Vigorous Exercise Reduces Mortality Risk in Cancer Survivors

A regular program of vigorous exercise can significantly reduce all-cause and cause-specific mortality in adult survivors of childhood cancer, a new study concludes.

"These findings may be of importance for the large and rapidly growing global population of adult survivors of childhood cancer [who are] at substantially higher risk of mortality due to multiple competing risks," the authors comment.

The study, led by Jessica M. Scott, PhD, and Lee W. Jones, PhD, both from Memorial Sloan Kettering Cancer Center in New York City, was published online June 3 in JAMA Oncology and also presented at American Society of Clinical Oncology (ASCO) 2018.

"Our findings are consistent with the wealth of data in the general population showing that regular exercise is associated with substantial reductions in all-cause and cause- specific mortality," the study authors write.

However, compared to the general population, cancer survivors have an elevated mortality risk due to disease recurrence and late cardiovascular effects associated with cancer treatment, Jones noted.

"This is a different disease pathophysiology, so it was unclear if exercise would be effective in this unique situation as well, but it was," Jones told Medscape Medical News.

The team found that exercise exposure of 15 to 18 metabolic equivalent task (MET) hours per week, which is equivalent to brisk walking for about 60 minutes a day, 5 days a week, "seemed to be the optimal dose." Beyond this, benefit was attenuated, "suggesting an upper threshold, at least in this unique cohort of adult survivors of childhood cancer."

"All we want clinicians to do is recommend exercise to patients who are cancer survivors whenever appropriate," Jones told Medscape Medical News.

"This will go a long way to having a positive impact on patients' behavior," he added.

Survivors should meet with a certified exercise professional, preferably someone with expertise in cancer, Jones suggested. The study showed that an increase of about 40 minutes of vigorous activity a week was associated with a significant health benefit, which also meets national physical activity guidelines for cancer survivors of 150 minutes of moderate-intensity exercise per week or 5 days a week for 30 minutes, he said.

Study Details

The new results come from a cohort analysis of 15,450 participants from the longitudinal Childhood Cancer Survivor Study (CCSS). The team found a significant inverse association between exercise and all-cause mortality after a median follow-up of 10 years (P = .02 for trend). This was observed after adjustment for chronic health conditions, including cardiovascular disease (CVD), and key treatment exposures, the researchers say.

At 15 years, the cumulative incidence of all-cause mortality was 11.7% for nonexercisers (0 MET hours per week), 8.6% for those with 3 to 6 MET hours per week, 7.4% for those with 9 to 12 MET hours per week, and 8.0% for those with15 to 21 MET hours per week (P < .001).

This apparent lack of a dose-dependent relationship between exercise and mortally is "in contrast to some but not all studies," the researchers comment.

In a subset of 5689 survivors, increased vigorous exercise averaging 8 MET hours per week for 8 years was associated with an adjusted 40% decrease in all-cause mortality when compared to peers who maintained a low level of exercise of 3 to 6 MET hours per week or less (rate ratio, 0.60; P = .001).

Data From Self-reported Questionnaire

For the study, the researchers analyzed data on self-reported exercise frequency from two separate questionnaires taken by CCSS participants after enrollment. All survivors had been diagnosed before age 21 years and treated at 27 pediatric tertiary hospitals in the United States and Canada between January 1, 1970, and December 31, 1999.

In the "baseline" questionnaire, which was given a median of 17.8 years after cancer diagnosis, CCSS participants were asked how many times in the past 7 days they had worked up a sweat exercising or playing sports for 20 minutes. The median age of the respondents was 25.9 years and 52.8% were male.

The questionnaire showed that survivors who exercised frequently and vigorously were younger at cancer diagnosis, more likely to be nonsmokers, and had fewer risk factors for CVD and chronic conditions of grade 3 and 4 severity.

A median of 9.6 years after the baseline questionnaire, participants underwent reassessment of vigorous exercise propensity in a follow-up survey. Of 70% who indicated a change in exercise behavior, 40% said they were exercising less often than at the time of the previous survey, 20% said they were exercising more often, and 10% said they had maintained their prior high level of vigorous exercise.

Survivors who maintained or increased their exercise frequency were more likely to be nonsmokers and less likely to have any preexisting comorbidities than were low exercisers or nonexercisers, the researchers say.

In the time between the baseline and follow-up surveys, there were 1063 deaths in the cohort: 120 due to recurrence or progression of primary cancer and 811 due to health-related causes, including CVD.

To minimize the risk of reverse-causation bias associated with observational studies, the researchers adjusted all analyses for clinical covariates that could have altered the relationship between exercise and clinical outcomes. They also conducted analytical procedures to exclude participants with recurrence or subsequent malignant neoplasms at baseline.

"Given these measures, and consistency of our findings across multiple outcomes, we contend that our findings, in conjunction with prior work, support the general conclusion that exercise confers significant health benefit for cancer survivors," the investigators say. "Nevertheless, the contribution of confounding cannot be disregarded and only data from randomized clinical trials can definitively prove causality."

Discussing this study at the ASCO meeting, Leontien Kremer, MD, PhD, from the Emma Children's Hospital and Academic Medical Center in Amsterdam, the Netherlands, said this was "a really important study" and that it was "of a very high quality."

"It includes a multivariable analysis, and this is really important because there are many confounders for a healthy lifestyle and the outcomes," she continued, including diet and alcohol consumption.

Kremer also commented that the optimal dose of exercise found in this study is "a lot of exercise because it's vigorous exercise. It's not only a walk or something like that."

"Another important question for survivors of childhood cancer is, Can every survivor do sports?" she said. "In our guideline for cardiotoxicity after childhood cancer, we advise survivors who have been treated with a very high dose of anthracyclines first to see a cardiologist," she noted.

This study was funded by the National Cancer Institute, the American Lebanese-Syrian Associated Charities (ALSAC), AKTIV Against Cancer, and the Kavli Trust. Scott, Jones, and the study coauthors have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2018. Presented June 3, 2018. Abstract 10512

JAMA Oncol. Published June 3, 2018. Abstract

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