Molecular determinants of clinical outcomes for anaplastic lymphoma kinase-positive non-small cell lung cancer in Chinese patients: A retrospective study.

Gene complexity affects the clinical outcomes of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we reviewed the medical records of patients with NSCLC between September 2015 and December 2020 in a single institution. We examined the clinical and genomic predictors of these outcomes using multivariate Cox proportional hazards analysis. Overall, 105 patients with ALK-rearranged NSCLC were included. Echinoderm microtubule-associated protein-like 4 (EML4) was the predominant fusion partner (96.2%). Five patients (4.8%) had non-EML4 fusion partners; three had novel partners. EML4::ALK variant 3 (36.5%) was predominant. One patient had the following three subtypes: E13::A20, E6ins33::A20, and E20::A20. Median progression-free survival (PFS), but not overall survival (OS), was significantly different between patients with variants 3 and 1. TP53 was the most common concomitant mutation (21.4%). The presence of TP53 mutations was associated with shorter PFS among patients who received ALK-TKI. Patients with concomitant oncogene mutations presented significantly shorter OS and PFS than those with only ALK rearrangement. In a multivariate Cox regression model, concomitant oncogene mutations and variant 3 carrier status were prognostic factors for PFS, whereas baseline brain metastasis was a prognostic factor for OS.

Analysis of the relationship between Ki-67 expression and chemotherapy and prognosis in advanced non-small cell lung cancer.

BACKGROUND: To analyse the relationship between the Ki-67 index of advanced non-small cell lung cancer (NSCLC) and the objective response rate (ORR) and progression-free survival (PFS) of patients who received chemotherapy. METHODS: The Ki-67 index of advanced NSCLC pathology was established by immunohistochemistry; using univariate and multivariate analyses, we retrospectively analysed the relationship between the Ki-67 index of 112 advanced NSCLC patients in our hospital and chemotherapy response and PFS. Both epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) were found to be wild type in adenocarcinoma patients, and no gene testing was performed for those with squamous cell carcinoma. All selected patients received four cycles of platinum-based chemotherapy, and according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), the curative effect was evaluated after every two cycles. RESULTS: In the univariate and multivariate analyses, the Ki-67 index was significantly associated with the objective response to chemotherapy (B =-0.069, P=0.000). Ki-67 expression could also accurately predict the ORR of chemotherapy [P<0.0001, area under the curve (AUC) =0.7467, 95% confidence interval (CI): 0.6578-0.8356]: squamous cell carcinoma group [P=0.0003, AUC =0.8065 (95% CI: 0.6922-0.9208)], adenocarcinoma group [P=0.0193, AUC =0.6810 (95% CI: 0.5360-0.8262)]. The overexpression of Ki-67 was a negative prognostic factor for PFS in advanced NSCLC (P<0.0001): squamous cell carcinoma (P=0.0055), adenocarcinoma (P<0.0001). According to the multivariate Cox analysis, Ki-67 index (P=0.000) and stage (P=0.001) were negative factors of PFS. CONCLUSIONS: The Ki-67 index might be a clinically significant biomarker in advanced NSCLC and may be able to predict the efficacy of chemotherapy. High expression of Ki-67 might also be an indicator of shortened PFS time.

Survival analysis of patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitor (TKI) treatment: A multi-center retrospective study.

BACKGROUND: The study was conducted to assess differences in overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving different treatment modalities of tyrosine kinase inhibitors (TKIs). METHODS: A total of 463 NSCLC patients receiving TKI treatment were included. OS was compared according to treatment timing in all patients, the elderly, and patients positive for EGFR mutations. RESULTS: One hundred and seventy two patients received TKIs as first-line treatment, 220 as second-line, and 67 as third-line. The results between the three groups were not statistically significant: the one, two, and three-year OS rates were: 55.3%, 22.3%, and 11.3% (first-line); 59.6%, 27.8%, and 14.9% (second-line); and 53.8%, 41.3%, and 29.5% (third-line), respectively (P = 0.095). Results between the three groups of elderly patients were also not statistically significant (P = 0.469). The one and two-year OS rates in EGFR mutation-positive patients receiving first-line treatment were 48% and 17.5%, respectively. The one, two, and three-year OS rates of patients receiving second-line treatment were: 54.2%, 30.3%, and 20.2%, respectively. There were no statistically significant differences between the groups with EGFR mutations receiving first-line or second-line treatment. Thirteen EGFR mutation-positive patients received third-line TKI treatment for a median duration of 7 months. Their one and two-year OS rates were 69.8% and 58.2%, respectively, which were higher than in the other two groups (P = 0.015). CONCLUSION: Three lines of TKI therapy can prolong survival in NSCLC patients. Elderly patients can benefit from TKI therapy. EGFR mutation-positive patients can benefit from second-line or third-line TKI therapy.