Objectives: To establish an evidence-based cutoff to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. Summary Background Data: A clear definition of “early recurrence” after pancreatic ductal adenocarcinoma resection is currently lacking. Methods: Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrencewere assessed with logistic regression models. Results: Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P< 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P< 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0cm on computed tomography (OR 1.53) and CA 19–9 > 210U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19–9 > 37U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. Conclusion: A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

Surgical resection of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of patients (20%) and is associated with significantly longer median overall survival.

Procedure-specific prescribing recommendations may help provide guidance to clinicians who are currently overprescribing opioids after surgery. Multidisciplinary, patient-centered consensus guidelines for more procedures are feasible and may serve as a tool in combating the opioid crisis.

Objectives: To describe the survival outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LAPDAC) who have a pathologic complete response (pCR) following neoadjuvant chemoradiation. Background: Patients with BR/LA-PDAC are often treated with neoadjuvant chemoradiation in an attempt to downstage the tumor. Uncommonly, a pCR may result. Methods: A retrospective review of a prospectively maintained database was performed at a single institution. pCR was defined as no viable tumor identified in the pancreas or lymph nodes by pathology. A near complete response (nCR) was defined as a primary tumor less than 1 cm, without nodal metastasis. Overall survival (OS) and disease-free survival (DFS) were reported. Results: One hundred eighty-six patients with BR/LA-PDAC underwent neoadjuvant chemoradiation and subsequent pancreatectomy. Nineteen patients (10%) had a pCR, 29 (16%) had an nCR, and the remaining 138 (74%) had a limited response. Median DFS was 26 months in patients with pCR, which was superiorto nCR (12 months, P = 0.019) and limited response (12 months, P < 0.001). The median OS of nCR (27 months, P = 0.003) or limited response (26 months, P = 0.001) was less than that ofpCR (more than 60 months). in multivariable analyses pCR was an independent prognostic factorforDFS (HR = 0.45;0.22–0.93, P = 0.030) and OS (HR=0.41;0.17–0.97, P = 0.044). Neoadjuvant FOLFIRINOX (HR=0.47; 0.26–0.87, P =0.015) and negative lymph node status (HR=0.57; 0.36–0.90, P = 0.018) were also associated with improved survival. Conclusions: Patients with BR/LA-PDAC who had a pCR after neoadjuvant chemoradiation had a significantly prolonged survival compared with those who had nCR or a limited response.

Objective: Patients with pancreatic cancer (PDAC) who undergo surgical resection and receive effective chemotherapy have the best chance of long-term survival. Unfortunately, we lack predictive biomarkers to guide optimal systemic treatment. Ex-vivo generation of patient-derived organoids (PDO) for pharmacotyping may serve as predictive biomarkers in PDAC. The goal of the current study was to demonstrate the clinical feasibility of a PDOguided precision medicine framework of care.Methods: PDO cultures were established from surgical specimens and endoscopic biopsies, expanded in Matrigel, and used for high-throughput drug testing (pharmacotyping).Efficacy of standard-of-care chemotherapeutics was assessed by measuring cell viability after drug exposure.Results: A framework for rapid pharmacotyping of PDOs was established across a multiinstitutional consortium of academic medical centers. Specimens obtained remotely and shipped to a central biorepository maintain viability and allowed generation of PDOs with 77% success. Early cultures maintain the clonal heterogeneity seen in PDAC with similar phenotypes (cystic-solid). Late cultures exhibit a dominant clone with a pharmacotyping profile similar to early passages. The biomass required for accurate pharmacotyping can be minimized by leveraging a high-throughput technology. Twenty-nine cultures were pharmacotyped to derive a population distribution of chemotherapeutic sensitivity at our center. Pharmacotyping rapidly-expanded PDOs was completed in a median of 48 (range 18-102) days.Conclusions: Rapid development of PDOs from patients undergoing surgery for PDAC is eminently feasible within the perioperative recovery period, enabling the potential for pharmacotyping to guide post-operative adjuvant chemotherapeutic selection. Studies validating PDOs as a promising predictive biomarker are ongoing.

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Introduction Approximately, 20% of patients with pancreatic ductal adenocarcinoma have resectable disease at diagnosis. Given improvements in locoregional and systemic therapies, some patients with borderline resectable pancreatic cancer (BRPC) can now undergo successful resection. The outcomes of patients with BRPC after neoadjuvant therapy remain unclear. Methods A prospectively maintained single-institution database was utilized to identify patients with BRPC who were managed at the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC) between 2013 and 2016. BRPC was defined as any tumor that presented with radiographic evidence of the involvement of the portal vein (PV) or superior mesenteric vein (SMV) that was deemed to be technically resectable (with or without the need for reconstruction), or the abutment (< 180° involvement) of the common hepatic artery (CHA) or superior mesenteric artery (SMA), in the absence of involvement of the celiac axis (CA). We collected data on treatment, the course of the disease, resection rate, and survival. Results Of the 866 patients evaluated at the PMDC during the study period, 151 (17.5%) were staged as BRPC. Ninety-six patients (63.6%) underwent resection. Neoadjuvant chemotherapy was administered to 142 patients (94.0%), while 78 patients (51.7%) received radiation therapy in the neoadjuvant setting. The median overall survival from the date of diagnosis, of resected BRPC patients, was 28.8 months compared to 14.5 months in those who did not (p < 0.001). Factors associated with increased chance of surgical resection included lower ECOG performance status (p = 0.011) and neck location of the tumor (p = 0.001). Forty-seven patients with BRPC (31.1%) demonstrated progression of disease; surgical resection was attempted and aborted in 12 patients (7.9%). Eight patients (5.3%) were unable to tolerate chemotherapy; six had disease progression and two did not want to pursue surgery. Lastly, four patients (3.3%) were conditionally unresectable due to medical comorbidities at the time of diagnosis due to comorbidities and failed to improve their status and subsequently had progression of the disease. Conclusion After initial management, 31.1% of patients with BRPC have progression of disease, while 63.6% of all patients successfully undergo resection, which was associated with improved survival. Factors associated with increased likelihood of surgical resection include lower ECOG performance status and tumor location in the neck.