Wismans Leonoor V, Hendriks Tessa E, Suurmeijer J Annelie, Nuyttens Joost J, Bruynzeel Anna M, Intven Martijn P, van Driel Lydi M, Haen Roel, de Wilde Roeland F, Groot Koerkamp Bas, Busch Olivier R, Stoker Jaap, Verheij Joanne, Farina Arantza, de Boer Onno J, Doukas Michail, de Hingh Ignace H, Lips Daan J, van der Harst Erwin, van Tienhoven Geertjan, van Eijck Casper H, Besselink Marc G
Erasmus Medical Center Cancer Institute, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Br J Surg. 2025 Feb 1;112(2). doi: 10.1093/bjs/znae327.
Postoperative pancreatic fistula is the main driver of morbidity and mortality after pancreatoduodenectomy. In high-risk patients, the rate of postoperative pancreatic fistula approaches 50%, whereas it is below 5% in patients with pancreatic cancer who receive neoadjuvant chemoradiotherapy. The aim of this study was to evaluate the safety, feasibility, and efficacy of preoperative stereotactic body radiotherapy on the pancreatic neck transection margin in high-risk patients undergoing pancreatoduodenectomy to prevent postoperative pancreatic fistula.
In this prospective multicentre open-label single-arm trial (progressing from a safety run-in phase to a phase II design), patients undergoing pancreatoduodenectomy for neoplasms other than pancreatic ductal adenocarcinoma received a single preoperative stereotactic body radiotherapy dose of 12 Gy. Primary endpoints included safety (less than or equal to 15% grade 3-5 toxicity), feasibility (a significant change in pancreatic texture measured using a durometer), and efficacy (a 15% reduction in the grade B/C postoperative pancreatic fistula rate compared with patients from the Dutch Pancreatic Cancer Audit who were eligible but not included in this study). Secondary endpoints assessed tissue fibrosis (collagen density).
Overall, 38 patients were included, of whom 33 (87%) completed the study protocol and were included in the per-protocol analysis. The safety cut-off was met, with 3% grade 3-5 toxicity. Pancreatic tissue treated with stereotactic body radiotherapy showed increased firmness using a durometer (median of 47 (interquartile range 36-57) versus 37 (interquartile range 30-41) Shore OO units; P < 0.001) and a higher collagen density (median of 6.1% (interquartile range 4.4%-9.5%) versus 4.6% (interquartile range 2.5%-7.4%); P = 0.003). The grade B/C postoperative pancreatic fistula rate with stereotactic body radiotherapy was 57.6% (95% c.i. 41% to 74%), compared with 34% (95% c.i. 27% to 42%) in audit controls (P = 0.011).
Preoperative stereotactic body radiotherapy is safe in high-risk patients undergoing pancreatoduodenectomy and increases parenchymal firmness and fibrosis, but fails to show evidence of efficacy.
术后胰瘘是胰十二指肠切除术后发病和死亡的主要原因。在高危患者中，术后胰瘘发生率接近50%，而接受新辅助放化疗的胰腺癌患者术后胰瘘发生率低于5%。本研究旨在评估术前立体定向体部放疗对接受胰十二指肠切除术的高危患者胰腺颈部切断边缘的安全性、可行性和有效性，以预防术后胰瘘。
在这项前瞻性多中心开放标签单臂试验（从安全性导入阶段进展到II期设计）中，因非胰腺导管腺癌肿瘤接受胰十二指肠切除术的患者术前接受单次12 Gy的立体定向体部放疗剂量。主要终点包括安全性（3 - 5级毒性小于或等于15%）、可行性（使用硬度计测量胰腺质地有显著变化）和有效性（与荷兰胰腺癌审计中符合条件但未纳入本研究的患者相比，术后B/C级胰瘘发生率降低15%）。次要终点评估组织纤维化（胶原密度）。
总共纳入38例患者，其中33例（87%）完成研究方案并纳入符合方案分析。达到了安全性截止标准，3 - 5级毒性为3%。接受立体定向体部放疗的胰腺组织使用硬度计测量显示硬度增加（肖氏OO单位中位数为47（四分位间距36 - 57），而对照组为37（四分位间距30 - 41）；P < 0.001），胶原密度更高（中位数为6.1%（四分位间距4.4% - 9.5%），而对照组为4.6%（四分位间距2.5% - 7.4%）；P = 0.003）。接受立体定向体部放疗的患者术后B/C级胰瘘发生率为57.6%（95%置信区间41%至74%），而审计对照组为34%（95%置信区间27%至42%）（P = 0.011）。
术前立体定向体部放疗对接受胰十二指肠切除术的高危患者是安全的，可增加实质硬度和纤维化，但未显示出有效性证据。
