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Lung Adenocarcinoma: Next Generation Sequencing and Outcome in Regional Community Oncology Setting

Author(s): Laura E Skacel, Michael J Babcock, Antoine Harb, Adam D Curtis, Carter L Liou, Kathleen T Brawn, Frantisek Sandor, Marek Skacel

Purpose

To analyze lung adenocarcinomas (LUAD) from a geographically unique population of rural Maine by next generation sequencing (NGS), correlate mutational findings with clinical features, patient outcomes and published data from other populations.

Methods

210 consecutive LUADs diagnosed in 2017-2018 were analyzed for 50 oncogene/tumor suppressor gene hot spots by NGS. ALK, ROS-1, RET and MET were assessed by FISH, PD-L1 by immunohistochemistry. Findings were correlated with age, gender, smoking history, stage, overall (OS) and progression-free survival (PFS) and compared to published literature.

Results

The cohort included 113 (54%) women and 97 (46%) men, ages 33 to 91 (mean: 67.4 years), 52% active and 41% former smokers, 79 (38%) of advanced stage (stage IV). Most frequently detected mutations included TP53 (47.6%), KRAS (38.1%), EGFR (10%), STK11 (8.6%), BRAF (4.8%), MET (3.8%), ABL-1, ATM, CDKN2A, PIK3CA, (all 2.9%), RB-1 and NRAS (2.4%), APC, ERBB4, PTPN11, SMAD4, (all 1.9%), CTNNB1 and ERBB2 (both 1.4%). MET amplification occurred in 3.3%, RET and ALK/ROS-1 rearrangements in 1.4% and 0.5%, high PD-L1 expression in 35.2%. Treatment included surgery/radiation/adjuvant chemotherapy for stages I-II, definitive chemo/radiation therapy and immunotherapy for stage III, immunotherapy, chemo-immunotherapy, targeted therapy, palliative radiation for stage IV. At median of 26 months (minimum 21 month for surviving patients), OS/PFS were 44.3%/39.5%. Stage, male gender, TP53 mutation and KRAS/STK11 co-mutations correlated with adverse OS. In stages I-II, KRAS/TP53 co-mutation was unfavorable.

Conclusion

NGS testing in a regional oncology setting identified established prognostic/therapeutic markers, as well as additional molecular features correlating with outcome. Our findings support prognostic stratification of LUAD based on the presence of gene mutations outside of the current NCCN guidelines: TP53, KRAS and STK11.

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