ImportanceNational guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear.ObjectiveTo compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC.Design, Setting, and ParticipantsThis prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021.InterventionsArm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours).Main Outcomes and MeasuresEach treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection.ResultsOf 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively.Conclusions and RelevanceThis randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting.Trial RegistrationClinicalTrials.gov Identifier: NCT02839343.

A 71-year-old man with gallbladder adenocarcinoma and no history of dyslipidemia presented with serum triglyceride level of 912 mg/dL after two months of starting Capecitabine. The lipemia due to elevated triglyceride also led to hemolysis, causing analytical interference to other biochemical tests and complete blood count.

Background and Objectives The purpose of this article is to describe the procedural safety, technical success, and clinical success of endovascular management of portal and mesenteric venous obstruction in patients with hepatobiliary neoplasms. Methods Institutional Review Board (IRB)-approved HIPAA compliant retrospective review of 21 consecutive patients with hepatobiliary malignancies who underwent endovascular portal vein recanalization and stent placement between January 2012 and March 2020. Clinical diagnoses were pancreatic cancer (n = 19), colon cancer metastatic to the liver (n = 1), and cholangiocarcinoma (n = 1). Presenting signs and symptoms included: ascites, abdominal pain, abnormal liver function tests, diarrhea, and gastrointestinal bleeding. Stent patency and patient survival are presented with Kaplan-Meier method. Results The technical success rate was 100%. A transhepatic approach was used in 20 cases (95.2%); trans-splenic access in one. Primary stent patency was 95.2%, 84%, and 68% at 1, 3, and 6 months, respectively. All stent occlusions were caused by tumor progression. A total of 80% of patients reported symptomatic improvement. Patient survival at 10 months was 40%. The early death rate was 4.76%. There were no bleeding complications from the percutaneous tracts. Conclusion Endovascular recanalization with stent placement is safe with high technical and clinical success.

Abstract Background:Obstruction of the splenoportal or mesoportal venous system occurs in approximately 15-25 % of patients with hepatobiliary malignancies. These patients are prone to develop obstruction of the portal and mesenteric veins both because of local factors (tumor compression, stenosis after surgery) and systemic factors (hypercoagulability). Diagnosis requires a high index of clinical suspicion because symptoms may be non-specific and directly attributed to the existing malignancy. Cross-sectional imaging methods (contrast-enhanced CT scan and MRI) are key to diagnosis. The best treatment strategy has not been established. The purpose of this article is to describe a single center experience in the endovascular management of portal and mesenteric venous obstruction with metallic stent placement on patients with hepatobiliary neoplasms.Results:IRB approved, HIPAA compliant study. Retrospective review of medical and imaging records of 21 consecutive patients with hepato-biliary malignancy who underwent endovascular portal vein recanalization and stent placement between January 2012 and March 2020. Clinical diagnoses were pancreatic cancer (n=19), colon cancer metastatic to the liver (n=1) and cholangiocarcinoma (n=1). The presenting symptoms were: ascites (n=5), abdominal pain, portal vein thrombosis, abnormal liver function tests and ascites (n=4), abdominal pain and ascites (n=4), abdominal pain and diarrhea (n=3), gastrointestinal bleed (n=3) and abdominal pain (n=2). Study results are presented in means and percentages. Stent patency and patient survival are presented with Kaplan-Meier method. The technical success rate was 100%. Self-expandable and balloon-expandable stents were placed. A transhepatic approach was used in 20 cases (95.2%); trans-splenic access in one. Primary stent patency was 95.2%, 84%, and 68% at 1, 3 and 6 months respectively. All stent occlusions were caused by tumor progression. A total of 80% of patients reported symptomatic improvement. Patient survival at 10 months was 40%. The early death rate was 4.76%. Portal vein perforation with massive bleeding was seen in one patient and managed with self-expandable stent-graft placement. There were no bleeding complications from the percutaneous tracts.ConclusionEndovascular recanalization with stent placement is safe with high technical and clinical success. Stent patency is acceptable and determined by disease progression.

COVID‐19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID‐19 or other large‐scale disruptions in cancer care.

