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e15135 Background: While the use of monoclonal antibodies targeting the PD-1 axis in metastatic non-small cell lung cancer (NSCLC) continues to expand since initial FDA approval in 2015, factors predictive of response still remain to be determined. Mutation status may provide insight as to which subgroups exhibit resistance to checkpoint inhibitor therapy. Methods: We conducted a single center retrospective analysis of patients with metastatic NSCLC treated at the University of Miami / Sylvester Comprehensive Cancer Center who underwent next-generation sequencing (NGS) and identified patients that harbor either STK11 mutation alone (S) or co-mutations with STK11 and KRAS (S/K). Genomic results were obtained from Guardant360 and Foundation One testing in blood and tissue, respectively. Results: We identified 37 S patients and 36 S/K patients and determined no significant differences in progression-free survival (PFS). However, overall survival (OS) was significantly increased in patients with S/K co-mutation (20.3 ± 4.1 months) vs. patients with S alone (11.9 ± 1.9 months, p = 0.028). Furthermore, S/K patients who received immunotherapy had longer OS (20.7 ± 5.6 months) vs. S patients (13.6 ± 3.4 months, p = 0.049). We further investigated any population-specific factors that may contribute to the enhanced survival in the S/K cohort that had received immunotherapy, as previous studies have reported that STK11/KRAS co-mutations may confer a resistance to PD-1 axis-directed therapy. We found that S/K patients were older at diagnosis and were more likely to have received nivolumab (as compared to newer therapies pembrolizumab and atezolizumab). In addition, S/K patients were more likely to have longer smoking histories (81% smoked more than 30 pack-years at diagnosis) vs. S patients (53%, p = 0.01) and also had a higher number of additional targetable mutations found on NGS (4.7 ± 0.4 vs. 2.9 ± 0.3, p = 0.001). The most commonly identified mutations were TP53 (30%), KEAP1 (19%), CDKN2A/B (18%), SMARCA4/BRG1 (16%), and ARID1A (11%). Conclusions: Our study reveals an interesting analysis of potential predictors of resistance to immunotherapy with the utilization of precision medicine in combination with patient characteristics to identify the most appropriate treatment regimens for patients with NSCLC. Further studies will explore whether patients receiving immunotherapy as first line could overcome any inherent resistance to PD-1 axis-directed therapy from non-modifiable factors at diagnosis.

Background To match medical students into residency training programs, both the program and student create rank order lists (ROLs). We aim to investigate temporal trends in ROL lengths across 7 match cycles between 2014 and 2021 for both matched and unmatched residency applicants and programs. Methods retrospective study of ROLs of 7 match cycles, 2014-2021. Residency match and ROL data were extracted from the NRMP database to assess the number of programs filled and unfilled, length of ROLs, position matched, and average ranks per position for osteopathic (DO) and allopathic (MD) medical programs. Results For filled residency programs, the average ROL length consistently increased from 70.72 in 2015 to 88.73 in 2021 ( P = .003), with ROL lengths consistently longer for filled vs unfilled residency programs ( P < .001). The average ROL length for matched applicants increased consistently from 10.41 in 2015 to 12.35 in 2021 ( P = .002), with matched applicants having consistently longer ROLs than unmatched applicants ( P < .001). From 2015 to 2021, in both MD and DO applicants, progressively lower proportions of applicants matched their first and second choices. Conclusion Trends across the past 7 residency match cycles suggest that ROL lengths for both programs and applicants have been increasing with matched programs and applicants submitting significantly longer ROLs than unmatched applicants. Additionally, fewer applicants are matching at their preferred programs over time. Our findings support the mounting evidence that the Match has become increasingly congested and we discuss the possible factors that may be contributing to the current state of the Match as well as potential solutions.