The Impact of Resistance Exercise on Muscle Mass in Glioblastoma in Survivors (RESIST): Protocol for a Randomized Controlled Trial

Abstract

Background Glioblastoma is the most common primary brain malignancy in adults, accounting for approximately 48% of all brain tumors. Standard treatment includes radiation and temozolomide chemotherapy. Glioblastomas are highly vascular and can cause vasogenic brain edema and mass effect, which can worsen the neurologic symptoms associated with the disease. The steroid dexamethasone (DEX) is the treatment of choice to reduce vasogenic edema and intracranial pressure associated with glioblastoma. However high-dose DEX or long-term use can result in muscle myopathy in 10%-60% of glioblastoma patients, significantly reducing functional fitness and quality of life (QOL). There is a wealth of evidence to support the use of exercise as an adjuvant therapy to improve functional ability as well as help manage treatment-related symptoms. Specifically, resistance training has been shown to increase muscle mass, strength, and functional fitness in aging adults and several cancer populations. Although studies are limited, research has shown that exercise is safe and feasible in glioblastoma populations. However, it is not clear whether resistance training can be successfully used in glioblastoma to prevent or mitigate steroid-induced muscle myopathy and associated loss of function. Objective The primary purpose of this study is to establish whether an individualized circuit-based program will reduce steroid-induced muscle myopathy, as indicated by maintained or improved functional fitness for patients on active treatment and receiving steroids. Methods This is a 2-armed, randomized controlled trial with repeated measures. We will recruit 38 adult (≥18 years) patients diagnosed with either primary or secondary glioblastoma who are scheduled to receive standard radiation and concurrent and adjuvant temozolomide chemotherapy postsurgical debulking and received any dose of DEX through the neurooncology clinic and the Nova Scotia Health Cancer Center. Patients will be randomly allocated to a standard of care waitlist control group or standard of care + circuit-based resistance training exercise group. The exercise group will receive a 12-week individualized, group and home-based exercise program. The control group will be advised to maintain an active lifestyle. The primary outcome, muscle myopathy (functional fitness), will be assessed using the Short Physical Performance Battery and hand grip strength. Secondary outcome measures will include body composition, cardiorespiratory fitness, physical activity, QOL, fatigue, and cognitive function. All measures will be assessed pre- and postintervention. Participant accrual, exercise adherence, and safety will be assessed throughout the study. Results This study has been funded by the Canadian Cancer Society Atlantic Cancer Research Grant and the J.D. Irving Limited–Excellence in Cancer Research Fund (grant number 707182). The protocol was approved by the Nova Scotia Health and Acadia University’s Research Ethics Boards. Enrollment is anticipated to begin in March 2022. Conclusions This study will inform how individualized circuit-based resistance training may improve functional independence and overall QOL of glioblastoma patients. Trial Registration ClinicalTrails.gov NCT05116137; https://www.clinicaltrials.gov/ct2/show/NCT05116137 International Registered Report Identifier (IRRID) DERR1-10.2196/37709

Rehabilitation in People Living with Glioblastoma: A Narrative Review of the Literature

“…While reduced muscle strength may represent a neurologic symptom, the chronic use of corticosteroids (prescribed to treat vasogenic edema and reduce intracranial pressure) combined with the neurotoxic side effects of chemotherapy is thought to exacerbate muscle wasting in this clinical population [44]. To counteract the side effects of medications, exercise-based interventions involving resistance training may represent a suitable strategy to restore muscle function and promote anabolic processes [45]. In this respect, multicomponent exercise programs involving resistance training and moderate-intensity aerobic exercise have been shown to be feasible, safe, and well-tolerated in people living with a glioblastoma [46][47][48][49].…”