Citations

291 Background: Cholangiocarcinoma (CCA) has limited treatment options. Genomic analyses have led to development of targeted therapies now in clinical trials, and may enable discovery of new treatment options. However, biopsy often yields limited tissue, thus hampering tissue-based profiling opportunities. Comparative data regarding circulating tumor DNA (ctDNA) analysis and tissue based profiling in CCA are limited. Methods: We performed ctDNA NGS analysis along with tissue based profiling in pts with advanced CCA (January 2015- February 2018). ctDNA analysis was performed using Guardant 360 (Guardant Health, CA) which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in up to 73 different genes and the majority of tissue based profiling using Foundation One. The mutant allele fraction (MAF) for detected alterations was calculated relative to wild type in ctDNA. Therapeutic relevance was defined as alterations within OncoKB levels 1-3B and R1. The study was conducted in accordance with Mayo Clinic IRB requirements. Results: Among 124 pts and 139 total samples, ctDNA NGS revealed at least one genomic alteration (excluding variants of uncertain significance and synonymous mutations) in 89% of pts. Median number of alterations per pt was 3 [range, 1-15], with a median MAF of 0.42% (range, 0.1% - 94.2%). The total number of unique alterations was 321. The most commonly altered genes: TP53 (31%), KRAS (11%), FGFR2 (7%), APC and PIK3CA (each 5%) and ARID1A (3%). Amplifications were noted in 14 genes: BRAF, CCND1, CCND2, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, MET, MYC, PDGFRA, and PIK3CA. Tissue-based profiling was available in 57 (46%) pts, with a median of 63 days between liquid and tissue biopsy. IDH1, FGFR2, TP53 and KRAS were most common gene mutations found in pts who had both liquid and tissue biopsy done. (Comparative results to be shown). Conclusions: ctDNA plasma profiling of pts with advanced CCA is a feasible alternative method to gather comprehensive genomic data. Further larger cohort studies comparing landscape of alterations seen on ctDNA versus tissue-based assays are needed.

289 Background: PDAC has limited treatment options. Genomic analyses have led to development of targeted therapies now in several clinical trials, and may enable the discovery of new treatment options. However, biopsy often yields limited tissue, thus hampering tissue-based profiling opportunities. Data regarding circulating tumor DNA (ctDNA) profiling in PDAC during real time clinical practice is limited. Methods: We performed ctDNA NGS analysis in pts with advanced PDAC (December 2014–August 2018). ctDNA analysis was performed using Guardant 360 (Guardant Health, CA), which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in up to 73 different genes. The mutant allele fraction (MAF) for detected alterations was calculated relative to wild type in ctDNA. Therapeutic relevance (TR) was defined as possible treatments within OncoKB levels 1-3B and R1. The study was conducted in accordance with Mayo Clinic Institutional Review Board requirements. Results: Among 171 pts and 206 total samples, ctDNA NGS revealed at least one genomic alteration in 150 pts (88%). Median number of alterations per patient was 3 [range, 1-15]. The total number of unique alterations was 450 with the most commonly altered genes being: TP53 (181 alterations, 40%), followed by KRAS (118 alterations, 26%), CDKN2A (23 alterations, 5%), SMAD4 (15 alterations, 3%), EGFR (11 alterations, 2.4%), PIK3CA (9 alterations, 2%), GNAS (8 alterations, 1.5%). Amplifications were noted in 16 genes, including BRAF, CCND2, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, KIT, KRAS, MET, MYC, PDGFRA, PIK3CA and RAF1. Therapeutically relevant alterations were seen in 95 pts of the 150 pts (63%). Tissue based profiling (Results to be shown) was done in 56 (33%) pts of total 171 pts with a median of 130 days between ctDNA and tissue biopsy. KRAS and TP53 were the most common gene mutations found in patients with both liquid and tissue biopsy results. Conclusions: ctDNA plasma profiling of pts with advanced PDAC is a feasible alternative method to gather comprehensive genomic data.

