Exercise should be standard part of cancer care during treatment, ASCO guideline states
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It is well known that obesity, physical inactivity and a poor diet increase the risk for various cancer types and contribute to adverse outcomes among adults with certain malignancies.
However, less is known about the effect of weight loss, diet management and exercise during cancer treatment.
In May, ASCO published guidance on these lifestyle interventions for adults with cancer undergoing chemotherapy or radiotherapy or who are in the perioperative period.
“This guideline was informed by clinical trials that randomly assigned patients to make changes in exercise, diet or weight and then looked at the effects of those changes,” Jennifer A. Ligibel, MD, associate professor of medicine at Harvard Medical School and senior physician in adult oncology at Dana-Farber Cancer Institute, told Healio | HemOnc Today “We examined systematic reviews, which is what made this evidence so strong — it wasn’t based on one or two trials but on more than 100 trials that had been conducted.”
The systematic reviews included 42 for exercise, nine for diet and one for weight management, which, along with 23 randomized controlled trials, comprised the evidence base. The most common cancer types studied included breast, lung, colorectal and prostate.
Ligibel said when ASCO convened an expert panel to create the recommendations, no guidance existed on lifestyle changes for adults while they are receiving active cancer treatment.
“This is important for us as oncologists because we often have our patients sitting in front of us and asking what they should be eating, whether they should be exercising and whether they should lose weight,” Ligibel said. “We wanted to develop guidance to be able to tell the clinician who is talking to their patient that this is what you should or shouldn’t be doing during treatment.”
The panel found clear and consistent evidence that exercise during cancer treatment reduces fatigue, prevents decline in cardiorespiratory fitness and strength, and improves mood and quality of life. Based on these findings, the panel recommended aerobic and strength training exercise become a standard part of the care of adults with cancer being treated with systemic antineoplastic therapy and radiation, or in the perioperative period. Conversely, insufficient research evidence existed to provide recommendations on what patients with cancer should eat during specific treatments or whether weight loss for patients with overweight or obesity is advantageous during active therapy.
“We looked hard to find trials that could help us provide guidance on these topics, but there were few or no data,” Ligibel said. “There is a dire need for research examining what people should eat and whether weight loss or avoidance of weight gain is something that’s beneficial to patients during treatment.”
Healio | HemOnc Today spoke with oncologists about the guideline; the impact of exercise during cancer treatment on cardiorespiratory fitness, physical strength, fatigue and quality of life; the need for research on diet and weight management; and ongoing efforts to address the lack of data.
Exercise
More than 100 clinical trials have examined the effects of exercise during cancer treatment, according to Ligibel.
“This was something that we found quite striking — how many more research studies have been conducted on exercise vs. diet or weight management,” she said. “The good news is that because we had so much evidence about exercise programs during cancer treatment, we were able to make more definitive recommendations regarding the beneficial role of exercise during cancer treatment. There was clear and consistent evidence that exercise had benefits during chemotherapy, during radiation and specifically for patients with lung cancer immediately before and immediately after surgery.”
According to the guideline, providers should recommend that patients undergoing active treatment with curative intent engage in regular aerobic and resistance exercise to mitigate adverse effects of therapy. Exercise interventions during this period reduce fatigue and preserve cardiorespiratory fitness, physical functioning and strength, as well as improve quality of life and reduce anxiety and depression for certain populations, research showed. For patients with lung cancer, preoperative exercise resulted in a reduction in length of hospital stay and postoperative complication rates.
However, data are lacking on whether exercise during treatment improves the efficacy of treatments, treatment completion rates or survival outcomes or reduces risk for cancer recurrence.
“Initially, we aimed to identify the types of benefits that exercise may have on survival and recurrence, as well as on quality of life and treatment toxicity, but there was insufficient evidence to inform us of the effect of exercise on disease outcomes because the studies haven’t been conducted or trials have been too small to show whether these types of programs contribute to longevity,” Ligibel said. “There was very clear evidence that starting an exercise program — whether it be aerobic, strength training or a combination of the two — led to benefits in terms of how people felt. Exercise reduced treatment-related side effects, especially fatigue and deconditioning, anxiety and depression. Individuals who engaged in regular exercise during treatment had better quality of life and fitness, and felt better overall.”
