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



The clinical records of 8,405 consecutive patients with lung cancer who had ALK detection and 2,187 consecutive patients with lung cancer who underwent KRAS testing at Guangdong Provincial People's Hospital (GDPH) between September 2010 and January 2018 were retrospectively reviewed. This study was approved by the Ethics and Scientific Committees of Guangdong Provincial People's Hospital [No. GDREC2016175H(R2)]. In our center, patients with lung cancer were routinely tested for ALK gene rearrangements. Of the 8,405 ALKscreening patients, 3,782 patients had stage I–IIIa and 4,623 had stage IIIb–IV disease. Among the patients who underwent KRAS testing, 834 patients and 1,353 patients had stage I–IIIa and stage IIIb–IV disease, respectively (Figure 1). ALK was assayed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) or next-generation gene sequencing (NGS). The age at initial diagnosis was extracted. In the resected patients, the T and N staging were from the results of surgical resection, and TNM staging in unresectable patients was based on the comprehensive imaging results. The T, N, and M stages were classified according to the International Association for the Study of Lung Cancer (IASLC) 7th TNM staging project. The mean age was compared between the ALK-positive and KRAS-mutant patients at various TNM stages. The patients were divided into the following four groups stratified by age: <40, 40–49, 50–59 and ≥60 years; the clinical features and survival of the different age groups were analyzed. Stage I–IIIa was usually defined as resectable or potentially resectable and stage IIIb–IV was considered to have no curative treatment. For each included patient, we collected the following data: age; sex; smoking history; pathology; Eastern Cooperative Oncology Group (ECOG) score; TNM stage; presence of brain metastasis at initial diagnosis; major treatments including surgery; targeted therapy; chemotherapy or/and radiotherapy; and overall survival (OS).

Figure 1.

Study flow chart. ALK, anaplastic lymphoma kinase; KRAS, Kirsten rat sarcoma viral oncogene homolog.

Statistical Analysis

Statistical analyses were performed using SPSS (version 20.0; SPSS Inc., Chicago, IL, USA). The Chi-square test or Fisher's exact test was used to compare categorical variables, and the Wilcoxon rank sum test was used for continuous variables. The Spearman correlation test was applied to assess the relations between age and clinical stages or various TNM categories. Furthermore, a linear regression test was used to estimate the trend between the percentage of stage IIIb–IV disease in various age groups. Univariate and multivariable Cox proportional hazards models were used to identify prognostic factors for survival. OS was defined as the time from the initial diagnosis until death from any cause. Survival curves were constructed using the Kaplan-Meier approach and compared using the log-rank test. A two-sided P value of <0.05 was considered statistically significant.