Unique profiles of targetable genomic alterations and prognosis in young Chinese patients with lung adenocarcinoma

Abstract

ObjectiveLung adenocarcinoma in young patients is a rare entity, and the targetable genomic alterations (GAs) are poorly studied. In other cancers, it has been demonstrated that young age defines unique disease biology. Here, the association of young age with GAs and prognosis is studied in a large cohort of Chinese patients. MethodsWe retrospectively screened 1000 consecutive patients, and identified 181 patients aged 40 years or younger. GAs were identified by next-generation sequencing (NGS) assay. The clinical and genetic characteristics were analyzed. ResultsAmong younger group, 167(92.3%) patients were diagnosed withadvanced-stage adenocarcinoma, 98(54.1%) were female, 27(14.9%) were smokers, and the median age was 35 years. Targetable GAs which were significantly more common in the younger population (P < 0.001), were associated with young age (P < 0.05). The frequency of ALK translocations, EGFR and KRAS mutations was 37.6%, 34.3% and 6.1%, respectively. Younger patients had a higher prevalence of rare GAs including HER2, ROS1 and MET (P < 0.05). Prognosis for younger patients was similar (median OS of patients with GAs, 23.91 vs 23.67 months, P > 0.05) or better than that for older population (median OS of patients without GAs, 44.28 vs 41.88 months, P < 0.05) according to GAs. Therapy modality was an independent prognostic factor (P < 0.05), and 83% of death rate decreased if given preferred therapy. ConclusionYounger patients with lung adenocarcinoma had unique prevalence of targetable GAs. Comprehensive genotyping including NGS is recommended for personalized therapy and prognosis evaluation in this population.