Advantages and Limitations in the Use of Combination Therapies with Charged Particle Radiation Therapy

Studies are currently underway to help provide basic and clinical evidence for combination particle beam radiation therapy, on which there are few published reports. The purpose of this article is to summarize the current status in the use of particle beams combined with other modalities.

Following from experiences in x-ray radiation therapy, combination therapy with proton beams (PBT) has been attempted, and several clinical studies have reported improved survival rates for patients with non-small cell lung cancer, pancreatic cancers, esophageal cancers, and glioblastomas. Recently, basic studies combining PBT with PARP inhibitors and histone deacetylase inhibitors have also reported promising results. In the area of carbon ion therapy (CIT), there are few clinical reports on combination therapy; however, the number of basic research reports exceeds that for PBT. So far, the combined use of cytotoxic drugs with CIT yields independent additive effects. In addition, it is notable that combination therapy with CIT is effective against radioresistant cancer stem-like cells. Recent evidence also suggests that local radiation therapy can induce an effective antitumor immune response. There has been an increased use of combination immune-modulating agents and cytokines with particle beams, especially CIT. The field of radiation therapy is evolving from a strong reliance on local-regional treatment to a growing reliance on systemic immunotherapy.

The combined use of anticancer agents with particle radiation therapy has a considerable potential effect. Future research in molecular targeting therapy and immunotherapy may help identify the most efficacious approach for combination therapy with protons and carbon ions.