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.

Local Magnetoelectric Effect in La-Doped BiFeO3 Multiferroic Thin Films Revealed by Magnetic-Field-Assisted Scanning Probe Microscopy.

Multiferroic La-doped BiFeO3 thin films have been prepared by a sol-gel plus spin-coating process, and the local magnetoelectric coupling effect has been investigated by the magnetic-field-assisted scanning probe microscopy connected with a ferroelectric analyzer. The local ferroelectric polarization response to external magnetic fields is observed and a so-called optimized magnetic field of ~40 Oe is obtained, at which the ferroelectric polarization reaches the maximum. Moreover, we carry out the magnetic-field-dependent surface conductivity measurements and illustrate the origin of local magnetoresistance in the La-doped BiFeO3 thin films, which is closely related to the local ferroelectric polarization response to external magnetic fields. This work not only provides a useful technique to characterize the local magnetoelectric coupling for a wide range of multiferroic materials but also is significant for deeply understanding the local multiferroic behaviors in the BiFeO3-based systems.

Local electrical conduction in polycrystalline La-doped BiFeO3 thin films.

Local electrical conduction behaviors of polycrystalline La-doped BiFeO3 thin films have been investigated by combining conductive atomic force microscopy and piezoelectric force microscopy. Nanoscale current measurements were performed as a function of bias voltage for different crystal grains. Completely distinct conducting processes and resistive switching effects were observed in the grain boundary and grain interior. We have revealed that local electric conduction in a grain is dominated by both the grain boundary and ferroelectric domain, and is closely related to the applied electric field and the as-grown state of the grain. At lower voltages the electrical conduction is dominated by the grain boundary and is associated with the redistribution of oxygen vacancies in the grain boundary under external electric fields. At higher voltages both the grain boundary and ferroelectric domain are responsible for the electrical conduction of grains, and the electrical conduction gradually extends from the grain boundary into the grain interior due to the extension of the ferroelectric domain towards the grain interior. We have also demonstrated that the conduction dominated by the grain boundary exhibits a much small switching voltage, while the conduction of the ferroelectric domain causes a much high switching voltage in the grain interior.