Clinicopathological profile of ALK and ROS1-positive lung tumors: a single-centre retrospective study from Nepal

Anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1) rearrangements are actionable drivers in non-small cell lung cancer (NSCLC), occurring in approximately 4–5% and 1–2% of cases, respectively. Data from low- and middle-income countries, including Nepal, remain limited. To evaluate the clinicopathological characteristics and ALK/ROS1 immunohistochemistry-based profile of NSCLC patients in a tertiary care setting. This retrospective single-center observational study included 6,078 cancer cases, of which 670 were lung cancers and 560 were NSCLC. All NSCLC cases underwent immunohistochemistry-based screening for ALK and ROS1. A total of 51 patients with ALK or ROS1-positive NSCLC or ALK-positive inflammatory myofibroblastic tumor, with complete clinical data, were analyzed. Descriptive statistics were used, and exploratory comparisons between ALK and ROS1 subgroups were performed using the Mann-Whitney U test and Fisher’s exact test. Time to TKI initiation, first-line TKI treatment duration, time to first-line TKI discontinuation, progression-free survival (PFS), and overall survival (OS) were assessed from available clinical follow-up data. Kaplan-Meier methods were used to estimate time to TKI discontinuation, PFS, and OS. The median age was 53 years (range, 26–82), with a slight male predominance (53%). Most patients were non-smokers (80%) and presented with advanced disease, with 71% in Stage IV. Adenocarcinoma was the predominant subtype (65%). Among the 51 IHC-positive cases, 42 (82.4%) were ALK-positive and 9 (17.6%) were ROS1-positive; two of the ALK-positive cases were inflammatory myofibroblastic tumors. No statistically significant differences were observed between the ALK and ROS1 subgroups in the evaluated clinicopathological characteristics. All 51 patients had documented initiation of first-line crizotinib. The median time from diagnosis to TKI initiation was 0.82 months (interquartile range [IQR], 1.25), while the median observed duration of first-line TKI treatment was 17.9 months (IQR, 22.6). Twelve patients (23.5%) subsequently received lorlatinib. The estimated median time to first-line TKI discontinuation was 36.4 months (95% CI, 27.0-not reached). The median PFS was 41.7 months (95% CI, 27.0-not reached), whereas the median OS was not reached. In this single-center Nepalese cohort, ALK and ROS1-positive NSCLC was characterized by frequent non-smoking history and advanced-stage presentation. Exploratory comparison between ALK and ROS1 groups did not show statistically significant differences in the evaluated clinicopathological characteristics. The findings support the need for improved access to confirmatory molecular testing and broader genomic profiling in this resource-limited setting.