed in [whites] or maybe Americans. This is an only-Asian [population]," he noted, and it is possible that there are genetic differences in how ALC is metabolized.
Dr. Barton, the discussant, took a cautionary view, saying that "there are some things to consider before going out and telling patients to consider acetyl-carnitine for their peripheral neuropathy."
It was unclear from the results reported whether the two treatment groups were well balanced and what criteria were used to define improvement for the secondary outcomes, she noted. Additionally, "outcome measures were all provider graded, [and there were] no self-report measures, so it is difficult to understand the impact of treatment on symptoms, particularly from the patient perspective," she noted.
Dr. Hershman, Dr. Sun, and Dr. Barton disclosed no relevant conflicts of interest; the ZHAOKE-2007L03540 trial was sponsored by Lee’s Pharmaceutical Limited.
AT THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Patients taking ALC for prevention were more likely to have a greater than 5-point worsening of FACT-NTX score (38% vs. 28%), whereas patients taking ALC for treatment were more likely to have an improvement of at least one grade in neuropathy (51% vs. 24%).
Data Source: Investigators presented separate, randomized, placebo-controlled phase III trials among 410 women receiving adjuvant taxane chemotherapy for breast cancer and 239 patients with cancer and chemotherapy-induced peripheral neuropathy.
Disclosures: Dr. Hershman, Dr. Sun, and Dr. Barton disclosed no relevant conflicts of interest; the ZHAOKE-2007L03540 trial was sponsored by Lee’s Pharmaceutical Limited.
Radiation to Pancreas Linked with Diabetes in Childhood Cancer Survivors
Radiation therapy to the pancreas during childhood confers an increased risk of diabetes during adulthood, according to findings from a retrospective cohort study involving more than 2,500 survivors of childhood cancer.
Specifically, a dose-response relationship was seen between radiation to the tail of the pancreas – where the islets of Langerhans are concentrated – and subsequent diabetes development, reported Florent de Vathaire, Ph.D., of the Center for Epidemiology and Public Health of INSERM at Gustave Roussy Institute in Villejuif, France, and colleagues.
The findings are published online in the Aug. 23 issue of The Lancet Oncology.
Of 2,520 survivors of childhood cancer who returned a survey for the study, 1,632 received radiotherapy during childhood, and 65 had verifiable diabetes, which the authors said was likely type II in most cases. The cumulative incidence of diabetes at age 45 years was significantly greater in those who received radiation therapy (6.6% vs. 2.3%), and those who received radiotherapy to the tail of the pancreas at a dose of 10 Gy or more during childhood were significantly more likely to develop diabetes than were those who did not receive radiotherapy (cumulative incidence of 16.3%).
This relationship persisted even after adjustment for body-mass index (relative risk of 12.6 at a mean radiation dose of 24.2 Gy), the investigators said.
The risk, which was similar in men and women, increased strongly in a dose-dependent fashion up to 20-29 Gy, reaching a plateau at higher doses, they noted (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70323-6]).
No association was found between radiotherapy to other parts of the pancreas and subsequent diabetes development.
Of note, diabetes was diagnosed in 3% of 739 patients who were younger than age 2 years at diagnosis, and the increase per Gy was higher in these patients, compared with older patients. Also, diabetes incidence strongly varied based on the type of childhood cancer, with a cumulative incidence of diabetes at age 45 of 14.7% in survivors of nephroblastoma, compared with 3.1% in survivors of other cancers.
Although these variations by cancer type were explained by differences in age at radiotherapy and by radiation dose to the pancreas tail, patients with nephroblastoma comprised the majority of patients who received high radiation doses to the tail of the pancreas, which raises uncertainty about the attribution of cause, the investigators noted.
No evidence of a significant role for chemotherapy in the calculation of diabetes risk or for chemotherapy overall acting as a modifier of the dose-response for radiation was found in this study, they said.
For the study, the investigators surveyed survivors of childhood cancer – including solid cancer or lymphoma, but excluding leukemia – who were treated in eight centers in France and the United Kingdom before 1986 and followed for a mean of 30 years. Radiation doses to the tail, body, and head of the pancreas were estimated using mathematical modeling, details from the patients’ records, and information about equipment, treatment techniques, and guideline used at the time of treatment.
Though limited by factors such as the high proportion of survivors not included in the analysis and inherent difficulties with estimating radiation dose, the findings of the specificity of the radiation dose to the tail of the pancreas is "plausibly explained by the fact that the islet of Langerhans concentration is higher in the tail than in the body and head of the pancreas," they noted.
"Our investigation emphasizes the importance of long-term follow-up of childhood cancer survivors; almost no diabetes mellitus was seen in our cohort, or those of others, before 20 years of follow-up," they said, noting that the findings also underscore the need for contouring the pancreas when planning radiation therapy to achieve the lowest possible radiation dose to the organ.
This study was funded by Ligue National Contre le Cancer, Institut de Recherche en Santé Publique, Programme Hospitalier de Recherche Clinique, Institut National du Cancer, Agence Française de Sécurité Sanitaire et des Produits de Santé and Fondation Pfizer pour la santé de l’enfant et de l’adolescent. The authors reported having no conflicts of interest.
