69 results on '"Kalinka-Warzocha E"'
Search Results
2. 954P Cemiplimab with platinum-based chemotherapy (chemo) for first-line (1L) locally advanced non-small cell lung cancer (laNSCLC): EMPOWER-Lung 3 subgroup analysis
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Kalinka-Warzocha, E., primary, Gogishvili, M., additional, Makharadze, T., additional, Dvorkin, M., additional, Penkov, K.D., additional, Laktionov, K., additional, Nechaeva, M., additional, Rozhkova, I., additional, He, X., additional, Quek, R., additional, Pouliot, J-F., additional, Seebach, F., additional, Lowy, I., additional, Gullo, G., additional, and Rietschel, P., additional
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- 2022
- Full Text
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3. Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: a multicenter study on 3856 Polish Caucasian patients
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Krawczyk, P., Reszka, K., Ramlau, R., Powrózek, T., Pankowski, J., Wojas-Krawczyk, K., Kalinka-Warzocha, E., Szczęsna, A., Nicoś, M., Jarosz, B., Szyszka-Barth, K., Bryl, M., Adamowicz, K., Szumiło, J., and Milanowski, J.
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- 2016
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4. Haplotype-specific pattern of association of human major histocompatibility complex with non-Hodgkinʼs lymphoma outcome
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Nowak, J., Kalinka-Warzocha, E., Juszczyński, P., Mika-Witkowska, R., Zajko, M., Graczyk-Pol, E., Coiffier, B., Salles, G., and Warzocha, K.
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- 2008
5. Survival Outcomes in Patients with Previously Untreated BRAF Wild-Type Advanced Melanoma Treated with Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial
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Ascierto, P.A. Long, G.V. Robert, C. Brady, B. Dutriaux, C. Di Giacomo, A.M. Mortier, L. Hassel, J.C. Rutkowski, P. McNeil, C. Kalinka-Warzocha, E. Savage, K.J. Hernberg, M.M. Lebbé, C. Charles, J. Mihalcioiu, C. Chiarion-Sileni, V. Mauch, C. Cognetti, F. Ny, L. Arance, A. Svane, I.M. Schadendorf, D. Gogas, H. Saci, A. Jiang, J. Rizzo, J. Atkinson, V.
- Abstract
Importance: This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors. Objective: To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma. Design, Setting, and Participants: This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation. Interventions: Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m2 every 3 weeks plus nivolumab-matched placebo every 2 weeks). Main Outcome and Measure: Overall survival. Results: At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P
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- 2019
6. A phase 2 study of investigational TORC1/2 inhibitor TAK-228 and TAK-228 plus investigational PI3Kα-selective inhibitor TAK-117 vs everolimus in adults with advanced or metastatic clear-cell renal cell carcinoma (ccRCC) that has progressed on VEGF-targeted therapy
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Choueiri, T.K., primary, Porta, C., additional, Suarez Rodriguez, C., additional, Alter, R., additional, Czaykowski, P., additional, Duran, I., additional, Gross-Goupil, M., additional, Kalinka-Warzocha, E., additional, Melichar, B., additional, Patel, C., additional, Neuwirth, R., additional, Enke, A., additional, Zohren, F., additional, and Powles, T., additional
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- 2017
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7. Nivolumab in previously untreated melanoma without BRAF mutation
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Robert, C. Long, G.V. Brady, B. Dutriaux, C. Maio, M. Mortier, L. Hassel, J.C. Rutkowski, P. McNeil, C. Kalinka-Warzocha, E. Savage, K.J. Hernberg, M.M. Lebbé, C. Charles, J. Mihalcioiu, C. Chiarion-Sileni, V. Mauch, C. Cognetti, F. Arance, A. Schmidt, H. Schadendorf, D. Gogas, H. Lundgren-Eriksson, L. Horak, C. Sharkey, B. Waxman, I.M. Atkinson, V. Ascierto, P.A.
- Abstract
BACKGROUND: Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS: We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. RESULTS: At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P
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- 2015
8. Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.
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Nanda, VGY, Peng, W, Hwu, P, Davies, MA, Ciliberto, G, Fattore, L, Malpicci, D, Aurisicchio, L, Ascierto, PA, Croce, CM, Mancini, R, Spranger, S, Gajewski, TF, Wang, Y, Ferrone, S, Vanpouille-Box, C, Wennerberg, E, Pilones, KA, Formenti, SC, Demaria, S, Tang, H, Fu, Y-X, Dummer, R, Puzanov, I, Tarhini, A, Chauvin, J-M, Pagliano, O, Fourcade, J, Sun, Z, Wang, H, Sanders, C, Kirkwood, JM, Chen, T-HT, Maurer, M, Korman, AJ, Zarour, HM, Stroncek, DF, Huber, V, Rivoltini, L, Thurin, M, Rau, T, Lugli, A, Pagès, F, Camarero, J, Sancho, A, Jommi, C, de Coaña, YP, Wolodarski, M, Yoshimoto, Y, Gentilcore, G, Poschke, I, Masucci, GV, Hansson, J, Kiessling, R, Scognamiglio, G, Sabbatino, F, Marino, FZ, Anniciello, AM, Cantile, M, Cerrone, M, Scala, S, D’alterio, C, Ianaro, A, Cirin, G, Liguori, G, Bott, G, Chapman, PB, Robert, C, Larkin, J, Haanen, JB, Ribas, A, Hogg, D, Hamid, O, Testori, A, Lorigan, P, Sosman, JA, Flaherty, KT, Yue, H, Coleman, S, Caro, I, Hauschild, A, McArthur, GA, Sznol, M, Callahan, MK, Kluger, H, Postow, MA, Gordan, R, Segal, NH, Rizvi, NA, Lesokhin, A, Atkins, MB, Burke, MM, Ralabate, A, Rivera, A, Kronenberg, SA, Agunwamba, B, Ruisi, M, Horak, C, Jiang, J, Wolchok, J, Liszkay, G, Maio, M, Mandalà, M, Demidov, L, Stoyakovskiy, D, Thomas, L, de la Cruz-Merino, L, Atkinson, V, Dutriaux, C, Garbe, C, Wongchenko, M, Chang, I, Koralek, DO, Rooney, I, Yan, Y, Dréno, B, Sullivan, R, Patel, M, Hodi, S, Amaria, R, Boasberg, P, Wallin, J, He, X, Cha, E, Richie, N, Ballinger, M, Smith, DC, Bauer, TM, Wasser, JS, Luke, JJ, Balmanoukian, AS, Kaufman, DR, Zhao, Y, Maleski, J, Leopold, L, Gangadhar, TC, Long, GV, Michielin, O, VanderWalde, A, Andtbacka, RHI, Cebon, J, Fernandez, E, Malvehy, J, Olszanski, AJ, Gause, C, Chen, L, Chou, J, Stephen Hodi, F, Brady, B, Mortier, L, Hassel, JC, Rutkowski, P, McNeil, C, Kalinka-Warzocha, E, Lebbé, C, Ny, L, Chacon, M, Queirolo, P, Loquai, C, Cheema, P, Berrocal, A, Eizmendi, KM, Bar-Sela, G, Hardy, H, Weber, JS, Grob, J-J, Marquez-Rodas, I, Schmidt, H, Briscoe, K, Baurain, J-F, Wolchok, JD, Pinto, R, De Summa, S, Garrisi, VM, Strippoli, S, Azzariti, A, Guida, G, Guida, M, Tommasi, S, Jacquelot, N, Enot, D, Flament, C, Pitt, JM, Vimond, N, Blattner, C, Yamazaki, T, Roberti, M-P, Vetizou, M, Daillere, R, Poirier-Colame, V, la Semeraro, M, Caignard, A, Slingluff, CL, Sallusto, F, Rusakiewicz, S, Weide, B, Marabelle, A, Kohrt, H, Dalle, S, Cavalcanti, A, Kroemer, G, Di Giacomo, AM, Wong, P, Yuan, J, Umansky, V, Eggermont, A, Zitvogel, L, Anna, P, Marco, T, Stefania, S, Francesco, M, Mariaelena, C, Gabriele, M, Antonio, AP, Franco, S, Roberti, MP, Enot, DP, Semeraro, M, Jégou, S, Flores, C, Kwon, BS, Anderson, AC, Borg, C, Aubin, F, Ayyoub, M, De Presbiteris, AL, Cordaro, FG, Camerlingo, R, Fratangelo, F, Mozzillo, N, Pirozzi, G, Patriarca, EJ, Caputo, E, Motti, ML, Falcon, R, Miceli, R, Capone, M, Madonna, G, Mallardo, D, Carrier, MV, Panza, E, De Cicco, P, Armogida, C, Ercolano, G, Botti, G, Cirino, G, Sandru, A, Blank, M, Balatoni, T, Olasz, J, Farkas, E, Szollar, A, Savolt, A, Godeny, M, Csuka, O, Horvath, S, Eles, K, Shoenfeld, Y, Kasler, M, Costantini, S, Capone, F, Moradi, F, Berglund, P, Leandersson, K, Linnskog, R, Andersson, T, Prasad, CP, Nigro, CL, Lattanzio, L, Proby, C, Syed, N, Occelli, M, Cauchi, C, Merlano, M, Harwood, C, Thompson, A, Crook, T, Bifulco, K, Ingangi, V, Minopoli, M, Ragone, C, Pessi, A, Mannavola, F, D’Oronzo, S, Felici, C, Tucci, M, Doronzo, A, Silvestris, F, Ferretta, A, Guida, S, Maida, I, Cocco, T, Passarelli, A, Quaresmini, D, Franzese, O, Palermo, B, Di