Dear Colleagues,

Although it is well known that dose escalation is one of methods to successfully control many cancers by radiation therapy (RT), dose–volume effects on late toxicities in at-risk organs have been also observed. Protons offer advantageous physical properties for RT, as they can create favorable dose distributions to the target volume using fewer portals compared with photon-based RT. Thus, dose escalation using protons is a reasonable approach to improve cancer control and reduce short- and long-term complications, including the risk of secondary cancers. However, due to limited clinical evidence, proton therapy has long been regarded as a costly RT from an economic point of view. Particle Therapy Co-Operative Group (PTCOG) was founded in 1985 to promote the science, technology, and practical application of particle therapy and, step by step, clinical advantages of proton therapy have been shown through prospective studies.

Recent advances in molecular biology and immunology have allowed us to understand the mechanisms of induction of systemic antitumor effects via radiation-induced cell death, and the combination of immune checkpoint inhibitors with irradiation is of primary focus in radiation oncology. In actuality, there is an abundance of prospective studies of combination therapy. On the other hand, some investigators have revealed that radiation-associated lymphopenia during therapy is associated with poor prognosis, and proton therapy is expected to be a lymphocyte-sparing RT, especially in chemoradiation for esophageal cancer and stage III non-small cell lung cancer.

Based on the accumulation of evidence that demonstrates the efficacy of proton therapy in various cancer treatments, the number of proton therapy facilities has been increasing worldwide. This is in spite of the fact that there still exists the important question regarding whether it provides an overall advantage compared to photon-based RT, which is still under discussion. We are currently facing an important point at which proton therapy can be compared directly with not only other RTs, but also surgery or pharmacotherapy, from several points of view, such as survival, adverse events, QOL, and cost. The Special Issue will highlight the perspective of proton therapy in cancer treatment, covering biology, physics, and economic studies as well as clinical trials.

Prof. Dr. Hitoshi Ishikawa
Guest Editor

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• Proton therapy
• Dose escalation
• Toxicity
• Quality of life
• Radiation-induced immune reaction
• Image-guided radiation therapy
• Multimodal treatment