Ligibel said research has also showed a low risk for adverse events related to exercise during cancer treatment.
“We found a very low rate of injury reported in any of the studies that were conducted that reported on this,” she said. “The studies enrolled patients with many different cancer types and during different types of treatments and there was no signal that there was a particular group of patients that should avoid exercise.”
A gray area exists for the patient who has preexisting medical conditions, experiences disabling adverse effects due to cancer treatment or has undergone a surgery that leaves them with functional impairment, Ligibel added.
“We don’t think those patients need to avoid exercise, but there are groups of people that need to start working with exercise professionals vs. exercising on their own,” Ligibel said. “Another effort that we hope comes from this guideline is creation of a better platform or programs to help triage patients who may need more specialized attention before they start an exercise program on their own.”
Diet
Data to inform guidance on diet and nutrition during cancer treatment is scarce, according to the guideline authors.
“There is very little evidence to suggest that dietary changes are either beneficial or harmful,” Wendy Demark-Wahnefried, PhD, RD, associate director of cancer prevention and control at O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, told Healio | HemOnc Today.
However, there was one area in which the panel agreed. The guideline recommends against neutropenic diets — namely those that exclude raw fruits and vegetables — to reduce infection risk among patients with cancer undergoing treatment.
“There is no good evidence to suggest that neutropenic diets are helpful at all, and they may actually result in patients needlessly avoiding these healthy foods,” Demark-Wahnefried said. “That recommendation is something that is new in these guidelines and that will be helpful for our patients.”
Due to the profound lack of research, the panel made no recommendations for or against various popular dietary interventions during cancer therapy, including ketogenic or low-carbohydrate diets, low-fat diets, non-nutrient supplements, functional foods or fasting to improve quality of life, reduce treatment adverse events or improve cancer outcomes. In contrast to extensive data on the impact of diet and weight on cancer risk and prevention, very little quality research is available focusing specifically upon the cancer treatment phase.
The panel noted that diet and weight management strategies that provide health benefits to the general population, such as the Dietary Guidelines for Americans as defined by the USDA, could also provide important benefits to people undergoing cancer treatment, and made it clear that the guideline was not meant to discourage clinicians from discussing diet and weight with their patients.
“Although there’s not a lot of evidence to undertake many dietary changes during the time of active treatment, diet is important for long-term health of cancer survivors, and it is important for clinicians to take advantage of the teachable moment of the cancer diagnosis to ‘plant the seed,’” Demark-Wahnefried said. “We know that healthy plant-based diets are important for cancer prevention and that cancer survivors are at increased risk for another cancer later on. Although we may not have evidence during this narrow period of time of during cancer treatment, individuals who make healthful lifestyle changes will find that their long-term health will be better.”
Ligibel said the NCI is seeking to fill the research gaps through its Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) in Cancer Survivors Consortium.
“In addition to the ENICTO program, there are interesting preclinical data looking at intermittent fasting and other dietary changes, but there is no evidence in humans that these kinds of changes provide benefits during treatment,” she said. “We clearly need more research to develop evidence-based guidance regarding diet during cancer treatment.”
Weight management
Experts with whom Healio | HemOnc Today spoke said weight management during cancer treatment is the area with the least amount of evidence available. The few studies conducted in this space have suggested intentional weight loss may be feasible during therapy, specifically for those with breast cancer and potentially for men with prostate cancer, but the effect of such on-treatment interventions remains unclear.
“Unfortunately, the vast majority of Americans fall into the current pandemic of weight gain and overweight, as well as not closely following the dietary guidelines that have been established by NIH and the USDA,” Steven K. Clinton, MD, PhD, professor of medical oncology at The James Cancer Hospital of The Ohio State University, told Healio | HemOnc Today. “We have a lot of room for research in weight management that will not only enhance cancer therapy but improve quality of life and promote healthy cancer survivorship.”
Clinton said lifestyle changes for patients undergoing cancer treatment need to be considered “in a whole new paradigm.”