Donna, C, Sperduti, I, Foddai, M, Stabile, H, Gismondi, A, Santoni, A, Nisticò, P, Sponghini, AP, Platini, F, Marra, E, Rondonotti, D, Alabiso, O, Fierro, MT, Savoia, P, Stratica, F, Quaglino, P, Di Monta, G, Corrado, C, Di Marzo, M, Ugo, M, Di Cecilia, ML, Nicola, M, Fusciello, C, Marra, A, Guarrasi, R, Baldi, C, Russo, R, Di Giulio, G, Faiola, V, Zeppa, P, Pepe, S, Gambale, E, Carella, C, Di Paolo, A, De Tursi, M, Marra, L, De Murtas, F, Sorrentino, V, Voinea, S, Panaitescu, E, Bolovan, M, Stanciu, A, Cinca, S, Botti, C, Aquino, G, Anniciello, A, Fortes, C, Mastroeni, S, Caggiati, A, Passarelli, F, Zappalà, A, Capuano, M, Bono, R, Nudo, M, Marino, C, Michelozzi, P, De Biasio, V, Battarra, VC, Formenti, S, Ascierto, ML, McMiller, TL, Berger, AE, Danilova, L, Anders, RA, Netto, GJ, Xu, H, Pritchard, TS, Fan, J, Cheadle, C, Cope, L, Drake, CG, Pardoll, DM, Taube, JM, Topalian, SL, Gnjatic, S, Nataraj, S, Imai, N, Rahman, A, Jungbluth, AA, Pan, L, Venhaus, R, Park, A, Lehmann, FF, Lendvai, N, Cohen, AD, Cho, HJ, Daniel, S, Hirsh, V, Nanda, VGY, Peng, W, Hwu, P, Davies, MA, Ciliberto, G, Fattore, L, Malpicci, D, Aurisicchio, L, Ascierto, PA, Croce, CM, Mancini, R, Spranger, S, Gajewski, TF, Wang, Y, Ferrone, S, Vanpouille-Box, C, Wennerberg, E, Pilones, KA, Formenti, SC, Demaria, S, Tang, H, Fu, Y-X, Dummer, R, Puzanov, I, Tarhini, A, Chauvin, J-M, Pagliano, O, Fourcade, J, Sun, Z, Wang, H, Sanders, C, Kirkwood, JM, Chen, T-HT, Maurer, M, Korman, AJ, Zarour, HM, Stroncek, DF, Huber, V, Rivoltini, L, Thurin, M, Rau, T, Lugli, A, Pagès, F, Camarero, J, Sancho, A, Jommi, C, de Coaña, YP, Wolodarski, M, Yoshimoto, Y, Gentilcore, G, Poschke, I, Masucci, GV, Hansson, J, Kiessling, R, Scognamiglio, G, Sabbatino, F, Marino, FZ, Anniciello, AM, Cantile, M, Cerrone, M, Scala, S, D’alterio, C, Ianaro, A, Cirin, G, Liguori, G, Bott, G, Chapman, PB, Robert, C, Larkin, J, Haanen, JB, Ribas, A, Hogg, D, Hamid, O, Testori, A, Lorigan, P, Sosman, JA, Flaherty, KT, Yue, H, Coleman, S, Caro, I, Hauschild, A, McArthur, GA, Sznol, M, Callahan, MK, Kluger, H, Postow, MA, Gordan, R, Segal, NH, Rizvi, NA, Lesokhin, A, Atkins, MB, Burke, MM, Ralabate, A, Rivera, A, Kronenberg, SA, Agunwamba, B, Ruisi, M, Horak, C, Jiang, J, Wolchok, J, Liszkay, G, Maio, M, Mandalà, M, Demidov, L, Stoyakovskiy, D, Thomas, L, de la Cruz-Merino, L, Atkinson, V, Dutriaux, C, Garbe, C, Wongchenko, M, Chang, I, Koralek, DO, Rooney, I, Yan, Y, Dréno, B, Sullivan, R, Patel, M, Hodi, S, Amaria, R, Boasberg, P, Wallin, J, He, X, Cha, E, Richie, N, Ballinger, M, Smith, DC, Bauer, TM, Wasser, JS, Luke, JJ, Balmanoukian, AS, Kaufman, DR, Zhao, Y, Maleski, J, Leopold, L, Gangadhar, TC, Long, GV, Michielin, O, VanderWalde, A, Andtbacka, RHI, Cebon, J, Fernandez, E, Malvehy, J, Olszanski, AJ, Gause, C, Chen, L, Chou, J, Stephen Hodi, F, Brady, B, Mortier, L, Hassel, JC, Rutkowski, P, McNeil, C, Kalinka-Warzocha, E, Lebbé, C, Ny, L, Chacon, M, Queirolo, P, Loquai, C, Cheema, P, Berrocal, A, Eizmendi, KM, Bar-Sela, G, Hardy, H, Weber, JS, Grob, J-J, Marquez-Rodas, I, Schmidt, H, Briscoe, K, Baurain, J-F, Wolchok, JD, Pinto, R, De Summa, S, Garrisi, VM, Strippoli, S, Azzariti, A, Guida, G, Guida, M, Tommasi, S, Jacquelot, N, Enot, D, Flament, C, Pitt, JM, Vimond, N, Blattner, C, Yamazaki, T, Roberti, M-P, Vetizou, M, Daillere, R, Poirier-Colame, V, la Semeraro, M, Caignard, A, Slingluff, CL, Sallusto, F, Rusakiewicz, S, Weide, B, Marabelle, A, Kohrt, H, Dalle, S, Cavalcanti, A, Kroemer, G, Di Giacomo, AM, Wong, P, Yuan, J, Umansky, V, Eggermont, A, Zitvogel, L, Anna, P, Marco, T, Stefania, S, Francesco, M, Mariaelena, C, Gabriele, M, Antonio, AP, Franco, S, Roberti, MP, Enot, DP, Semeraro, M, Jégou, S, Flores, C, Kwon, BS, Anderson, AC, Borg, C, Aubin, F, Ayyoub, M, De Presbiteris, AL, Cordaro, FG, Camerlingo, R, Fratangelo, F, Mozzillo, N, Pirozzi, G, Patriarca, EJ, Caputo, E, Motti, ML, Falcon, R, Miceli, R, Capone, M, Madonna, G, Mallardo, D, Carrier, MV, Panza, E, De Cicco, P, Armogida, C, Ercolano, G, Botti, G, Cirino, G, Sandru, A, Blank, M, Balatoni, T, Olasz, J, Farkas, E, Szollar, A, Savolt, A, Godeny, M, Csuka, O, Horvath, S, Eles, K, Shoenfeld, Y, Kasler, M, Costantini, S, Capone, F, Moradi, F, Berglund, P, Leandersson, K, Linnskog, R, Andersson, T, Prasad, CP, Nigro, CL, Lattanzio, L, Proby, C, Syed, N, Occelli, M, Cauchi, C, Merlano, M, Harwood, C, Thompson, A, Crook, T, Bifulco, K, Ingangi, V, Minopoli, M, Ragone, C, Pessi, A, Mannavola, F, D’Oronzo, S, Felici, C, Tucci, M, Doronzo, A, Silvestris, F, Ferretta, A, Guida, S, Maida, I, Cocco, T, Passarelli, A, Quaresmini, D, Franzese, O, Palermo, B, Di Donna, C, Sperduti, I, Foddai, M, Stabile, H, Gismondi, A, Santoni, A, Nisticò, P, Sponghini, AP, Platini, F, Marra, E, Rondonotti, D, Alabiso, O, Fierro, MT, Savoia, P, Stratica, F, Quaglino, P, Di Monta, G, Corrado, C, Di Marzo, M, Ugo, M, Di Cecilia, ML, Nicola, M, Fusciello, C, Marra, A, Guarrasi, R, Baldi, C, Russo, R, Di Giulio, G, Faiola, V, Zeppa, P, Pepe, S, Gambale, E, Carella, C, Di Paolo, A, De Tursi, M, Marra, L, De Murtas, F, Sorrentino, V, Voinea, S, Panaitescu, E, Bolovan, M, Stanciu, A, Cinca, S, Botti, C, Aquino, G, Anniciello, A, Fortes, C, Mastroeni, S, Caggiati, A, Passarelli, F, Zappalà, A, Capuano, M, Bono, R, Nudo, M, Marino, C, Michelozzi, P, De Biasio, V, Battarra, VC, Formenti, S, Ascierto, ML, McMiller, TL, Berger, AE, Danilova, L, Anders, RA, Netto, GJ, Xu, H, Pritchard, TS, Fan, J, Cheadle, C, Cope, L, Drake, CG, Pardoll, DM, Taube, JM, Topalian, SL, Gnjatic, S, Nataraj, S, Imai, N, Rahman, A, Jungbluth, AA, Pan, L, Venhaus, R, Park, A, Lehmann, FF, Lendvai, N, Cohen, AD, Cho, HJ, Daniel, S, and Hirsh, V
- Abstract
MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intracellular tumor antigens as a source of targets of antibody-based immunotherapy of melanoma Yangyang Wang, Soldano Ferrone Combination therapies K5 Harnessing radiotherapy to improve responses to immunotherapy in cancer Claire Vanpouille-Box, Erik Wennerberg, Karsten A. Pilones, Silvia C. Formenti, Sandra Demaria K6 Creating a T cell-inflamed tumor microenvironment overcomes resistance to checkpoint blockade Haidong Tang, Yang Wang, Yang-Xin Fu K7 Biomarkers for treatment decisions? Reinhard Dummer K8 Combining oncolytic therapies in the era of checkpoint inhibitors Igor Puzanov K9 Immune checkpoint blockade for melanoma: should we combine or sequence ipilimumab and PD-1 antibody therapy? Michael A. Postow News in immunotherapy K10 An update on adjuvant and neoadjuvant therapy for melanom Ahmad Tarhini K11 Targeting multiple inhibitory receptors in melanoma Joe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sanders, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. Zarour K12 Improving adoptive immune therapy using genetically engineered T cells David F. Stroncek Tumor microenvironment and biomarkers K13 Myeloid cells and tumor exosomes: a crosstalk for assessing immunosuppression? Veronica Huber, Licia Rivoltini K14 Update on the SITC biomarker taskforce: progress and challenges Magdalena Thurin World-wide immunosc
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- 2016
9. Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis
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Duchnowska, R, Peksa, R, Radecka, B, Mandat, T, Trojanowski, T, Jarosz, B, Czartoryska-Arlukowicz, B, Olszewski, WP, Och, W, Kalinka-Warzocha, E, Kozlowski, W, Kowalczyk, A, Loi, S, Biernat, W, Jassem, J, Duchnowska, R, Peksa, R, Radecka, B, Mandat, T, Trojanowski, T, Jarosz, B, Czartoryska-Arlukowicz, B, Olszewski, WP, Och, W, Kalinka-Warzocha, E, Kozlowski, W, Kowalczyk, A, Loi, S, Biernat, W, and Jassem, J
- Abstract
BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment. RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01). CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.