377 Background: Neoadjuvant therapy has been associated with a median overall survival (OS) of 18 – 23 months (mo) in patients (pts) with BR pancreatic ductal adenocarcinoma (PDAC). To establish reference regimens to which novel treatments can be compared in future studies, we evaluated neoadjuvant mFOLFIRINOX with or without RT in BR PDAC in a phase II National Clinical Trials Network (NCTN) trial. Methods: Pts with ECOG PS 0-1 and BR PDAC confirmed by central real-time radiographic review after pre-registration were randomized to either arm A: 8 cycles of neoadjuvant mFOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 over 46 hours), or arm B: 7 cycles of mFOLFIRINOX followed by stereotactic body RT (SBRT, 33-40 Gy in 5 fractions [fx]) or hypofractionated image guided RT (HIGRT, 25 Gy in 5 fx). Pts in either arm without disease progression underwent pancreatectomy, then 4 cycles of adjuvant mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and infusional 5-fluorouracil 2400 mg/m 2 over 46 hours). The primary endpoint, 18-mo OS rate, of each arm was compared to a historical control of 50%. Planned interim analysis mandated closure of either arm in which <11 of first 30 accrued pts underwent R0 resection. Results: 155 pts pre-registered and 126 pts were enrolled to arm A (N=70; 54 randomized, 16 following closure of arm B) or arm B (N=56; closed at interim analysis, all pts randomized prior to closure). Median age (A: 63y, B: 67y), median CA 19-9 level (A: 171 U/ml, B: 248 U/ml) and ECOG PS (A: 51% PS 0, B: 57% PS 0) of registered pts were similar between arms (p > 0.05). Treatment detailed in Table. The 18-mo OS rate based on Kaplan Meier estimates was 67.9% (95%CI: 54.6 – 78.0) in arm A and 47.3% (95%CI: 33.7 – 59.7) in arm B. Among pts who underwent pancreatectomy, 18-mo OS rate was 93.1% (95%CI: 84.3 – 100) and 78.9% (95%CI: 62.6 – 99.6) in arm A and B, respectively. With median follow-up of 27 and 31 mo, median OS was 31.0 (95%CI: 22.2 – NE) mo and 17.1 (95%CI: 12.8 – 24.4) mo in arm A and B, respectively. Conclusions: Neoadjuvant mFOLFIRINOX was associated with favorable OS relative to historical data in pts with BL PDAC in this phase II NCTN trial. mFOLFIRINOX with hypofractionated RT did not improve OS compared to historical data. mFOLFIRINOX represents a reference regimen in this setting and a backbone on which to add novel agents. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org Clinical trial information: NCT02839343. [Table: see text]

Importance Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value. Objective To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma. Design, Setting, and Participants This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019. Interventions Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg). Main Outcomes and Measures Margin-negative resection rate and PRG. Results A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]). Conclusions and Relevance In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients. Trial Registration ClinicalTrials.gov Identifier: NCT02366819.

4050 Background: Complete resection (R0) and pathologic response grade (PRG) correlate with long-term GEA outcome. FOLFIRINOX demonstrated efficacy in advanced GEA; gFOLFIRINOX improved tolerability. We evaluated R0, PRG and tolerability in this pilot P study. Methods: Gastric body (GB) + esophagogastric (EGJ) GEA patients (pts) with ≥T3Nx or TxN+ were enrolled & treated with 4 pre + 4 postoperative biweekly cycles of gFOLFIRINOX (5-FU 2400mg/m2 over 46 hrs; oxaliplatin 85mg/m2; iri: 180mg/m2 for UGT1A1 genotype 6/6, 135mg/m2 for 6/7, 90mg/m2 for 7/7) (+ trastuzumab (T) 6mg/kg then 4mg/kg for HER2+) with prophylactic peg-filgastrim. 1°endpoint R0 resection required 36 pts to assess for a 90% R0 rate (intention to treat (ITT)) with 90% power + 0.05 alpha; ≥30/36 R0 considered positive. Co-1°endpoint was PRG (Becker); 36 pts provided 85% power with 0.05 alpha for a complete (pCR G1a) rate of 16%. 2°endpoints were safety/toxicity, PET response, & R0/PRG by tumor site, histologic subtype, HER2 status, & UGT1A1 genotype. We report efficacy and toxicity data from the neoadjuvant (Neo) portion of the study; postop data & survival outcomes will be presented at the meeting. Results: 4 sites enrolled 36 ITT pts between 2/2014-8/2018; 75% male, median age 66 (range 27-85). All pts completed all 4 cycles of Neo therapy: 10% had any dose reduction of iri (16%/0%/25% by genotype 6/6, 6/7, 7/7); any G3+ toxicity occurred in 35% of pts (32% 6/6, 29% 6/7, 75% 7/7). G3+ toxicity in ≥5% of pts: diarrhea (17.5%; 6/6 21%, 6/7 11%, 7/7 25%), anemia (5%), vomiting (5%). Efficacy is shown in the Table. Of pts going to surgery, both R1 resections were GB linitus. PRG1(a+b) was achieved in 36% of ITT pts, 46% of intestinal type histology. Conclusions: Neo gFOLFIRINOX was tolerable with surrogate efficacy comparable to FLOT. Clinical trial information: NCT02366819. [Table: see text]

