Aug 27, 2014
Oncologists must begin to play a larger role in addressing overweight and obesity
By Leah Lawrence, Contributing Writer
If asked, most people would know that tobacco and smoking are associated with a higher risk for cancer. The same may not be true for obesity and cancer. As rates of overweight and obesity continue to increase in the United States, research is revealing its link to an increased risk for many of the most common cancer types and to poorer outcomes among patients diagnosed with cancer.
“Right now, obesity is projected to replace tobacco as the leading modifiable risk factor for many cancers,” said ASCO Immediate Past President Clifford A. Hudis, MD, FACP.
When addressing ASCO membership at the 2014 ASCO Annual Meeting, Dr. Hudis stressed that obesity has the potential to reverse the gains oncologists have made in fighting cancer during the past 50 years.
To try to prevent this potential backslide, ASCO identified cancer and obesity as one of its key initiatives for 2013-2014, and it has issued a call to action for its members to get involved. The Energy Balance Work Group was created to help develop ASCO initiatives related to obesity and cancer, and earlier this year it released “Obesity and Cancer: A Guide for Oncology Providers” (available at asco.org/obesity) as a guide to help oncology providers begin to address the issues of overweight and obesity with their patients. The provider guide is funded through the Conquer Cancer Foundation with the generous support of Ethicon and Roche.
A growing problem
Overweight and obesity are not new health problems, but they are affecting an increasing number of Americans each year. The Centers for Disease Control and Prevention estimates that about 70% of U.S. adults are overweight and about 35% are obese, with no state in the country having an obesity rate of less than 20%.1
“Within the period of one generation, we have gone from the majority of people being of normal weight to a time when almost everyone is overweight and a significant portion of people are obese,” said Jennifer A. Ligibel, MD, Assistant Professor in the Department of Medicine at Harvard Medical School and Chair of the ASCO Energy Balance Work Group. “If we continue on these rates, in 15 years, 40% of the adult population in every state will be obese.”
Although obesity is traditionally associated with an increased risk for heart disease and diabetes, a growing body of data shows that obesity is linked to developing and dying from cancer. One of the first reports to show evidence of this link was published in 2003 in the New England Journal of Medicine.2 Calle et al. studied excess body weight and the risk of death from cancer in almost one million U.S. adults and found that those adults who were the heaviest had cancer mortality rates 50% to 60% higher than their normalweight counterparts. These increased rates were seen in almost every type of cancer studied, including esophageal, colon, rectal, liver, gallbladder, pancreas, kidney, non-Hodgkin lymphoma, and multiple myeloma.
Since then, evidence has only mounted. A study using NCI Surveillance, Epidemiology, and End Results (SEER) data estimated that there were about 84,000 new cases of obesityrelated cancer diagnosed in 2007.3 Considering these trends, another study projected that by 2030, obesity would cause half a million new cancer cases.4
Research is also showing that once patients are diagnosed with cancer, their weight can have an effect on their treatment and outcomes. Overweight and obesity pose technical challenges for treatment by reducing image quality, increasing setup and other errors when undergoing radiation therapy, complicating surgical management, and increasing the risk for surgical complications such as infection and lymphedema.
Although obesity and adverse outcomes have not yet been proven for all cancer types, more links are found each year. A 2014 meta-analysis of 80 studies examining the relationship of weight and diagnosis and outcomes in women with breast cancer showed that obese women were at significantly higher risk of breast cancer–related and overall mortality compared to leaner women.5 Studies have also linked obesity with prostate cancer outcomes. Results from a subanalysis of the Prostate Cancer Prevention Trial showed that men with a body mass index (BMI) greater than 30 had an almost 30% increased risk for high grade disease.6 Shortly after that, another large study showed that men with higher BMIs had anywhere from a 25% to a 112% increased risk for prostate cancer mortality.7
“People typically associated cancer as a disease of wasting, but the reality is that a lot of people also gain a significant amount of weight during their cancer treatment,” Dr. Ligibel said. “We have to encourage an active lifestyle with safe exercise throughout chemotherapy and radiation treatment.”
Additionally, as cancer treatments continue to improve, some forms of the disease are becoming chronic conditions, resulting in an increasing number of cancer survivors. However, research has shown that many survivors are overweight or obese. In addition, a 2008 study showed that fewer than 20% of almost 10,000 cancer survivors who completed a national survey were maintaining a healthy intake of fruits and vegetables, and less than half were getting the recommended amount of physical activity.8
“People are surviving cancer thanks to the effort of oncologists, and we really do want them to face a healthy and happy life,” said Wendy Demark- Wahnefried, PhD, RD, Webb Endowed Chair of Nutrition Sciences at the University of Alabama at Birmingham and a member of the ASCO Energy Balance Work Group. “If they are unable to control their obesity, though, they will be more likely to die of heart disease, diabetes, or other malignancies.”
| Obesity's Link to Cancer
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According to Dr. Hudis, ASCO did not make the decision to enter into the obesity arena casually.
