ABSTRACT
BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Protein Kinase Inhibitors/adverse effects , ErbB Receptors/genetics , MutationABSTRACT
OBJECTIVE: To explore the correlation between tumor-associated macrophages and the proliferation and invasion of type I endometrial carcinoma. METHODS: Immunohistochemistry was used to investigate the infiltration of macrophages in normal and different types of hyperplastic endometrial lesions. The proliferation and invasion ability of type I endometrial carcinoma cell line RL95-2 influenced by mononuclear macrophage cell line THP-1 (constructed M2 type macrophages) was detected by CCK8 and transwell technologies respectively. Transwell was used to evaluate the recruiting ability of RL95-2 on THP-1 cells. Otherwise, the western blot was also used to detect the expression of CyclinD1 and MMP-2 in RL95-2 with the influence of THP-1. RESULTS: Immunohistochemistry result showed a positive correlation between the number of infiltrating macrophages and the progression of endometrial hyperplasia. THP-1 recruited by RL95-2 could promote its proliferation and invasion and enhance the expression of the CyclinD1 and MMP-2 protein in a time dependent manner (P < 0.05). CONCLUSIONS: Increase of the number of infiltrating macrophages and its contribution to the tumor inflammatory microenvironment may result in the development of the type I endometrial carcinoma.
