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Diet, exercise modifications can have ‘tremendous impact’ on pediatric cancer outcomes
Diet and exercise may improve treatment outcomes among pediatric patients with cancer, according to a study conducted at The University of Texas MD Anderson Children’s Cancer Hospital.
In addition, introducing energy balance interventions may reduce the risk for late effects during survivorship.
Researchers at MD Anderson reviewed 67 pediatric oncology studies to evaluate the relationship between diet and exercise. They investigated how energy balance interventions may impact tumor growth, and the positive effects such programs could have on patients with obesity.
“The purpose of the review was to delineate between obesity reduction as a goal for energy balance interventions versus simply changing diet or adding exercise,” lead investigator Joya Chandra, PhD, associate professor of pediatric research at MD Anderson, said in a press release. “For example, our review confirmed modifying diet or adding moderate exercise can improve chemotherapy efficacy independent of weight loss.”
HemOnc Today spoke with Chandra and co-investigator Keri Schadler, PhD, assistant professor of pediatric research at MD Anderson, about their findings, how to incorporate energy balance interventions into treatment practices, and discussions oncologists should have with patients and their parents.
Question: Why is this an important research area?
Chandra: In contrast to new drugs that require years of testing and evaluation for safety and efficacy, diet or exercise interventions are likely to have very few side effects and can be implemented across the world. If we can find ways to modulate these behaviors to improve outcomes, it has a tremendous impact on pediatric oncology globally.
Schadler: Diet or exercise interventions are extremely cost-effective, low-risk ways to improve standard of care. Diet and exercise interventions generally do not need an insurance approval making these interventions accessible to virtually all patients. They are ways patients can make changes in their own behaviors to improve their own outcomes.
Q: Physicians are reported to be cautious about administering an exercise regimen in a cancer care setting . Why is that?
Chandra: A lot of physicians are not convinced exercise is safe, particularly for patients with bone tumors — who may have had an amputation — or even broadly across pediatric patients with cancer, who may be weak, dizzy or disoriented from their treatment. These side effects can affect coordination. Doing exercise in a controlled setting with supervision is important.
Schadler: Historically, it was thought that patients with cancer should stay in bed, and avoid physical activity. Modern research shows the opposite approach may be beneficial. Even very frail patients are capable of at least low-intensity physical activity. Generally, the more patients move, the better they feel and the better their physical functioning. It tends to be good for their immune system and lung function. We realize now that physical activity, even at moderate levels, is better than nonactivity.
Q: What was the aim of your study?
Chandra: We set the stage for studies to look at how specific diets and exercise regimens can improve chemotherapy outcomes in pediatric leukemias and bone tumors. The energy-balance modifications we suggest are not difficult. They include 30 minutes of treadmill walking per day and dietary modifications using foods that are amended, but not unfamiliar.
Our review highlights a need for testing and delivering these energy-balance interventions in pediatric oncology patients and identifies some of the controversies in the field regarding whether poor outcomes are associated with obesity, or the nutritional content of the foods kids eat during treatment or lack of exercise during treatment.
Schadler: This review took a global view of the pediatric cancer research to understand a few key points. First, are there any very clear recommendations that we should make regarding diet or exercise? Can we base those recommendations on existing clinical studies?
The second goal was to determine whether diet and exercise intervention can be beneficial, independent of obesity and weight management, or whether weight management needs to be our goal in all situations. Our third goal was to evaluate preclinical laboratory research to identify exciting areas of diet or exercise research that may become clinically relevant in the next couple of years.
Q: What did you find?
Chandra: Our review highlights a lot of animal studies in diverse types of cancer where things like high-sugar or high-fat diets worsen outcomes in various mouse models. Some of those observations also have been confirmed in patients. However, very few of these studies have been done in pediatric patients with cancer or in mouse models for pediatric cancers. There are reports of diet and exercise playing a role in mouse models and epidemiologic studies in adults; however, this needs to be probed more carefully in pediatrics.
We know that if children are overweight or obese, they are likely to have a worse outcome than a normal-weight patient. However, weight fluctuates during the course of treatment. We highlight studies of patients with acute lymphoblastic leukemia that identify weight gain that occurs during treatment and show the persistence of weight gain into. Thus, tackling the issue of weight gain, diet modification and physical activity during treatment has potential to impact survivorship.
Further, changing behaviors during treatment affects children after they have survived their cancer. Pediatric patients face many treatment-related side effects, including cardiovascular disease, diabetes, metabolic disease and risk for secondary cancers. By lessening obesity rates in survivors, we can mitigate some of those risks for late effects.
Schadler: We found that the literature demonstrates that exercise is feasible, meaning we can design exercise interventions for these patients, and they will adhere to them. Patients completed approximately 65% to 90% of their recommended exercise programs, which is very good adherence compared with how well patients adhere to taking a prescription drug. The literature also reported no adverse events, which means exercise is overwhelmingly safe.
