Entity

Time filter

Source Type

St.Petersburg, Russia

Kelly K.,University of California at Davis | Altorki N.K.,New York Presbyterian HospitalWeill Cornell Medical Center | Eberhardt W.E.E.,University of Duisburg - Essen | OBrien M.E.R.,Royal Marsden Hospital | And 12 more authors.
Journal of Clinical Oncology | Year: 2015

Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have proven efficacy in advanced nonsmall-cell lung cancer (NSCLC). We hypothesized that erlotinib would be efficacious in the adjuvant setting. Patients and Methods An international randomized, double-blind, placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization. Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years. Stratification factors were stage, histology, previous adjuvant chemotherapy, smoking status, EGFR amplification status, and country. The primary end point was disease-free survival (DFS); key secondary end points were overall survival (OS) and DFS and OS in patients whose tumors had EGFR-activating mutations (EGFRm-positive). Results A total of 973 patients were randomly assigned (November 26, 2007, to July 7, 2010). There was no statistically significant difference in DFS (median, 50.5 months for erlotinib and 48.2 months for placebo; hazard ratio, 0.90; 95% CI, 0.74 to 1.10; P = .324). Among the 161 patients (16.5%) in the EGFRm-positive subgroup, DFS favored erlotinib (median, 46.4 v 28.5 months; hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .039), but this was not statistically significant because of the hierarchical testing procedure. OS data are immature. Rash and diarrhea were common adverse events occurring in 528 (86.4%) and 319 (52.2%) patients treated with erlotinib, respectively, versus 110 (32.1%) and 54 (15.7%) patients receiving placebo. The most common grade 3 adverse events in patients treated with erlotinib were rash (22.3%) and diarrhea (6.2%). Conclusion Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup. Further evaluation of erlotinib is warranted in the EGFRmpositive subgroup. © 2015 by American Society of Clinical Oncology. Source


Nevorotin A.,Ip Pavlov Medical University
Cellular Therapy and Transplantation | Year: 2010

The author of this compact essay and also of a book on the same topic [1] has always realized that the successful submission of manuscripts to English-language journals invariably requires not only good English but also a high level of research and-in my compatriot's view-a very special style in which the results should be presented. These prerequisites for successful submission are indispensable, because an editorial board will flatly reject as unreliable even the most interesting results if they are vague, poorly substantiated, and/or the manuscript is incomprehensible. In this study, these three pre-requisites-the level of the results, style of content presentation, and language-will be considered in relation to research articles (RA) intended for submission to English-language journals. Special attention will be paid to the clear differences-despite globalization-in mentalities between Russian scientists and those originating from English-speaking environments, which will both facilitate success and alleviate the sense of bitterness amongst Russian scientists in the case of refusal by encouraging the researcher to adopt the appropriate method in subsequent efforts. Regardless of nationality, the potential contributor to a given journal should clearly understand that when submitting an RA manuscript, the author must either adhere to the journal's standards or not waste his/her efforts. As the Russian proverb states: "Nobody goes to another monastery with one's own charter." For convenience, the term author will be used hereafter to denote either a single person, tandem authors, or a team of researchers united by the aim of submitting an RA manuscript-this one included-to an English-language journal. Source


Pfeifer W.,Nn Petrov Institute Of Oncology | Sokolenko A.P.,Saint Petersburg State University | Potapova O.N.,Nn Petrov Institute Of Oncology | Bessonov A.A.,City Cancer Center | And 8 more authors.
Breast Cancer Research and Treatment | Year: 2014

Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6 %) and 8 CHEK2 (1.9 %) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6 %) vs. 46/388 (11.9 %), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6 %) vs. 28/247 (11.3 %), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50 %) vs. 333/388 (85.5 %), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes. © 2014, Springer Science+Business Media New York. Source


Mitiushkina N.V.,Nn Petrov Institute Of Oncology | Iyevleva A.G.,Saint Petersburg State Pediatric Medical Academy | Poltoratskiy A.N.,Ip Pavlov Medical University | Ivantsov A.O.,Nn Petrov Institute Of Oncology | And 6 more authors.
Cancer Cytopathology | Year: 2013

BACKGROUND: Although the molecular analysis of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in archived lung cancer tissues is relatively well established, the genetic testing of cytological material has not yet become a routine. METHODS: The current study used cell samples that were obtained by bronchial brushing, transthoracic needle aspiration, or biopsy imprint preparation between 1993 and 2008. Islets of malignant cells were visually located on the archived cytological slides, lysed in situ by a drop of sodium dodecyl sulfate-containing buffer, and subjected to the standard DNA and RNA extraction. Examination of paraffin-embedded tissue blocks (resection specimens or biopsy material) from the same patients was performed in parallel. RESULTS: A total of 75 cytological/histological lung adenocarcinoma sample pairs underwent polymerase chain reaction analysis for the EGFR mutation. Two cytological samples and 1 morphological sample failed to produce DNA. Concordance for the wild-type and mutation status was observed in 54 of 72 and 14 of 72 informative pairs, respectively; 3 pairs and 1 pair, respectively, had mutation only in the cytological or histological material. The discrepancies could be explained by the failure to ensure a high percentage of lung cancer cells in the analyzed samples or, alternatively, by the genuine intratumoral molecular heterogeneity of some neoplasms. RNA extraction followed by reverse transcriptase-polymerase chain reaction analysis for the EML4-ALK translocation was performed for 44 EGFR mutation-negative sample pairs; failures were observed for 2 cytological and 6 histological specimens. All informative pairs were concordant either for the norm (32 of 36 pairs) or for the presence of EML4-ALK gene fusion (4 of 36 pairs). CONCLUSIONS: Archived cytological slides appear to be well suited both for EGFR and ALK analysis. Cancer (Cancer Cytopathol) 2013;121:370-6. © 2013 American Cancer Society. Source

Discover hidden collaborations