Impact of somatic mutations on clinical and pathologic outcomes in borderline resectable and locally advanced pancreatic cancer treated with neoadjuvant chemotherapy and stereotactic body radiotherapy followed by surgical resection
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.,
소속 상세정보
( Reddy Abhinav V. )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
( Hill Colin S. )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
( Sehgal Shuchi )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
( Ding Ding )
Johns Hopkins University School of Medicine Department of Oncology
( Hacker-Prietz Amy )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
( He Jin )
Johns Hopkins University School of Medicine Department of Surgery
( Zheng Lei )
Johns Hopkins University School of Medicine Department of Oncology
( Herman Joseph M. )
Northwell Health Cancer Institute Department of Radiation Oncology
( Meyer Jeffrey )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
( Narang Amol K. )
Johns Hopkins University School of Medicine Department of Radiation Oncology and Molecular Radiation Sciences
Abstract
Purpose: 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).
Materials and Methods: 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.
Results: 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).
Conclusion: 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.
키워드
Pancreatic cancer; Stereotactic body radiotherapy; Mutations; Notch proteins; KRAS genes
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