Amanjit Bal¹, Parul Gupta¹, Navneet Singh², Tamanna Thakur¹, Suvradeep Mitra^1
1Departments of Histopathology; ²Pulmonary Medicine PGIMER, Chandigarh, India

Background: Besides EGFR, ALK and ROS1, molecular alterations in BRAF and KRAS represent a novel therapeutic target for the treatment of advanced NSCLC.

Methods: EGFR/ALK/ROS1 negative lung adenocarcinoma patients (N=107) were enrolled in this retrospective study. Baseline demographic characteristics including age, gender, smoking index, TNM stage, performance status, were recorded. Patients were tested for KRAS p.G12C; KRAS p.G12D and BRAF p.V600E variation using digital droplet PCR. 

Results: Out of 107, 30% were females, 70% were males and the median age was 63(IQR-55-68). Sixty-five patients were smokers and majority (78%) had stage IV disease. Thirteen patients were positive for KRAS p.G12C and KRAS p.G12D each and one patient had both the variations. Only one female never smoker patients had BRAF p.V600E variation. Histologically 4/13 patients with KRAS p.G12D and one patient with BRAF p.V600E had lepidic predominant pattern, one patient with both KRAS p.G12D and KRAS p.G12C had mixed morphology of lepidic+mucinous adenocarcinoma. Seven out of 13 patients with KRAS p.G12C variation had mucinous adenocarcinoma. No correlation between smoking index, TNM stage, ECOG, KPS, gender and the mutation status was noted. 

Conclusion: Molecular alterations beyond EGFR/ALK/ROS1 should be tested as these can impact treatment decisions and prognosis of the patients.