Makoto Shinoto

Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer

The authors evaluated the tolerance and efficacy of carbon‐ion radiotherapy (CIRT) as a short‐course, preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue.

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer.

PURPOSE To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. METHODS AND MATERIALS Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m(2) under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. RESULTS Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m(2). The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m(2)) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. CONCLUSIONS Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

Postoperative radiotherapy in patients with salivary duct carcinoma: clinical outcomes and prognostic factors

This study sought to investigate the clinical outcome and the role of postoperative radiotherapy for patients with salivary duct carcinoma (SDC) who had undergone surgery and postoperative radiotherapy. We performed a retrospective analysis of 25 SDC patients treated between 1998 and 2011 with surgery and postoperative radiotherapy. The median prescribed dose was 60 Gy (range, 49.5–61.4 Gy). The clinical target volume (CTV) was defined as the tumor bed in four patients, the tumor bed and ipsilateral neck in 14 patients, and the tumor bed and bilateral neck in six patients. Local control (LC), disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The 5-year LC, DFS and OS were 67%, 45% and 47%, respectively. Disease recurrence was found in 12 patients: seven as local, four as regional and eight as distant failure. Perineural and lymphovascular invasion was a significant prognostic factor for LC (P = 0.03). Local failure was common, and the presence of local recurrence significantly affected the OS (P < 0.05). We conclude that surgery and postoperative radiotherapy is expected to decrease the risk of local failure and contribute to good prognoses for patients with SDC. It might be advisable to have the CTV include the cranial nerves involved and the corresponding parts of the skull base in cases of pathologically positive perineural invasion.

Comparison of carbon-ion passive and scanning irradiation for pancreatic cancer

PURPOSE To compare carbon-ion beam dose distribution between passive and scanning radiation therapies for locally advanced pancreatic cancer. MATERIALS AND METHODS Thirteen pancreatic cancer patients were included in this study. Four types of treatment planning with respiratory gating were calculated for each patient: a four-field box with passive irradiation (Plan 1), scanning irradiation (Plan 2), a three-field (150°, 180° and 210°) protocol with passive irradiation (Plan 3), and scanning irradiation (Plan 4). The irradiation plans each delivered 55.2Gy (RBE) to the planning target volume (PTV) and were compared with respect to doses to the PTV and organs at risk (OARs). RESULTS Plan 3 exceeded the dose assessment metrics to the spinal cord. Scanning irradiation plans (Plan 2 and, particularly, Plan 4) offered significantly reduced dosage to the stomach and the duodenum compared with passive irradiation. CONCLUSION Three-field oblique scanning irradiation for pancreatic cancer has the potential to reduce gastrointestinal exposure and influence of peristalsis on dose distribution.

Prediction of outcome with FDG-PET in definitive chemoradiotherapy for esophageal cancer

The purpose of this study was to assess the efficacy of 18F-fluoro-2-deoxy-glucose uptake positron emission tomography (FDG-PET) for the prediction of outcome in definitive chemoradiotherapy (CRT) for esophageal cancer. We enrolled 56 patients with esophageal cancer treated with definitive CRT and examined by FDG-PET before treatment. We examined the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of the primary tumor with overall survival (OS), progression-free survival (PFS), local control (LC) and response of the primary tumor. After definitive CRT, 30 patients had a clinical complete response (CR), making the CR rate 54%. For all 56 patients, the 2-year OS rate, PFS rate and LC rates were 64%, 38% and 51%, respectively. We divided the patients into two groups according to SUVmax: SUVmax < 10 (low-SUV) and ≥10 (high-SUV). The 2-year OS rates in the low- and high-SUV groups were 100% and 41%, the PFS rates were 73% and 19%, the LC rates were 71% and 39%, and the CR rates were 100% and 32%, respectively. A univariate analysis revealed significant differences between the low- and high-SUV group in OS, PFS, LC and response (P = 0.0005, 0.0002, 0.048, and <0.0001, respectively). SUVmax and T stage were significantly associated with OS, PFS, LC and response. A multivariate analysis showed significant differences between the SUVmax <10 and ≥10 groups in overall survival and response (P < 0.05). Our result suggests that the SUVmax in FDG-PET of the primary tumor before treatment may have prognostic value for esophageal cancer.

