Mutation Count, A Potential Surrogate For Tumor Mutation Load, Of Circulating Tumor Dna (Ctdna) Using Targeted Panel Sequencing Correlates With Clinical Outcomes In Late Stage Lung Adenocarcinoma And Small Cell Lung Cancer.

12045 Background: Studies show that mutation count can be used as a biomarker to predict whether or not a patient may respond to immunotherapy or chemoradiation therapy. However, mutation count is usually determined by whole exome sequencing or large targeted panel sequencing of tumor tissue DNA. Tissue biopsy is often inaccessible for many late stage lung cancer patients. Methods: We assessed mutation count using the AVENIO ctDNA Surveillance Kit, a targeted next-generation sequencing panel of 198 kilobases, on pre-treatment plasma samples from a prospective, observational study, where 43 late stage lung adenocarcinoma and 72 late stage small cell lung cancers (SCLC) treated with first-line chemo or chemoradiation therapies were initially assessed. Synonymous and prevalent driver mutations were filtered out from the detected somatic mutations prior to calculating a mutation count per megabase. Subjects were classified as high mutation count if the filtered somatic mutation count was above the bottom tertile of their cancer type. Results: We detected somatic variants in all 43 lung adenocarcinoma and 72 SCLC subjects with a median mutation count of 9 and 14, respectively. Lung adenocarcinoma subjects with low mutation count showed better survival in terms of overall survival (OS) (18.3 vs 7.8 mo, HR 0.41, p = 0.026) and progression free survival (PFS) (6.2 vs 4.3 mo, HR 0.51, p = 0.042). SCLC subjects with low mutation count had shorter OS (9.3 vs 14.1 mo, HR 1.75, p = 0.034) and a similar trend in PFS. Conclusions: We were able to derive a ctDNA-based mutation count from a panel the size of one-fifth of a megabase and identified an association between low mutation count and better prognosis in subjects with late stage lung adenocarcinoma treated with chemo or chemoradiation therapy. In late stage SCLC, however, high mutation count correlated with better prognosis. Our findings suggest differences in lung cancer histology are key to understanding measurements of mutation count and their potential to predict outcome on chemotherapy. Studies to further validate these results are ongoing.