Role of Hyperbaric Oxygenation Plus Hypofractionated Stereotactic Radiotherapy in Recurrent High-Grade Glioma

Abstract

BackgroundThe presence of hypoxic cells in high-grade glioma (HGG) is one of major reasons for failure of local tumour control with radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of oxygen deficiency in poorly oxygenated regions of the tumour. We propose an innovative approach to improve the efficacy of hypofractionated stereotactic radiotherapy (HSRT) after HBO (HBO-RT) for the treatment of recurrent HGG (rHGG) and herein report the results of an ad interim analysis.MethodsWe enrolled a preliminary cohort of 9 adult patients (aged >18 years) with a diagnosis of rHGG. HSRT was administered in daily 5-Gy fractions for 3-5 consecutive days a week. Each fraction was delivered up to maximum of 60 minutes after HBO.ResultsMedian follow-up from re-irradiation was 11.6 months (range: 3.2-11.6 months). The disease control rate (DCR) 3 months after HBO-RT was 55.5% (5 patients). Median progression-free survival (mPFS) for all patients was 5.2 months (95%CI: 1.34-NE), while 3-month and 6-month PFS was 55.5% (95%CI: 20.4-80.4) and 27.7% (95%CI: 4.4-59.1), respectively. Median overall survival (mOS) of HBO-RT was 10.7 months (95% CI: 7.7-NE). No acute or late neurologic toxicity >grade (G)2 was observed in 88.88% of patients. One patient developed G3 radionecrosis.ConclusionsHSRT delivered after HBO appears to be effective for the treatment of rHGG, it could represent an alternative, with low toxicity, to systemic therapies for patients who cannot or refuse to undergo such treatments.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT 03411408.

Hyperbaric Oxygen Therapy as a Complementary Treatment in Glioblastoma—A Scoping Review

“…This review followed the PRISMA criteria (15). Inclusion criteria consisted of (1) review articles of HBOT; (2) articles and expert meetings of clinical practice recommendations for GBM management; (3) articles regarding the physiological effects of oxygen on GBM; (4) case series of patients with GBM treated with HBOT; (5) case reports of patients with GBM treated with HBOT; (6) articles detailing preclinical data on the effects of oxygen on tumor cells; (7) articles/abstracts with available translations in Portuguese, English, Spanish, or French. The exclusion criteria comprised the following: (1) articles not mentioning GBM and/or HBOT at any point; (2) articles that only comprised normobaric oxygen use.…”

“…Despite being a highly vascularized tumor, GBM is characterized by extensive necrotic areas with surrounding hypoxia (6). Hypoxia has been associated with an increase in glioma stem-like cell properties, glioma growth, changes in cancer cell metabolism, and treatment resistance.…”

“…Arpa et al (6) published their experience with HBOT and RT in a pilot study for recurrent high-grade glioma patients. In their small series of nine patients, RT was administered in daily 5-Gy fractions for 3-5 consecutive days.…”

“…Currently, the standard of care consists of a multimodality treatment approach, including surgical resection, radiotherapy (RT), systemic therapy (chemotherapy-CT, targeted therapy), and supportive care. However, the overall prognosis remains unsatisfactory, long-term survival is rare, and the associated morbidity related to declining neurologic function and quality of life has a devastating impact on patients and their supportive social context (5,6).…”

A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities

“…Hypofractionated stereotactic radiotherapy (HSRT) after HBO (HBO-RT) appears to be effective for the treatment of recurrent high-grade glioma (rHGG), as pointed out on a cohort of 9 adult rHGG patients. It could represent an alternative, with low toxicity, to systemic therapies for patients who cannot or refuse to undergo such treatments [ 173 ]. However, although non-tumour cells are less sensitive, radiation could also affect them, altering multiple cellular signaling pathways or inducing apoptosis, hence explaining its multiple adverse effects [ 174 ] One of the most severe consequences resulted from irradiation is the appearance of post-radiation injuries, a process starting during radiotherapy that involves the dysregulation of multiple bioactive compounds, particularly fibrogenic cytokines like TGF-β [ 175 ].…”