The findings of Dr. de Vathaire and colleagues substantially extend the current understanding of the late effect of cancer therapy on diabetes development, and have important clinical implications, Dr. Kevin C. Oeffinger and Dr. Charles A. Sklar wrote in an accompanying editorial.
The investigators demonstrate a dose-response relationship between radiation to the tail of the pancreas and subsequent development of diabetes, and since radiation remains an integral part of therapy for many children with Wilms’ tumor or neuroblastoma, concerns about diabetes – a major risk factor for all-cause cardiovascular mortality – are valid in these patients (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70340-6]).
"Additionally, visceral adiposity and insulin resistance are important in tumorigenesis," they said, noting that further study is needed to elucidate the mechanisms underlying diabetes after abdominal radiation.
"Understanding these mechanisms will, hopefully, result in the development of targeted interventions that will lead to a reduction in risk in this population."
Dr. Oeffinger and Dr. Sklar are with Memorial Sloan-Kettering Cancer Center, New York. They reported receiving research grants from the National Institutes of Health, but had no conflicts of interest to report.
The findings of Dr. de Vathaire and colleagues substantially extend the current understanding of the late effect of cancer therapy on diabetes development, and have important clinical implications, Dr. Kevin C. Oeffinger and Dr. Charles A. Sklar wrote in an accompanying editorial.
The investigators demonstrate a dose-response relationship between radiation to the tail of the pancreas and subsequent development of diabetes, and since radiation remains an integral part of therapy for many children with Wilms’ tumor or neuroblastoma, concerns about diabetes – a major risk factor for all-cause cardiovascular mortality – are valid in these patients (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70340-6]).
"Additionally, visceral adiposity and insulin resistance are important in tumorigenesis," they said, noting that further study is needed to elucidate the mechanisms underlying diabetes after abdominal radiation.
"Understanding these mechanisms will, hopefully, result in the development of targeted interventions that will lead to a reduction in risk in this population."
Dr. Oeffinger and Dr. Sklar are with Memorial Sloan-Kettering Cancer Center, New York. They reported receiving research grants from the National Institutes of Health, but had no conflicts of interest to report.
The findings of Dr. de Vathaire and colleagues substantially extend the current understanding of the late effect of cancer therapy on diabetes development, and have important clinical implications, Dr. Kevin C. Oeffinger and Dr. Charles A. Sklar wrote in an accompanying editorial.
The investigators demonstrate a dose-response relationship between radiation to the tail of the pancreas and subsequent development of diabetes, and since radiation remains an integral part of therapy for many children with Wilms’ tumor or neuroblastoma, concerns about diabetes – a major risk factor for all-cause cardiovascular mortality – are valid in these patients (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70340-6]).
"Additionally, visceral adiposity and insulin resistance are important in tumorigenesis," they said, noting that further study is needed to elucidate the mechanisms underlying diabetes after abdominal radiation.
"Understanding these mechanisms will, hopefully, result in the development of targeted interventions that will lead to a reduction in risk in this population."
Dr. Oeffinger and Dr. Sklar are with Memorial Sloan-Kettering Cancer Center, New York. They reported receiving research grants from the National Institutes of Health, but had no conflicts of interest to report.
Radiation therapy to the pancreas during childhood confers an increased risk of diabetes during adulthood, according to findings from a retrospective cohort study involving more than 2,500 survivors of childhood cancer.
Specifically, a dose-response relationship was seen between radiation to the tail of the pancreas – where the islets of Langerhans are concentrated – and subsequent diabetes development, reported Florent de Vathaire, Ph.D., of the Center for Epidemiology and Public Health of INSERM at Gustave Roussy Institute in Villejuif, France, and colleagues.
The findings are published online in the Aug. 23 issue of The Lancet Oncology.
Of 2,520 survivors of childhood cancer who returned a survey for the study, 1,632 received radiotherapy during childhood, and 65 had verifiable diabetes, which the authors said was likely type II in most cases. The cumulative incidence of diabetes at age 45 years was significantly greater in those who received radiation therapy (6.6% vs. 2.3%), and those who received radiotherapy to the tail of the pancreas at a dose of 10 Gy or more during childhood were significantly more likely to develop diabetes than were those who did not receive radiotherapy (cumulative incidence of 16.3%).
This relationship persisted even after adjustment for body-mass index (relative risk of 12.6 at a mean radiation dose of 24.2 Gy), the investigators said.
The risk, which was similar in men and women, increased strongly in a dose-dependent fashion up to 20-29 Gy, reaching a plateau at higher doses, they noted (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70323-6]).
No association was found between radiotherapy to other parts of the pancreas and subsequent diabetes development.
Of note, diabetes was diagnosed in 3% of 739 patients who were younger than age 2 years at diagnosis, and the increase per Gy was higher in these patients, compared with older patients. Also, diabetes incidence strongly varied based on the type of childhood cancer, with a cumulative incidence of diabetes at age 45 of 14.7% in survivors of nephroblastoma, compared with 3.1% in survivors of other cancers.
Although these variations by cancer type were explained by differences in age at radiotherapy and by radiation dose to the pancreas tail, patients with nephroblastoma comprised the majority of patients who received high radiation doses to the tail of the pancreas, which raises uncertainty about the attribution of cause, the investigators noted.
