Abstract：
OBJECTIVE: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy.
METHODS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2).
RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%).
CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.
METHODS: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022. Patients had PDAC of the pancreatic head and underwent R0 or R1 resection and adjuvant modified FOLFIRINOX (mFFX) chemotherapy. The primary endpoint was to determine the dosing schedule of adjuvant PBT (5 Gy × 5 fractions) using limited treatment volumes given between cycles 6 and 7 of mFFX. Patients received PBT on days 15 to 19 in a 28-day cycle before starting cycle 7 (dose level 1, DL1) or on days 8 to 12 in a 21-day cycle before starting cycle 7 (DL2).
RESULTS: The median patient age was 66 years (range, 52-78), and the follow-up time from mFFX initiation was 12.5 months (range, 6.2-37.4 months). No patients received preoperative therapy. Four had R1 resections and 5 had node-positive disease. Three patients were enrolled on DL1 and 6 patients on DL2. One dose-limiting toxicity (DLT) occurred at DL2 (prolonged grade 3 neutropenia resulting in discontinuation of mFFX after cycle 7). No other DLTs were observed. Four patients completed 12 cycles of mFFX (range, 7-12; median, 11). No patients have had local recurrence. Five of 9 patients had recurrence: 3 in the liver, 1 in the peritoneum, and 1 in the bone. Six patients are still alive, 4 of whom are recurrence-free. The median time to recurrence was 12 months (95% CI, 4 to not reached [NR]), and median overall survival was NR (95% CI, 6 to NR; 2-year survival rate, 57%).
CONCLUSIONS: PBT integrated within adjuvant mFFX was well tolerated, and no local recurrence was observed. These findings warrant further exploration in a phase 2 trial.
摘要：
目标：尽管全身治疗有所改善，胰腺导管腺癌(PDAC)患者常出现局部复发.我们试图确定辅助化疗期间大分割质子束放疗（PBT）的安全性。
方法：在2019年至2022年之间，有9名患者参加了一项单机构I期试验（NCTXXXXXX）。患者胰头PDAC，并接受R0或R1切除术和辅助改良FOLFIRINOX（mFFX）化疗。主要终点是使用在mFFX的周期6和7之间给予的有限治疗体积来确定佐剂PBT(5Gy×5级分)的给药方案。患者在开始周期7之前的28天周期中的第15-19天（剂量水平1，DL1）或在开始周期7之前的21天周期中的第8-12天接受PBT（DL2）。
结果：患者年龄中位数为66（范围52-78），从mFFX开始的随访时间为12.5个月（范围6.2-37.4个月）。无患者接受术前治疗。4例进行了R1切除，5例进行了淋巴结阳性疾病。3名患者在DL1上登记，6名患者在DL2上登记。一种剂量限制性毒性(DLT)发生在DL2(延长的3级中性粒细胞减少症,导致mFFX在第7周期后停止)。没有观察到其他DLT。四名患者完成了12个周期的mFFX（范围7-12，中位数11）。无患者出现局部复发。9例患者中有5例复发：3例在肝脏，1在腹膜中，1在骨头里。六个病人还活着,其中4人无复发。中位复发时间为12个月（95%置信区间[CI]4-未达到[NR]），中位总生存期为NR（95%CI6-NR，2年生存率57%)。
结论：在mFFX佐剂中整合的PBT具有良好的耐受性，未观察到局部复发。这些发现在第二阶段试验中得到证实。
方法：在2019年至2022年之间，有9名患者参加了一项单机构I期试验（NCTXXXXXX）。患者胰头PDAC，并接受R0或R1切除术和辅助改良FOLFIRINOX（mFFX）化疗。主要终点是使用在mFFX的周期6和7之间给予的有限治疗体积来确定佐剂PBT(5Gy×5级分)的给药方案。患者在开始周期7之前的28天周期中的第15-19天（剂量水平1，DL1）或在开始周期7之前的21天周期中的第8-12天接受PBT（DL2）。
结果：患者年龄中位数为66（范围52-78），从mFFX开始的随访时间为12.5个月（范围6.2-37.4个月）。无患者接受术前治疗。4例进行了R1切除，5例进行了淋巴结阳性疾病。3名患者在DL1上登记，6名患者在DL2上登记。一种剂量限制性毒性(DLT)发生在DL2(延长的3级中性粒细胞减少症,导致mFFX在第7周期后停止)。没有观察到其他DLT。四名患者完成了12个周期的mFFX（范围7-12，中位数11）。无患者出现局部复发。9例患者中有5例复发：3例在肝脏，1在腹膜中，1在骨头里。六个病人还活着,其中4人无复发。中位复发时间为12个月（95%置信区间[CI]4-未达到[NR]），中位总生存期为NR（95%CI6-NR，2年生存率57%)。
结论：在mFFX佐剂中整合的PBT具有良好的耐受性，未观察到局部复发。这些发现在第二阶段试验中得到证实。
