ABSTRACT
Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan−Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox's proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33−65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96−3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.
ABSTRACT
In this prospective study, a new strategy for the prescription of neoadjuvant chemotherapy (NAC) was prospectively tested and depended on the presence of stemness gene amplifications in the tumor before treatment, which in our early studies showed a connection with metastasis. The study included 92 patients with grade IIA-IIIB luminal B breast cancer. Patients underwent a biopsy before treatment, and with the use of a CytoScan HD Array microarray (Affymetrix, Santa Clara, CA, USA), the presence of stemness gene amplifications (3q, 5p, 6p, 7q, 8q, 13q, 9p, 9q, 10p, 10q21.1, 16p, 18chr, 19p) in the tumor was determined. In group 1 (n = 41), in the presence of two or more amplifications, patients were prescribed a personalized NAC regimen. In group 2 (n = 21), if there was no amplification of stemness genes in the tumor, then patients were not prescribed NAC, and treatment began with surgery. Group 3 (n = 30) served as a historical control. The frequency of an objective response to NAC in groups 1 and 3 was 79%. Nonmetastatic survival was found in 100% of patients in group 2, who did not undergo NAC. In patients in group 1, the frequency of metastasis was 10% (4/41). At the same time, in patients in group 3, who received NAC, the rate of metastasis was 47% (14/30). The differences between group 1 and group 3 and between group 2 and group 3 were statistically significant, both by Fisher's criterion and a log-rank test. The appointment of NAC was most feasible in patients with clones with stemness gene amplifications in the primary tumor, while in the absence of amplifications, preoperative chemotherapy led to a sharp decrease in metastasis-free survival. This strategy of NAC prescription allowed us to achieve 93% metastatic survival in patients with breast cancer.
