PROBLEM: Glioblastoma multiforme (GBM) is the most common brain malignancy accounting for
approximately 48% of all brain tumors. GBMs are highly vascular and can cause vasogenic brain
edema and mass effect, which can worsen the neurologic symptoms associated with the disease.
Corticosteroids (i.e., Dexamethasone; DEX) are the treatment of choice to reduce vasogenic
edema and intercranial pressure associated with GBM. However, the use of steroids comes at a
cost. High dose steroid therapy and/or long-term use results in muscle myopathy (i.e., muscle
weakness) in 10-60% of GBM patients, significantly reducing functional ability as well as
quality of life (QOL). Thus, adjuvant therapies are needed to help patients maintain their
functional ability and 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. Resistance training (RT) has been shown to increase muscle mass, strength, and
functional ability in aging adults and several cancer populations. While limited, studies in
GBM have shown that exercise is safe and feasible for this population and that it can improve
functional performance. However, no specific research has been performed to determine whether
RT can be successfully used in GBM to prevent or reduce steroid induced muscle myopathy.
Therefore, the primary purpose of this study is to establish whether an individualized
circuit-based RT program will improve functional fitness for patients on active treatment and
receiving steroids.
METHODS: This is a two-armed randomized control trial with repeated measures. Thirty-eight
adult (18+ years) patients diagnosed with either primary or secondary GBM who are scheduled
to receive standard radiation and concurrent adjuvant Temozolomide chemotherapy post-surgical
debulking as well as received any dose of DEX will be recruited through the neuro-oncology
clinic and the QEII Cancer Center. Patients will be randomly allocated to a standard of care
group (SOC) or SOC+RT group (EX). Those in the SOC group will be advised to maintain an
active lifestyle for the 12-week intervention whereas those in the EX group will receive a
personalized 12-week circuit-based RT program. This program will consist of 3-4 supervised RT
sessions/wk. During each session participants will perform a RT program that is comprised of
3 circuits. Each circuit will include 3 sets of 3 different exercises. Each exercise set will
be 1 minute in duration (20 seconds/exercise) with 1 minute of rest between sets. Initial
exercise intensity will be light and will increase throughout the program based on the
participant's progress. All exercise programs will be designed and supervised by a Clinical
Exercise Physiologist (CEP). The primary outcome measure for the study is functional
performance which will be assessed using the Short Physical Performance Battery and hand grip
strength. Secondary outcome measures will include body composition, aerobic fitness, physical
activity levels, general health, QOL, fatigue, and cognitive function. All measures will be
assessed pre/post-intervention. Safety and exercise adherence will be assessed throughout the
study.
ANALYSIS: Descriptive statistics will be used to describe the population, accrual, program
adherence and safety. Outcome data will be analyzed using an intention to treat approach. All
participants will be entered into a mixed effects model with participant group assignment
(EX, SOC) at randomization and timepoint (pre- and post-test) as fixed factors and
participant entered as a random factor. Due to feasibility in recruiting participants in the
allotted time, the study will not be fully powered to detect sex-based differences; however,
effect sizes associated with the intervention will be calculated and presented separately for
each sex.
SIGNIFICANCE: This study will demonstrate the not only is RT safe and feasible for those with
GBM, but that it also significantly improves functional status by protecting against
myopathy. This will help GBM patients maintain their independence which could lead to marked
improvements in QOL.