Search

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 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.

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 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 up-front RT vs. no RT; we now report the pre-specified interim analysis at 68% accrual.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/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.A total of 133 patients (n = 65 TKI only, n = 68 TKI+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+RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI+RT arm. Based on the efficacy results of this pre-specified interim analysis, the ethics committee recommended premature cessation of this trial.As compared to a first-line TKI alone, addition of up-front local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

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 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.