Charged particle therapy for high-grade gliomas in adults: a systematic review

High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1-2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity-modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.