Abstract Lung cancer in never‐smokers has a distinct genomic profile characterized by lower tumor mutational burden, more tumor‐promoting mutations, and fewer somatic copy number variations (CNVs) compared to smokers. While CNVs are linked to poor outcomes in advanced‐stage cancer, their role in early‐stage lung adenocarcinoma remains unclear. In a cohort of 210 treatment‐naive never‐smokers with early‐stage lung adenocarcinoma, hierarchical clustering of CNVs identified three distinct groups: CNV low ( n = 86 41%), CNV moderate ( n = 75 36%), and CNV high ( n = 49 23%). CNV low tumors had minimal CNV burden, CNV moderate tumors exhibited loss of heterozygosity in chromosomes 3, 9, 13, 15, and 18, and CNV high tumors showed genome‐wide amplifications and whole‐genome doubling. Recurrence occurred in 42 patients (20%), with a significantly lower 5‐year cumulative incidence in the CNV low group (14% 95% CI, 7%–25%) compared to the CNV moderate (31% 95% CI, 18%–44%) and CNV high group (48% 95% CI, 27%–66%) ( p = .004). Adjusted hazard ratios for recurrence were 2.30 ( p = .074) and 2.65 ( p = .037) for CNV moderate and CNV high, respectively. These findings suggest CNV status is an independent predictor of recurrence, with CNV low tumors being associated with the most favorable prognosis.
Vanstraelen et al. (Tue,) studied this question.