Clinical results of definitive chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma and esophageal cancer.

Objectives:To assess the efficacy and toxicity of radical chemoradiotherapy for patients with synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal cancer (EC). Methods:Thirty-four patients with synchronous HNSCC and EC were treated mainly with radical chemoradiotherapy at the same time. Median external radiation dose for HNSCC and EC was 70 Gy (range, 60–70.5 Gy), except for 2 patients with tongue cancer, who underwent brachytherapy and 60 Gy (range, 45–70 Gy), respectively. Thirty-one patients were treated with concurrent chemoradiotherapy with cisplatin and/or 5-fluorouracil or TS-1 (oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2, 4-dihydoroxypyridine, and potassium oxonate). Results:Thirty-three patients completed the intended treatment. The response rate was 94%, with 26 complete responses (76%) and 6 partial responses (18%). At a median follow-up of 17.3 months, 2-year rates of overall survival, cause-specific survival, and disease-free survival were 44%, 52%, and 33%, respectively. Initial failure patterns were local failure in 14 patients (63%), regional progression in 3 patients (13%), and distant metastasis in 6 patients (27%). The most common acute toxicity was myelosuppression, with 8 patients experiencing grade 3–4 toxicity. Three patients experienced grade 3 mucositis and pharyngitis. No patients experienced late morbidity of grade 3 or higher. Conclusions:Definitive chemoradiotherapy for patients with synchronous HNSCC and EC is feasible with a low mortality rate and acceptable morbidity.

Dosimetric analysis of upper gastrointestinal ulcer after carbon-ion radiotherapy for pancreatic cancer.

PURPOSE The aim of this study was to clarify the incidence, clinical risk factors, and dose-volume relationship of upper gastrointestinal (GI) ulcer after carbon-ion radiotherapy (C-ion RT) for pancreatic cancer. MATERIALS AND METHODS Fifty-eight pancreatic cancer patients were treated with C-ion RT from April 2014 to December 2015. The total dose was 55.2Gy (RBE) in 12 fractions. D2cm3 of GI tracts were restricted under 46Gy (RBE); RBE-weighted absorbed dose. The association between dosimetric parameters (V10-50, Dmax, D1cm3, D2cm3) and GI ulcer was examined using Spearmans correlation. The incidence of GI ulcer was compared between the two groups divided by the cutoff value. RESULTS Twelve patients (21%) experienced gastric ulcer including only one (2%) grade 3 ulcer. There was no grade 4/5 toxicity or duodenal ulcer. V10-30 was significantly associated with gastric ulcer. The 1-year estimated risk of gastric ulcer for the determined cutoff values were 51% vs. 10% (V10, ⩾102cm(3) or less), 42% vs. 9% (V20, ⩾24cm(3) or less), 34% vs. 4% (V30, ⩾6cm(3) or less). CONCLUSIONS The incidence of GI ulcer after C-ion RT was very low with the dose constraint of D2cm3 <46Gy (RBE). To further minimize the risk of GI ulcer, V10-30 should also be reduced.

Percutaneous osteoplasty for hypervascular bone metastasis

We report three cases of percutaneous osteoplasty for the treatment of hypervascular bone metastasis. Four hypervascular bone metastases were treated in three consecutive patients by percutaneous osteoplasty under fluoroscopic or computed tomographic guidance. Primary malignant tumors included pheochromocytoma and renal cell carcinoma. Pain relief after osteoplasty was achieved in all three patients. There was no major complication. Projectile bleeding and subcutaneous hematoma were noted during or after osteoplasty but were easily controlled conservatively. Percutaneous osteoplasty for hypervascular bone metastases is not only a highly effective but also a minimally invasive technique that provides immediate pain relief without major complication.

Postoperative Recurrence of Rectal Cancer

To improve long-term local control and survival of locally recurrent rectal cancer, we have initiated a radiation dose-escalation trial using carbon ion beams. The purpose of this study is to evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with locally recurrent rectal cancer.

Particle Radiation Therapy for Gastrointestinal Cancers

Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer.