Exercise During and After Neoadjuvant Rectal Cancer Treatment

• Author / Creator

  Morielli, Andria R.

• Background: A standard treatment option for locally advanced rectal cancer includes 5-6 weeks of neoadjuvant chemoradiation (NACRT) followed by surgery about 6-8 weeks later. NACRT improves outcomes for rectal cancer patients but also causes acute toxicities which may impede quality of life (QoL), treatment completion, treatment response, and long-term prognosis. Moreover, even if completed, only 15-27% of patients achieve a pathologic complete response (pCR) to NACRT which is associated with better long-term survival. Interventions to manage toxicities and improve treatment outcomes that are safe, tolerable, and low-cost are highly desirable. Evidence from other cancer patient groups has demonstrated that exercise may be an effective intervention for mitigating some treatment-related side effects and improving QoL. Moreover, limited research suggests that exercise may improve cancer treatment outcomes. To date, however, only preliminary research has examined the feasibility of exercise during and after NACRT for rectal cancer and no study has examined the potential benefits of exercise in this clinical setting. Purpose: The purpose of this dissertation was to further examine the feasibility and safety of exercise during and after NACRT for rectal cancer and to test its effect on various outcomes in this clinical setting. Methods: This dissertation included two studies. Study 1, a phase I single-arm trial, explored the motivational outcomes and predictors of adherence to a supervised moderate-intensity aerobic exercise program during NACRT followed by ≥ 150 minutes of unsupervised moderate-intensity aerobic exercise/week after NACRT. Study 2 was a phase II randomized controlled trial called the Exercise During and After Neoadjuvant Rectal Cancer Treatment (EXERT) Trial which assessed the feasibility, safety, and efficacy of a supervised high-intensity interval training (HIIT) program during NACRT followed by ≥ 150 minutes of unsupervised moderate-to-vigorous intensity continuous exercise/week after NACRT. Assessments were completed at baseline (pre-NACRT), post-NACRT, and pre-surgery. The primary outcome was cardiorespiratory fitness post-NACRT. Secondary outcomes included symptom management, QoL, and clinical endpoints (i.e. treatment toxicities, treatment completion, and treatment response). Results: Analyses from the phase I trial revealed that rectal cancer patients (N=18) found exercise during NACRT to be more enjoyable and less difficult than anticipated despite several treatment-related barriers. Moreover, they identified potential benefits but also potential harms of exercise during NACRT that were tracked in the phase II trial. From June 2017 to August 2019, 36 rectal cancer patients were enrolled in the EXERT Trial (18 exercise; 18 usual care). Median attendance at supervised HIIT sessions during NACRT was 82% and median self-reported exercise minutes/week post-NACRT was 90 minutes. Exercise did not improve fitness, treatment toxicities, or treatment completion rates; however, exercise, compared to usual, significantly improved the rate of pCR/near pCR (56% vs. 18%; p=0.020). Furthermore, during NACRT, exercise significantly worsened stool frequency (p=0.022; d=0.99), role functioning (p=0.039; d=-0.90), emotional functioning (p=0.028; d=-0.80), and cognitive functioning (p=0.004; d=-0.58) compared to usual care. After NACRT, exercise significantly worsened diarrhea (p=0.030; d=0.59) and embarrassment (p=0.003; d=0.68) compared to usual care. Conclusions: Exercise during and after NACRT is feasible and may improve treatment response without improving cardiorespiratory fitness, treatment toxicities, or treatment completion rates. Moreover, exercise may worsen some symptoms and QoL during NACRT; however, most of these effects appear to dissipate prior to surgery. Larger trials are warranted to confirm the beneficial effects of exercise on treatment response and the harmful effects of exercise on symptoms and QoL. If the clinical benefit of exercise is confirmed, then the modest symptom exacerbation during NACRT may be tolerable; however, in the absence of any clinical benefit, exercise may be contraindicated in this clinical setting.

• Subjects / Keywords

  • Quality of life
  • Radiation therapy
  • Physical fitness
  • Cancer
  • treatment outcome
  • Symptom burden
  • Exercise

• Graduation date

  Fall 2020

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-8bhm-fz70

• License

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