Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.
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).
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Hideyuki
H
Harada
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Hiroshi
H
Fuji
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Akira
A
Ono
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Hirotsugu
H
Kenmotsu
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Tateaki
T
Naito
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Haruo
H
Yamashita
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Hirofumi
H
Asakura
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Tetsuo
T
Nishimura
Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Toshiaki
T
Takahashi
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
Shigeyuki
S
Murayama
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods*; D011879:Radiotherapy Dosage
Dose escalation; esophagus; late toxicity; non-small cell lung cancer; proton beam therapy