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- 2016
10. The prostate cancer registry: Patient characteristics, treatments and preliminary outcomes from a large observational study of metastatic castration-resistant prostate cancer (mCRPC)
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Chowdhury, S., primary, Birtle, A.J., additional, Bjartell, A., additional, Costa, L.A.M., additional, Feyerabend, S., additional, Galli, L., additional, Kalinka-Warzocha, E., additional, Kramer, G., additional, Rey, J.P. Maroto, additional, Lumen, N., additional, Matveev, V.B., additional, Paiss, T., additional, Spaeth, D., additional, Antoni, L., additional, Klumper, E., additional, Wapenaar, R., additional, and Lee, E., additional
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- 2016
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11. The Prostate Cancer Registry: Analysis of Medical Resource Utilisation (Mru) in An International, Prospective, Observational Study of Men with Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
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Chowdhury, S, primary, Birtle, A, additional, Bjartell, A, additional, Costa, L, additional, Feyerabend, S, additional, Galli, L, additional, Lumen, N, additional, Kalinka-Warzocha, E, additional, Maroto, P, additional, Matveev, V, additional, Paiss, T, additional, Spaeth, D, additional, Dearden, L, additional, Klumper, E, additional, Thingstad, T, additional, Wapenaar, R, additional, and Lee, E, additional
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- 2015
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12. 2548 The Prostate Cancer Registry: First results from an international, prospective, observational study of men with metastatic castration-resistant prostate cancer (mCRPC)
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Chowdhury, S., primary, Birtle, A.J., additional, Bjartell, A., additional, Costa, L., additional, Feyerabend, S., additional, Galli, L., additional, Lumen, N., additional, Kalinka-Warzocha, E., additional, Maroto, P., additional, Matveev, V.B., additional, Paiss, T., additional, Spaeth, D., additional, Klumper, E., additional, Thingstad, T., additional, Wapenaar, R., additional, and Lee, E., additional
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- 2015
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13. Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases
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Duchnowska, R., primary, Sperinde, J., additional, Chenna, A., additional, Huang, W., additional, Weidler, J. M., additional, Winslow, J., additional, Haddad, M., additional, Paquet, A., additional, Lie, Y., additional, Trojanowski, T., additional, Mandat, T., additional, Kowalczyk, A., additional, Czartoryska-Ar ukowicz, B., additional, Radecka, B., additional, Jarosz, B., additional, Staszkiewicz, R., additional, Kalinka-Warzocha, E., additional, Chudzik, M., additional, Biernat, W., additional, and Jassem, J., additional
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- 2015
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14. 925TiP - A phase 2 study of investigational TORC1/2 inhibitor TAK-228 and TAK-228 plus investigational PI3Kα-selective inhibitor TAK-117 vs everolimus in adults with advanced or metastatic clear-cell renal cell carcinoma (ccRCC) that has progressed on VEGF-targeted therapy
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Choueiri, T.K., Porta, C., Suarez Rodriguez, C., Alter, R., Czaykowski, P., Duran, I., Gross-Goupil, M., Kalinka-Warzocha, E., Melichar, B., Patel, C., Neuwirth, R., Enke, A., Zohren, F., and Powles, T.
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- 2017
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15. Attitudes of Physicians Toward Risk Assessment and Use of Granulocyte-Colony Stimulating Factor (G-Csf) As Primary Prophylaxis (Pp) in Patients (Pts) Receiving Chemotherapy with an Intermediate Risk of Febrile Neutropenia (Fn)
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Freyer, G., primary, Kalinka-Warzocha, E., additional, Syrigos, K., additional, Marinca, M., additional, Tonini, G., additional, Ng, S.L., additional, Wong, Z.W., additional, Salar, A., additional, Steger, G.G., additional, Abdelsalam, M., additional, Decosta, L., additional, and Szabo, Z., additional
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- 2014
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16. Abstract P6-11-07: Quantitative p95HER2 levels in primary breast cancers and in matched brain metastases
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Duchnowska, R, primary, Sperinde, J, additional, Chenna, A, additional, Huang, W, additional, Weidler, J, additional, Winslow, J, additional, Haddad, M, additional, Paquet, A, additional, Lie, Y, additional, Trojanowski, T, additional, Mandat, T, additional, Kowalczyk, A, additional, Czartoryska-Arlukowicz, B, additional, Radecka, B, additional, Jarosz, B, additional, Staszkiewicz, R, additional, Kalinka-Warzocha, E, additional, Chudzik, M, additional, Biernat, W, additional, and Jassem, J, additional
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- 2013
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17. 746P - The prostate cancer registry: Patient characteristics, treatments and preliminary outcomes from a large observational study of metastatic castration-resistant prostate cancer (mCRPC)
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Chowdhury, S., Birtle, A.J., Bjartell, A., Costa, L.A.M., Feyerabend, S., Galli, L., Kalinka-Warzocha, E., Kramer, G., Rey, J.P. Maroto, Lumen, N., Matveev, V.B., Paiss, T., Spaeth, D., Antoni, L., Klumper, E., Wapenaar, R., and Lee, E.