No evidence of a significant role for chemotherapy in the calculation of diabetes risk or for chemotherapy overall acting as a modifier of the dose-response for radiation was found in this study, they said.
For the study, the investigators surveyed survivors of childhood cancer – including solid cancer or lymphoma, but excluding leukemia – who were treated in eight centers in France and the United Kingdom before 1986 and followed for a mean of 30 years. Radiation doses to the tail, body, and head of the pancreas were estimated using mathematical modeling, details from the patients’ records, and information about equipment, treatment techniques, and guideline used at the time of treatment.
Though limited by factors such as the high proportion of survivors not included in the analysis and inherent difficulties with estimating radiation dose, the findings of the specificity of the radiation dose to the tail of the pancreas is "plausibly explained by the fact that the islet of Langerhans concentration is higher in the tail than in the body and head of the pancreas," they noted.
"Our investigation emphasizes the importance of long-term follow-up of childhood cancer survivors; almost no diabetes mellitus was seen in our cohort, or those of others, before 20 years of follow-up," they said, noting that the findings also underscore the need for contouring the pancreas when planning radiation therapy to achieve the lowest possible radiation dose to the organ.
This study was funded by Ligue National Contre le Cancer, Institut de Recherche en Santé Publique, Programme Hospitalier de Recherche Clinique, Institut National du Cancer, Agence Française de Sécurité Sanitaire et des Produits de Santé and Fondation Pfizer pour la santé de l’enfant et de l’adolescent. The authors reported having no conflicts of interest.
Radiation therapy to the pancreas during childhood confers an increased risk of diabetes during adulthood, according to findings from a retrospective cohort study involving more than 2,500 survivors of childhood cancer.
Specifically, a dose-response relationship was seen between radiation to the tail of the pancreas – where the islets of Langerhans are concentrated – and subsequent diabetes development, reported Florent de Vathaire, Ph.D., of the Center for Epidemiology and Public Health of INSERM at Gustave Roussy Institute in Villejuif, France, and colleagues.
The findings are published online in the Aug. 23 issue of The Lancet Oncology.
Of 2,520 survivors of childhood cancer who returned a survey for the study, 1,632 received radiotherapy during childhood, and 65 had verifiable diabetes, which the authors said was likely type II in most cases. The cumulative incidence of diabetes at age 45 years was significantly greater in those who received radiation therapy (6.6% vs. 2.3%), and those who received radiotherapy to the tail of the pancreas at a dose of 10 Gy or more during childhood were significantly more likely to develop diabetes than were those who did not receive radiotherapy (cumulative incidence of 16.3%).
This relationship persisted even after adjustment for body-mass index (relative risk of 12.6 at a mean radiation dose of 24.2 Gy), the investigators said.
The risk, which was similar in men and women, increased strongly in a dose-dependent fashion up to 20-29 Gy, reaching a plateau at higher doses, they noted (Lancet Oncology 2012 Aug. 23 [doi:10/1016/S1470-2045(12)70323-6]).
No association was found between radiotherapy to other parts of the pancreas and subsequent diabetes development.
Of note, diabetes was diagnosed in 3% of 739 patients who were younger than age 2 years at diagnosis, and the increase per Gy was higher in these patients, compared with older patients. Also, diabetes incidence strongly varied based on the type of childhood cancer, with a cumulative incidence of diabetes at age 45 of 14.7% in survivors of nephroblastoma, compared with 3.1% in survivors of other cancers.
Although these variations by cancer type were explained by differences in age at radiotherapy and by radiation dose to the pancreas tail, patients with nephroblastoma comprised the majority of patients who received high radiation doses to the tail of the pancreas, which raises uncertainty about the attribution of cause, the investigators noted.
No evidence of a significant role for chemotherapy in the calculation of diabetes risk or for chemotherapy overall acting as a modifier of the dose-response for radiation was found in this study, they said.
For the study, the investigators surveyed survivors of childhood cancer – including solid cancer or lymphoma, but excluding leukemia – who were treated in eight centers in France and the United Kingdom before 1986 and followed for a mean of 30 years. Radiation doses to the tail, body, and head of the pancreas were estimated using mathematical modeling, details from the patients’ records, and information about equipment, treatment techniques, and guideline used at the time of treatment.
Though limited by factors such as the high proportion of survivors not included in the analysis and inherent difficulties with estimating radiation dose, the findings of the specificity of the radiation dose to the tail of the pancreas is "plausibly explained by the fact that the islet of Langerhans concentration is higher in the tail than in the body and head of the pancreas," they noted.
"Our investigation emphasizes the importance of long-term follow-up of childhood cancer survivors; almost no diabetes mellitus was seen in our cohort, or those of others, before 20 years of follow-up," they said, noting that the findings also underscore the need for contouring the pancreas when planning radiation therapy to achieve the lowest possible radiation dose to the organ.
This study was funded by Ligue National Contre le Cancer, Institut de Recherche en Santé Publique, Programme Hospitalier de Recherche Clinique, Institut National du Cancer, Agence Française de Sécurité Sanitaire et des Produits de Santé and Fondation Pfizer pour la santé de l’enfant et de l’adolescent. The authors reported having no conflicts of interest.
