Search

Your search keyword '"Denys H"' showing total 327 results
Start Over Author "Denys H"
327 results on '"Denys H"'

1. Conceptual principles of international cooperation in labour relations

Author

Nataliia O. Melnychuk, Liudmyla V. Kulachok-Titova, Denys H. Sevryukov, Yuliya O. Ostapenko, and Vlada M. Shkoda

Subjects
Labor. Work. Working class, HD4801-8943
Abstract

In today’s world, the issue of respect for and observance of human rights in the field of labour relations is rather important. Ensuring human rights and freedoms is no longer just a domestic affair, but the goal of the entire world. The purpose of the study is to analyse the current state of Ukraine’s international cooperation with foreign countries in general, and the European Union in particular. It identifies problematic aspects of implementing international standards in the field of labour protection using national legislation and solutions.

Published
2022
Full Text
View/download PDF

2. Estilos de humor, afrontamiento y soporte social en padres de niños con cáncer

Author

Mariela Margarita Villegas Chavez, Denys H. Contreras, Mónica Cassaretto, and María Lourdes Ruda S.

Subjects
humor, soporte social, progenitores, niños con cáncer, Psychology, BF1-990
Abstract

Objetivo: Analizar el rol predictivo de las estrategias de afrontamiento y el soporte social percibido, sobre los estilos de humor en padres migrantes de niños con cáncer. Método: Se empleó un diseño cuantitativo transaccional-correlacional y un muestreo no probabilístico por conveniencia. Participaron 62 progenitores (11 hombres y 51 mujeres) entre los 20 y 61 años, quienes respondieron la Escala del Sentido del Humor (HSQ), el Cuestionario de Estimación del Afrontamiento (COPE) y el Medical Outcomes Study Social Support Survey (MOS-SSS). Resultados: Se establecieron modelos de regresión para el humor afiliativo (R²=0,19, p

Published
2023
Full Text
View/download PDF

5. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author

Vergote, I., Ausems, M., Brasiuniene, B., Brenton, J., Büttner, R., Colombo, N., González-Martín, A., Harter, P., Lambrechts, D., Lorusso, D., Madry, R., Mirza, M.R., Pujol, P., Ray-Coquard, I., Abreu, M., Balboni, S., Banerjee, S., Barberis, M., Barretina Ginesta, M.P., Baurain, J.-F., Bignami, M., Bjorge, L., Blecharz, P., Bruchim, I., Capilna, M., Cerana, N., Cicchetti, A., Collins, D., Concin, N., D’Incalci, M., Davidson, B., de la Motte Rouge, T., De Iaco, P., Demirkiran, F., Denys, H., Doerk, T., Dorum, A., Ferrero, A., Fidalgo, A.P., Genuardi, M., Gladieff, L., Glasspool, R., Grimm, C., Gultekin, M., Hahnen, E., Hasenburg, A., Hegmane, A., Heinzelmann, V., Hogdall, E., Janavicius, R., Jarmalaite, S., Kalachand, R., Kaneva, R., Kilickap, S., Kocian, R., Kolencik, D., Kristeleit, R., Kryzhanivska, A., Leary, A., Lemley, B., Ligtenberg, M., López-Guerrero, J.A., Lord, C.J., Avall-Lundqvist, E., Maenpaa, J., Mahner, S., Marmé, F., Marth, C., McNeish, I., Merkelbach-Bruse, S., Mourits, M., Normanno, N., Oaknin, A., Ojamaa, K., Papdimitriou, C., Penault-Llorca, F., Perrone, A.M., Pignata, S., Pikarsky, E., Rouleau, E., Rubio, M., Sapino, A., Schmalfeldt, B., Sehouli, J., Shapira, R., Steffensen, K.D., Sukhin, V., Syrios, J., Szallasi, Z., Taskiran, C., Terzic, M., Tischkowitz, M., Toth, I., Van de Vijver, K., Vardar, M.A., Wasag, B., Wimberger, P., Witteveen, E., Brenton, J.D., and Ausems, M.G.E.M.

