@misc{oai:repo.qst.go.jp:00065106,
 author = {Shinoto, Makoto and 篠藤 誠},
 month = {Aug},
 note = {Carbon Ion Therapy of Rectal and Pancreatic Cancer
Introduction: Pancreatic cancer is the fifth leading cause of cancer death and is considered to be one of the most lethal cancers in Japan. Chemotherapy and/or chemoradiotherapy are usually selected as standard treatment for unresectable pancreatic cancer. However, since pancreatic cancer is often resistant to chemotherapy and radiotherapy, the local control rate is very low. We initiated a phase I/II clinical trial of carbon-ion radiotherapy (C-ion RT) combined with gemcitabine in patients with locally advanced pancreatic cancer. Materials and Methods: The eligibility criteria for this study were as follows: locally advanced pancreatic cancer that involved the celiac trunk or superior mesenteric artery without distant metastasis. All patients had histologically or cytologically proven pancreatic adenocarcinoma. The radiation fractions were fixed at 12 fractions over three weeks, and the doses of gemcitabine and
radiation were gradually increased. First, the radiation dose was fixed at 43.2 GyE/8 fractions, and the gemcitabine dose was increased from 400 to 700 to 1,000 mg/m2. Subsequently, the gemcitabine dose was fixed at 1,000 mg/m2 and the radiation dose was increased from 43.2 GyE to 55.2 GyE in 5% increments. Gemcitabine was administered for three consecutive weeks, once a week. 
Results: Seventy-five patients were registered from April 2007 through February 2012. Of these patients, 71 were clinically eligible for the study. Four patients were ineligible and excluded from the analyses due to liver metastases that became obvious before the administration of C-ion RT (n=3) and the inadequacy of histological confirmation (n=1). The median age was 63 (range: 39-74) years. The performance status was 0 in 10 patients, 1 in 48 patients and 2 in one patient. The clinical stage according to the UICC was stage III in 53 cases and stage IV in 18 cases. The most common grade 3 acute toxicities were hematological toxicity (51%) and anorexia (8%). Dose limiting toxicity (DLT) developed as an early adverse event in three of the 71 patients: grade 3 cholangitis in one patient and grade 4 leukopenia in two patients, indicating a low incidence. With regard to late toxicities, one patient treated at the 50.4 GyE dose level developed a grade 3 gastric ulcer 10 months after undergoing CIRT; however, the patient recovered with conservative management. No other serious adverse events were observed. The combination therapies with full-dose gemcitabine (1,000 mg/m2) were not
associated with an increased incidence of adverse events with dose escalation. The median survival time was 21 months. Among all patients, the two-year local control rate and two-year overall survival rate were 74% and 39%, respectively. In the high-dose group (n=47), in which the patients were irradiated with at least 45.6 GyE, the two-year local control rate and two-year overall survival rate were 86% and 49%, respectively.
Conclusions: C-ion RT is well tolerable even when concomitantly administered with the highest dose of gemcitabine (1,000 mg/m2). Long-term survival or a radical cure can be expected following further dose escalation or the administration of maintenance chemotherapy., The Cancer Symposium: Advanced Radiation Oncology Treatment Strategies with Photon, Proton, and Carbon Ion Radiation},
 title = {Carbon Ion Therapy of Rectal and Pancreatic Cancer},
 year = {2013}
}