“We are testing so many novel treatments, targeted therapies and immunotherapeutics that will have an enormous benefit for our patients, but there’s so little known about how we can intervene with weight management, diet and exercise in order to make these treatments more impactful both in terms of being more effective and reducing toxicity,” he said. “Investing in that type of research is critical to maximize outcomes and reduce costs of cancer care.”
A challenge of the American health care system, according to Clinton, is the lack of adequate insurance coverage for clinical dietitians to consult with patients and provide the frequency and intensity of education and monitoring necessary to help individuals make healthy changes.
“We need to support dietitians and exercise physiologists because they are the ones who can truly have an impact on our patients,” he said. “Not only do we need more research, but once we have the data, we need to continually update guidelines and, most importantly, to invest in implementation. Most oncologists, nurses and staff simply do not have the training, resources, or time to conduct the proper counseling needed on diet, weight management and exercise. We really have a challenge here, not only in collecting the data and having the evidence-based recommendations, but in ensuring that it can be implemented for the benefit of everyone.”
Call for research
Ligibel said the systematic review highlighted the need for research on the effect of diet, weight management and exercise interventions during cancer treatment, some of which is underway.
“Through its ENICTO initiative, NCI has recently funded four studies that will examine different diet and exercise interventions during treatment to fill in some of the gaps in our knowledge,” she said. “Still, it will be a few years before the results become available.”
Clinton said the lack of knowledge on the impact of diet and weight management during specific cancer treatments is startling.
“When looking at this field of diet, nutrition, exercise and cancer, I’ll estimate that about 98% of the research relates to etiology and prevention of cancer, and then some research is in the survivorship space after people have completed therapy,” Clinton said. “But what we know about specific interventions to complement therapies — to achieve the critical goals of improving the efficacy of therapy and reducing the side effects or toxicity of cancer therapy — so little is known in this space and very little research has been devoted to this.”
Demark-Wahnefried said that in the past, NCI had heavily invested in trials that tested purified dietary supplements rather than focusing on food choices and patterns, but the trials did not yield beneficial results.
“After that, many have decided to not investigate more in that area and we have been hampered by that,” she said. “Hopefully, we’ll get more diet-related research soon.”
Ligibel said research also is needed to assess whether exercise increases longevity or reduces risk for cancer recurrence and mortality.
“We currently do not have sufficient information to determine whether lifestyle changes during cancer treatment reduce the risk for cancer recurrence or mortality,” she said. “Additionally, we still need more information regarding the best ways to support patients in making positive lifestyle changes during cancer treatment.”
Clinton said it is important to keep in mind that exercise, diet composition and weight management are interrelated.
“It’s hard to compartmentalize these and focus research on each component individually, given how one impacts the other, and our studies need to be integrative. At this time, it is important to at least make oncologists aware of the state of the science,” he said. “Although this report is not quite a paradigm shift in what we do as oncologists in clinic, having this information can truly enhance awareness, promote healthy diet and exercise interventions, and stimulate research.”
Investment in this area is tremendously important to patients, Clinton added.
“The vast majority of our patients want to feel empowered that they are contributing to the outcome of their cancer treatment,” he said. “So many of our patients and their families focus on diet and nutrition, exercise and fitness, and weight management as part of that approach. What we have to be able to do is give them far better guidance with regard to how to achieve those goals.”
References
- Ligibel JA, et al. J Clin Oncol. 2022;doi:10.1200/JCO.22.00687.
- Ligibel JA, et al. JCO Oncol Pract. 2022;doi:10.1200/OP.22.00277.
For more information
Steven K. Clinton, MD, PhD, can be reached at The James Cancer Hospital of The Ohio State University, 460 W. 10th Ave., Columbus, OH 43210; email: steven.clinton@osumc.edu.
Wendy Demark-Wahnefried, PhD, RD, can be reached at O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham, 1824 Sixth Ave. South, Birmingham, AL 35233; email: demark@uab.edu.
Jennifer A. Ligibel, MD, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: jennifer_ligibel@dfci.harvard.edu.
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