Herman Joseph M, Chang Daniel T, Goodman Karyn A, Dholakia Avani S, Raman Siva P, Hacker-Prietz Amy, Iacobuzio-Donahue Christine A, Griffith Mary E, Pawlik Timothy M, Pai Jonathan S, O'Reilly Eileen, Fisher George A, Wild Aaron T, Rosati Lauren M, Zheng Lei, Wolfgang Christopher L, Laheru Daniel A, Columbo Laurie A, Sugar Elizabeth A, Koong Albert C
Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer. 2015 Apr 1;121(7):1128-37. doi: 10.1002/cncr.29161. Epub 2014 Dec 23.
This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC).
A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m(2)) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT.
The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade ≥ 2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P<.001]). The median overall survival was 13.9 months (95% confidence interval, 10.2 months-16.7 months). Freedom from local disease progression at 1 year was 78%. Four patients (8%) underwent margin-negative and lymph node-negative surgical resections.
Fractionated SBRT with GEM results in minimal acute and late gastrointestinal toxicity. Future studies should incorporate SBRT with more aggressive multiagent chemotherapy.
本2期多机构研究旨在确定，与先前一项针对局部晚期胰腺癌（LAPC）患者开展的吉西他滨（GEM）联合单次立体定向体部放疗（SBRT）的试验相比，GEM联合分割立体定向体部放疗是否会导致可接受的2至4级晚期胃肠道毒性。
共有49例LAPC患者接受了最多3剂GEM（1000 mg/m²），随后休息1周，然后接受SBRT（5次分割，共33.0格雷[Gy]）。SBRT后，患者继续接受GEM治疗，直至疾病进展或出现毒性反应。使用美国国立癌症研究所不良事件通用术语标准[第4.0版]和放射肿瘤学组放射发病率评分标准评估毒性。患者在SBRT前、SBRT后4周和4个月完成欧洲癌症研究与治疗组织生活质量问卷（QLQ-C30）和胰腺癌特异性QLQ-PAN26模块。
中位随访时间为13.9个月（范围3.9 - 45.2个月）。患者的中位年龄为67岁，84%的患者肿瘤位于胰头。急性和晚期（主要终点）≥2级胃炎、瘘管、肠炎或溃疡毒性反应的发生率分别为2%和11%。QLQ-C30总体生活质量评分从基线到SBRT后保持稳定（基线时为67分，两次随访的中位变化均为0分；两次比较P均>.05）。患者在SBRT后4周的QLQ-PAN26问卷中报告胰腺疼痛有显著改善（P = .001）。SBRT后血浆糖类抗原19-9（CA 19-9）水平中位数降低（SBRT后的中位时间为4.2周；220 U/mL对62 U/mL [P<.001]）。中位总生存期为13.9个月（95%置信区间，10.2个月至- 16.7个月）。1年时无局部疾病进展的比例为78%。4例患者（8%）接受了切缘阴性和淋巴结阴性的手术切除。
GEM联合分割SBRT导致的急性和晚期胃肠道毒性最小。未来的研究应将SBRT与更积极的多药化疗相结合。
