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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.

The developments of medicine always follow innovations in science and technology. In the past decade, such innovations have made cancer-related targeted therapies possible. In general, the term "targeted therapy" has been used in reference to cellular and molecular level oriented therapies. However, improvements in the delivery and planning of traditional radiation therapy have also provided cancer patients more options for "targeted" treatment, notably stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). In this review, the progress and controversies of SRS and SBRT are discussed to show the role of stereotactic radiation therapy in the ever evolving multidisciplinary care of cancer patients.

Heparanase (Hpa) is an endoglycosidase that degrades heparin sulfate--the main polysaccharide constituent of extracellular matrix (ECM) and basement. It can enhance the invasive and metastatic potential of malignant tumors and cell lines by destroying ECM and basement. This study was to explore the effects of heparanase gene on the invasive ability of colorectal cancer cell line HT29.Heparanase gene was transfected into HT29 cells. Cell growth kinetics was assessed by MTT assay, and in vitro invasive ability was assessed with Boyden chamber. Xenograft and orthotopic implantation of histologically intact tumor in nude mice were constructed to observe the effect of exogenous expression of heparanase gene on invasive ability of HT29 cells.After transfection, the growth rate of heparanase-transfected HT29 (HT29-Hpa) cells was obviously higher than those of untransfected HT29 cells and empty vector-transfected HT29 (HT29-KZ) cells; the invasive cell number was significantly larger in HT29-Hpa cells than in untransfected HT29 cells and HT29-KZ cells (45.5+/-0.5 vs. 29.3+/-0.1 and 30.1+/-0.2, P0.01). The entity neoplasm formed by HT29-Hpa cells (12 mm x 9 mm x 10 mm) was bigger than that formed by untransfected HT29 cells (6 mm x 8 mm x 6 mm). The prevalence of liver metastasis caused by orthotopic implantation of xenograft was significantly higher in HT29-Hpa group than in control group (71.43% vs. 14.29%, P0.01).Exogenous heparanase gene can facilitate the growth, invasion, and metastasis of HT29 cells.

To explore the expressions of acetyl-heparanase mRNA, laminin ( LN) and laminin receptor ( LR) in 50 ovarian carcinoma, 33 ovarian carcinoma with lymph node metastasis, and 10 serous ovarian cystadenoma as well as their role in the metastasis of ovarian cancer.The transcription level of acetyl-heparanase mRNA, expressions of LN and LR were detected by in situ hibridization and immunohistochemical staining, respectively.The transcription level of acetyl-heparanase mRNA in ovarian carcinoma tissue and metastatic lymph nodes increased significantly, but its expression in primary focus was notably higher than that in metastatic lymph nodes (P0. 05 ). There was low expression of acetyl-heparanase mRNA in serous ovarian cystadenoma. The expression of acetyl-heparanase mRNA in malignant and benign tumor tissues had markedly difference (P0. 01 ). Expressions LN in both tissues mentioned above decreased while LR expression was high. The expression of acetyl-heparanase mRNA was negative correlation with that of LN, while positive with that of LR.The correlation among expressions of acetyl-heparanase mRNA, LN and LR suggests that heparanase is involved in the growth, invasion and metastasis of ovarian carcinoma.