288 Background: Obesity is a risk factor for developing cholangiocarcinoma (CCA). However, the effect of obesity on survival of CCA is unclear. The primary aim of this study was to analyze the impact of obesity upon overall survival of CCA patients. Secondary aims were to analyze impact of obesity upon other disease characteristics such as tumor site, stage, age, sex, BMI and Ca 19-9. Methods: A total of 411 unique pts diagnosed with CCA at Mayo Clinic Florida between 2000 and 2018 were retrieved from our collective SDMS database. Variables evaluated included:demographics, Body Mass Index (BMI), AJCC stage, tumor location and Ca 19-9.A total of 185 pts had all data available pertaining to these variables. We further restricted the analysis to pts with intrahepatic CCA classified BMI as per CDC criteria normal (18.5-25kg/m2), overweight (25-29.9kg/m2) and obese (≥30 kg/m2), thus leaving a total of 152 pts. Continuous and categorical variables were compared across BMI groups using Chi-squared or Fisher’s exact test. Overall survival rates after diagnosis at 1, 2 and 3 years were estimated using Kaplan-Meier method. Results: Among 152 pts included in the study, 28% were normal weight, 40% were overweight and 32% were obese. The overall survival rate at 1, 2 and 3 years for normal weight pts with all stages combined was 54.1%, 35%, and 30.7%, respectively. The overall survival rate at 1, 2 and 3 years for overweight pts with all stages combined was 59.7 %, 32.6%, and 25.4%, respectively. The overall survival rate at 1, 2 and 3 years for obese pts with all stages combined was 63.9%, 37.6%, and 26.7%, respectively(p = 0.8766). Multivariate analysis demonstrated is no significant difference in overall survival for obese pts compared to normal or overweight pts.(Table to be shown) However it showed, gender and Ca19-9 were statistically significant predictors of overall survival, with males and pts with Ca19-9≥100 doing worse (HR1.65 (CI = 1.05, 2.61, p = 0.031) and HR 2.31 (CI = 1.49, 3.59, p = < 0.01), respectively). Conclusions: BMI did not make a significant impact on the overall survival, though there may be a trend toward worse OS for ptswith higher BMI. A larger, stage focused evaluation is warranted for further exploration of this trend.

Purpose (1) To determine the radiographic correction/healing rate, patient‐reported outcomes, reoperation rate, and complication rate after distal femoral osteotomy (DFO) for the valgus knee with lateral compartment pathology. (2) To summarize the reported results of medial closing wedge and lateral opening wedge DFO. Methods We conducted a systematic review of PubMed, MEDLINE, and CINAHL to identify studies reporting outcomes of DFOs for the valgus knee. Keywords included “distal femoral osteotomy,” “chondral,” “cartilage,” “valgus,” “joint restoration,” “joint preservation,” “arthritis,” and “gonarthrosis.” Two authors first reviewed the articles; our study exclusion criteria were then applied, and the articles were included on the basis relevance defined by the aforementioned criteria. The Methodological Index for Nonrandomized Studies scale judged the quality of the literature. Sixteen studies were relevant to the research questions out of 191 studies identified by the original search. Results Sixteen studies were identified reporting on 372 osteotomies with mean follow‐up of 45 to 180 months. All studies reported mean radiographic correction to a near neutral mechanical axis, with 3.2% nonunion and 3.8% delayed union rates. There was a 9% complication rate and a 34% reoperation rate, of which 15% were converted to arthroplasty. There were similar results reported for medial closing wedge and lateral opening wedge techniques, with a higher conversion to arthroplasty in the medial closing wedge that was confounded by longer mean follow‐up in this group (mean follow‐up 100 v 58 months). Conclusions DFOs for the valgus knee with lateral compartment disease provide improvements in patient‐reported knee health–related quality of life at midterm follow‐up but have high rates of reoperation. No evidence exists proving better results of either the lateral opening wedge or medial closing wedge techniques. Level of Evidence Level IV, systematic review of Level IV studies.