In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion beam therapy (CIBT), and boron neutron capture therapy (BNCT). PBT and CIBT have been reported to have excellent therapeutic results owing to the physical characteristics of their Bragg peaks. Variable drug therapies, such as chemotherapy, hormone therapy, and immunotherapy, are combined in various treatment strategies, and treatment effects have been improved. BNCT has a high dose concentration for cancer in terms of nuclear reactions with boron. BNCT is a next-generation RT that can achieve cancer cell-selective therapeutic effects, and its effectiveness strongly depends on the selective ¹⁰B accumulation in cancer cells by concomitant boron preparation. Therefore, drug delivery research, including nanoparticles, is highly desirable. In this review, we introduce both clinical and basic aspects of particle beam therapy from the perspective of multidisciplinary treatment, which is expected to expand further in the future.

Long‐term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long‐term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0–2, Child–Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0–77.0 GyE was administered in 10–35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression‐free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5‐year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5‐year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1–2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long‐term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).

Cancer is a major cause of childhood death, with central nervous system (CNS) neoplasms being the second most common pediatric malignancy, following hematological cancer. Treatment of pediatric CNS malignancies requires multimodal treatment using a combination of surgery, chemotherapy, and radiotherapy, and advances in these treatments have given favorable results and longer survival. However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems. Proton beam therapy (PBT) is a particle radiotherapy with excellent dose localization that permits treatment of liver and lung cancer by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Thus, PBT has the potential advantages for pediatric cancer. In this context, we review the current knowledge on PBT for treatment of pediatric CNS malignancies.

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long‐term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow‐up period was 8.1 years (5.0–31.2 years). The 5‐, 10‐ and 20‐year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10‐ and 20‐year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow‐up is needed to confirm the benefits of PBT for pediatric tumors.

The number of patients treated by proton beam therapy in Japan since 2000 has increased; in 2016, 11 proton facilities were available to treat patients. Notably, proton beam therapy is very useful for pediatric cancer; since the pediatric radiation dose to normal tissues should be reduced as much as possible because of the effect of radiation on growth, intellectual development, endocrine organ function and secondary cancer development. Hepatocellular carcinoma is common in Asia, and most of the studies of proton beam therapy for liver cancer have been reported by Japanese investigators. Proton beam therapy is also a standard treatment for nasal and paranasal lesions and lesions at the base of the skull, because the radiation dose to critical organs such as the eyes, optic nerves and central nervous system can be reduced with proton beam therapy. For prostate cancer, comparative studies that address adverse effects, safety, patient quality of life and socioeconomic issues should be performed to determine the appropriate use of proton beam therapy for prostate cancer. Regarding new proton beam therapy applications, experience with proton beam therapy combined with chemotherapy is limited, although favorable outcomes have been recently reported for locally advanced lung cancer, esophageal cancer and pancreatic cancer. Therefore, ‘chemoproton’ therapy appears to be a very attractive field for further clinical investigations. In conclusion, there are cost issues and considerations regarding national insurance for the use of proton beam therapy in Japan. Further studies and discussions are needed to address the use of proton beam therapy for several types of cancers, and for maintaining the quality of life of patients while retaining a high cure rate.

The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC.