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PURPOSE Effective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX)-based treatment and imaging-based biomarkers for borderline resectable PDAC. METHODS Eligible patients had treatment-naïve, histology-confirmed PDAC and one or more high-risk features: mesenteric vessel involvement, CA 19-9 level of 500 mg/dL or greater, and indeterminate metastatic lesions. Patients received modified FOLFIRINOX and chemoradiation before anticipated pancreatectomy. Tumors were classified on baseline computed tomography as high delta (well-defined interface with parenchyma) or low delta (ill-defined interface). We designated computed tomography interface response after therapy as type I (remained or became well defined) or type II (became ill defined). The study had 80% power to differentiate a 60% from 40% resection rate (α = .10). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and subgroups were compared using log-rank tests. RESULTS Thirty-three patients initiated therapy; 45% underwent pancreatectomy. The median OS was 24 months (95% CI, 16.2 to 29.6 months). For patients who did and did not undergo pancreatectomy, the median OS was 42 months (95% CI, 17.7 months to not estimable) and 14 months (95% CI, 9.0 to 24.8 months), respectively. Patients with high-delta tumors had lower 3-year PFS (4% v 40%) and 3-year OS rates (20% v 60%) than those with low-delta tumors (both P < .05). Patients with type II interface responses had lower 3-year PFS (0% v 29%) and 3-year OS rates (16% v 47%) than those with type I responses (both P < .001). CONCLUSION Preoperative FOLFIRINOX followed by chemoradiation for high-risk borderline resectable PDAC was associated with a resection rate of 45% and median OS of approximately 2 years. Our imaging-based biomarker validation indicates that personalized treatment may be achieved using these biomarkers at baseline and post-treatment.

e15609 Background: Locally advanced unresectable intrahepatic cholangiocarcinoma (IHCC) remains incurable. Prior data has shown the effectiveness of hypofractionated radiation therapy (HRT) with biological equivalent doses (BED) greater than 80.5 Gy in improving local control and survival for this patient population. This is an updated report of our IHCC experience with HRT in 15 or 25 fractions using a simultaneous integrated boost technique. Methods: A retrospective analysis of 63 patients (median age 64, range 29-87) diagnosed between 2007-2016 who received HRT was performed. RT dose ranged from 58-90 Gy in 15 fractions and 62.5-100 Gy in 25 fractions, translating to a median BED of 97.5 (range 78.1-144 Gy). Median primary tumor size at diagnosis was 7.8 cm (2.4-17cm). Forty-eight (76%) patients received gemcitabine-based therapy prior to HRT. Results: Median follow up was 31 months (4-110). The 2 year overall-survival (OS), local-progression-free-survival (LPFS), intrahepatic-distant-metastasis-free-survival (IH-DMFS) and extraheptic-distant-metastasis-free-survival (EH-DMFS) were 71% (95% CI 58-82), 67% (95% CI 50-80), 40% (95% CI 28-54) and 40% (95% CI 27-54) respectively. Pattern of failure analysis revealed 16 patients with local failure after HRT, of which only 5 (8% of total) progressed within the high iso-dose field line (BED > 80.5). After HRT, 41 (65%) patients had intrahepatic metastasis that occurred outside the radiation field, and 34 (54%) patients developed extrahepatic metastasis. On multi-variate analysis, T-stage was an independent predictor of OS, LPFS, IH-DMFS, and EH-DMFS. Larger normal liver volume and 15 fraction treatments were independently associated with better LPFS and IH-MFS respectively. There were no significant HRT-related toxicities. Conclusions: HRT demonstrates safety and efficacy for durable local control and prolonged overall survival in patients with unresectable IHCC. Dominant modes of failure are outside the HRT field. Improvements in systemic therapies could further improve outcomes for this patient population.

284 Background: There is currently no reliable biomarker for assessing the response to therapy of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated how changes in the tumor/parenchyma interface associate with response. Methods: We reviewed pre- and post-therapy scans of patients who received chemotherapy and/or chemoradiation for both localized and metastatic PDAC. We classified the interface between the PDAC tumor and surrounding pancreas parenchyma as stable (remains or becomes well-defined) or unstable (becomes poorly defined) using a novel visual scoring system and quantified changes in enhancement at this interface (Philips Intellispace Portal, quantitative European Association for the Study of Liver [qEASL]). Results: Three retrospective datasets were used to develop this method with consensus visual scoring performed by 3 radiologists. The first dataset included 99 patients with localized PDAC who received neoadjuvant chemoradiation. Patients who were classified as having a stable interface had significantly higher probability of achieving a complete or near-complete pathologic response (21% vs 0%, p = 0.01) and additionally demonstrated an improved median disease-free survival (DFS, 20.9 vs 7.9 mos., p < 0.01) and overall survival (OS, 47.7 vs 19.1 mos., p < 0.01). These results were validated in a separate dataset of 94 patients receiving protocol-based chemotherapy and chemoradiation (chemoRT cohort) and a cohort of 86 patients with stage IV disease. In both cohorts, a stable interface was associated with a significant improvement in progression free survival (PFS, Hazard Ratio [HR] 0.44, p = 0.01 for chemoRT and HR 0.70, p = 0.16 for stage IV) and OS (HR 0.42, p < 0.01 for chemoRT and HR 0.59, p = 0.05 for stage IV). Multivariate analyses for each cohort showed interface stability to be independently associated with both DFS/PFS and OS. Measurements obtained using qEASL were concordant with the visual scoring results. Conclusions: The interface stability of PDAC is an early readout of response to therapy. Integration of this imaging feature into clinical trials for localized and metastatic PDAC may aid in the future development of adaptive treatment strategies.