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


Transl Lung Cancer Res. 2019;8(2) 

In This Article

Abstract and Introduction


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.


Non-small cell lung cancer (NSCLC) is increasingly understood to be a heterogeneous disease.[1,2] Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3–7% of NSCLC patients.[3]ALK rearrangements define a distinct subgroup of NSCLC that typically occurs in young patients who have never smoked and who have adenocarcinoma histological characteristics.[4–6] Several studies have demonstrated that the ALK gene has a high incidence in advanced NSCLC.[7,8] However, there was no consensus on the frequency of surgical patients with ALK-positive lung cancer.[9–11] Among NSCLC patients with a targetable genomic alteration, it suggested that younger patients were associated with an increased likelihood of initially presenting with stage IV disease[11,12] and exhibiting a poorer survival than older patients.[12]

To clearly investigate the associations between age, tumor-nodes-metastasis (TNM) staging and frequency of ALK-positive lung cancer, we performed an analysis of ALK-positive lung cancer cases in a large-scale cohort and compared to the results to those of another clinically relevant cohort: Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung cancer cases.