FROM THE LANCET ONCOLOGY
Major Finding: Cancer survivors who received radiotherapy to the tail of the pancreas at a dose of 10 Gy or more during childhood were significantly more likely to develop diabetes than were those who did not receive radiotherapy (cumulative incidence of 16%).
Data Source: Childhood cancer survivors from France and the United Kingdom returned 2,520 questionnaires in this retrospective cohort study.
Disclosures: This study was funded by Ligue National Contre le Cancer, Institut de Recherche en Santé Publique, Programme Hospitalier de Recherche Clinique, Institut National du Cancer, Agence Française de Sécurité Sanitaire et des Produits de Santé and Fondation Pfizer pour la santé de l’enfant et de l’adolescent. The authors reported having no conflicts of interest.
Experimental Drug Improves Muscle Strength in Cancer
HOUSTON – An experimental drug significantly improved physical function in men with cancer-related muscle wasting, compared with placebo – and more so in the men with low testosterone levels – in a secondary analysis of a randomized, double-blind, phase II clinical trial.
In all, 60% of the 93 men for whom baseline testosterone levels were available had hypogonadism when the patients were randomized to treatment with daily placebo or 1 mg or 3 mg of enobosarm for 16 weeks. Before treatment, the eugonadal males showed significantly better physical function, as measured by stair-climb power, compared with the hypogonadal patients (174 W vs. 147 W). Lower testosterone levels correlated with lower physical function.
Enobosarm significantly improved physical function (a secondary end point in the trial) with an average 17% increase in stair-climb power in hypogonadal men, and a 12% increase in power in eugonadal men, compared with baseline, Dr. Adrian Dobs and her associates reported at the annual meeting of the Endocrine Society.
Among men on placebo, stair-climb power increased by about 10% in hypogonadal men and by roughly 1% in eugonadal men, compared with baseline, but the changes were not statistically significant, said Dr. Dobs, professor of medicine and oncology at Johns Hopkins University, Baltimore.
Adverse events included fatigue in 21% of both treatment groups, anemia in 19% of those on enobosarm and 15% in those on placebo, nausea in 18% on enobosarm and 14% on placebo, diarrhea in 16% on enobosarm and 14% on placebo, vomiting in 12% of each treatment group, weight decrease in 12% on enobosarm and 10% on placebo, and constipation in 14% on enobosarm and 4% on placebo.
The investigators defined hypogonadism as a testosterone level below 300 ng/dL.
Enobosarm is a nonsteroidal SARM (selective androgen receptor modulator) that produces anabolic effects in bone and muscle without causing the prostate effects in men or hair growth in women that is seen with steroids.
The analysis used data from a larger trial in 159 people with cancer (65% of whom were men) who had lost at least 2% (and an average of 8%) of their weight in the previous 6 months. The men were older than 45 years of age, the women were postmenopausal, and each had a body mass index less than 35 mg/kg2.
The multicenter study as a whole met its primary end point of increasing lean body mass (muscle) and its secondary end point of improving physical function, Dr. Dobs said in an interview. Those results were reported on the website of the company that is developing the drug, GTx Inc., and at previous medical meetings, according to an interview in the Los Angeles Times.
Dr. Dobs did not report results for lean body mass in the current analysis based on gonadal status.
Cancer diagnoses included colorectal cancer, non–small cell lung cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and breast cancer. Patients participated in the study prior to or between courses of chemotherapy. Rates of hypogonadism were similar for each type of cancer. Patients with hypogonadism were less likely to complete the study than were eugonadal men.
Patients with cancer develop cachexia (muscle wasting) because of reduced anabolic activity, increased catabolic activity, or both, accounting for a progressive catabolic state. Up to 50% of patients with lung cancer show severe cachexia at the time of diagnosis, and the muscle wasting increases throughout the course of the malignancy, Dr. Dobs said.
Two phase III clinical trials are underway to study effects of 3 mg/day of enobosarm for the prevention and treatment of muscle wasting in patients with non–small cell lung cancer.
GTx Inc., the company that is developing enobosarm, funded the current study. Dr. Dobs reported having no other financial disclosures.
HOUSTON – An experimental drug significantly improved physical function in men with cancer-related muscle wasting, compared with placebo – and more so in the men with low testosterone levels – in a secondary analysis of a randomized, double-blind, phase II clinical trial.
In all, 60% of the 93 men for whom baseline testosterone levels were available had hypogonadism when the patients were randomized to treatment with daily placebo or 1 mg or 3 mg of enobosarm for 16 weeks. Before treatment, the eugonadal males showed significantly better physical function, as measured by stair-climb power, compared with the hypogonadal patients (174 W vs. 147 W). Lower testosterone levels correlated with lower physical function.
Enobosarm significantly improved physical function (a secondary end point in the trial) with an average 17% increase in stair-climb power in hypogonadal men, and a 12% increase in power in eugonadal men, compared with baseline, Dr. Adrian Dobs and her associates reported at the annual meeting of the Endocrine Society.
Among men on placebo, stair-climb power increased by about 10% in hypogonadal men and by roughly 1% in eugonadal men, compared with baseline, but the changes were not statistically significant, said Dr. Dobs, professor of medicine and oncology at Johns Hopkins University, Baltimore.