Purpose: 5-Fluorouracil (5-FU)/leucovorin, irinotecan, and nab-paclitaxel are all active agents in gastrointestinal cancers; the combination, FOLFIRABRAX, has not been previously evaluated. UDP Glucuronosyltransferase 1A1 (UGT1A1) clears SN-38, the active metabolite of irinotecan. UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity and predisposes to toxicity. We performed a trial to assess the safety and tolerability of FOLFIRABRAX with UGT1A1 genotype–guided dosing of irinotecan. Patients and Methods: Patients with previously untreated, advanced gastrointestinal cancers received FOLFIRABRAX with prophylactic pegfilgrastim every 14 days. UGT1A1 *1/*1, *1/*28, and *28/*28 patients received initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2,400 mg/m2 over 46 hours, leucovorin 400 mg/m2, and nab-paclitaxel 125 mg/m2 were administered. Doses were deemed tolerable if the dose-limiting toxicity (DLT) rate during cycle 1 was ≤35% in each genotype group. DLTs were monitored using a sequential procedure. Results: Fifty patients enrolled, 30 pancreatic, 9 biliary tract, 6 gastroesophageal, and 5 others. DLTs occurred in 5 of 23 (22%) *1/*1 patients, 1 of 19 (5%) *1/*28 patients, and 0 of 7 *28/*28 patients. DLTs were all grade 3: diarrhea (3 patients), nausea (2 patients), and febrile neutropenia (1 patient). The overall response rate was 31%. Response rates in pancreatic, gastroesophageal, and biliary tract cancers were 34%, 50%, and 11%, respectively. Eighteen patients (36%) received therapy for at least 24 weeks. Conclusions: FOLFIRABRAX with genotype-guided dosing of irinotecan is tolerable in patients with advanced gastrointestinal cancer and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Too few *28/*28 patients were enrolled to provide conclusive results. Responses occurred across multiple tumor types.

663 Background: Infusional-5-fluorouracil (inf-5FU), administered over 48 hours every 2 weeks, is frequently prescribed for the treatment of gastrointestinal cancers. A portable infusion device (ID) may be used for this purpose to enable treatment at home. At our institution, patients are educated by an oncology nurse as to what to expect, and how to function once they leave the infusion center. However, there is no formal process in place to report their experience and to record and analyze the results. The intended goal of this study was to accomplish this, such that the data could improve the education and experience of future patients. Methods: After verbal consent, a sequential cohort of patients, who had received 2 or more treatments with inf-5FU for gastrointestinal cancer, was invited to complete a de-identified paper questionnaire concerning their experience. Eleven specific questions suggested by the GI group were included, with an opportunity to add comments. The surveys were then collated and reviewed. Results: See table. Conclusions: While most patients felt well prepared by their medical team as to what to expect from the ID (93.1%), ≥ 25% had issues with bathing (73.6%), sleep (37.5%), exercising (30.6%), intimacy (26.4%), social interactions (25%) and anxiety (25%). These insights will be used to improve the education of future patients and a second assessment will follow. 72/72 patients approached over 6 months completed the survey with results below: [Table: see text]

