Shaib Walid L, Hawk Natalyn, Cassidy Richard J, Chen Zhengjia, Zhang Chao, Brutcher Edith, Kooby David, Maithel Shishir K, Sarmiento Juan M, Landry Jerome, El-Rayes Bassel F
Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):296-303. doi: 10.1016/j.ijrobp.2016.05.010. Epub 2016 May 24.
A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC.
A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT.
Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached).
The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.
可切除边缘性胰腺癌（BRPC）治疗中的一项挑战是后缘阳性（PM）率较高。立体定向体部放射治疗（SBRT）能够以适形方式给予更高的放射剂量。本研究使用SBRT评估了BRPC中剂量递增至45 Gy的最大耐受剂量。
采用单机构3+3期1临床试验设计，评估分3次给予计划靶体积（PTV）的4个SBRT剂量水平，并同时对PM进行野内推量（SIB）。剂量水平（DL）1为PTV 30 Gy，剂量水平2至4（DL2-DL4）的剂量为36 Gy。DL-1、DL-2、DL-3和DL-4对PM的SIB剂量分别为6、6、7.5和9 Gy。所有患者在SBRT前接受4周期改良FOLFIRINOX（氟尿嘧啶、亚叶酸钙、伊立替康、奥沙利铂）治疗。
纳入13例患者，中位年龄64岁。中位随访时间为18个月。肿瘤位于胰头（n=12）和钩突/颈部（n=1）。1例患者未接受SBRT。无3级或4级毒性反应。5例患者因疾病进展未接受手术切除（1例局部进展，4例远处转移）；8例患者PM切缘R0切除，其中5例进行了血管重建。2例患者疾病分期从T3降至T1和T2。4例患者仍存活，3例无疾病进展。切除患者的中位总生存期未达到（9.3：未达到）。
分3次给予36 Gy的SBRT剂量并对PM进行9 Gy的SIB（总计45 Gy）安全且耐受性良好。未达到45 Gy剂量的剂量限制毒性，未来试验需要进一步增加剂量。
