Clinicopathological and Demographical Characteristics of Non-Small Cell Lung Cancer Patients with ALK Rearrangements: A Systematic Review and Meta-Analysis

Abstract

ObjectiveThis meta-analysis aimed to comprehensively examine the relationship between the clinicopathological and demographical characteristics and ALK rearrangements in patients with non-small cell lung cancer (NSCLC).Methods and Main FindingsIn total, 62 qualified articles including 1178 ALK rearranged cases from 20541 NSCLC patients were analyzed, and the data were extracted independently by two investigators. NSCLC patients with ALK rearrangements tended to be younger than those without (mean difference: −7.16 years; 95% confidence interval (95% CI): −9.35 to −4.96; P<0.00001), even across subgroups by race. Compared with female NSCLC patients, the odds ratio (OR) of carrying ALK rearrangements was reduced by 28% (95% CI: 0.58–0.90; P = 0.004) in males, and this reduction was potentiated in Asians, yet in opposite direction in Caucasians. Likewise, smokers were less likely to have ALK rearrangements than never-smokers (OR = 0.33; 95% CI: 0.25–0.44; P<0.00001), even in race-stratified subgroups. Moreover, compared with NSCLC patients with tumor stage IV, ALK rearrangements were underrepresented in those with tumor stage I–III (OR = 0.58; 95% CI: 0.44–0.78; P = 0.0002). Patients with lung adenocarcinomas had a significantly higher rate of ALK rearrangements (7.2%) than patients with non-adenocarcinoma (2.0%) (OR = 2.25; 95% CI: 1.54–3.27; P<0.0001).ConclusionOur findings demonstrate that ALK rearrangements tended to be present in NSCLC patients with no smoking habit, younger age and tumor stage IV. Moreover, race, age, gender, smoking status, tumor stage and histology might be potential sources of heterogeneity.

Detection of ALK translocation in non-small cell lung carcinoma (NSCLC) and its clinicopathological significance using the Ventana immunohistochemical staining method: a single-center large-scale investigation of 1,504 Chinese Han patient

“…In NSCLC, ALK rearrangement is associated with distinct clinicopathologic features, including young age at onset and adenocarcinoma histology in patients with a history of never smoking or light smoking and no indication of an EGFR mutation (17-19). Generally, most of the clinicopathologic features of ALK-positive patients in the present study were similar to that of previous studies, including younger age and high grade clinical staging (18-20).…”

Actualización de las recomendaciones para la determinación de biomarcadores en el carcinoma de pulmón avanzado de célula no pequeña. Consenso Nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica

“…Estos pacientes tienden a ser jóvenes, y no hay diferencias de género. Se trata en su mayoría de adenocarcinomas, con frecuencia asociados a determinadas características morfológicas, por ejemplo células «en anillo de sello» o patrón cribiforme 9 . Los reordenamientos de ALK no suelen coexistir con las mutaciones de EGFR 10 .…”

Biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

“…Most of these tumours are adenocarcinomas, often associated with certain morphological features, e.g. ''signet-ring'' cells or a cribriform pattern [9]. ALK rearrangements tend not to coexist with EGFR mutations [10].…”