Gastrointestinal Cancer

SS 38 - GI 4 - Hepato-Pancreatic-Biliary

276 - Circulating Tumor DNA to Predict Surgical Outcome after Neoadjuvant Chemoradiation for Borderline Resectable/Locally Advanced Pancreatic Cancer

Wednesday, October 24
11:20 AM - 11:30 AM
Location: Room 206

Circulating Tumor DNA to Predict Surgical Outcome after Neoadjuvant Chemoradiation for Borderline Resectable/Locally Advanced Pancreatic Cancer
S. McDuff1, A. S. Parikh2, M. Hazar-Rethinam2, H. Zheng3, E. Van Seventer2, B. Nadres2, J. K. Lennerz4, D. P. Ryan2, C. Weekes2, J. W. Clark2, C. Fernandez-del Casti2, C. R. Ferrone2, K. Lillemoe2, L. Goyal2, A. X. Zhu2, J. Y. Wo5, L. S. Blaszkowsky2, J. N. Allen2, R. Corcoran6, and T. S. Hong7; 1Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Massachusetts General Hospital Biostatistics Center, Boston, MA, 4Department of Pathology, Massachusetts General Hospital, Boston, MA, 5Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 6Massachusetts General Hospital Cancer Center, Boston, MA, 7Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Boston, MA

Purpose/Objective(s): Curative resection is possible following neoadjuvant treatment for borderline resectable/locally advanced pancreatic cancer (BR/LAPC), yet there is no method to identify patients in advance who will have a favorable surgical outcome. This study was designed to assess the ability of circulating tumor DNA (ctDNA) measured during neoadjuvant chemoradiation (CRT) to predict surgical outcome for BR/LAPC.

Materials/Methods: 41 patients with newly diagnosed BR/LAPC were enrolled at our institution between 10/2015 - 5/2017. Patients received neoadjuvant FOLFIRINOX followed by CRT: either short-course (n = 10, 25 Gy/5 fractions), or long-course (n = 31, 50.4 Gy/28 fractions). Serum ctDNA was measured at baseline, weekly during CRT, preoperatively, and postoperatively. After extracting DNA from plasma, the BioRad KRAS multiplex droplet digital PCR assay was used empirically to detect the presence of 7 possible KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D), given that >90% of pancreatic ductal adenocarcinomas are expected to harbor KRAS mutations. The following clinical and pathologic outcomes were compiled: CA19-9, CEA, preoperative imaging response assessment, tumor grade, T stage, centrally-reviewed tumor regression grade, R-resection status, pathologically involved lymph nodes, LVI, and PNI.

Results: The median age of the cohort was 66 years (IQR: 59-73 years). Following CRT, 33 (80.5%) were operable. The overall R0-node negative (R0-NN) resection rate was 63.4% for the entire cohort. The rate of R0-NN resection was significantly higher among patients with an undetectable preoperative ctDNA (n = 25) compared to those with a detectable (n = 16) preoperative ctDNA (80% R0-NN vs 37.5% R0-NN, respectively, Fisher’s exact p = 0.009). On univariate logistic regression, ctDNA status and CA19-9 were significantly associated with R0-NN resection (p = 0.008, and p = 0.0385, respectively), whereas preoperative imaging response assessment and CEA were not associated. On multivariable logistic regression, only ctDNA remained a significant predictor for R0-NN resection when controlling for CA19-9 (p = 0.018). For patients who received surgery, the ctDNA allele fraction was significantly correlated with tumor regression grade (Pearson R = 0.35, p = 0.049).

Conclusion: Undetectable preoperative ctDNA is associated with R0-NN surgical outcome in a cohort of patients treated with neoadjuvant CRT for BR/LAPC. Validation of these results is ongoing as we perform next generation sequencing of each patient’s primary tumor to design a mutation-specific droplet digital PCR assay for each patient. This approach is worthy of further study to establish guidelines for incorporating ctDNA into clinic with the goal of improving patient selection for surgery.

Author Disclosure: S. McDuff: None. A.S. Parikh: None. M. Hazar-Rethinam: None. H. Zheng: None. E. Van Seventer: None. J.K. Lennerz: None. J.W. Clark: None. C. Fernandez-del Casti: None. J.Y. Wo: None. T.S. Hong: Research Grant; Novartis, Taiho.

Susan McDuff, MD, PhD

Disclosure:
Employment
Harvard Radiation Oncology Program: Resident Physician: Employee

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