Adverse events included fatigue in 21% of both treatment groups, anemia in 19% of those on enobosarm and 15% in those on placebo, nausea in 18% on enobosarm and 14% on placebo, diarrhea in 16% on enobosarm and 14% on placebo, vomiting in 12% of each treatment group, weight decrease in 12% on enobosarm and 10% on placebo, and constipation in 14% on enobosarm and 4% on placebo.
The investigators defined hypogonadism as a testosterone level below 300 ng/dL.
Enobosarm is a nonsteroidal SARM (selective androgen receptor modulator) that produces anabolic effects in bone and muscle without causing the prostate effects in men or hair growth in women that is seen with steroids.
The analysis used data from a larger trial in 159 people with cancer (65% of whom were men) who had lost at least 2% (and an average of 8%) of their weight in the previous 6 months. The men were older than 45 years of age, the women were postmenopausal, and each had a body mass index less than 35 mg/kg2.
The multicenter study as a whole met its primary end point of increasing lean body mass (muscle) and its secondary end point of improving physical function, Dr. Dobs said in an interview. Those results were reported on the website of the company that is developing the drug, GTx Inc., and at previous medical meetings, according to an interview in the Los Angeles Times.
Dr. Dobs did not report results for lean body mass in the current analysis based on gonadal status.
Cancer diagnoses included colorectal cancer, non–small cell lung cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and breast cancer. Patients participated in the study prior to or between courses of chemotherapy. Rates of hypogonadism were similar for each type of cancer. Patients with hypogonadism were less likely to complete the study than were eugonadal men.
Patients with cancer develop cachexia (muscle wasting) because of reduced anabolic activity, increased catabolic activity, or both, accounting for a progressive catabolic state. Up to 50% of patients with lung cancer show severe cachexia at the time of diagnosis, and the muscle wasting increases throughout the course of the malignancy, Dr. Dobs said.
Two phase III clinical trials are underway to study effects of 3 mg/day of enobosarm for the prevention and treatment of muscle wasting in patients with non–small cell lung cancer.
GTx Inc., the company that is developing enobosarm, funded the current study. Dr. Dobs reported having no other financial disclosures.
HOUSTON – An experimental drug significantly improved physical function in men with cancer-related muscle wasting, compared with placebo – and more so in the men with low testosterone levels – in a secondary analysis of a randomized, double-blind, phase II clinical trial.
In all, 60% of the 93 men for whom baseline testosterone levels were available had hypogonadism when the patients were randomized to treatment with daily placebo or 1 mg or 3 mg of enobosarm for 16 weeks. Before treatment, the eugonadal males showed significantly better physical function, as measured by stair-climb power, compared with the hypogonadal patients (174 W vs. 147 W). Lower testosterone levels correlated with lower physical function.
Enobosarm significantly improved physical function (a secondary end point in the trial) with an average 17% increase in stair-climb power in hypogonadal men, and a 12% increase in power in eugonadal men, compared with baseline, Dr. Adrian Dobs and her associates reported at the annual meeting of the Endocrine Society.
Among men on placebo, stair-climb power increased by about 10% in hypogonadal men and by roughly 1% in eugonadal men, compared with baseline, but the changes were not statistically significant, said Dr. Dobs, professor of medicine and oncology at Johns Hopkins University, Baltimore.
Adverse events included fatigue in 21% of both treatment groups, anemia in 19% of those on enobosarm and 15% in those on placebo, nausea in 18% on enobosarm and 14% on placebo, diarrhea in 16% on enobosarm and 14% on placebo, vomiting in 12% of each treatment group, weight decrease in 12% on enobosarm and 10% on placebo, and constipation in 14% on enobosarm and 4% on placebo.
The investigators defined hypogonadism as a testosterone level below 300 ng/dL.
Enobosarm is a nonsteroidal SARM (selective androgen receptor modulator) that produces anabolic effects in bone and muscle without causing the prostate effects in men or hair growth in women that is seen with steroids.
The analysis used data from a larger trial in 159 people with cancer (65% of whom were men) who had lost at least 2% (and an average of 8%) of their weight in the previous 6 months. The men were older than 45 years of age, the women were postmenopausal, and each had a body mass index less than 35 mg/kg2.
The multicenter study as a whole met its primary end point of increasing lean body mass (muscle) and its secondary end point of improving physical function, Dr. Dobs said in an interview. Those results were reported on the website of the company that is developing the drug, GTx Inc., and at previous medical meetings, according to an interview in the Los Angeles Times.
Dr. Dobs did not report results for lean body mass in the current analysis based on gonadal status.
Cancer diagnoses included colorectal cancer, non–small cell lung cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and breast cancer. Patients participated in the study prior to or between courses of chemotherapy. Rates of hypogonadism were similar for each type of cancer. Patients with hypogonadism were less likely to complete the study than were eugonadal men.
Patients with cancer develop cachexia (muscle wasting) because of reduced anabolic activity, increased catabolic activity, or both, accounting for a progressive catabolic state. Up to 50% of patients with lung cancer show severe cachexia at the time of diagnosis, and the muscle wasting increases throughout the course of the malignancy, Dr. Dobs said.
