Weatherly, J.

4086 Background: Mutations in DNA repair pathway were identified in 13% of Biliary Tract Cancers (BTC) [ Cancer2016;122:3838–3847]. High TMB tumors including melanoma, lung cancer and those with microsatellite instability (MSI-H) are associated with susceptibility to immune blockade using checkpoint inhibitors. TMB data in BTC is limited and its association with actionable somatic mutation (mut) profiles in BTC is unknown. Methods: Comprehensive genomic profiling (CGP) of 309 FFPE tissue blocks of BTC pts with a hybrid capture of all coding exons of 236 cancer-related genes and 47 introns of 19 genes rearranged in cancer was done using FoundationOne. Base substitutions, indels, gene fusion/rearrangements, TMB, and MSI status were assessed. TMB was calculated by counting mutations across a 1.25Mb region and classified into high (TMBH; ≥20 mut/Mb), intermediate (TMBI; 6 - 19mut/Mb) and low (TMBL; < 6mut/Mb). MSI high (MSIH) and Stable (MSS) status was assigned by a computational algorithm examining 114 intronic homopolymer loci. Patients with TMB ≥6 mut/Mb (N = 60) were included in the clinical correlative portion of this study. Results: Sixty patients with TMB ≥6 mut were identified out of 309 pts of which 9 (15%) were TMBH and 51 (85%) were TMBI. These included 3 (5%) MSIH and 18 (30 %) MSS. The median age was 59 years (range: 29-86), 35 (58%) were females, majority were intrahepatic cholangiocarcinoma (n = 31; 52%) and 28 (47%) presented with advanced disease at diagnosis. Twenty three (38%) pts had received radiation therapy, 28 (47%) surgery and 3 (5%) received immunotherapy. Most frequent co-existing mut seen was TP53 (N = 35; 58%). APC mut was seen in 7 (12%) pts. DNA repair pathway muts ( MSH6, BRCA1, BRCA2, ATM, MLH1, or MSH2 genes) were identified in 78% of TMBH versus 16% in TMBI cases (p < 0.0001). Frequency of PIK3CA mut differed significantly between TMBH and TMBI (44% vs 10%, p < 0.0001). Pts with TMBI had a significantly better median OS (110 weeks) as compared to TMBH (43 weeks) (p = 0.003). Conclusions: DNA repair pathway and PIK3CA mut maybe associated with TMBH in BTC. A better understanding of TMB and associated actionable mutations in BTC may be of value for the management of BTC patients with targeted agents and immunotherapy.

65 Background: Cholangiocarcinoma (CC) accounts for approximately 3% of all gastrointestinal cancers and have a poor incident to mortality rate. The incidence in the United States (US) is 2,000-3,000 cases annually, with this rate steadily increasing during the last twenty years; this trend is not solely observed in US but also seen in Europe, Australia and Japan. The highest incidence is seen in Southeast Asia due to parasitic infection. CC presents many challenges to healthcare professionals due to the anatomic nature of CC (Lowe et al, 2015). The worldwide increase in incidence of CC is indication for the essential development of nursing practice guidelines underpinned by expert evidence and knowledge and regarding the key aspects of care. Methods: A collaboration of nursing professionals representing major cancer research institutions from around the country and the United Kingdom worked together to identify key aspects of care, the aim being to develop Clinical Nursing Practice Guidelines. The process included an exhaustive literature review using Pubmed, Uptodate, Medline, and CINAHL databases; submission of respective institutional practices; group consensus on guideline content, evidence-based scoring assignment and approval by the Cholangiocarcinoma Medical Advisory Board. Results: The guidelines developed include the care of the patient: (1) with external biliary drains and internal bile duct stents, (2) with intractable nausea and vomiting resulting from disease process, (3) with fatigue resulting from disease process, (4) undergoing chemotherapy, (5) undergoing photon radiation, (6) undergoing radiation on a clinical trial, and (7) preparing for liver transplantation. The purpose of the guidelines are to advance the scientific knowledge of the symptoms experienced, quality of life of patients with CCA, establish standards in patient care, and improve quality of care and satisfaction for patients diagnosed with CC. Conclusions: Creation of evidence-based guidelines will provide a springboard for expanded competent knowledge and a model to test for improvement in the care and quality of life of the patient with CC.