Enhancing cardiorespiratory fitness and quality of life in high-grade glioma through an intensive exercise intervention during chemotherapy: Proof of concept

Abstract

Background: High-grade glioma (HGG) patients experience enormous disease burden both from tumor- and treatment-related symptoms. Exercise can improve physical fitness and quality of life (QoL); yet experience in neuro-oncology, especially with high-intensity exercise, remains limited. This study evaluated feasibility, safety, and efficacy of the intensive, structured 16-week strength and endurance program, "Active in Neuro-Oncology" (ActiNO) for HGG patients undergoing chemotherapy.

Methods: In this prospective, oligocentric, single-arm proof-of-concept trial, 54 HGG patients participated in ActiNO, with twice-weekly supervised exercise sessions. The primary endpoint was cardiorespiratory fitness, assessed via physical working capacity (PWC75%)-the workload (W/kg body weight) achieved at 75% of age-adjusted maximum heart rate during a maximal cardiopulmonary exercise test. Secondary endpoints included peak oxygen uptake (VO2peak), peak power output (Ppeak), and QoL (EORTC QLQ-C30). Analyses focused on within-subject changes from pre- to post-intervention. Additionally, comparisons to normative data were performed. Feasibility was assessed via accrual, adherence, and attrition; safety via adverse event monitoring (CTCAE).

Results: Program tolerance was high, with few exercise-related adverse events (all CTCAE grade 1-2). Over 16 weeks, significant improvements were observed in PWC75% (1.023-1.256 W/kg BW, +23%), VO2peak (23.04-26.09 ml/min/kg BW, +13%), and Ppeak (1.771-2.104 W/kg BW, +19%). QoL, including global health and physical functioning, improved, reaching normative values. Adherence was high (85%), though attrition was 48%, mainly due to disease progression or physical constraints.

Conclusions: High-intensity exercise is feasible and safe in HGG patients undergoing chemotherapy. The observed improvements in physical fitness and QoL support incorporating structured exercise into neuro-oncology care.

Keywords: Active in Neuro-Oncology (ActiNO); cardiopulmonary exercise testing; glioblastoma; physical activity; supportive therapy.