315 research outputs found
The management of stage I nonseminomatous testicular germ cell tumors
No full textTesticular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors ( NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal- cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic disease in stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve- sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin- based chemotherapy. All available treatment modalities produce excellent results, with a long- term survival of almost 100%. Consequently, therapy- induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient’s preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer
Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study
No full textBevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review
No full textAs increased angiogenesis has been linked with the progression of ovarian cancer, a number of anti-angiogenic agents have been investigated, or are currently in development, as potential treatment options for patients with advanced disease. Bevacizumab, a recombinant monoclonal antibody against vascular endothelial growth factor, has gained European Medicines Agency approval for the front-line treatment of advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in combination with carboplatin and paclitaxel, and for the treatment of first recurrence of platinum-sensitive ovarian cancer in combination with carboplatin and gemcitabine. We conducted a systematic literature review to identify available efficacy and safety data for bevacizumab in ovarian cancer as well as for newer anti-angiogenic agents in development. We analyzed published data from randomized, controlled phase II/III clinical trials enrolling women with ovarian cancer to receive treatment with bevacizumab. We also reviewed available data for emerging anti-angiogenic agents currently in phase II/III development, including trebananib, aflibercept, nintedanib, cediranib, imatinib, pazopanib, sorafenib and sunitinib. Significant efficacy gains were achieved with the addition of bevacizumab to standard chemotherapy in four randomized, double-blind, phase III trials, both as front-line treatment (GOG-0218 and ICON7) and in patients with recurrent disease ( OCEANS and AURELIA). The type and frequency of bevacizumab-related adverse events was as expected in these studies based on published data. Promising efficacy data have been published for a number of emerging anti-angiogenic agents in phase III development for advanced ovarian cancer. Further research is needed to identify predictive or prognostic markers of response to bevacizumab in order to optimize patient selection and treatment benefit. Data from phase III trials of newer anti-angiogenic agents in ovarian cancer are awaited
Two cycles of carboplatin-based adjuvant chemotherapy for high-risk clinical stage I and stage IM non-seminomatous germ cell tumours of the testis: a HECOG trial.
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Quality of Life in Patients Receiving High-Dose Interferon Alfa-2b After Resected High-Risk Melanoma Reply
No full textBevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review
No full textAbstract 1755: The fate of germline BRCA related mutations in breast tumor tissues
No full textAbstract
Background - aim: Germline mutation carriers in BRCA1 and related genes frequently develop triple-negative breast carcinomas (TNBC) that presumably preserve the inherited mutation. Herein, we examined the clinicopathologic features and prognostic impact of paired germline and tumor genotypes in this disease.
Methods: We compared baseline germline and paraffin tumor genotype data (next generation [NGS] and Sanger sequencing) from 194 patients with operable TNBC who were treated with anthracyclines-taxanes based chemotherapy within adjuvant trials by our Group. Because tissue NGS did not target BRCA-related genes, we additionally interrogated the presence of germline mutations in tumor and non-cancerous breast tissues, in carriers with available tissue material (n=33). We validated all NGS germline mutations with Sanger sequencing and ensured matched germline/tumor identity with microsatellite testing.
Results: We identified 50 (26%) germline mutation carriers, 39 in BRCA1, 4 in BRCA2 and the rest in RAD51C, BARD1, RAD50, NBN, MRE11A and BRIP1. BRCA1 carriers were younger as compared to non-BRCA1 carriers (median 42y.o. vs. 56y.o, respectively; p=0.020), premenopausal (p=0.014), and had lower nodal status (p<0.001). Somatic mutations were found in 136 tumors, TP53 in 113 (81%). The germline mutant allele was lost in 14/33 (42%) tumor and matched normal tissues (mut-LOH). Loss affected 12 BRCA1 mutations, among them the common pathogenic p.Q1756fsX74 (c.5266dupC) and p.G1738R (c.5212G>A), and 2 BRCA2 mutations. In one such tumor, the germline mutation was replaced by a somatic BRCA1 (p.Q1811X [c.5431C>T]). Tumors with mut-LOH were more often TP53 mutant as compared to those with preserved germline mutations, which had mutations in other genes as well (p=0.034). Overall though, TP53 mutations were not associated with germline status. Germline mutations and tumor TP53 mutations were not individually associated with patient disease-free survival (DFS) but interacted with each other: in non-carriers, TP53 status did not affect outcome; in carriers, those with mutant TP53 had unfavorable DFS compared to those with wild-type TP53 tumors (interaction p, multivariate analysis: 0.053).
Conclusions: Germline BRCA-related TNBC may be distinguished into two groups with potentially different biological characteristics, those with preserved and lost inherited mutation. The interaction between germline status and tumor TP53 mutations may have treatment implications and seems worthy pursuing in larger studies. Combined germline/tumor genotype testing may be needed for TNBC patient classification, especially in the context of clinical trials.
Citation Format: Vassiliki Kotoula, Florentia Fostira Fostira, Kyriaki Papadopoulou, Paraskevi Apostolou, Eleftheria Tsolaki, Georgios Lazaridis, Kyriaki Manoussou, Flora Zagouri Zagouri, Dimitrios Pectasides, Ioannis Vlachos, Ioannis Tikas, Sotiris Lakis, Irene Konstantopoulou, George Pentheroudakis, Helen Gogas, Pavlos Papakostas, Christos Christodoulou, Drakoulis Yannoukakos, George Fountzilas. The fate of germline BRCA related mutations in breast tumor tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1755. doi:10.1158/1538-7445.AM2017-1755</jats:p
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