Two phase III clinical trials are underway to study effects of 3 mg/day of enobosarm for the prevention and treatment of muscle wasting in patients with non–small cell lung cancer.
GTx Inc., the company that is developing enobosarm, funded the current study. Dr. Dobs reported having no other financial disclosures.
AT THE ANNUAL MEETING OF THE ENDOCRINE SOCIETY
Major Finding: The experimental drug enobosarm significantly improved physical function on a stair-climb test by 17% in hypogonadal men with cancer and by 12% in eugonadal men with cancer, compared with nonsignificant improvements in men on placebo.
Data Source: Data are from an analysis of data on a secondary end point (physical function) in 93 men from a randomized, double-blind, multicenter trial in 159 cancer patients.
Disclosures: GTx, the company that is developing enobosarm, funded the study. Dr. Dobs reported having no other financial disclosures.
When the Cancer Patient Isn't a Kid Anymore
CHICAGO – Every parent of a teenager has heard some variation of the demand, "Stop treating me like a kid!" The same can be said for adolescent and young adult survivors of childhood cancers, investigators say.
With childhood cancer survivorship rates hovering around 80% (according to Surveillance, Epidemiology and End Results data from 1996 to 2003), many patients are outgrowing their pediatricians and their pediatric oncologists. The patients still need regular follow-up, but just who will do that follow-up and how thoroughly is still an open question, said Dr. Karim Thomas Sadak, a pediatric oncology fellow at the Center for Cancer and Blood Disorders at Children’s National Medical Center in Washington, D.C.
He and his colleagues surveyed 103 cancer survivors aged 16-24 years and asked them to identify what they found to be the most important factors in their decision to make the transition from a survivorship program at a children’s hospital to a similar program at an adult institution.
"They told us some things we were very surprised to hear about their preferences for care. By far, the most commonly selected component of their clinical care that was rated as very important was the acceptability of their insurance. We might expect to hear that from 30-year-olds, but these people are most likely on their parents’ insurance, as they are under 25," Dr. Sadak said in an interview at the annual meeting of the American Society of Clinical Oncology.
Based on the responses, Dr. Sadak and his associates asked a social worker who helps young patients make the transition to adult care to discuss insurance options with patients and their parents before and during patient visits and in follow-up.
"She gained knowledge about different insurances, reimbursements, copays, and policy issues related to survivorship care, and then she was able to proactively address these concerns with survivors," he said.
Survivors also rated flexible scheduling and comprehensive care as either very important or important. Paradoxically, while 97% of responders said that they wanted to make a transition that promoted independence, 96% wanted their primary childhood cancer provider present during the transition.
Conversely, "availability of vocational training and peer networking as well as considering readiness and a gradual introduction appear to be least important" factors in the decision to make the transition, Dr. Sadak said.
Internists Willing but Uncertain
In a different study, investigators from the United States and Canada surveyed U.S. internists about their knowledge of caring for childhood cancer survivors and found that most general internists said they are willing to follow adolescent and young adult survivors of childhood cancers but many also said that they would feel more comfortable doing so in collaboration with a cancer center.
Internists need to know that there are a wide variety of resources available to help them care for such patients, said coauthor Dr. Eugene Suh, a fellow in pediatric oncology at the University of Chicago Medical Center.
"Internists are really good at gathering information, but I don’t think they necessarily know that this information is out there to help guide them in taking care of these cancer survivors," he said in an interview.
In their survey of a random sample of 2,000 U.S. general internists, 1,025 of whom responded, the investigators found that 72% of those who had seen pediatric cancer survivors in the past 5 years said they never received a treatment summary or survivorship care plan documenting diagnosis, cancer therapy, and plan for follow-up.
Additionally, on a 7-point scale rating familiarity with the Children’s Oncology Group (COG) long-term follow-up guidelines, most respondents reported being "very unfamiliar" (mean score of 5.2 points) with the recommendations.
When presented with a clinical vignette of a female survivor of Hodgkin’s lymphoma treated at age 16 with 25 Gy of mantle radiation and cumulative doses of doxorubicin 150 mg/m2 and cyclophosphamide 15 g/m2, 73% did not recommend yearly breast cancer surveillance, 85% did not recommend cardiac surveillance, and 23% did not recommend thyroid surveillance.
The investigators plan to conduct intervention studies aimed at improving general physicians’ comfort with and knowledge of long-term care for survivors.
Research Resource
One source for survivorship studies could be vertically integrated health care systems, said Dr. Robert M. Cooper and colleagues from Kaiser Permanente Southern California in Los Angeles.
They found that, 5 years after diagnosis, 77% of 4,782 adolescent and young adult cancer patients were still being cared for by Kaiser physicians, as were 62% at 10 years.
"The lengthy insurance retention of adolescent/young adult cancer survivors makes a vertically integrated medical care system an ideal population laboratory for adolescent/young adult cancer survivorship research," they wrote in a poster presented at ASCO 2012.
Patient, Advocate for Thyself
Dr. Sadak said that patients also have to be willing to step up to the plate and act as their own best advocates.