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- 2016
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18. R-CVP lub R-CHOP w indukcji remisji i rytuksymab w leczeniu podtrzymującym chorych na chłoniaki o przebiegu powolnym. Wieloośrodkowe badanie randomizowane PLRG-4 Polskiej Grupy Badawczej Chłoniaków
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Walewski, J., primary, Kraszewska, E., additional, Szpila, T., additional, Jurczak, W., additional, Giza, A., additional, Zaucha, J.M., additional, Kalinka-Warzocha, E., additional, Zimowska-Curylo, D., additional, Wieczorkiewicz-Kabut, A., additional, Butrym, A., additional, Knopińska-Posłuszny, W., additional, Mazur, G., additional, Paszkiewicz-Kozik, E., additional, Dąbrowska-Iwanicka, A., additional, Romejko-Jarosińska, J., additional, Borawska, A., additional, Wyleżoł, I., additional, Popławska, L., additional, Szymczyk, M., additional, Osowiecki, M., additional, Świerkowska-Czeneszew, M., additional, Domańska-Czyż, K., additional, Stobiecki, J., additional, Druzd-Sitek, A., additional, Konecki, R., additional, Owczarek-Kaczmarek, J., additional, Targoński, Ł., additional, Jamrozek-Jedlińska, M., additional, Zawilska, K., additional, Gruszecka-Czopek, B., additional, Lange, A., additional, Porowska, A., additional, Romanowicz, A., additional, Deptała, A., additional, Ciechańska, M., additional, Hołda, W., additional, Kwant, S., additional, Hellmann, A., additional, Stella-Hołowiecka, B., additional, Kuliczkowski, K., additional, Skotnicki, A.B., additional, and Warzocha, K., additional
- Published
- 2013
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19. PCN296 - The Prostate Cancer Registry: Analysis of Medical Resource Utilisation (Mru) in An International, Prospective, Observational Study of Men with Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
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Chowdhury, S, Birtle, A, Bjartell, A, Costa, L, Feyerabend, S, Galli, L, Lumen, N, Kalinka-Warzocha, E, Maroto, P, Matveev, V, Paiss, T, Spaeth, D, Dearden, L, Klumper, E, Thingstad, T, Wapenaar, R, and Lee, E
- Published
- 2015
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20. Haplotype-specific pattern of association of human major histocompatibility complex with non-Hodgkin’s lymphoma outcome
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Nowak, J., primary, Kalinka-Warzocha, E., additional, Juszczyński, P., additional, Mika-Witkowska, R., additional, Zajko, M., additional, Graczyk-Pol, E., additional, Coiffier, B., additional, Salles, G., additional, and Warzocha, K., additional
- Published
- 2007
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21. 1496P - Attitudes of Physicians Toward Risk Assessment and Use of Granulocyte-Colony Stimulating Factor (G-Csf) As Primary Prophylaxis (Pp) in Patients (Pts) Receiving Chemotherapy with an Intermediate Risk of Febrile Neutropenia (Fn)
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Freyer, G., Kalinka-Warzocha, E., Syrigos, K., Marinca, M., Tonini, G., Ng, S.L., Wong, Z.W., Salar, A., Steger, G.G., Abdelsalam, M., Decosta, L., and Szabo, Z.
- Published
- 2014
- Full Text
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22. Guidelines for the diagnosis and management of osteoporosis in Poland. Update 2017,Zalecenia postȩpowania diagnostycznego i leczniczego w osteoporozie w Polsce. Aktualizacja 2017
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Lorenc, R., Głuszko, P., Franek, E., Jabłoński, M., Jaworski, M., Kalinka-Warzocha, E., Karczmarewicz, E., Kostka, T., Ksiȩzopolska-Orłowska, K., Ewa Marcinowska-Suchowierska, Misiorowski, W., and Wiȩcek, A.
23. Recommendations for diagnostics and therapy of cutaneous melanoma,Czerniaki skóry - Zasady postȩpowania diagnostyczno- terapeutycznego w 2013 roku
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Rutkowski, P., Piotr Wysocki, Nowecki, Z. I., Rudnicka, L., Nasierowska-Guttmejer, A., Fijuth, J., Kalinka-Warzocha, E., Świtaj, T., Wojtukiewicz, M., Zegarski, W., Jeziorski, A., Krzemieniecki, K., Zaucha, R., Filipczyk-Cisarz, E., Herman, K., and Krzakowski, M.
24. Zalecenia postępowania diagnostycznego i leczniczego w osteoporozie w Polsce. Aktualizacja 2017
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Lorenc, R., Piotr Głuszko, Franek, E., Jabłoński, M., Jaworski, M., Kalinka-Warzocha, E., Karczmarewicz, E., Kostka, T., Księżopolska-Orłowska, K., Marcinowska-Suchowierska, E., Misiorowski, W., and Więcek, A.
25. Rituximab maintenance treatment in first and further remissions in patients with follicular lymphoma,Leczenie podtrzymuja̧ce rytuksymabem u chorych na chłoniaka grudkowego w pierwszej i kolejnych remisjach choroby
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Kalinka-Warzocha, E. and Ewa Lech-Maranda
26. PCN296 The Prostate Cancer Registry: Analysis of Medical Resource Utilisation (Mru) in An International, Prospective, Observational Study of Men with Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
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Chowdhury, S, Birtle, A, Bjartell, A, Costa, L, Feyerabend, S, Galli, L, Lumen, N, Kalinka-Warzocha, E, Maroto, P, Matveev, V, Paiss, T, Spaeth, D, Dearden, L, Klumper, E, Thingstad, T, Wapenaar, R, and Lee, E
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27. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer
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CheckMate 026 Investigators, Carbone, David P, Reck, Martin, Paz-Ares, Luis, Creelan, Benjamin, Horn, Leora, Steins, Martin, Felip, Enriqueta, van den Heuvel, Michel M, Ciuleanu, Tudor-Eliade, Badin, Firas, Ready, Neal, Hiltermann, T Jeroen N, Nair, Suresh, Juergens, Rosalyn, Peters, Solange, Minenza, Elisa, Wrangle, John M, Rodriguez-Abreu, Delvys, Borghaei, Hossein, Blumenschein, George R, Villaruz, Liza C, Havel, Libor, Krejci, Jana, Corral Jaime, Jesus, Chang, Han, Geese, William J, Bhagavatheeswaran, Prabhu, Chen, Allen C, Socinski, Mark A, CheckMate 026 Investigators, Lupinacci, L., Martin, C., Pilnik, N., Richardet, M.E., Varela, M.S., Adams, J., Boyer, M., John, T., Moore, M., OByrne, K., Eckmayr, J., Pirker, R., Decoster, L., van Meerbeeck, J., Vansteenkiste, J., Surmont, V., Barrios, C.H., Franke, F.A., Pinto, G., Blais, N., Foley, M.C., Juergens, R., Leighl, N., Morris, D.G., Havel, L., Kolek, V., Krejci, J., Reiterer, P., Roubec, J., Ahvonen, J., Jekunen, A., Maasilta, P., Barlesi, F., Dansen, E., Fraboulet, G., Lena, H., Mennecier, B., Zalcman, G., Frickhofen, N., Kohlhaeufl, M., Reck, M., Repp, R., Steins, M., Wolf, J., Agelaki, S., Syrigos, K., Albert, I., Ostoros, G., Szilasi, M., Cappuzzo, F., Crino, L., De Marinis, F., Gridelli, C., Morabito, A., Roila, F., Atagi, S., Fujita, S., Hida, T., Hirashima, T., Maemondo, M., Minato, K., Nakagawa, K., Nishio, M., Nogami, N., Ohe, Y., Saka, H., Sakai, H., Satouchi, M., Takeda, K., Tanaka, H., Yamamoto, N., Arrieta-Rodriguez, O., De la Mora Jimenez, E., Flores Wilbert, V., Aerts, J., Hiltermann, TJN, Van Den Heuvel, M., Chmielowska, E., Czyzewicz, G., Gabrys, J., Kalinka-Warzocha, E., Pluzanski, A., Kim, H.R., Kim, S.W., Park, K., Cainap, C., Ciuleanu, T.E., Ghizdavescu, D., Blasco, A., Corral Jaime, J., De Castro, J., Felip, E., Paz-Ares, L., Rodriguez Abreu, D., Trigo, J., Kölbeck, K.G., Lindskog, M., Curioni-Fontecedro, A., Mark, M., Peters, S., Chen, Y.M., Karaca, H., Chao, D., Mulatero, C., Summers, Y., Arledge, S., Badin, F., Batus, M., Blumenschein, G., Borghaei, H., Camidge, R., Boyd, T., Brahmer, J., Carbone, D., Cetnar, J., Chachoua, A., Chaft, J., Chen, H., Creelan, B., Gainor, J., Gettinger, S., Gerber, D.E., Horn, L., Kaywin, P., Kessler, R., Langer, C.J., McCracken, J., Nair, S., Oyola, R., Pillai, R., Quddus, F., Rangachari, D., Ready, N., Reynolds, C., Rosenberg, R., Sharma, N., Stinchcombe, T., Villaruz, L., Wakelee, H., Wrangle, J., Clinical sciences, Medical Oncology, Laboratory for Medical and Molecular Oncology, van Meerbeeck, Jan, et al., and Translational Immunology Groningen (TRIGR)
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0301 basic medicine ,Oncology ,Lung Neoplasms ,medicine.medical_treatment ,THERAPY ,B7-H1 Antigen ,Lung Neoplasms/chemically induced ,0302 clinical medicine ,PACLITAXEL PLUS CARBOPLATIN ,Carcinoma, Non-Small-Cell Lung ,Clinical endpoint ,Carcinoma, Non-Small-Cell Lung/chemically induced ,DOCETAXEL ,General Medicine ,CHEMOTHERAPY ,OPEN-LABEL ,3. Good health ,Docetaxel ,030220 oncology & carcinogenesis ,oncology ,TRIAL ,Nivolumab ,medicine.drug ,B7-H1 Antigen/metabolism ,medicine.medical_specialty ,Antigens, CD274/metabolism ,Antineoplastic Agents ,Disease-Free Survival ,Humans ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Article ,03 medical and health sciences ,CISPLATIN ,MAINTENANCE BEVACIZUMAB ,Internal medicine ,medicine ,Carcinoma ,Lung cancer ,neoplasms ,Cisplatin ,Chemotherapy ,business.industry ,medicine.disease ,PHASE-III ,Gemcitabine ,respiratory tract diseases ,030104 developmental biology ,GEMCITABINE ,Human medicine ,business - Abstract
BACKGROUNDNivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC.METHODSWe randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more.RESULTSAmong the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P = 0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy.CONCLUSIONSNivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533.)
