TNM stages inversely correlate with the age at diagnosis in ALK-positive lung cancer

Wenfang Tang, Yuanyuan Lei, Jian Su, Chao Zhang, Rui Fu, Jin Kang, Honghong Yan, Xuening Yang, Haiyan Tu, Yilong Wu, Wenzhao Zhong


Background: To clearly reveal the correlations between age at diagnosis, tumor-nodes-metastasis (TNM) stages and frequency of ALK-positive lung cancer.
Methods: We reviewed patients who presented with ALK rearrangements (n=411) or KRAS-mutations (n=122) between September 2010 and January 2018. The clinical characteristics and overall survival were analyzed for the two genotype cohorts and stratified by different age categories (<40, 40–49, 50–59, ≥60 years).
Results: In the ALK-positive cohort, the younger group showed more frequent disease in the T3/4 stage (P=0.014), lymph node metastasis (P=0.011) and distant metastasis (P=0.015) than the older groups. Meanwhile, the mean age at diagnosis for the ALK-positive patients showed a significant inverse correlation with the clinical stages (stage I/II vs. III vs. IV, 54.7 vs. 52.0 vs. 49.7 years; P<0.001), as well as with the T, N, and M categories. However, KRAS-mutant patients did not exhibit similar relationships to those observed in ALK-positive patients. Importantly, for ALK-positive patients, the frequency of stage IIIb–IV disease was almost twice that of stage I–IIIa disease (6.1% vs. 3.4%, P<0.001); there was a similar incidence of the different disease stages in KRAS-mutant lung cancer (P=0.924). Lastly, in ALK-positive patients, the ≥60 years group was associated with a trend toward better survival than the other younger groups.
Conclusions: The TNM stages exhibited a significant inverse correlation with age at diagnosis for ALK-positive lung cancer patients. More unique therapeutic strategies should be required in these young patients.