Patients benefitted from physical activity or exercise programs, as well. Physical activity reduced chemotherapy-associated fatigue, prevented muscle function loss that occurs with long inpatient hospitalization stays, and increased physical function and strength among long-term survivors.
Q: How can oncologists discuss energy balance with pediatric patients and their families?
Chandra: Some of this work would be best done in collaborative groups. We need to figure out exactly what diet modifications work best in different pediatric cancer populations. In the short term, oncologists can encourage parents to keep their patients active and provide as healthy of a diet as possible. General guidelines for fruit and vegetable consumption and dietary fat consumption are applicable to kids with cancer. Unfortunately, permissive behaviors can lead to adopting poor food habits, and those poor habits can persist into survivorship. The main message oncologists can give to parents is to stick to guidelines for a healthy diet and physical activity as best they can even during treatment.
Schadler: Data allow a physician to give the best information possible to patients and their parents. We want to arm physicians with data, and we hope that this review makes it clear to pediatric oncologists that it is completely safe and reasonable for physicians to recommend exercise to their patients.
Q: What additional research are you conducting?
Chandra: My particular interest is in diet modifications in pediatric patients with cancer. My lab is using mouse models for pediatric cancers, modelling their treatment with agents that are used in children and then feeding these mice different types of diets that are low in fat, low in sugar, low in both, etc., to see the cancer burden. We want to know if there is a synergistic effect of combining these diet modifications with standard chemotherapies. We also are looking at whether diet modifications can reduce cardiac late effects associated with some of these chemotherapies.
We work extensively with our pediatric patients with cancer to teach healthy principles of eating. We have an online cookbook with more than 500 recipes with carefully selected foods that are not too elaborate and are easy to find. We have videos that show parents how to cook some of these foods, and we have cooking classes for kids. We are studying how cooking can be measured more effectively. We are looking at how patients eat during a treatment window — calorie, fat and protein intake — and how that tracks with oxidative stress in peripheral blood.
Schadler: In our mouse models with pediatric tumors, I study how exercise affects drug delivery to the tumor. I try to understand how exercise changes the blood vessels structure within a tumor and whether the blood vessels can be improved to get more chemotherapy into the tumor to improve its antitumor effect.
We collaborate with clinical colleagues to offer exercise interventions in the clinic. For example, we have an open clinical trial for pediatric patients with new diagnoses of osteosarcoma or Ewing sarcoma. Patients are randomly assigned to a control group or a group that meets with a physical therapist three times a week to perform an exercise intervention for the entire duration between diagnosis and surgery — about 12 weeks — when they are getting chemotherapy and/or radiation. We look at various factors in their blood and imaging in their tumor that are important for improving the chemotherapy delivery.
The other project led by my clinical colleagues is an intervention called Team Me — Totally Excited About Mobility, Movement and Exercise. It is an intervention to get inpatients in the pediatric unit up and out of bed. We set up routes of the hallway, which equates to a certain distance. Walking each route earns a patient a certain amount of tickets, which can be exchanged for prizes to incentivize patients to get out of bed and move. To make Team Me a research study, we are writing the institutional review board protocol to get research approved to help us understand whether getting out of bed changes factors in the blood that may correlate with better patient outcomes.
Q: Is there anything else you would like to discuss?
Chandra: The main message is that physicians should promote healthy diets for patients, and kids should continue to eat healthily throughout their cancer treatment. A lot of physicians are enablers of permissive diet behaviors. They are more focused on keeping up calories than the composition of calories during cancer treatment.
We hope the resources we have developed such as the online cookbook will show oncologists and parents that you can eat healthily, accommodate side effects and keep calories up during a treatment window. A lot of the advice parents receive from oncologists is to let their kids eat whatever they want, because that is the easy thing to do. We want to provide parents and oncologists with resources to help kids eat healthy during treatment, which will potentially improve their response to treatment.
Schadler: We are working on getting a trial together at MD Anderson with a “front door protocol,” in which every patient will receive an activity monitor. Then we will be able to monitor their activity throughout their entire duration as a patient — from diagnosis through long-term follow-up survivorship. That will create an enormous database on physical activity for pediatric patients with cancer, encompassing all diagnoses at all phases of care. Then, we can use that data to ask questions such as: Do patients who stay more active during chemotherapy do better? Do patients who meet a certain number of steps per day have a lower risk for secondary infection? – by Kristie L. Kahl
For more information:
Joya Chandra, PhD, can be reached at jchandra@mdanderson.org.
Keri Schadler, PhD, can be reached at kschadler@mdanderson.org.
To visit the online cookbook, visit www.mdanderson.org/recipes.
Disclosures: The University of Texas MD Anderson Foundation Multidisciplinary Research Program funded this study. Chandra and Schadler report no relevant financial disclosures.