“There are decades of experience from hard-working, well-motivated groups that demonstrate that weight control remains a vexing problem,” he said.
“But oncologists may have a unique, teachable moment with patients, during which they can help those who just need a little extra motivation to successfully manage their weight and counsel others with established obesity.”
ASCO does not expect oncologists to become weight-loss experts, but instead encourages them to guide patients to resources to help with weight loss by assessing, advising, and referring:
Assess a patient’s weight.
An important first step for oncologists is to take the opportunity to assess a patient’s weight using the BMI. A patient’s BMI can be evaluated by using a chart available in the “Obesity and Cancer: A Guide for Oncology Providers” or by dividing a patient’s weight in kilograms by their height in meters squared (kg/ m2). A BMI of 25 or greater is considered overweight and of 30 or greater is considered obese.
Simply addressing the issue of weight can be informative to a patient, who in some cases, may have never been told by a physician that it was a concern.
Advise them on a healthy lifestyle.
If it is determined that the patient is overweight or obese, oncologists should advise patients to lose weight. Weight loss can be achieved in most cases through the combination of increased physical activity and a decrease in caloric intake. “Obesity and Cancer: A Guide for Oncology Providers” offers oncologists tips on how to help patients start thinking about achieving a healthy lifestyle.
“Oncologists do not have to spend a lot of time with this, but the very act of telling the patient that they are overweight or obese, and planting a simple message that weight control is important can be a great start,” Dr. Demark- Wahnefried said.
Refer the patient for additional counseling.
Oncologists may not always have the time or resources to fully address weight loss with their patients. However, oncologists can play an important role by giving patients information on locally available resources, and in some cases, referring them to a primary care physician or dietitian.
Oncologists can also provide ASCO’s booklet, “Managing Your Weight After a Cancer Diagnosis: A Guide for Patients and Families,” which is available as a free printable PDF online at cancer.net/obesity. Providers may also purchase these booklets in bulk for their practice at cancer.net/estore. Two products are offered: one with both provider and patient guides and one with only patient guides.
In addition to the actionable steps of “assess, advise, and refer,” ASCO’s new obesity guide for providers includes the following:
- Tools to help physicians and patients communicate effectively about common challenges patients face;
- Links to Clinical Practice Guidelines dealing with nutrition, physical activity, and obesity released by the American Cancer Society, the American College of Sports Medicine, and the National Heart, Lung, and Blood Institute;
- Guidance on insurance coverage and reimbursement for care related to obesity, including behavioral counseling, rehabilitation services, and medical interventions;
- Details on obesity-related services available through the Affordable Care Act; and
- Links to nationally available programs aimed at helping cancer survivors maintain healthy lifestyles.
|Energy Balance Work Group
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Change can be hard but it is possible. The same study that estimated 500,000 new cancer cases by 2030 also found that if every adult reduced their weight by about 2 pounds, 100,000 cancer cases could be avoided. As oncologists try to bring about change, they are likely to encounter challenges.
“This is a little bit different from earlier decades when oncologists were telling patients to stop smoking,” said Dr. Demark-Wahnefried. “It is a lesscomplicated message to tell someone to stop smoking than to tell them to stop overeating.”
For many oncologists, addressing weight loss may be a new area of discussion. The ASCO obesity guide is designed to provide oncologists with a quick primer on the research and guidance surrounding obesity and its link to cancer. As with any new topic, Dr. Demark-Wahnefried said that discussing obesity may feel uncomfortable to oncologists until it becomes part of their standard repertoire.
It is also widely known that oncologists are facing increasing demands on their time, and the addition of a conversation about weight may sometimes seem like a low-level priority. However, with the ever-increasing amount of research linking obesity with cancer treatments, mortality, toxicities, and survivorship, it will soon become a central issue.
“ASCO is not suggesting that oncologists become weight experts,” Dr. Ligibel said. “Instead, help your patients to identify the connections between obesity and cancer, and point them in the right direction.”
Many patients may feel overwhelmed by their cancer diagnosis without the additional burden of talking about their weight. Because there are so many aspects of the cancer that patients cannot control, oncologists may find success by framing exercise and diet as areas where a patient can maintain control and make a difference in their health.
Finally, with the majority of Americans being overweight or obese, some oncologists may feel uncomfortable discussing weight loss with patients when they have their own issues with weight and food habits.
“In those cases, an oncologist may feel like ‘the pot calling the kettle black,’” Dr. Demark-Wahnefried said. “I would address the topic by saying something like, ‘Even I could stand to lose 10 or 20 pounds, so I know that weight is a hard issue and weight loss can be challenging.’”
The ASCO obesity guide discusses more challenges related to addressing weight loss with patients and provides suggested provider responses that may help oncologists become more comfortable incorporating this topic into their patient visits.
