Hyperbaric Oxygen Therapy plus Hypofractionated Stereotactic Radiotherapy in Recurrent Glioblastoma

Abstract

Hypoxia is thought to play a role in tumor development, angiogenesis and growth, and resistance to chemotherapy, antiangiogenic therapy and radiotherapy (RT) in a large number of human cancers. Brain tumors, especially highly aggressive GBM with its necrotic tissue, are more likely to be affected by hypoxia. The median partial pressure of oxygen (PO2) of high-grade gliomas in patients under anesthesia was approximately 5-7 mmHg, with a significant proportion of PO2 values <2.5 mmHg. The radiosensitivity of brain tumors could potentially be increased by performing hyperbaric oxygenation (HBO) before the RT session. We propose an innovative approach to improve the efficacy of accelerated hypofractionated Stereotactic Radiotherapy (HSRT) after HBO (HBO-RT) for the treatment of recurrent HGG (rHGG). The primary objective of this study is to evaluate the disease control rate (DCR) at 3 months. The secondary Objectives are: - Safety assessment (acute and late toxicity). - Overall Survival (OS), - Progression Free Survival (PFS). We enrolled 14 patients (aged >18 years) with rHGG detected using MRI. A total dose of 15-25 Gy was administered in daily 5-Gy fractions for 3-5 consecutive days after daily HBO. Median follow-up from re-irradiation was 22.8 months (range: 2.0-24.2 months). The disease control rate 3-months after HBO-RT was 50% (23.0-76.9). Six- and 12-month Progression-free survival was 35.7% (95% CI: 13-59.4) and 10.7% (95% CI: 0.8-35.4), respectively. Median overall survival of HBO-RT was 10.7 months (95% CI: 6.6-24.2). No acute or late neurologic toxicity >grade (G)2 was observed. HSRT combined to HBO seems effective and safe in the treatment of rHGG.