Norfolk and Norwich University Hospitals NHS Foundation Trust, United Kingdom.
Oxford University Hospitals NHS Foundation Trust, United Kingdom; CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, United Kingdom.
Radiother Oncol. 2021 Feb;155:278-284. doi: 10.1016/j.radonc.2020.11.007. Epub 2020 Nov 18.
Following resection of pancreatic cancer, risk of positive margins and local recurrence remain high, especially for borderline-resectable pancreatic cancer (BRPC). We aimed to establish the maximum tolerated dose of a margin-intensified five-fraction stereotactic body radiotherapy (SBRT) regimen designed to treat the region at risk.
We conducted a prospective multicentre phase-1 rolling-six dose-escalation study. BRPC patients received pre-operative SBRT, with one dose to the primary tumour and an integrated boost to the region where tumour was in contact with vasculature. Four dose-levels were proposed, with starting dose 30 Gy to primary PTV and 45 Gy to boost volume (PTV_R), in five daily fractions. Primary endpoint was maximum tolerated dose (MTD), defined as highest dose where zero of three or one of six patients experienced dose-limiting toxicity (DLT).
Twelve patients were registered, eleven received SBRT. Radiotherapy was well tolerated with all treatment completed as scheduled. Dose was escalated one level up from starting dose without encountering any DLT (prescribed 32.5 Gy PTV, 47.5 Gy PTV_R). Nine serious adverse reactions or events occurred (seven CTCAE Grade 3, two Grade 4). Two patients went on to have surgical resection. Median overall survival for SBRT patients was 8.1 months. The study closed early when it was unable to recruit to schedule.
Toxicity of SBRT was low for the two dose-levels that were tested, but MTD was not established. Few patients subsequently underwent resection of pancreatic tumour after SBRT, and it is difficult to draw conclusions regarding the safety or toxicity of these therapies in combination.
胰腺癌切除术后，切缘阳性和局部复发的风险仍然很高，尤其是对于交界可切除胰腺癌（BRPC）。我们旨在确定旨在治疗风险区域的边缘强化五部分立体定向体放射治疗（SBRT）方案的最大耐受剂量。
我们进行了一项前瞻性多中心 6 例滚动剂量递增的 1 期研究。BRPC 患者接受术前 SBRT，一次照射原发肿瘤，一次照射与血管接触的肿瘤区域。提出了四个剂量水平，原发肿瘤的起始剂量为 30Gy，增强剂量为 45Gy（PTV_R），共 5 个每日剂量。主要终点是最大耐受剂量（MTD），定义为 3 名或 6 名患者中有 0 名或 1 名发生剂量限制毒性（DLT）的最高剂量。
共登记了 12 名患者，11 名患者接受了 SBRT。所有治疗均按计划完成，放射治疗耐受性良好。剂量从起始剂量增加了一个水平，没有遇到任何 DLT（规定 PTV 为 32.5Gy，PTV_R 为 47.5Gy）。发生了 9 起严重不良事件或不良反应（7 起 CTCAE 3 级，2 起 4 级）。有 2 名患者随后接受了手术切除。SBRT 患者的中位总生存期为 8.1 个月。当无法按照计划招募患者时，该研究提前关闭。
在测试的两个剂量水平下，SBRT 的毒性较低，但未确定 MTD。在 SBRT 后，少数患者随后接受了胰腺肿瘤切除，因此难以得出关于这些联合治疗安全性或毒性的结论。
