Reddy Abhinav V, Hill Colin S, Sehgal Shuchi, Ding Ding, Hacker-Prietz Amy, He Jin, Zheng Lei, Herman Joseph M, Meyer Jeffrey, Narang Amol K
Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Radiat Oncol J. 2021 Dec;39(4):304-314. doi: 10.3857/roj.2021.00815. Epub 2021 Dec 17.
The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT).
Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes.
Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009-0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57-10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41-9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25-9.16; p = 0.017).
In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.
本研究旨在确定在接受新辅助化疗和立体定向体部放疗（SBRT）的临界可切除胰腺癌（BRPC）或局部晚期胰腺癌（LAPC）患者中，体细胞突变是否与临床和病理结局相关。
纳入2016年8月至2019年1月期间接受新辅助化疗和SBRT后行手术切除且对其原发性肿瘤进行了二代测序的患者。二代测序采用实体瘤检测板或FoundationOne CDx在内部进行。进行单因素（UVA）和多因素分析（MVA）以确定体细胞突变与病理和临床结局之间的关联。
35例患者纳入本研究。化疗方案包括改良FOLFIRINOX、吉西他滨和白蛋白结合型紫杉醇，或吉西他滨和卡培他滨。患者接受SBRT，剂量为33 Gy，分5次。在UVA和MVA中，与其他KRAS突变的肿瘤相比，具有KRAS G12V突变的肿瘤对新辅助治疗表现出更好的病理肿瘤退缩分级（TRG）（比值比 = 0.087；95%置信区间[CI]，0.009 - 0.860；p = 0.036）。在UVA和MVA中，NOTCH1/2突变与较差的总生存期（风险比[HR] = 4.15；95% CI，1.57 - 10.95；p = 0.004）和无进展生存期（HR = 3.61；95% CI，1.41 - 9.28；p = 0.008）相关。在UVA中，仅NOTCH1/2突变与较差的无远处转移生存期相关（HR = 3.38；95% CI，1.25 - 9.16；p = 0.017）。
在BRPC和LAPC中，KRAS G12V突变与化疗和SBRT后更好的TRG相关。此外，NOTCH1/2突变与较差的总生存期、无远处转移生存期和无进展生存期相关。