Increase in research
ASCO is also encouraging ongoing research on effective treatments and interventions that may help to reduce obesity-related cancers.
To date, several possible mechanisms linking obesity and cancer have been identified. Research has shown that fat tissue produces higher amounts of estrogen, which may be driving the development of certain obesity-related cancers, including estrogen-sensitive breast cancers and endometrial cancers. The increased amount of fat cells in obese people may have an effect on certain tumor growth regulators, including the mammalian target of rapamycin and AMP-activated protein kinase. In addition, obese people sometimes have hyperinsulinemia or insulin resistance, which may promote the development of certain tumors. Finally, obese people often have chronic low-level inflammation, and research has been ongoing looking at the link between inflammation and cancer.
According to Dr. Hudis, if oncologists are going to start to give advice about weight and weight loss, it needs to be evidence-based. Therefore, there is a great need for continued research and innovation in this area.
As a catalyst for this effort, ASCO is hosting a Research Planning Symposium to bring together physicians and scientists from a variety of fields, including oncology, nutrition, physical activity, and behavioral medicine. According to Dr. Ligibel, ASCO hopes this multidisciplinary forum will foster a discussion of unmet needs and opportunities for research regarding obesity, weight loss, and cancer.
“We know that doing definitive studies in this area is complicated and involves partnerships between a lot of different groups,” Dr. Ligibel said. “ASCO is encouraging the study of weight loss or other lifestyle interventions that may help patients, and encourages oncologists to make an effort to enroll patients in those trials.”
1. Centers for Disease Control and Prevention. Overweight and Obesity. cdc.gov/ obesity/data/adult.html. Accessed 1 July 2014.
2. Calle EE, Rodriguez C, Walker-Thurmond K, et al. N Engl J Med. 2003;348:1625-38.
3. Polednak AP. Cancer Detect Prev. 2008; 32:190-99.
4. Wang YC, McPherson K, March T, et al. Lancet. 2011;378: 815-25.
5. Chan DS, Vieira AR, Aune D, et al. Ann Oncol. Epub 2014 Apr 27.
6. Gong Z, Neuhouser ML, Goodman PJ, et al. Cancer Epidemiol Biomarkers Prev. 2006;10:1977-83.
7. Wright ME, Chang SC, Schatzkin A, et al. Cancer. 2007;109:675-684.
8. Blanchard CM, Courneya KS, Stein K. J Clin Oncol. 2008;26:2198-2204.
Chemotherapy Dosing in Adult Patients Who Are Obese
In 2012, ASCO released a Clinical Practice Guideline on the appropriate chemotherapy dosing for obese adult patients with cancer. The guideline recommended that, in most cases, there be no dose limits imposed upon chemotherapy given in the curative setting in patients who are obese.
“We know that obesity is both a risk factor for and a poor prognostic factor in patients with most solid tumors,” said Jennifer J. Griggs, MD, MPH, Professor in the Department of Health Management and Policy at the University of Michigan, and a member of the ASCO panel. “As the incidence of obesity rises, appropriate dose selection is becoming increasingly important in the United States and worldwide.”
According to Dr. Griggs, before 1985, the majority of clinical trials required that doses be limited in people who are obese. However, after that time most of the cooperative groups required that actual body weight be used to calculate body surface area, which in turn is used to calculate the majority of the chemotherapy drugs used in the treatment of cancer.
Unfortunately, this change in practice was not made clear. Research had shown that despite chemotherapy doses being based on patient body weight and body surface area, as many as 40% of obese patients received only limited doses of the appropriate therapy. “
The variation in dose selection with the first cycle of therapy indicates uncertainty in what constitutes best practices,” said Dr. Griggs. “The guidelines were motivated by a need to address this uncertainty in an increasing proportion of our patients undergoing curative chemotherapy.”
Based on a review of evidence from studies conducted between 1996 and 2010, the ASCO panel recommended that, in most cases, there should be no dose limits imposed upon chemotherapy given in the curative setting in patients who are obese. In addition, the guideline said that in adults with solid tumors treated with curative intent, there is no evidence of increased toxicity when actual body weight is used to calculate body surface area and that, in fact, toxicity appears to be lower among patients who are obese.
Members of the panel listed several exceptions to this recommendation. The guidelines specifically excluded recommendations regarding pediatric patients, patients with leukemia, patients undergoing bone marrow transplantation, and patients being treated with palliative intent. In addition, the guidelines excluded recommendations regarding dose selection for bleomycin, vincristine, and carboplatin, in which the safety of weight-based dosing is uncertain.
The guideline also did not address newer agents commonly referred to as “targeted” or “biologic” agents. Moving forward, Dr. Griggs said that pharmacokinetic, pharmacodynamic, and pharmacogenomic factors of newer agents should be investigated so that more precise dose selection can be used in place of body size, which she said can be “a rather crude way of selecting drug doses.”