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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 < .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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Inhibidores de Proteínas Quinasas/efectos adversos , Receptores ErbB/genética , MutaciónRESUMEN
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.
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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.
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Neoplasias/cirugía , Radiocirugia , Ensayos Clínicos Fase III como Asunto , Humanos , Neoplasias Pulmonares/cirugía , Dosificación Radioterapéutica , Tasa de SupervivenciaRESUMEN
BACKGROUND & OBJECTIVE: 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. METHODS: 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. RESULTS: 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, P<0.01). 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%, P<0.01). CONCLUSION: Exogenous heparanase gene can facilitate the growth, invasion, and metastasis of HT29 cells.
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Neoplasias del Colon/patología , Glucuronidasa/biosíntesis , Animales , Proliferación Celular , Neoplasias del Colon/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Glucuronidasa/genética , Células HT29/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Metástasis de la Neoplasia , Trasplante de Neoplasias , ARN Mensajero/biosíntesis , ARN Mensajero/genética , TransfecciónRESUMEN
AIM: 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. METHODS: The transcription level of acetyl-heparanase mRNA, expressions of LN and LR were detected by in situ hibridization and immunohistochemical staining, respectively. RESULTS: 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 (P < 0. 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 (P < 0. 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. CONCLUSION: 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.