427 Background: FOLFIRINOX improves survival compared with gemcitabine in advanced pancreatic cancer (PC), but with significant toxicity (Conroy, NEJM 2011). UGT1A1 clears SN-38, the active metabolite of irinotecan (IRI); UGT1A1*28 polymorphism reduces enzymatic activity and predisposes to severe IRI toxicity. We hypothesized that dosing mFOLFIRINOX based on UGT1A1 genotype would improve tolerability. The primary objective of this study (NCT01643499) was to determine whether genotype-guided dosing of IRI in mFOLFIRINOX is tolerable. A secondary objective was to describe objective response rates (ORR) in PC and biliary tract cancers (BTC). Methods: mFOLFIRINOX was given every 14 days. CT scans were obtained every 8 weeks. UGT1A1 *1/*1, *1/*28, and *28/*28 pts received initial IRI doses of 180, 135, and 90 mg/m2, respectively. 5-FU dose was 2400 mg/m2 over 46 hours (no bolus); leucovorin 400 mg/m2; oxaliplatin 85 mg/m2. In cohort 1 (tolerability cohort by genotype), prophylactic pegfilgrastim was not allowed in cycle 1 (28 days) unless clinically indicated. In cohort 2 (expansion tolerability cohort in PC and BTC), prophylactic pegfilgrastim was given. DLT during cycle 1 was defined as Grade (Gr) 3/4 neutropenia with fever; Gr 4 neutropenia lasting ≥ 5 days; Gr 4 thrombocytopenia, or Gr 3/4 non-hematologic toxicity despite optimal medical management. Doses were tolerable if the DLT rate during cycle 1 was ≤ 33% with 70-80% statistical confidence. Results: In cohort 1, DLTs were observed in 2/15 (13%) *1/*1 pts; 2/16 (13%) *1/*28 pts; 3/9 (33%) *28/*28 pts. In cohort 2, DLTs were observed in 6/19 (32%) PC pts and 4/19 (21%) BTC pts. DLTs in cohort 1 (some pts with multiple): neutropenic fever (5); Gr 3 fatigue (4); Gr 3 diarrhea (2). DLTs in cohort 2: Gr 3 fatigue (3); Gr 3 diarrhea (3); Gr 3 nausea/vomiting (2); Gr 5 sepsis without neutropenia (1); Gr 5 multi-organ failure (1); neutropenic fever (1); Gr 3 anorexia (1). To date, ORR is 13/39 (33%) in PC and 6/28 (21%) in BTC. Conclusions: mFOLFIRINOX is not tolerable in PC and BTC, even with UGT1A1 genotype-guided dosing of IRI and prophylactic pegfilgrastim. More needs to be done to improve the tolerability of this regimen. Clinical trial information: NCT01643499.

e16241 Background: 5-FU, IRI, and NP are active in GI cancers; the combination, FOLFIRABRAX, has not been evaluated. UGT1A1 clears SN-38, the active metabolite of IRI. UGT1A1*28 polymorphism reduces enzymatic activity and predisposes to severe IRI toxicity. Dose adjustment in pts with this allele may be warranted. Primary endpoint: dose-limiting toxicity (DLT) rate of FOLFIRABRAX with genotype-guided dosing of IRI. Secondary endpoints include objective response rates (RR) in select GI cancers. Methods: Pts with previously untreated GI cancers and ECOG performance status 0/1 received FOLFIRABRAX with prophylactic pegfilgrastim Q14 days. CT scans were obtained Q8 weeks. UGT1A1 *1/*1, *1/*28, and *28/*28 pts received initial IRI doses of 180, 135, and 90 mg/m2, respectively. 5-FU 2400 mg/m2 over 46 hours (no bolus), leucovorin 400 mg/m2, and NP 125 mg/m2 were given IV Q14 days. DLT during cycle 1 was defined as Grade (Gr) 3/4 febrile neutropenia (FN), Gr 4 neutropenia ≥ 5 days, Gr 3/4 non-hematologic toxicity despite medical management, or treatment delay > 14 days due to toxicity. Doses were tolerable if DLT rate during cycle 1 was ≤ 35%. Enrollment of 17 pts per genotype allowed for an alpha level of 0.05 with 80% power under a sequential toxicity monitoring procedure, with 6 or fewer DLTs deemed tolerable. Results: 50 pts are evaluable for toxicity: 30 pancreatic cancer (PC), 9 biliary tract cancer (BTC), 6 gastroesophageal adenocarcinoma (GEA), 4 unknown GI primary, and 1 neuroendocrine. DLTs were observed in 5/23 (21.7%) *1/*1 pts, 1/20 (5%) *1/*28 pts, and 0/7 *28/*28 pts. DLTs were Gr 3 diarrhea (3 pts), Gr 3 nausea (2 pts), and Gr 3 FN (1 pt). RR is 12/39 (30.7%), with responses in PC (9/25 evaluable pts, 36%), GEA (3/6 pts, 50%), but not in BTC (0/8 pts). Ten pts continued therapy beyond 24 weeks. Conclusions: FOLFIRABRAX with genotype-guided dosing of IRI is tolerable in pts with advanced GI cancers and UGT1A1*1*1 or UGT1A1*1*28 genotypes. Responses were observed in PC and GEA but not in BTC. Clinical trial information: NCT02333188.

