Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
University of South Carolina School of Medicine, Columbia, South Carolina.
Pract Radiat Oncol. 2022 Nov-Dec;12(6):511-523. doi: 10.1016/j.prro.2022.02.009. Epub 2022 Mar 17.
In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.
This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform.
Median induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus >180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P = .04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change.
SBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes.
在一项前瞻性多中心研究中，吉西他滨单药治疗后序贯立体定向体部放射治疗（SBRT）在局部晚期胰腺癌（LAPC）患者中的耐受性良好，其疗效与放化疗相当。最近的临床试验报告称，采用多药化疗（MA-CTX）单药治疗可提高生存率。本前瞻性试验旨在探讨 MA-CTX 后能否安全地进行 SBRT。在此，我们报告 LAPC 患者在 MA-CTX 后接受 SBRT 的长期结果，并评估 SBRT 前标本的基因谱是否影响结果。
本前瞻性非随机对照 2 期试验于 2012 年至 2015 年在一家高容量胰腺癌中心，对 44 例 LAPC 和 4 例局部复发性患者进行多学科评估后入组。诱导 CTX 时，大多数患者接受改良 FOLFIRINOX（mFFX）或吉西他滨联合 nab-紫杉醇（GnP）治疗，然后进行 5 次 SBRT。在进行基准定位时，采集活检样本，提取 DNA，使用 Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets 平台进行靶向测序。
诱导 CTX 持续时间中位数≥4 个月，31 例患者接受 mFFX（65%）治疗。在 44 例 LAPC 患者中，17 例（39%）进行了手术探查，16 例中的 12 例（75%）实现了 RO 切除。诊断和 SBRT 后中位总生存期（mOS）分别为 20.2 和 14.6 个月。SBRT 后 1 年和 2 年的 OS 分别为 58%和 28%。诊断和 SBRT 后 RO 切除患者的 mOS 分别为 28.6 和 22.4 个月。诊断和 SBRT 后中位局部无进展生存期分别为 23.9 和 15.8 个月。SBRT 前 CA 19-9≤180 U/mL 与>180 U/mL 患者的 mOS 分别为 23.1 和 11.3 个月（风险比，0.53；P=0.04）。只有 1 例（2.1%）患者出现归因于 SBRT 的迟发性≥2 级胃肠道毒性。尽管有显著的化疗预处理，但 88%的肿瘤标本均能有效测序；生存结果与特定的突变模式无显著相关性。采用 EORTC QLQ-C30 和 PAN26 问卷前瞻性地收集 SBRT 前后的生活质量，显示无显著变化。
在 MA-CTX 基础上联合 SBRT 治疗，安全性良好，毒性最小。相当比例的 LAPC 患者接受了 RO 切除术，获得了良好的生存结果。
