Harada Hideyuki, Fuji Hiroshi, Ono Akira, Kenmotsu Hirotsugu, Naito Tateaki, Yamashita Haruo, Asakura Hirofumi, Nishimura Tetsuo, Takahashi Toshiaki, Murayama Shigeyuki
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Cancer Sci. 2016 Jul;107(7):1018-21. doi: 10.1111/cas.12955. Epub 2016 Jun 20.
The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585).
本研究的目的是确定不可切除的Ⅲ期非小细胞肺癌（NSCLC）质子束治疗（PBT）的推荐剂量（RD）。我们测试了两种PBT处方剂量：分别在第1组和第2组中，33次分割给予66 Gy（相对生物效应[RBE]）和37次分割给予74 Gy（RBE）。计划靶体积（PTV）包括原发肿瘤和具有足够边界的转移淋巴结。同步化疗包括静脉注射顺铂（60 mg/m²，第1天）和口服S-1（根据体表面积为80、100或120 mg，第1 - 14天），每4周重复4个周期。剂量限制毒性（DLT）定义为第1 - 90天期间与PBT相关的3级或严重毒性。每个剂量水平在3名患者中进行，如果未发生DLT，则升级到下一个水平。当1名患者出现DLT时，再纳入3名患者。总体而言，共纳入9名患者（5名男性，4名女性；中位年龄72岁），其中第1组6名，第2组3名。中位随访时间为43个月，中位无进展生存期为15个月。在第1组中，6名患者中有1名发生3级感染，但未报告其他DLT。同样，第2组未发生DLT。然而，第2组有1名患者在PBT开始后9个月出现3级食管瘘。因此，从临床角度我们确定66 Gy（RBE）为RD。（临床试验注册号：UMIN000005585）