Published
2022
Full Text
View/download PDF

6. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Coleman, Robert L, Oza, Amit M, Lorusso, Domenica, Aghajanian, Carol, Oaknin, Ana, Dean, Andrew, Colombo, Nicoletta, Weberpals, Johanne I, Clamp, Andrew, Scambia, Giovanni, Leary, Alexandra, Holloway, Robert W, Gancedo, Margarita Amenedo, Fong, Peter C, Goh, Jeffrey C, O'Malley, David M, Armstrong, Deborah K, Garcia-Donas, Jesus, Swisher, Elizabeth M, Floquet, Anne, Konecny, Gottfried E, McNeish, Iain A, Scott, Clare L, Cameron, Terri, Maloney, Lara, Isaacson, Jeff, Goble, Sandra, Grace, Caroline, Harding, Thomas C, Raponi, Mitch, Sun, James, Lin, Kevin K, Giordano, Heidi, Ledermann, Jonathan A, investigators, ARIEL3, Buck, M, Dean, A, Friedlander, ML, Goh, JC, Harnett, P, Kichenadasse, G, Scott, CL, Denys, H, Dirix, L, Vergote, I, Elit, L, Ghatage, P, Oza, AM, Plante, M, Provencher, D, Weberpals, JI, Welch, S, Floquet, A, Gladieff, L, Joly, F, Leary, A, Lortholary, A, Lotz, J, Medioni, J, Tredan, O, You, B, El-Balat, A, Hänle, C, Krabisch, P, Neunhöffer, T, Pölcher, M, Wimberger, P, Amit, A, Kovel, S, Leviov, M, Safra, T, Shapira-Frommer, R, Stemmer, S, Bologna, A, Colombo, N, Lorusso, D, Pignata, S, Sabbatini, RF, Scambia, G, Tamberi, S, Zamagni, C, Fong, PC, O'Donnell, A, Gancedo, M Amenedo, Herraez, A Casado, Garcia-Donas, J, Guerra, EM, Oaknin, A, Palacio, I, Romero, I, Sanchez, A, Banerjee, SN, Clamp, A, Drew, Y, Gabra, HG, Jackson, D, Ledermann, JA, McNeish, IA, Parkinson, C, and Powell, M

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Clinical Research, Cancer, Genetics, Clinical Trials and Supportive Activities, Ovarian Cancer, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 6.2 Cellular and gene therapies, Aged, Disease-Free Survival, Double-Blind Method, Female, Follow-Up Studies, Humans, Indoles, Internationality, Maintenance Chemotherapy, Middle Aged, Molecular Targeted Therapy, Neoplasm Recurrence, Local, Ovarian Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Risk Assessment, Survival Rate, Treatment Outcome, ARIEL3 investigators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundRucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.FindingsBetween April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16-0·34]; p

Published
2017

8. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Buck, M, Dean, A, Friedlander, M L, Goh, J C, Harnett, P, Kichenadasse, G, Scott, C L, Denys, H, Dirix, L, Vergote, I, Elit, L, Ghatage, P, Oza, A M, Plante, M, Provencher, D, Weberpals, J I, Welch, S, Floquet, A, Gladieff, L, Joly, F, Leary, A, Lortholary, A, Lotz, J, Medioni, J, Tredan, O, You, B, El-Balat, A, Hänle, C, Krabisch, P, Neunhöffer, T, Pölcher, M, Wimberger, P, Amit, A, Kovel, S, Leviov, M, Safra, T, Shapira-Frommer, R, Stemmer, S, Bologna, A, Colombo, N, Lorusso, D, Pignata, S, Sabbatini, R F, Scambia, G, Tamberi, S, Zamagni, C, Fong, P C, O'Donnell, A, Gancedo, M Amenedo, Herraez, A Casado, Garcia-Donas, J, Guerra, E M, Oaknin, A, Palacio, I, Romero, I, Sanchez, A, Banerjee, S N, Clamp, A, Drew, Y, Gabra, H G, Jackson, D, Ledermann, J A, McNeish, I A, Parkinson, C, Powell, M, Aghajanian, C, Armstrong, D K, Birrer, M J, Buss, M K, Chambers, S K, Chen, L-m, Coleman, R L, Holloway, R W, Konecny, G E, Ma, L, Morgan, M A, Morris, R T, Mutch, D G, O'Malley, D M, Slomovitz, B M, Swisher, E M, Vanderkwaak, T, Vulfovich, M, Coleman, Robert L, Oza, Amit M, Lorusso, Domenica, Aghajanian, Carol, Oaknin, Ana, Dean, Andrew, Colombo, Nicoletta, Weberpals, Johanne I, Clamp, Andrew, Scambia, Giovanni, Leary, Alexandra, Holloway, Robert W, Gancedo, Margarita Amenedo, Fong, Peter C, Goh, Jeffrey C, O'Malley, David M, Armstrong, Deborah K, Garcia-Donas, Jesus, Swisher, Elizabeth M, Floquet, Anne, Konecny, Gottfried E, McNeish, Iain A, Scott, Clare L, Cameron, Terri, Maloney, Lara, Isaacson, Jeff, Goble, Sandra, Grace, Caroline, Harding, Thomas C, Raponi, Mitch, Sun, James, Lin, Kevin K, Giordano, Heidi, and Ledermann, Jonathan A

Published
2017
Full Text
View/download PDF

9. Clear cell carcinoma of the endometrium

Author

Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Kim, J, Candido dos Reis, F, Mariani, A, Leitao, M, Makker, V, Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Bini, M, Lopez, S, Raspagliesi, F, Panici, P, di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Lorusso D., Coleman R., Vaughan M. M., Takano M., Provencher D., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Kim J. -W., Candido dos Reis F. J., Mariani A., Leitao M. M., Makker V., Rustum N. A., Vergote I., Zannoni G. F., Tan D. S. P., McCormack M., Bini M., Lopez S., Raspagliesi F., Panici P. B., di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., Monk B. J., Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Kim, J, Candido dos Reis, F, Mariani, A, Leitao, M, Makker, V, Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Bini, M, Lopez, S, Raspagliesi, F, Panici, P, di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Lorusso D., Coleman R., Vaughan M. M., Takano M., Provencher D., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Kim J. -W., Candido dos Reis F. J., Mariani A., Leitao M. M., Makker V., Rustum N. A., Vergote I., Zannoni G. F., Tan D. S. P., McCormack M., Bini M., Lopez S., Raspagliesi F., Panici P. B., di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., and Monk B. J.