- Published
- 2017
28. First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4.
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Walewski J, Paszkiewicz-Kozik E, Michalski W, Rymkiewicz G, Szpila T, Butrym A, Giza A, Zaucha JM, Kalinka-Warzocha E, Wieczorkiewicz A, Zimowska-Curyło D, Knopińska-Posłuszny W, Tyczyńska A, Romejko-Jarosińska J, Dąbrowska-Iwanicka A, Gruszecka B, Jamrozek-Jedlińska M, Borawska A, Hołda W, Porowska A, Romanowicz A, Hellmann A, Stella-Hołowiecka B, Deptała A, and Jurczak W
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cyclophosphamide pharmacology, Doxorubicin pharmacology, Doxorubicin therapeutic use, Female, Humans, Male, Middle Aged, Poland, Prednisone pharmacology, Rituximab pharmacology, Vincristine pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Immunotherapy methods, Lymphoma, Follicular drug therapy, Prednisone therapeutic use, Rituximab therapeutic use, Vincristine therapeutic use
- Abstract
R-CVP (cyclophosphamide, vincristine, prednisone) and R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non-Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression-free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R-CVP to R-CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R-CVP or R-CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m
2 q 2 months for 12 cycles. Primary endpoint was event-free survival (EFS). Two-hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R-CHOP: 127, R-CVP: 123). Median age was 56 years (21-85), 44% were male, 90% were in stage III-IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R-CHOP and R-CVP groups (P = 0·218) respectively. After a median follow-up of 67, 66, and 70 months, five-year EFS was 61% vs. 56% (not significant), progression-free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R-CHOP vs. the R-CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients., in the R-CHOP and the R-CVP groups respectively. This multicentre randomized study with >five-year follow-up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R-CVP or R-CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R-CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second-line therapy., (© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2020
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29. Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group .
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Wróbel T, Biecek P, Rybka J, Szulgo A, Sorbotten N, Giza A, Tyczyńska A, Nowara E, Badora-Rybicka A, Adamowicz K, Kulikowski W, Kroll-Balcerzak R, Balcerzak A, Spychałowicz W, Kalinka-Warzocha E, Kumiega B, Drozd-Sokołowska J, Subocz E, Sałek A, Machaczka M, Hołojda J, Pogrzeba J, Dobrzyńska O, Chmielowska E, Jurczak W, Knopińska-Posłuszny W, Leśniewski-Kmak K, and Maciej Zaucha J
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- Age Factors, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Comorbidity, Female, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Poland epidemiology, Population Surveillance, Prognosis, Retrospective Studies, Treatment Outcome, Hodgkin Disease epidemiology
- Abstract
We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.
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- 2019
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30. Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial.
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Ascierto PA, Long GV, Robert C, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Ny L, Arance A, Svane IM, Schadendorf D, Gogas H, Saci A, Jiang J, Rizzo J, and Atkinson V
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- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Immunological adverse effects, Dacarbazine adverse effects, Disease Progression, Double-Blind Method, Female, Humans, Male, Melanoma genetics, Melanoma mortality, Melanoma pathology, Middle Aged, Nivolumab adverse effects, Skin Neoplasms genetics, Skin Neoplasms mortality, Skin Neoplasms pathology, Time Factors, Treatment Outcome, Young Adult, Antineoplastic Agents, Alkylating therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Dacarbazine therapeutic use, Melanoma drug therapy, Nivolumab therapeutic use, Proto-Oncogene Proteins B-raf genetics, Skin Neoplasms drug therapy
- Abstract
Importance: This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors., Objective: To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma., Design, Setting, and Participants: This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation., Interventions: Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m2 every 3 weeks plus nivolumab-matched placebo every 2 weeks)., Main Outcome and Measure: Overall survival., Results: At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P < .001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of dacarbazine-treated patients. There were no deaths due to study drug toxic effects., Conclusions and Relevance: Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma., Trial Registration: ClinicalTrials.gov identifier: NCT01721772.
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- 2019
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31. Analysis of KRAS, NRAS, BRAF, and PIK3CA mutations could predict metastases in colorectal cancer: A preliminary study.
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Wojas-Krawczyk K, Kalinka-Warzocha E, Reszka K, Nicoś M, Szumiło J, Mańdziuk S, Szczepaniak K, Kupnicka D, Lewandowski R, Milanowski J, and Krawczyk P
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- Age Factors, Class I Phosphatidylinositol 3-Kinases, Female, Humans, Male, Membrane Proteins, Poland, Real-Time Polymerase Chain Reaction, Sex Factors, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, GTP Phosphohydrolases genetics, Mutation genetics, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Background: Colorectal cancer (CRC) is usually diagnosed in the metastatic stage, when chemotherapy and molecularly-targeted therapies, instead of surgery, play the most important therapeutic role. Application of anti-epidermal growth factor receptor (EGFR) therapy requires the analysis of RAS mutation status and only RAS wild-type (wt) patients are qualified for the therapy., Objectives: The objective of this study was to analyze driver mutations in KRAS, NRAS, BRAF, and PIK3CA genes in CRC patients., Material and Methods: We assessed the KRAS, NRAS, BRAF, and PIK3CA genes in 102 inoperable, locally advanced and advanced CRC patients. Real-time polymerase chain reaction (RT-PCR) and high resolution melt PCR (HRM-PCR) techniques with DNA intercalating dye were applied in the study., Results: Forty-six patients demonstrated the presence of examined mutations (45.1%). No significant differences in driver mutation occurrence between men and women, as well as between younger (<65 years) and older (≥65 years) patients were found. The mutations were present significantly more frequently in metastatic than in primary tumors (p = 0.039) due to the high incidence of KRAS gene mutations in metastatic tissue. BRAF and PIK3CA mutations were found only in primary tumors. The incidence of PIK3CA mutations was significantly higher (11.77%) in early than in advanced stages of the disease (1.96%; p = 0.05); NRAS mutations were found only in metastatic cancer (7.85%; p = 0.041). Only a single mutation of the PIK3CA and no mutations of NRAS were found in rectal cancer., Conclusions: Our results have shown low occurrence of driver mutations in Polish CRC patients, involving also mutations in rarely tested genes. The extent of the research panel of additional mutations could contribute to creating a better method of qualifying patients for molecularly targeted therapies and obtaining a better outcome for these therapeutic strategies.
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- 2019
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32. Polymorphism in IKZF1 gene affects clinical outcome in diffuse large B-cell lymphoma.
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Bielska M, Borowiec M, Jesionek-Kupnicka D, Braun M, Bojo M, Pastorczak A, Kalinka-Warzocha E, Prochorec-Sobieszek M, Robak T, Warzocha K, Młynarski W, and Lech-Marańda E
- Subjects
- Adult, Disease-Free Survival, Female, Humans, Lymphoma, Large B-Cell, Diffuse therapy, Male, Middle Aged, Survival Rate, Genotype, Ikaros Transcription Factor genetics, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse mortality, Neoplasm Proteins genetics, Polymorphism, Genetic
- Abstract
IKZF1 encodes a transcription factor involved in B-cell maturation and differentiation. We genotyped 218 diffuse large B-cell lymphoma (DLBCL) patients and 715 unrelated controls using a TaqMan allelic discrimination assay. No statistical difference was observed in the genotype distribution of the IKZF1 rs4132601 polymorphism between DLBCL patients and controls. However, the 2-year PFS rate of patients with the IKZF1 TT genotype was 54.3% compared to 68.6% in those with the IKZF1 G+ genotypes. Moreover, the IKZF1 rs4132601 polymorphism retained its independent prognostic impact on PFS. A more pronounced effect of the IKZF1 TT genotype on PFS was detected in patients with low/intermediate low IPI-risk group. When analysis was restricted to patients with GCB-type pattern, those with the IKZF1 TT genotype achieved a lower 5-year OS rate than the patients with the IKZF1 G+ genotypes (19.6 vs. 56%). This study provides the first evidence for the association of IKZF1 variants with DLBCL outcome.
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- 2017
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33. Comparison of the effectiveness of erlotinib, gefitinib, and afatinib for treatment of non-small cell lung cancer in patients with common and rare EGFR gene mutations.
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Krawczyk P, Kowalski DM, Ramlau R, Kalinka-Warzocha E, Winiarczyk K, Stencel K, Powrózek T, Reszka K, Wojas-Krawczyk K, Bryl M, Wójcik-Superczyńska M, Głogowski M, Barinow-Wojewódzki A, Milanowski J, and Krzakowski M
- Abstract
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed. EGFR mutations were determined using RT-PCR and the EntroGen EGFR Mutations Analysis kit. Partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were analyzed. Demographic and clinical factors had no impact on PFS or OS in patients treated with EGFR-TKIs. Erlotinib, gefitinib, and afatinib showed similar efficacies based on treatment response, median PFS, and OS. The type of EGFR mutation had no impact on median OS; however, median PFS was significantly longer in patients with the exon 19 deletion compared to patients with the exon 21 p.Leu858Arg substitution and rare EGFR gene mutations (P=0.013). Patients with common EGFR mutations showed significantly longer median PFS than those with rare EGFR mutations (10 vs. 5 months; P=0.009). Erlotinib, gefitinib, and afatinib show similar efficacies in NSCLC patients with both common and rare EGFR mutations. When undergoing EGFR-TKI treatment, patients with rare EGFR mutations showed similar OS but poorer PFS. Further investigation into the associations between particular rare EGFR mutations and EGFR-TKIs treatment outcomes is required.
