Association Between Younger Age and Targetable Genomic Alterations and Prognosis in XXXX .

@entity1 @entity7041 @entity5 @entity470 @entity1149 @entity2 @entity8554 @entity31082 @entity420 @entity1722
IMPORTANCE: @entity1149 ( @entity1149 ) diagnosed in young @entity1 is rare, and the genomics and clinical characteristics of this disease are poorly understood. In contrast, the diagnosis of other @entity5 at a young age has been demonstrated to define unique disease biology. Herein, we report on the association of young age with targetable genomic alterations and prognosis in a cohort of 2237 @entity1 with @entity1149 . OBJECTIVE: To determine the relationship between young age at diagnosis and the presence of a potentially targetable genomic alteration, disease prognosis, and natural history. DESIGN, SETTING, AND @entity1 : A cohort of all 2237 @entity1 with @entity1149 who were genotyped at the Dana-Farber @entity5 Institute between January 2002 and December 2014 were identified. @entity5 genotype, @entity1 characteristics, and clinical outcomes were collected and studied at a National @entity5 Institute-designated comprehensive @entity5 center. Multivariate logistic regression was used to analyze the relationship between age and mutation status, and multivariate Cox proportional hazard models were fitted for survival analysis. MAIN OUTCOMES AND MEASURES: The frequency of targetable genomic alterations by defined age categories as well as the association of these age groups with survival. Age categories used in this analysis were younger than 40, 40 to 49, 50 to 59, 60 to 69, and 70 years or older. RESULTS: A cohort of 2237 @entity1 with @entity1149 was studied. Of the 2237 @entity1 , 1939 (87%) had histologically confirmed @entity420 , 269 (12%) had @entity1149 not otherwise specified, and 29 (1%) had squamous histologic findings; 1396 (63%) had either stage IIIB or IV @entity5 ; and median (range) age was 62 (20-95) years. We found that gene mutations for @entity470 (P   =   .02) and @entity7041 (P   <   .001) were associated with @entity5 diagnosis at a younger age, and a similar trend existed for @entity1722 (P   =   .15) and @entity31082 (P   =   .10) but not BRAF @entity8554 (P   =   .43). Among @entity1 tested for all 5 targetable genomic alterations (n   =   1325), younger age was associated with an increased frequency of a targetable genotype (P   <   .001). Those diagnosed at 50 years or younger have a 59% increased likelihood of harboring a targetable genotype. While presence of a potentially targetable genomic alteration treated with a targeted agent was associated with improved survival, the youngest and oldest age groups had similarly poor outcomes even when a targetable genotype was present. CONCLUSIONS AND RELEVANCE: Younger age is associated with an increased likelihood of harboring a targetable genotype and is an underappreciated clinical biomarker in @entity1149 . The survival of young @entity1 with NCSLC is unexpectedly poor compared with other age groups, suggesting more aggressive disease biology. These findings underscore the importance of comprehensive genotyping, including next-generation sequencing, in younger @entity1 with @entity2 .
