Abstract 2037: Association of molecular heterogeneity and actionable mutations with survival in lung cancer
Authors: Fricke Jeremy , Mambetsariev Isa , Pharaon Rebecca , Wang Yingyu , Chen Chen , Qiu Fang , Smith Lynette , Batra Surinder K. , Nasser Wasim M. , Massarelli Erminia , Koczywas Marianna , Reckamp Karen , Salgia Ravi 
Published: September 2020

Introduction: Today, the use of new technologies such as electronic medical records and testing methods are standard throughout healthcare centers. These new tools deliver an abundance of information to physicians, researchers, and the medical community. Harnessing the potential of this data can be an influential instrument to assist physicians in offering personalized medicine to patients and conduct complex research with ease. Nevertheless, the development, infrastructure, and implementation of distinct disease-specific registries for the collection, storage, and utilization of this data is crucial to benefit from this vital clinical and research information.

Patients and Methods: In this study, we utilized an institutional thoracic patient registry complete with clinical and genomic data to carry out an in-depth analysis on lung adenocarcinoma patients (N=415). The patients selected and evaluated for analysis were seen at City of Hope from 2008 to 2016. The data was collected between 2016 and 2018 through retrospective chart review and compiled within the Thoracic Oncology Registry. This study was approved by the Institutional Review Board at COH under IRB 18217 and was conducted according to the Declaration of Helsinki. Data was de-identified and analyzed anonymously.

Results: The lung adenocarcinoma median age was 64 (range, 22-92) years old, and the median OS was 33.29 months (95% CI, 29.77-39.48). The majority of patients were female (245/415; 59%). All the patients had metastatic disease, while the bulk of the patients (369/415; 89%) presented as Stage IV at the time of initial diagnosis. Oncogenes with the most commonly occurring mutations were found in EGFR (207/415; 50%), KRAS (97/352; 28%), and ALK rearrangement (28/377; 7%), while most frequent alterations in tumor suppressor genes were in TP53 (140/283; 49%), LRP1B (63/228; 28%), and STK11 (39/278; 14%). The top three actionable mutations identified include EGFR (177/415; 42.7%), ALK (28/377; 7.4%), and BRAF V600E (7/288; 2.4%). When survival was compared between the number of patients with actionable mutations (222/415; 53.5%) and wild-type patients (193/415; 46.5%), there was a substantial difference in median OS (39.8 months v 26.0 months, P&lt;0.001). Comparing the TCGA and AACR Project GENIE dataset to our database, there was a surprising difference in the percentage of actionable mutations (15.0% v 22.3% v 53.5%).

Conclusion: Our results showed an increased median overall survival in patients with lung adenocarcinoma that harbor actionable mutations compared to wild-type patients. Exploiting the appropriate use of clinical and genomic data collected and maintained in patient registries may better account for patient populations seen in the academic and community settings to improve cohort selection for clinical trials and survival outcomes.

Citation Format: Jeremy Fricke, Isa Mambetsariev, Rebecca Pharaon, Yingyu Wang, Chen Chen, Fang Qiu, Lynette Smith, Surinder K. Batra, Wasim M. Nasser, Erminia Massarelli, Marianna Koczywas, Karen Reckamp, Ravi Salgia. Association of molecular heterogeneity and actionable mutations with survival in lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2037.