Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

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.

A retrospective study comparing D1 limited lymph node dissection and D2 extended lymph node dissection for N3 gastric cancer.

BACKGROUND: In countries in East Asia, the typical treatment for curable gastric cancer is gastrectomy with D2 lymphadenectomy. However, whether D2 lymphadenectomy is beneficial for high-risk N3 node disease remains controversial. We conducted a multi-institution retrospective study on patients with high-risk, locally advanced gastric cancer. To compare the rates of disease-free survival (DFS) and overall survival (OS) between radical D2-type gastric resection and lymphadenectomy and the more limited D1 type resection and lymphadenectomy. METHODS: From July 2010 to June 2015, 74 patients out of 949 who underwent curative-intent R0 surgery were selected in pairs to compare the survival outcomes between those who underwent radical D2 type (n=37) vs. the more limited D1 type (n=37) gastric resection and lymphadenectomy. RESULTS: The median DFS was 9.72 and 7.81 months for the D2 and D1 types, respectively (P=0.746), and the OS was 16.39 and 15.85 months for the D2 and D1 types, respectively (P=0.937). CONCLUSIONS: No statistically significant differences in DFS and OS were noted between D1 and D2 procedures for those with N3 disease. Our results support the hypothesis that a novel multidisciplinary approach rather than a surgical approach alone is needed to improve the survival outcomes of high-risk patients with N3 gastric cancer.