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- 2017
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34. Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer.
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Duchnowska R, Jarząb M, Żebracka-Gala J, Matkowski R, Kowalczyk A, Radecka B, Kowalska M, Pfeifer A, Foszczyńska-Kłoda M, Musolino A, Czartoryska-Arłukowicz B, Litwiniuk M, Surus-Hyla A, Szabłowska-Siwik S, Karczmarek-Borowska B, Dębska-Szmich S, Głodek-Sutek B, Sosińska-Mielcarek K, Chmielowska E, Kalinka-Warzocha E, Olszewski WP, Patera J, Żawrocki A, Pliszka A, Tyszkiewicz T, Rusinek D, Oczko-Wojciechowska M, Jassem J, and Biernat W
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Brain Neoplasms epidemiology, Brain Neoplasms secondary, Estrogen Receptor alpha metabolism, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Neoplasm Staging, Prognosis, RNA, Messenger metabolism, Receptor, ErbB-2 metabolism, Receptors, Progesterone metabolism, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Triple Negative Breast Neoplasms pathology, Brain Neoplasms diagnosis, Gene Expression Profiling, Triple Negative Breast Neoplasms genetics
- Abstract
Background: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches., Patients and Methods: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM., Results: In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B., Conclusion: Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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35. Guidelines for the diagnosis and management of osteoporosis in Poland : Update 2017.
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Lorenc R, Głuszko P, Franek E, Jabłoński M, Jaworski M, Kalinka-Warzocha E, Karczmarewicz E, Kostka T, Księzopolska-Orłowska K, Marcinowska-Suchowierska E, Misiorowski W, and Więcek A
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Osteoporosis prevention & control, Osteoporosis rehabilitation, Osteoporotic Fractures prevention & control, Practice Guidelines as Topic, Bone Density Conservation Agents therapeutic use, Disease Management, Osteoporosis diagnosis, Osteoporosis drug therapy
- Abstract
In the rapidly ageing society in Poland, osteoporosis is a growing epidemiological problem, and osteoporosis-related fractures are a cause of chronic disability and considerable increase of death risk. It turns out that 80 to 90% of patients suffering from osteoporosis, including osteoporosis accompanied by fractures, do not receive adequate pharmacotherapy. In this paper, a Guideline Working Group of experts from the Multidisciplinary Osteoporosis Forum update the existing Polish guidelines concerning the diagnosis and management of osteoporosis (last revised in 2013), taking account of the latest literature, availability and reimbursement of drugs, and current health care organisation. In the revised guidelines, we still postulate that tasks are divided between primary care doctors (stage I) and specialists in osteoporosis management (stage II). We emphasise the necessity of early initiation of pharmacotherapy and rehabilitation in all patients with low-energy fractures. We recommend that the 10-year fracture risk should be estimated in all patients (including those without fractures) who are over 50 years of age, and that the Polish threshold for therapeutic intervention should be adopted: ≥ 10% for FRAX PL calculator. We add strategies of drug choice and therapy monitoring with imaging, and densitometric and biochemical diagnostics. We define basic guidelines concerning prevention of falls, rehabilitation, and dietary procedures, and elimination of environmental and other fracture risk factors. We point to two vital elements for improving osteoporosis management: 1) strategy of supervision over fractures management - Fracture Liaison Service (FLS), and, optimally, 2) strategies of short-term monitoring of the therapeutic efficacy with the use of biochemical markers.
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- 2017
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36. Zalecenia postępowania diagnostycznego i leczniczego w osteoporozie w Polsce. Aktualizacja 2017.
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Lorenc R, Głuszko P, Franek E, Jabłoński M, Jaworski M, Kalinka-Warzocha E, Karczmarewicz E, Kostka T, Księżopolska-Orłowska K, Marcinowska-Suchowierska E, Misiorowski W, and Więcek A
- Subjects
- Female, Humans, Male, Osteoporosis therapy, Poland, Osteoporosis diagnosis, Societies, Medical
- Published
- 2017
37. Does diabetes alter the risk of neoplasms? Real-world data analysis in Poland: incidence rates for selected neoplasms in patients with diabetes.
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Śliwczyński A, Kalinka-Warzocha E, Teter Z, Marczak M, Karnafel W, and Wierzba W
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- Aged, Female, Humans, Incidence, Male, Middle Aged, Neoplasms epidemiology, Poland epidemiology, Diabetes Complications, Neoplasms ethnology
- Published
- 2016
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38. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.
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Jesionek-Kupnicka D, Bojo M, Prochorec-Sobieszek M, Szumera-Ciećkiewicz A, Jabłońska J, Kalinka-Warzocha E, Kordek R, Młynarski W, Robak T, Warzocha K, and Lech-Maranda E
- Subjects
- Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Gene Expression Profiling, HLA-G Antigens metabolism, Histocompatibility Antigens Class II metabolism, Humans, Immunohistochemistry, Immunotherapy methods, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse mortality, Male, Middle Aged, Prednisone administration & dosage, Probability, Prognosis, Regression Analysis, Remission Induction, Rituximab, Treatment Outcome, Vincristine administration & dosage, Gene Expression Regulation, Neoplastic, HLA-G Antigens immunology, Histocompatibility Antigens Class II immunology, Lymphoma, Large B-Cell, Diffuse immunology
- Abstract
The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.
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- 2016
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39. Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis.
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Duchnowska R, Pęksa R, Radecka B, Mandat T, Trojanowski T, Jarosz B, Czartoryska-Arłukowicz B, Olszewski WP, Och W, Kalinka-Warzocha E, Kozłowski W, Kowalczyk A, Loi S, Biernat W, and Jassem J
- Subjects
- Astrocytes immunology, Astrocytes metabolism, Astrocytes pathology, B7-H1 Antigen genetics, B7-H1 Antigen metabolism, Biomarkers, Tumor, Brain Neoplasms metabolism, Brain Neoplasms mortality, Breast Neoplasms metabolism, Breast Neoplasms mortality, Combined Modality Therapy, Female, Gene Expression, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Microglia immunology, Microglia metabolism, Microglia pathology, Neoplasm Grading, Phenotype, Prognosis, Programmed Cell Death 1 Receptor genetics, Programmed Cell Death 1 Receptor metabolism, Proportional Hazards Models, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Brain Neoplasms immunology, Brain Neoplasms secondary, Breast Neoplasms immunology, Breast Neoplasms pathology, Tumor Microenvironment immunology
- Abstract
Background: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies., Methods: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment., Results: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01)., Conclusions: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.
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- 2016
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40. The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients.
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Kucharczyk T, Krawczyk P, Powrózek T, Kowalski DM, Ramlau R, Kalinka-Warzocha E, Knetki-Wróblewska M, Winiarczyk K, Krzakowski M, and Milanowski J
- Subjects
- Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Female, Follow-Up Studies, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Prognosis, Retrospective Studies, Survival Rate, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Pemetrexed therapeutic use, Polymorphism, Single Nucleotide genetics, Thymidylate Synthase genetics
- Abstract
In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.
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- 2016
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41. Attitudes of physicians toward assessing risk and using granulocyte colony-stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia.
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Freyer G, Kalinka-Warzocha E, Syrigos K, Marinca M, Tonini G, Ng SL, Wong ZW, Salar A, Steger G, Abdelsalam M, DeCosta L, and Szabo Z
- Subjects
- Adult, Aged, Antineoplastic Agents adverse effects, Febrile Neutropenia etiology, Female, Humans, Male, Middle Aged, Neoplasms drug therapy, Physicians, Risk Factors, Attitude of Health Personnel, Febrile Neutropenia prevention & control, Granulocyte Colony-Stimulating Factor therapeutic use, Guideline Adherence statistics & numerical data, Risk Assessment methods
- Abstract
Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy. This prospective, observational study describes physicians' approaches toward assessing FN risk in patients receiving chemotherapy regimens with an intermediate (10-20 %) FN risk. In the baseline investigator assessment, physicians selected factors considered important when assessing overall FN risk and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP). Physicians then completed patient assessments using the same lists of factors. The final FN risk scores and whether G-CSF PP was planned were reported. The final analysis included 165 physicians and 944 patients. The most frequently considered factor in both assessments was chemotherapy agents in the backbone (88 % of investigator and 93 % of patient assessments). History of FN (83 %), baseline laboratory values (76 %) and age (73 %) were commonly selected at baseline, whereas tumor type (72 %), guidelines (62 %) and tumor stage (43 %) were selected most during patient assessments. Median investigator-reported FN risk threshold for G-CSF PP was 20 % (range 10-85 %). G-CSF PP was planned in 82 % of patients with an FN risk at or above this threshold; therefore, almost one-fifth of qualifying patients would not receive G-CSF PP. Physicians generally follow guidelines, but also consider individual patient characteristics when assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may optimize the use of G-CSF PP, which may minimize the incidence of FN in patients undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov Identifier: NCT01813721.