Background: The benefit of adding external beam radiation to adjuvant chemotherapy in patients that have undergone a margin positive resection for early stage, pancreatic ductal adenocarcinoma has not been determined definitively. Methods: The National Cancer Data Base was queried to evaluate the utility of adjuvant radiation in patients with pathologic stage I-II pancreatic ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive margin (margin positive resection) between 2004 and 2013. Results: In the study, 1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive (pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox modeling stratified by nodal status demonstrated the benefit of radiation to be statistically significant only in node positive patients (hazard ratio 0.81, 95% confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2 months for those receiving adjuvant chemotherapy alone (P = .003). In patients who had negative nodes, there was no difference in overall survival with radiation (22.5 vs 23.6 months, P = .511). Conclusion: Addition of radiation to adjuvant chemotherapy after a margin positive resection confers a survival benefit albeit limited (about 2 months) in patients with node-positive pancreatic head cancer. (C) 2017 Elsevier Inc. All rights reserved.

TPS4151 Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and an R0 resection was achieved in 64% of operations. However, the individual contributions of preoperative chemotherapy and radiation therapy are poorly defined.This study, Alliance for Clinical Oncology Trial A021501, will help define a standard preoperative treatment regimen for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Methods: In this recently activated randomized phase II trial, 134 patients with a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed radiographic criteria for borderline resectable disease are randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy undergo pancreatectomy and subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Clinical trial information: NCT02839343.

97 Background: Node positive disease (N+) is frequent (~40%) following neoadjuvant therapy (NAT) and esophagectomy, yet limited data exist regarding the efficacy of adjuvant chemotherapy (AC) in this setting. There are no randomized studies addressing this question and single-institution, retrospective studies have reported mixed findings. Methods: A retrospective analysis was conducted using the National Cancer Database. 2,258 N+ patients were identified who had received NAT (83.3% chemoradiation and 17.7% chemotherapy alone) followed by esophagectomy. Patients with either incomplete staging or treatment data were excluded, as were those who died within 90 days following esophagectomy. Multivariate logistic regression was used to test for differences in patient characteristics between those who did (AC+) or did not (AC-) receive AC. Overall survival (OS) after surgery, by AC status, was analyzed using Cox regression in a sample propensity matched on relevant demographic and clinical factors. Results: 433/2258 patients received AC (19.2%). Patients who received AC tended to be younger (OR 0.98 per 1-year increase, P = .03) and had a higher socioeconomic status (SES) (OR 1.47 for high vs. low SES, P = .01). Although there were no significant differences in comorbidity (P = .32), AC+ patients had significantly shorter hospital stays after surgery (OR 0.98 per 1-day increase, P = .03). Pathologic T classification was unrelated to the likelihood of receiving AC (P = .39), however patients with a higher pathologic N stage were more likely receive AC (OR 2.12 for pN3 vs. pN1, P < .001). Those receiving AC had demonstrably longer OS from the time of surgery than those who did not (HR 0.78, P = .004). Median OS for the entire cohort was 22.6 months, whereas the administration of AC was associated with an improvement in median OS of 6.2 months (26.3 vs. 20.1 months). Conclusions: This retrospective analysis indicates that AC is associated with a significant improvement in OS (median 6.2 months) in N+ patients following NAT and esophagectomy. Further studies are needed to clarify the optimal role of AC in this setting.

Objective: Neoadjuvant protocols for early stage pancreatic adenocarcinoma (PDAC) frequently involve external beam radiation used in combination with systemic chemotherapy. The benefit of radiation in these protocols has not been determined.Methods: We examined patients with stage I and II PDAC within the National Cancer Data Base between 2006 and 2012. Propensity score matching was used to compare patients receiving neoadjuvant chemotherapy including radiation (NCRT) to those receiving neoadjuvant chemotherapy without radiation (NCT) prior to pancreaticoduodenectomy.Results: Prior to matching, NCRT patients had higher rates of T3 tumors (P = 0.046) and vascular abutment (P < 0.001). Propensity score matching (1:1) yielded 397 patients per group. Patients treated with NCRT were more likely to have node negative resections (P < 0.001) but had increased rates of 90-day mortality (P = 0.015) and demonstrated a trend towards shorter overall survival (P = 0.0502) than those receiving NCT.Conclusion: In early stage PDAC, the addition of radiation to NCT is often utilized with more advanced disease and is associated with higher perioperative mortality and no long-term overall survival benefit. (C) 2016 Elsevier Inc. All rights reserved.

In their article, Drs. Whisenant and Venook review data regarding the value of hepatic arterial infusion (HAI) chemotherapy for hepatic colorectal metastases. In fact, their analysis reveals the absence of any material progress in HAI therapy since the first reports of continuous infusion of chemotherapy through the hepatic artery.[1] During the same period, there has been dramatic improvement in hepatic imaging, outcome from hepatic resection, systemic chemotherapy, and survival following treatment of hepatic colorectal metastases. Failure of HAI therapy to advance in parallel with other treatments for liver metastases—whether used prior to or after resection, or as definitive treatment for unresectable disease apparently confined to the liver— suggests a limited role for HAI therapy in this disease. Several points warrant discussion.

Background. The value of neoadjuvant chemotherapy in the treatment of early stage pancreatic cancer is not yet clear.Methods. We evaluated patients from the National Cancer Data Base who underwent pancreatico-duodenectomy for clinical stage I and II pancreatic-adenocarcinoma between 2006 and 2012.Results. In total, 7,881 patients were identified. Of these, 27.5 % received no chemotherapy, 57.4% received adjuvant chemotherapy, 10.2% received neoadjuvant chemotherapy alone, and 4.9% received perioperative chemotherapy, both preoperative and postoperative chemotherapy. Neoadjuvant chemotherapy use (neoadjuvant chemotherapy alone and perioperative chemotherapy) increased from 12.0% in 2006 to 20.2% in 2012. Patients who received chemotherapy prior to the operation (neoadjuvant chemotherapy alone and perioperative chemotherapy) had greater rates of margin negative (80.2 % vs 73.0%, P <.001) and node negative (58.2% vs 28.7%, P <.001) resections and shorter mean durations of stay (12.0 vs 11.1 days, P =.012) than those receiving either adjuvant chemotherapy or no chemotherapy at all. There were no differences in 30 -day unplanned readmissions (P =.074) and 90-day mortality (P =.227). On Cox survival analysis, adjusted for clinical variables including age and comorbid disease, patients undergoing perioperative chemotherapy, adjuvant chemotherapy, and neoadjuvant chemotherapy alone demonstrated significantly improved overall survival relative to that of patients undergoing resection alone (all P <.001). Patients receiving perioperative chemotherapy demonstrated a significant overall survival advantage compared with those receiving adjuvant chemotherapy (hazard ratio 0.75; 95 % confidence interval, 0.65-0.85). Neoadjuvant chemotherapy alone had a marginal overall survival benefit compared with adjuvant chemotherapy (hazard ratio 0.89; 95 % confidence interval, 0.81-0.98).Conclusion. Early stage pancreatic cancer patients who receive perioperative chemotherapy have better overall survival than those receiving no chemotherapy, adjuvant chemotherapy, or neoadjuvant chemotherapy alone. Patterns of postoperative morbidity are similar regardless of the sequence of therapy. Neoadjuvant chemotherapy should be considered for patients presenting with early stage pancreatic cancer.

312 Background: Surgical resection plus adjuvant gemcitabine or 5-FU is standard therapy for resectable PDAC. Infusional 5-FU, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) has substantial activity in metastatic PDAC. Efficacy and tolerability of peri-operative FOLFIRINOX in resectable PDAC is unknown. Methods: Patients (pts) with ECOG PS 0/1 and resectable PDAC confirmed by multidisciplinary review received 4 cycles of mFOLFIRINOX (mFFX)(oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 day 1, 5-FU 2400 mg/m2 x 48 hours, peg-filgrastim 6 mg SQ day 3) pre- and 4 cycles post- surgery. Results: 21/21 enrolled pts started therapy (median age: 63 (47-78), 81% ECOG 0). 20/21 pts completed 4 cycles of preoperative mFFX (1 withdrew for toxicity), 17/21 pts had successful surgical resection (3 had disease noted in the liver at surgery) and 14/21 completed 4 cycles of postoperative mFFX (2 pts expired prior to postoperative mFFX within 90 days of surgery -1 from an M.I. and 1 from a GI bleed; ...