可切除及临界可切除胰腺癌的术前放化疗与直接手术对比：荷兰随机III期PREOPANC试验结果
Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial.
作者信息
Versteijne Eva, Suker Mustafa, Groothuis Karin, Akkermans-Vogelaar Janine M, Besselink Marc G, Bonsing Bert A, Buijsen Jeroen, Busch Olivier R, Creemers Geert-Jan M, van Dam Ronald M, Eskens Ferry A L M, Festen Sebastiaan, de Groot Jan Willem B, Groot Koerkamp Bas, de Hingh Ignace H, Homs Marjolein Y V, van Hooft Jeanin E, Kerver Emile D, Luelmo Saskia A C, Neelis Karen J, Nuyttens Joost, Paardekooper Gabriel M R M, Patijn Gijs A, van der Sangen Maurice J C, de Vos-Geelen Judith, Wilmink Johanna W, Zwinderman Aeilko H, Punt Cornelis J, van Eijck Casper H, van Tienhoven Geertjan
机构信息
Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
出版信息
J Clin Oncol. 2020 Jun 1;38(16):1763-1773. doi: 10.1200/JCO.19.02274. Epub 2020 Feb 27.
PURPOSE
Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.
PATIENTS AND METHODS
In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat.
RESULTS
Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; = .096). The resection rate was 61% and 72% ( = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery ( < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 19.8 months; 029). The proportion of patients who suffered serious adverse events was 52% versus 41% (096).
CONCLUSION
Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.
目的
术前放化疗可能提高可切除或临界可切除胰腺癌的根治性切除率，但总体获益尚未得到证实。
患者与方法
在这项由16个中心参与的随机III期试验中，将可切除或临界可切除胰腺癌患者随机分配，分别接受术前放化疗（包括3个疗程的吉西他滨，第2个疗程联合15×2.4 Gy放疗，随后进行手术及4个疗程的辅助吉西他滨治疗）或直接手术及6个疗程的辅助吉西他滨治疗。主要终点为意向性治疗的总生存期。
结果
2013年4月至2017年7月期间，246例符合条件的患者被随机分组；119例被分配接受术前放化疗，127例接受直接手术。意向性治疗的中位总生存期，术前放化疗组为16.0个月，直接手术组为14.3个月（风险比，0.78；95%CI，0.58至1.05；P = 0.096）。切除率分别为61%和72%（P = 0.058）。接受术前放化疗的患者R0切除率为71%（72例中的51例），分配接受直接手术的患者为40%（92例中的37例）（P < 0.001）。术前放化疗与显著更好的无病生存期和无局部区域复发生存期相关，同时病理淋巴结、神经周围侵犯和静脉侵犯的发生率显著更低。对接受肿瘤切除并开始辅助化疗的患者进行生存分析显示，术前放化疗可改善生存（35.2对19.8个月；P = 0.029）。发生严重不良事件的患者比例分别为52%和41%（P = 0.096）。
结论
可切除或临界可切除胰腺癌的术前放化疗未显示出显著的总生存期获益。尽管次要终点和预定义亚组分析的结果提示新辅助治疗方法具有优势，但仍需要更多证据。
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