- Published
- 2015
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42. Prognostic value of HER3, PTEN and p-HER2 expression in patients with HER2positive breast cancer.
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Dębska-Szmich S, Kusińska R, Czernek U, Szydłowska-Pazera K, Habib-Lisik M, Piekarski JH, Olas E, Kulig A, Ułańska M, Kalinka-Warzocha E, and Potemski P
- Subjects
- Breast Neoplasms diagnosis, Breast Neoplasms drug therapy, Female, Gene Expression, Humans, Immunohistochemistry, Middle Aged, Phosphorylation, Prognosis, Receptor, ErbB-2 drug effects, Receptor, ErbB-2 genetics, Treatment Outcome, Breast Neoplasms metabolism, PTEN Phosphohydrolase genetics, Receptor, ErbB-2 metabolism, Receptor, ErbB-3 genetics, Trastuzumab therapeutic use
- Abstract
Background: HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment., Aim: The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen., Material/methods: Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab., Results: HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen., Discussion: HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.
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- 2015
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43. Chemotherapy treatment patterns and neutropenia management in gastric cancer.
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Kalinka-Warzocha E, Plazas JG, Mineur L, Salek T, Hendlisz A, DeCosta L, Vogl FD, and Passalacqua R
- Subjects
- Adenocarcinoma secondary, Disease Management, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Prognosis, Prospective Studies, Stomach Neoplasms pathology, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Granulocyte Colony-Stimulating Factor administration & dosage, Neutropenia chemically induced, Neutropenia drug therapy, Stomach Neoplasms drug therapy
- Abstract
Background: Potentially myelosuppressive doublet and triplet chemotherapy combination regimens are considered the most active treatments in gastric cancer. This multicenter prospective observational study was designed to gain insight into the chemotherapy regimens being used in Europe and to evaluate neutropenia management in patients identified as at high risk for febrile neutropenia (FN)., Methods: Eligible patients had gastric cancer, were scheduled for ≥ 3 cycles of myelosuppressive chemotherapy, and had an investigator-assessed overall FN risk ≥ 20%. Data were collected for up to ten cycles. The primary endpoint was the proportion of patients who received granulocyte colony stimulating factor (G-CSF) primary prophylaxis (defined as G-CSF initiated on days 1-7 of cycle 1). Secondary endpoints included FN incidence, chemotherapy administration, and G-CSF use., Results: Of 199 patients who met the eligibility criteria and started at least one cycle of chemotherapy, mean age was 63 years, 76% were men, 83% had an ECOG score of 0 or 1, 54% had metastatic disease, and 24% had received prior chemotherapy. A total of 27 different backbone regimens were given; the most common regimen was modified docetaxel, cisplatin, and 5-fluorouracil (DCF). Despite all patients having been identified as having a ≥ 20% FN risk, only 70 (35%) received G-CSF primary prophylaxis. FN occurred in 14 patients overall (7%). Most FN events occurred in patients who received DCF/modified DCF (9/14 events, 64%)., Conclusions: The results of this study reveal a high use of myelotoxic treatment regimens in gastric cancer in Europe and low adherence to clinical practice guidelines for the use of primary and secondary G-CSF prophylaxis for FN.
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- 2015
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44. Human leukocyte antigen-G polymorphisms influence the clinical outcome in diffuse large B-cell lymphoma.
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Bielska M, Bojo M, Klimkiewicz-Wojciechowska G, Jesionek-Kupnicka D, Borowiec M, Kalinka-Warzocha E, Prochorec-Sobieszek M, Robak T, Warzocha K, Młynarski W, and Lech-Maranda E
- Subjects
- Adult, Case-Control Studies, Female, Humans, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse mortality, Male, Genetic Predisposition to Disease, HLA-G Antigens genetics, Lymphoma, Large B-Cell, Diffuse genetics, Polymorphism, Genetic
- Abstract
The role of HLA-G is extensively studied in cancer due to its inhibition of the immune response. Several polymorphisms in the HLA-G gene have been reported to significantly affect its expression. We, therefore, investigated whether functionally relevant HLA-G polymorphisms, HLA-G-725C/G/T, and HLA-G 14-base pair, have any influence on the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its clinical course. The polymorphisms were genotyped in 207 previously untreated patients with DLBCL and 150 unrelated controls. A significant difference in genotype distribution of HLA-G polymorphic genotypes between the patients and controls was found. The frequencies of the HLA-G-725GG or the HLA-G-725GC genotype were lower, and those of the HLA-G ins/ins genotype were higher in the patients compared with the controls. Patients carrying the HLA-G-725CC genotype presented a higher probability of overall survival (OS) than subjects with other genotype combinations of HLA-G-725C/G/T (P = 0.003). The homozygous HLA-G del/del had a lower probability of OS than subjects carrying the HLA-G deletion/insertion (del/ins) or the HLA-G ins/ins genotype (P = 0.009). Two HLA-G genotype-based risk groups were defined according to the genotype distribution. The high-risk (HR) group presented a shorter OS than low-risk (LR) patients (P = 0.001). In a multivariate analysis adjusted for International Prognostic Index (IPI) factors, both the intermediate high/high IPI-risk group (P < 0.0001) and the HR genotype group (P = 0.004) independently increased the risk of death. This is the first study indicating an important role of HLA-G polymorphisms for the clinical course of DLBCL. The potential influence of HLA-G polymorphisms on the susceptibility to DLBCL thus deserves further study., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
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45. Nivolumab in previously untreated melanoma without BRAF mutation.
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Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, and Ascierto PA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal adverse effects, Antineoplastic Agents adverse effects, Dacarbazine adverse effects, Disease-Free Survival, Double-Blind Method, Female, Humans, Male, Melanoma genetics, Melanoma mortality, Melanoma secondary, Middle Aged, Nivolumab, Proto-Oncogene Proteins B-raf genetics, Survival Rate, Young Adult, Antibodies, Monoclonal administration & dosage, Antineoplastic Agents administration & dosage, Dacarbazine administration & dosage, Melanoma drug therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Background: Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study., Methods: We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival., Results: At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine., Conclusions: Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).
- Published
- 2015
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46. The efficacy of EGFR gene mutation testing in various samples from non-small cell lung cancer patients: a multicenter retrospective study.
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Krawczyk P, Ramlau R, Chorostowska-Wynimko J, Powrózek T, Lewandowska MA, Limon J, Wasąg B, Pankowski J, Kozielski J, Kalinka-Warzocha E, Szczęsna A, Wojas-Krawczyk K, Skroński M, Dziadziuszko R, Jaguś P, Antoszewska E, Szumiło J, Jarosz B, Woźniak A, Jóźwicki W, Dyszkiewicz W, Pasieka-Lis M, Kowalski DM, Krzakowski M, Jassem J, and Milanowski J
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma secondary, Adenocarcinoma surgery, Aged, Carcinoma, Adenosquamous genetics, Carcinoma, Adenosquamous secondary, Carcinoma, Adenosquamous surgery, Carcinoma, Large Cell genetics, Carcinoma, Large Cell secondary, Carcinoma, Large Cell surgery, Carcinoma, Non-Small-Cell Lung secondary, Carcinoma, Non-Small-Cell Lung surgery, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell secondary, Carcinoma, Squamous Cell surgery, DNA-Binding Proteins genetics, Female, Follow-Up Studies, Humans, Lung Neoplasms pathology, Lung Neoplasms surgery, Male, Middle Aged, Neoplasm Staging, Polymerase Chain Reaction, Prognosis, Retrospective Studies, Transcription Factors, Carcinoma, Non-Small-Cell Lung genetics, DNA Mutational Analysis, ErbB Receptors genetics, Lung Neoplasms genetics, Mutation genetics
- Abstract
Introduction: Testing for the epidermal growth factor receptor (EGFR) gene mutations requires considerable multidisciplinary experience of clinicians (for appropriate patient selection), pathologists (for selection of appropriate cytological or histological material) and geneticists (for performing and reporting reliable molecular tests). We present our experience on the efficacy of routine EGFR testing in various types of tumor samples and the frequency of EGFR mutations in a large series of Polish non-small cell lung cancer (NSCLC) patients., Methods: Deletions in exon 19 and substitution L858R in exon 21 of EGFR gene were assessed using real-time PCR techniques in 1,138 small biopsies or cytological specimens and in 1,312 surgical samples., Results: Out of 2,450 diagnostic samples (containing >10% of tumor cells), the occurrence of EGFR gene mutations was 9%; more frequently in women (13.9%) and adenocarcinoma patients (10%), particularly with accompanying expression of TTF1 (13.0%). The frequency of EGFR gene mutations was similar in cytological and histological specimens, and in primary and metastatic lesions, and did not depend on the percentage of tumor cells and quality of isolated DNA. Cytological or small biopsy, compared to surgical specimens showed lower percentage of tumor cells, with no impact on the quality of real-time PCR assay., Conclusion: Cytological and small biopsy samples with low (10-20%) content of tumor cells and specimens from metastatic lesions are a sufficient source for EGFR mutation testing in NSCLC patients. The incidence of EGFR gene mutations in examined population was similar to those reported in other Caucasian populations.
