Carbon-ion radiotherapy (CIRT) has progressed rapidly in technological delivery, indications, and efficacy. Owing to a focused dose distribution in addition to high linear energy transfer and subsequently high relative biological effect, CIRT is uniquely able to target otherwise untreatable hypoxic and radioresistant disease, while opening the door for substantially hypofractionated treatment of normal and radiosensitive disease. CIRT has increasingly garnered international attention, and is nearing the tipping point for international adoption.

Charged particles can achieve better dose distribution and higher biological effectiveness compared to photon radiotherapy. Carbon ions are considered an optimal candidate for cancer treatment using particles. The National Institute of Radiological Sciences (NIRS) in Chiba, Japan was the first radiotherapy hospital dedicated for carbon ion treatments in the world. Since its establishment in 1994, the NIRS has pioneered this therapy with more than 69 clinical trials so far, and hundreds of ancillary projects in physics and radiobiology. In this review, we will discuss the evolution of carbon ion radiotherapy at the NIRS and some of the current and future projects in the field.

Lung cancer is frequently complicated by interstitial lung disease (ILD). Treatment protocols for lung cancer patients with ILD have not been established; surgery, chemotherapy, and radiotherapy can all cause acute exacerbation of ILD. This study evaluated the toxicity and efficacy of carbon ion radiotherapy (CIRT) in patients with non-small cell lung cancer (NSCLC) and ILD. Between June 2004 and November 2014, 29 patients diagnosed with NSCLC and ILD were treated with CIRT. No patient was eligible for curative surgery or conventional radiotherapy secondary to ILD. Owing to prior symptomology, radiation pneumonitis (RP) and symptom progression pre- and post-treatment were evaluated. The relationships between RP and clinical factors were investigated. Twenty-eight men and one woman, aged 62 to 90 years old, were followed for 2.7–77.1 months (median: 22.8 months). Single-grade symptomatic progression (grade 2–3) was observed in 4 patients, while 1 patient experiencedtwo-grade progression. Two patients experienced radiation-induced acute exacerbation. Local control at 3 years was 63.3% (72.2% for stage I disease); survival at 3 years was 46.3% (57.2% for stage I disease). Eighteen patients had died by the time of this writing, 10 of lung cancer progression. Radiation pneumonitis post-treatment progression correlated with dosimetric factors of the lungs (V5, V10) and a low pre-treatment serum surfactant protein-D. We found that CIRT may be useful as a low-risk, curative option for NSCLC patients with ILD, a population that is typically ineligible for conventional therapy. The DVH analysis showed that minimizing the low-dose region is important for reducing the risk of severe RP. NIRS-9404 . Registered 1 March 1994.

Objective:Pancreatic cancer is a difficult to treat disease with a persistently high mortality rate. We evaluated dose distribution simulation with respiratory-gated carbon-ion pencil beam scanning (C-PBS) with a simultaneous integrated boost (SIB) to increase tumour dose, sparing organs at risk (OARs).Methods:Using four-dimensional CT data of 12 patients, we delineated gross tumour volume and two clinical target volumes (CTVs). To consider beam range intrafractional uncertainty, we calculated field-specific target volumes, from which two planning target volumes (PTVs) were generated. PTV1 would receive a planned dose of 55.2 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] in 12 fractions, and PTV2 would receive an SIB dose up to 67.2 Gy (RBE). Dose assessments were conducted with regard to the targets and OARs.Results:CTV2 dose covering 95% of the volume (D95%) increased from 50.3 ± 5.1 Gy (RBE) to 62.5 ± 3.5 Gy (RBE) for a planned dose from 55.2 Gy (RBE) to 67.2 Gy (RBE). For 4 of 12...

Carbon-ion radiotherapy (C-ion RT) provides better dose distribution in cancer treatment compared to photons. Additionally, carbon-ion beams provide a higher biological effectiveness, and thus a higher tumor control probability. However, information regarding the dose constraints for organs at risk in C-ion RT is limited. This study aimed to determine the predictive factors for late morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus carcinomas. Between June 1995 and January 2010, 134 patients with uterus carcinomas were treated with C-ion RT with curative intent; prescription doses of 52.8–74.4 Gy (relative biological effectiveness) were delivered in 20–24 fractions. Of these patients, 132 who were followed up for > 6 months were analyzed. We separated the data in two subgroups, a 24 fractions group and a 20 fractions group. Late morbidities, proctitis, and cystitis were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The correlations of clinical and dosimetric parameters, V10–V60, D5cc, D2cc, and Dmax, with the incidence of ≥grade 1 morbidities were retrospectively analyzed. In the 24 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 32 and 19%, respectively. Regarding the dose–volume histogram data on the rectum, the D5cc and D2cc were significantly higher in patients with ≥grade 1 proctitis than in those without morbidity. In addition, the D5cc for the bladder was significantly higher in patients with ≥grade 1 cystitis than in those without morbidity. Results of univariate analyses showed that D2cc of the rectum was correlated with the development of ≥grade 1 late proctitis. Moreover, D5cc of the bladder was correlated with the development of ≥grade 1 late cystitis. The present study identified the dose–volume relationships in C-ion RT regarding the occurrence of late morbidities in the rectum and bladder. Assessment of the factors discussed herein would be beneficial in preventing late morbidities after C-ion RT for pelvic malignancies. Retrospectively registered ( NIRS: 16–040 ).

Surgical resection is considered a standard therapy for malignant melanoma (MM). However, it has not yet been established as an optimal treatment strategy for gynecological MMs, particularly owing to their very low incidence rates. We retrospectively analyzed clinical outcomes of carbon-ion radiotherapy (C-ion RT) for gynecological MMs. The eligibility criterion was the presence of histologically confirmed gynecological MM. Patients with pelvic or inguinal lymph node metastases were included, while those with distant metastases were excluded. The pelvic and inguinal lymph node regions were irradiated with up to 36 gray relative biological effectiveness (Gy (RBE)) followed by a gross tumor volume boost of up to 57.6 Gy (RBE) or 64 Gy (RBE) in 16 fractions over 4 weeks. Thirty-seven patients (median age: 71 years) were examined. In total, 22 patients had vaginal tumors, 12 had vulval tumors, and 3 had cervical uterine tumors. The median follow-up periods were 23 months (range: 5–103 months) for all patients and 53 months (range: 16–103 months) for survivors. Thirty of 37 patients (81%) achieved complete tumor disappearance. The 2-year local control, overall survival, and progression-free survival rates were 71%, 53%, and 29%, respectively. C-ion RT may be a definitive treatment option for patients with gynecological MM.