"At some point, we as the provider want to educate the patient ... to have some kind of responsibility for their own health care," he said. "The question is, at what age? It may not be 16, 17, or 18, especially in a population that’s been through a serious illness like childhood cancer. The bonds that these patients and their parents have created are very strong. We have to respect that, while still encouraging the survivor to take responsibility for his health."
Dr. Sadak’s study was funded by a Children’s Health Center Board grant. Dr. Suh’s study was funded by the National Institutes of Health. Dr. Cooper’s study was supported by Kaiser Permanente. All authors reported having no relevant conflicts of interest.
CHICAGO – Every parent of a teenager has heard some variation of the demand, "Stop treating me like a kid!" The same can be said for adolescent and young adult survivors of childhood cancers, investigators say.
With childhood cancer survivorship rates hovering around 80% (according to Surveillance, Epidemiology and End Results data from 1996 to 2003), many patients are outgrowing their pediatricians and their pediatric oncologists. The patients still need regular follow-up, but just who will do that follow-up and how thoroughly is still an open question, said Dr. Karim Thomas Sadak, a pediatric oncology fellow at the Center for Cancer and Blood Disorders at Children’s National Medical Center in Washington, D.C.
He and his colleagues surveyed 103 cancer survivors aged 16-24 years and asked them to identify what they found to be the most important factors in their decision to make the transition from a survivorship program at a children’s hospital to a similar program at an adult institution.
"They told us some things we were very surprised to hear about their preferences for care. By far, the most commonly selected component of their clinical care that was rated as very important was the acceptability of their insurance. We might expect to hear that from 30-year-olds, but these people are most likely on their parents’ insurance, as they are under 25," Dr. Sadak said in an interview at the annual meeting of the American Society of Clinical Oncology.
Based on the responses, Dr. Sadak and his associates asked a social worker who helps young patients make the transition to adult care to discuss insurance options with patients and their parents before and during patient visits and in follow-up.
"She gained knowledge about different insurances, reimbursements, copays, and policy issues related to survivorship care, and then she was able to proactively address these concerns with survivors," he said.
Survivors also rated flexible scheduling and comprehensive care as either very important or important. Paradoxically, while 97% of responders said that they wanted to make a transition that promoted independence, 96% wanted their primary childhood cancer provider present during the transition.
Conversely, "availability of vocational training and peer networking as well as considering readiness and a gradual introduction appear to be least important" factors in the decision to make the transition, Dr. Sadak said.
Internists Willing but Uncertain
In a different study, investigators from the United States and Canada surveyed U.S. internists about their knowledge of caring for childhood cancer survivors and found that most general internists said they are willing to follow adolescent and young adult survivors of childhood cancers but many also said that they would feel more comfortable doing so in collaboration with a cancer center.
Internists need to know that there are a wide variety of resources available to help them care for such patients, said coauthor Dr. Eugene Suh, a fellow in pediatric oncology at the University of Chicago Medical Center.
"Internists are really good at gathering information, but I don’t think they necessarily know that this information is out there to help guide them in taking care of these cancer survivors," he said in an interview.
In their survey of a random sample of 2,000 U.S. general internists, 1,025 of whom responded, the investigators found that 72% of those who had seen pediatric cancer survivors in the past 5 years said they never received a treatment summary or survivorship care plan documenting diagnosis, cancer therapy, and plan for follow-up.
Additionally, on a 7-point scale rating familiarity with the Children’s Oncology Group (COG) long-term follow-up guidelines, most respondents reported being "very unfamiliar" (mean score of 5.2 points) with the recommendations.
When presented with a clinical vignette of a female survivor of Hodgkin’s lymphoma treated at age 16 with 25 Gy of mantle radiation and cumulative doses of doxorubicin 150 mg/m2 and cyclophosphamide 15 g/m2, 73% did not recommend yearly breast cancer surveillance, 85% did not recommend cardiac surveillance, and 23% did not recommend thyroid surveillance.
The investigators plan to conduct intervention studies aimed at improving general physicians’ comfort with and knowledge of long-term care for survivors.
Research Resource
One source for survivorship studies could be vertically integrated health care systems, said Dr. Robert M. Cooper and colleagues from Kaiser Permanente Southern California in Los Angeles.
They found that, 5 years after diagnosis, 77% of 4,782 adolescent and young adult cancer patients were still being cared for by Kaiser physicians, as were 62% at 10 years.
"The lengthy insurance retention of adolescent/young adult cancer survivors makes a vertically integrated medical care system an ideal population laboratory for adolescent/young adult cancer survivorship research," they wrote in a poster presented at ASCO 2012.
Patient, Advocate for Thyself
Dr. Sadak said that patients also have to be willing to step up to the plate and act as their own best advocates.
"At some point, we as the provider want to educate the patient ... to have some kind of responsibility for their own health care," he said. "The question is, at what age? It may not be 16, 17, or 18, especially in a population that’s been through a serious illness like childhood cancer. The bonds that these patients and their parents have created are very strong. We have to respect that, while still encouraging the survivor to take responsibility for his health."
Dr. Sadak’s study was funded by a Children’s Health Center Board grant. Dr. Suh’s study was funded by the National Institutes of Health. Dr. Cooper’s study was supported by Kaiser Permanente. All authors reported having no relevant conflicts of interest.
CHICAGO – Every parent of a teenager has heard some variation of the demand, "Stop treating me like a kid!" The same can be said for adolescent and young adult survivors of childhood cancers, investigators say.
With childhood cancer survivorship rates hovering around 80% (according to Surveillance, Epidemiology and End Results data from 1996 to 2003), many patients are outgrowing their pediatricians and their pediatric oncologists. The patients still need regular follow-up, but just who will do that follow-up and how thoroughly is still an open question, said Dr. Karim Thomas Sadak, a pediatric oncology fellow at the Center for Cancer and Blood Disorders at Children’s National Medical Center in Washington, D.C.
He and his colleagues surveyed 103 cancer survivors aged 16-24 years and asked them to identify what they found to be the most important factors in their decision to make the transition from a survivorship program at a children’s hospital to a similar program at an adult institution.
"They told us some things we were very surprised to hear about their preferences for care. By far, the most commonly selected component of their clinical care that was rated as very important was the acceptability of their insurance. We might expect to hear that from 30-year-olds, but these people are most likely on their parents’ insurance, as they are under 25," Dr. Sadak said in an interview at the annual meeting of the American Society of Clinical Oncology.
Based on the responses, Dr. Sadak and his associates asked a social worker who helps young patients make the transition to adult care to discuss insurance options with patients and their parents before and during patient visits and in follow-up.
"She gained knowledge about different insurances, reimbursements, copays, and policy issues related to survivorship care, and then she was able to proactively address these concerns with survivors," he said.
Survivors also rated flexible scheduling and comprehensive care as either very important or important. Paradoxically, while 97% of responders said that they wanted to make a transition that promoted independence, 96% wanted their primary childhood cancer provider present during the transition.
Conversely, "availability of vocational training and peer networking as well as considering readiness and a gradual introduction appear to be least important" factors in the decision to make the transition, Dr. Sadak said.
Internists Willing but Uncertain
In a different study, investigators from the United States and Canada surveyed U.S. internists about their knowledge of caring for childhood cancer survivors and found that most general internists said they are willing to follow adolescent and young adult survivors of childhood cancers but many also said that they would feel more comfortable doing so in collaboration with a cancer center.
Internists need to know that there are a wide variety of resources available to help them care for such patients, said coauthor Dr. Eugene Suh, a fellow in pediatric oncology at the University of Chicago Medical Center.
"Internists are really good at gathering information, but I don’t think they necessarily know that this information is out there to help guide them in taking care of these cancer survivors," he said in an interview.
In their survey of a random sample of 2,000 U.S. general internists, 1,025 of whom responded, the investigators found that 72% of those who had seen pediatric cancer survivors in the past 5 years said they never received a treatment summary or survivorship care plan documenting diagnosis, cancer therapy, and plan for follow-up.
Additionally, on a 7-point scale rating familiarity with the Children’s Oncology Group (COG) long-term follow-up guidelines, most respondents reported being "very unfamiliar" (mean score of 5.2 points) with the recommendations.
When presented with a clinical vignette of a female survivor of Hodgkin’s lymphoma treated at age 16 with 25 Gy of mantle radiation and cumulative doses of doxorubicin 150 mg/m2 and cyclophosphamide 15 g/m2, 73% did not recommend yearly breast cancer surveillance, 85% did not recommend cardiac surveillance, and 23% did not recommend thyroid surveillance.
The investigators plan to conduct intervention studies aimed at improving general physicians’ comfort with and knowledge of long-term care for survivors.
Research Resource
One source for survivorship studies could be vertically integrated health care systems, said Dr. Robert M. Cooper and colleagues from Kaiser Permanente Southern California in Los Angeles.
They found that, 5 years after diagnosis, 77% of 4,782 adolescent and young adult cancer patients were still being cared for by Kaiser physicians, as were 62% at 10 years.
"The lengthy insurance retention of adolescent/young adult cancer survivors makes a vertically integrated medical care system an ideal population laboratory for adolescent/young adult cancer survivorship research," they wrote in a poster presented at ASCO 2012.
Patient, Advocate for Thyself
Dr. Sadak said that patients also have to be willing to step up to the plate and act as their own best advocates.
"At some point, we as the provider want to educate the patient ... to have some kind of responsibility for their own health care," he said. "The question is, at what age? It may not be 16, 17, or 18, especially in a population that’s been through a serious illness like childhood cancer. The bonds that these patients and their parents have created are very strong. We have to respect that, while still encouraging the survivor to take responsibility for his health."
Dr. Sadak’s study was funded by a Children’s Health Center Board grant. Dr. Suh’s study was funded by the National Institutes of Health. Dr. Cooper’s study was supported by Kaiser Permanente. All authors reported having no relevant conflicts of interest.
AT THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Among adolescent and young adult cancer survivors, 97% said acceptance of their insurance was important or very important for making the transition to an adult physician’s care.
Data Source: Investigators surveyed 103 survivors, aged 16-24 years, of pediatric cancers.
Disclosures: Dr. Sadak’s study was funded by a Children’s Health Center Board grant. Dr. Suh’s study was funded by the NIH. The study by Dr. Cooper and colleagues was supported by Kaiser Permanente. All authors reported having no relevant conflicts of interest.
