Makoto Shinoto1, Shigeru Yamada2, Kotaro Terashima3, Shigeo Yasuda2, Yoshiyuki Shioyama4, Hiroshi Honda3, Tadashi Kamada2, Hirohiko Tsujii2, Hiromitsu Saisho5. 1. Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: shinoto@saga-himat.jp. 2. Hospital of Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. 3. Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan. 5. Department of Internal Medicine and Clinical Oncology, Kaken Hospital, Chemotherapy Research Institute, Chiba, Japan.
Abstract
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.
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.
Authors: Arnold Pompos; Robert L Foote; Albert C Koong; Quynh Thu Le; Radhe Mohan; Harald Paganetti; Hak Choy Journal: Front Oncol Date: 2022-06-14 Impact factor: 5.738
Authors: Jeremy M Brownstein; Amy J Wisdom; Katherine D Castle; Yvonne M Mowery; Peter Guida; Chang-Lung Lee; Francesco Tommasino; Chiara La Tessa; Emanuele Scifoni; Junheng Gao; Lixia Luo; Lorraine Da Silva Campos; Yan Ma; Nerissa Williams; Sin-Ho Jung; Marco Durante; David G Kirsch Journal: Mol Cancer Ther Date: 2018-02-07 Impact factor: 6.009