e16007 Background: Due to the termination of the Codman pump, in order to administer hepatic arterial infusion (HAI) chemotherapy, the Medtronic pump has been used with the Codman catheter at MSKCC since 2018. Methods: Retrospective review of patients(pts) receiving HAI therapy via Medtronic pumps. Expected versus actual dose delivery of HAI FUDR, response rates and safety were reviewed. Results: Pts included; unresectable colorectal liver metastases (CRLM) (94 pts), resected CLRM (66 pts) and unresectable intrahepatic cholangiocarcinoma (ICC) (11 pts). Baseline characteristics of the 171 evaluable pts are shown in Table. In 120 pts with mCRC, 51.8% (n = 58) had 10 or more hepatic tumors and 23.2%( n = 26) had 50% or more liver involvement by metastases. 52 out of 171 pts (30.4%) had 100% of the expected FUDR doses by completion of the 3rdcycle. Another 49.7% (85/171) had greater than or equal to 50% of the expected FUDR dose. 96 pts had measurable disease (unresectable CLRM and ICC subgroups) evaluated by RECIST 1.1 with an MSK radiologist. The partial response for unresectable CRLM pts was 47% (41/87), and 28% (24/87) were stable. The partial response for ICC pts was 22% (2/9), and 33% (3/9) were stable. Conclusions: We evaluated 171 pts who were heavily pretreated and had extensive disease prior to pump placement. Partial response by RECIST 1.1 of 47% was evident in those pts with CRLM and 22% for pts with ICC. Dose delivery of HAI FUDR was compatible with that seen with the Codman pump and no increase in toxicity was noted. An updated analysis with additional evaluable pts will be presented at the meeting. [Table: see text]

653 Background: PanNENs represent 1-2% of all pancreatic neoplasms. The genomic landscape derived from PanNEN tumor tissue has been described previously. There are little data detailing the frequency of genetic alterations identified in cfDNA in an advanced PanNEN population, the plasma-tissue concordance of detected alterations, and the clinical utility of cfDNA. Methods: Patients (pts) with metastatic PanNENs underwent collection of cfDNA for NGS using the MSK-IMPACT 505 gene assay between March 2017 and April 2020. Matched tissue based NGS with the FDA authorized MSK-IMPACT gene assay was completed when tumor tissue was available. For some pts, plasma and tumor tissue were sequenced at multiple time points. Clinical actionability of sequence variants was annotated by OncoKB. Clinicopathologic characteristics were extracted, and data are herein reported. Results: 25 unique pts with metastatic PanNENs had 32 plasma samples analyzed. The majority had well differentiated (22/25; 88%), intermediate grade disease (13/25; 52%). 6 (24%) pts had well differentiated high grade disease and 3 (12%) had poorly differentiated neuroendocrine carcinomas. After extraction, median cfDNA yield per sample was 23.98ng (range: 3.2 to 500.1). Mutations were detected in 21(66%) of 32 samples (10 pre systemic therapy, 10 at progression, 12 post response to therapy or while stable on therapy). The most frequently mutated genes occurring in >10% of patients were DAXX (28%), TSC2 (24%), MEN1 (24%), ARID1B (20%), ARID1A (12%) and ATRX (12%). 23 (92%) pts underwent tumor tissue sequencing with MSK-IMPACT with a median time of 6.9 (range: 0.5-33.4) months between tissue collection and time of plasma analysis. NGS of cfDNA identified the most common mutations observed in tumor tissue for: DAXX (5/6; 83%), TSC2 (3/6; 50%), MEN1 (5/12; 42%), ARID1A (3/5; 60%) and ATRX (3/6; 50%). In 21/23 (91%) paired samples, additional mutations not seen in tissue were detected in plasma and included TSC2, TP53, EGFR, VHL, and BRCA2. Potentially actionable mutations were identified in sequenced cfDNA in 8/25 (32%) patients including 4 TSC2 mutations (level 3b), 1 ATM mutation (level 3b), 2 ARID1A mutations (level 4) and 1 KRAS mutation (level 4). One patient who was treated with larotrectinib for an ETV6:NTRK3 fusion detected on tumor sequencing ultimately developed resistance with a NRTK3 G623R alteration identified through sequencing of cfDNA at radiographic disease progression. Conclusions: NGS of cfDNA in metastatic PanNENs, across the spectrum of WHO-defined tumor grade/differentiation, revealed tumor-associated genetic alterations in 66% of plasma samples. Clonal evolution, actionable alterations, and resistance mechanisms can be detected through circulating cfDNA genotyping and may serve as a powerful tool to better understand disease biology of a disease that often changes over time and through therapy.

Background: Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease, but whether it is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. Methods: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. Results: Overall 383 patients were included, 107 (27.9%) with EO-PanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P<0.001) but had similar pathology features such as tumor grade (P=0.6), size (2.2 Vs. 2.3 cm, P=0.5) and stageof disease (P=0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P<0.001). With a median follow-up of 70 months (range 0–238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%–28%) and 17% (95% CI 13%–23%), in EO-PanNET and LO-PanNET (P=0.3). Five-year disease-specific survival was 99% (95% CI 98%–100%) with no difference with respect to PanNET onset time (P=0.26). Conclusions: In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET.