Disclosures: Guy’s and St. Thomas’ Charity and Center for Health and Human Performance in London supported the study. Davies reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
April 19, 2022
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Exercise may improve chemotherapy efficacy in esophageal cancer

Disclosures: Guy’s and St. Thomas’ Charity and Center for Health and Human Performance in London supported the study. Davies reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Patients with esophageal cancer who engaged in prehabilitation exercise demonstrated improved responses to neoadjuvant chemotherapy than those who did not, according to a study published in British Journal of Sports Medicine.

“Whilst we are always cautious about overstating the outcomes from relatively small trials, these results that showed an improvement in chemotherapy response in patients on an exercise program are undoubtedly exciting,” Andrew Davies, MSc, MBChB, MD, FRCS, consultant general surgeon at Guy’s and St. Thomas’ Hospitals NHS Trust in London, told Healio. “Not only is it the first time this relationship has been shown in a human trial, but the implications are more far-reaching than the patients with esophageal cancer enrolled in this study.”

Quote from Andrew Davies, MSc, MBChB, MD, FRCS.
Data derived from Zylstra J, et al. Br J Sports Med. 2022;doi:10.1136/bjsports-2021-104243.

Rationale and methods

Davies noted the documented benefits of exercise and growing interest in preparing patients for high-risk operations with prehabilitation programs.

“We also know that chemotherapy affects patients’ physical fitness nearly as much as a major cancer surgery. Therefore, it makes sense to start this process at the beginning of the treatment pathway, thus maximizing its potential benefit,” he said. “The main driver is to try to improve patients’ outcomes and their functional quality of life by equipping them with the physical and psychological capabilities to deal with the treatment in front of them.”

Davies and colleagues performed a prospective, nonrandomized trial that compared a prehabilitation exercise intervention during neoadjuvant chemotherapy (n = 21) with conventional practice (n = 19) among a small cohort of patients with esophageal cancer. The intervention consisted of moderate exercise involving aerobic and strength training until the day before surgery, for an average of 5 months.

The researchers performed biochemical and body composition analyses at multiple time points, with radiologic and pathologic markers of disease regression as outcome measures.

Key findings

The exercise intervention group experienced higher rates of tumor regression compared with the control group (75% vs. 36.8%; P = .025), even in adjusted analyses (OR = 6.57; 95% CI, 1.52-28.3).

Researchers additionally observed improvements in combined tumor and node downstaging (42.9% vs. 15.8%; P = .089) and fat-free mass index (17.8 kg/m² vs. 18.7 kg/m² and 16.3 kg/m² vs. 14.7 kg/m²; P = .026) between the intervention group and control group.

Moreover, patients in the intervention group experienced higher median T lymphocyte counts after neoadjuvant chemotherapy (CD3, 1,681.2 vs. 981.08; P = .03; CD8, 29.41 vs. 0.98; P = .03) and decreased tumor necrosis factor-alpha levels compared with an increase among controls (27.9% vs. 126.4%; P = .04).

“The exercise intervention group had significantly improved response to chemotherapy compared with controls. Numerous differences between the groups in terms of inflammatory and immune responses and body composition could be the mechanism by which this enhanced response came about,” Davies said. “The study included numerous outcome measures, and chemotherapy response was not our primary hypothesis. I think it’s fair to say that the strength of the relationship surprised us, although there is reasonable evidence in animal models to support exercise and chemotherapy response.”

Implications

“The novel finding of enhanced chemotherapy response with exercise should encourage further studies to verify the clinical findings and understand the basic science behind this relationship,” Davies said.

Larger, high-quality, prospective studies are needed to assess the range of benefits that may result from exercise among patients with cancer, he added.

“These would be best informed by working collaboratively to analyze the data from patients who have already been enrolled in exercise studies. However, prehabilitation should now be regarded as best practice, no longer in the realms of experimental — sufficient evidence supports its use in all patients with cancer and requires adequate resource allocation,” Davies said.

For more information:

Andrew Davies, MSc, MBChB, MD, FRCS, can be reached at Guy’s and St. Thomas’ Hospitals NHS Trust, London SE1 7EH, UK; email: andrew.davies1@gstt.nhs.uk.