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- 2015
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47. Multicentre, Prospective Observational Study of Pegfilgrastim Primary Prophylaxis in Patients at High Risk of Febrile Neutropenia in Poland: PROFIL Study.
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Jurczak W, Kalinka-Warzocha E, Chmielowska E, Duchnowska R, Wojciechowska-Lampka E, and Wieruszewska K
- Abstract
Aim of the Study: PROFIL was a prospective observational study conducted to investigate physicians' evaluation of febrile neutropenia (FN) risk and reasons for giving pegfilgrastim primary prophylaxis (PP) in routine clinical practice in Poland., Material and Methods: Adult cancer patients treated with chemotherapy (CT), assessed by investigators as having high overall FN risk, and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010. Investigators assessed FN risk of the CT regimen, individual risk factors, and overall FN risk, and were asked to provide the most important reasons for providing pegfilgrastim PP. Investigator-assessed CT FN risk was compared with guideline classification., Results: Data were analysed from 1006 breast, ovarian, and lung cancer, and non-Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease; these were consistent across tumour types and treatment intent. The investigators generally assessed high CT FN risk in agreement with guideline classification. Febrile neutropenia occurred in 4% of patients, most commonly in HL, NHL, and patients with advanced disease., Conclusions: High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Poland.
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- 2015
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48. Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients.
- Author
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Krawczyk P, Kucharczyk T, Kowalski DM, Powrózek T, Ramlau R, Kalinka-Warzocha E, Winiarczyk K, Knetki-Wróblewska M, Wojas-Krawczyk K, Kałakucka K, Dyszkiewicz W, Krzakowski M, and Milanowski J
- Subjects
- Aged, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung mortality, Female, Glutamates administration & dosage, Guanine administration & dosage, Guanine analogs & derivatives, Humans, Lung Neoplasms genetics, Lung Neoplasms mortality, Male, Middle Aged, Pemetrexed, Platinum administration & dosage, Proportional Hazards Models, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, DNA-Binding Proteins genetics, Endonucleases genetics, Lung Neoplasms drug therapy, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Polymorphism, Single Nucleotide, Thymidylate Synthase genetics
- Abstract
Purpose: We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy., Methods: The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5'-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3'-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations' results were correlated with disease control rate, progression-free survival (PFS) and overall survival., Results: Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality., Conclusion: The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.
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- 2014
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49. Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients.
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Powrózek T, Kowalski DM, Krawczyk P, Ramlau R, Kucharczyk T, Kalinka-Warzocha E, Knetki-Wróblewska M, Winiarczyk K, Dyszkiewicz W, Krzakowski M, and Milanowski J
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Female, Glutamates administration & dosage, Glutamates adverse effects, Guanine administration & dosage, Guanine adverse effects, Guanine analogs & derivatives, Humans, Male, Mesothelioma genetics, Mesothelioma mortality, Middle Aged, Mutagenesis, Insertional genetics, Pemetrexed, Pharmacogenetics, Platinum administration & dosage, Platinum adverse effects, Pleural Neoplasms genetics, Pleural Neoplasms mortality, Polymorphism, Genetic, Prognosis, Retrospective Studies, Survival Analysis, Tandem Repeat Sequences genetics, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, DNA-Binding Proteins genetics, Drug Resistance, Neoplasm genetics, Endonucleases genetics, Mesothelioma drug therapy, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Pleural Neoplasms drug therapy, Thymidylate Synthase genetics
- Abstract
Introduction: The combination of pemetrexed and platinum compound represents the standard regimen for first-line chemotherapy in malignant pleural mesothelioma patients. Pemetrexed is a multitarget antifolate agent that inhibits folate-dependent enzymes (eg, thymidylate synthase [TS]) and thus synthesis of nucleotides and DNA. Expression of TS and folate availability, regulated by gene polymorphisms, have implications for effectiveness of chemotherapy and the outcome of mesothelioma patients. The aim of this retrospective multicenter study was to assess the correlation between TS, 5,10-methylenetetrahydrofolate reductase (MTHFR) and excision repair cross-complementing group 1 (ERCC1) gene polymorphisms and the efficacy of pemetrexed-based first-line chemotherapy of mesothelioma patients., Patients and Methods: Fifty-nine mesothelioma patients (31 men with a median age of 62 years) treated in first-line chemotherapy with platinum in combination with pemetrexed or pemetrexed monotherapy were enrolled. Genomic DNA was isolated from peripheral blood. Using polymerase chain reaction and high resolution melt methods, the variable number of tandem repeat, the G>C single nucleotide polymorphism (SNP) in these repeats, and 6-base pair (bp) insertion/deletion polymorphism of the TS gene, the SNP of 677C>T in MTHFR, and 19007C>T in the ERCC1 gene were analyzed and correlated with disease control rate, progression-free survival (PFS), and overall survival (OS) of mesothelioma patients., Results: Greater risk of early disease progression (PD), and shortening of PFS and OS were associated with several clinical factors (eg, anemia for early PD and OS), weight loss (for PFS and OS), and previous surgical treatment (for early PD, PFS, and OS). Insertion of 6-bp in both alleles of the TS gene (1494del6) was the only genetic factor that increased the incidence of early progression (P = .028) and shortening of median PFS (P = .06) in patients treated with pemetrexed-based chemotherapy. In multivariate analysis, the 1494del6 in the 3' untranslated region (UTR) of the TS gene also had a predictive role for PFS (P = .0185; hazard ratio, 2.3258 for +6/+6 homozygotes) in analyzed mesothelioma patients., Conclusion: Most analyzed polymorphisms in TS, MTHFR, and ERCC1 genes failed to predict outcome in mesothelioma patients treated with pemetrexed-based chemotherapy. However, different variants of 1494del6 in the 3' UTR of the TS gene were associated with differences in disease control rate and PFS of our patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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50. Predictive value of ERCC1 and RRM1 gene single-nucleotide polymorphisms for first-line platinum- and gemcitabine-based chemotherapy in non-small cell lung cancer patients.
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Mlak R, Krawczyk P, Ramlau R, Kalinka-Warzocha E, Wasylecka-Morawiec M, Wojas-Krawczyk K, Kucharczyk T, Homa I, Kozioł P, Ciesielka M, Chudziak D, and Milanowski J
- Subjects
- Adult, Aged, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Humans, Lung Neoplasms genetics, Male, Middle Aged, Platinum administration & dosage, Polymorphism, Single Nucleotide, Prognosis, Ribonucleoside Diphosphate Reductase, Gemcitabine, Carcinoma, Non-Small-Cell Lung drug therapy, DNA-Binding Proteins genetics, Endonucleases genetics, Lung Neoplasms drug therapy, Tumor Suppressor Proteins genetics
- Abstract
Platinum-based chemotherapy with third generation drugs (such as gemcitabine) is an efficacious regimen of first-line treatment of patients with advanced, unresectable non-small cell lung cancer (NSCLC), without activating EGFR mutations. Mechanism of action of cytostatics are distortions in the DNA. ERCC1 and RRM1 are key proteins involved in the repair of DNA, thus, they may be responsible for the ineffectiveness of therapy. We investigated whether ERCC1 (19007C>T) and RRM1 (-37C>A) polymorphisms impact response to chemotherapy and survival in 62 patients with NSCLC treated with platinum and gemcitabine. Single nucleotide polymorphisms (SNPs) were assessed using a PCR-RFLP method in DNA isolated from PBLs. There were no statistically significant relationships between ERCC1 genotypes and response to therapy (p=0.581, χ2=1.09) as well as patient overall survival (OS). Carriers of the RRM1 AC genotype showed disease progression significantly more frequently (p=0.019, χ2=5.473) compared to carriers of the AA or CC genotypes. Carriers of the ERCC1/RRM1TT/CC genotype combination showed disease control significantly more frequently (p=0.047, χ2=3.95) compared to carriers of other genotype combinations. Patients with AA or CC genotypes of RRM1 showed significantly higher progression-free survival probability (p=0.0001, HR=0.39, 95% CI, 0.22-0.70) and OS probability (p=0.0104, HR=0.39, 95% CI, 0.18-0.82) compared to those with the AC genotype. In Cox regression model, poor performance status (p=0.0016, HR=4.78, 95% CI, 1.82-12.56), AC genotype of RRM1 gene (p=0.0414, HR=2.47, 95% CI, 1.04-5.87), lack of prior surgical treatment (p=0.0425, HR=4.71, 95% CI, 1.06-20.92) and lack of subsequent lines of treatment (p=0.0127, HR=3.23, 95% CI, 1.29-8.11) were significantly associated with shortening of patient survival. The analysis of RRM1 (-37C>A) more than ERCC1 (19007C>T) polymorphism may be a promising tool in the qualification of NSCLC patients for chemotherapy containing platinum compounds and gemcitabine.
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- 2013
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