Abstract

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Published
2022

10. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author

Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., Witteveen E., Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., and Witteveen E.

Abstract

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR de

Published
2022

11. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study

Author

Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, Pujade-Lauraine, E, Trillsch F., Mahner S., Ataseven B., Asher R., Aryal N., Dubot C., Clamp A., Penson R. T., Oza A., Amit A., Huzarski T., Casado A., Scambia G., Friedlander M., Colombo N., Fujiwara K., Sonke G. S., Denys H., Lowe E. S., Lee C. K., Pujade-Lauraine E., Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, Pujade-Lauraine, E, Trillsch F., Mahner S., Ataseven B., Asher R., Aryal N., Dubot C., Clamp A., Penson R. T., Oza A., Amit A., Huzarski T., Casado A., Scambia G., Friedlander M., Colombo N., Fujiwara K., Sonke G. S., Denys H., Lowe E. S., Lee C. K., and Pujade-Lauraine E.

Abstract

Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.

Published
2022

12. Integrating automated liquid handling in the separation workflow of extracellular vesicles enhances specificity and reproducibility

Author

Van Dorpe, S. (Sofie), Lippens, L. (Lien), Boiy, R. (Robin), Pinheiro, C. (Cláudio), Vergauwen, G. (Glenn), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Tummers, P. (Philippe), Denys, H. (Hannelore), De Wever, O. (Olivier), Hendrix, A. (An), Van Dorpe, S. (Sofie), Lippens, L. (Lien), Boiy, R. (Robin), Pinheiro, C. (Cláudio), Vergauwen, G. (Glenn), Rappu, P. (Pekka), Miinalainen, I. (Ilkka), Tummers, P. (Philippe), Denys, H. (Hannelore), De Wever, O. (Olivier), and Hendrix, A. (An)

Abstract

Background: Extracellular vesicles (EV) are extensively studied in human body fluids as potential biomarkers for numerous diseases. Major impediments of EV-based biomarker discovery include the specificity and reproducibility of EV sample preparation as well as intensive manual labor. We present an automated liquid handling workstation for the density-based separation of EV from human body fluids and compare its performance to manual handling by (in)experienced researchers. Results: Automated versus manual density-based separation of trackable recombinant extracellular vesicles (rEV) spiked in PBS significantly reduces variability in rEV recovery as quantified by fluorescent nanoparticle tracking analysis and ELISA. To validate automated density-based EV separation from complex body fluids, including blood plasma and urine, we assess reproducibility, recovery, and specificity by mass spectrometry-based proteomics and transmission electron microscopy. Method reproducibility is the highest in the automated procedure independent of the matrix used. While retaining (in urine) or enhancing (in plasma) EV recovery compared to manual liquid handling, automation significantly reduces the presence of body fluid specific abundant proteins in EV preparations, including apolipoproteins in plasma and Tamm-Horsfall protein in urine. Conclusions: In conclusion, automated liquid handling ensures cost-effective EV separation from human body fluids with high reproducibility, specificity, and reduced hands-on time with the potential to enable larger-scale biomarker studies.

Published
2023

13. Reply to Z.R. McCaw et al

Author

Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, Coleman, Robert L, Matulonis, U, Lorusso, D, Oaknin, A, Pignata, S, Dean, A, Denys, H, Colombo, N, Van Gorp, T, Konner, J, Marin, M, Harter, P, Murphy, C, Wang, J, Noble, E, Esteves, B, Method, M, Coleman, R, Matulonis, Ursula A, Lorusso, Domenica, Oaknin, Ana, Pignata, Sandro, Dean, Andrew, Denys, Hannelore, Colombo, Nicoletta, Van Gorp, Toon, Konner, Jason A, Marin, Margarita Romeo, Harter, Philipp, Murphy, Conleth G, Wang, Jiuzhou, Noble, Elizabeth, Esteves, Brooke, Method, Michael, and Coleman, Robert L

Published
2023

14. Endometrial carcinosarcoma

Author

Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, Monk, Bradley J, Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Caruso, G, Enomoto, T, Takehara, K, Denys, H, Lorusso, D, Coleman, R, Vaughan, M, Takano, M, Provencher, D, Sagae, S, Wimberger, P, Póka, R, Segev, Y, Kim, S, Kim, J, Candido Dos Reis, F, Ramirez, P, Mariani, A, Leitao, M, Makker, V, Abu-Rustum, N, Vergote, I, Zannoni, G, Tan, D, Mccormack, M, Paolini, B, Bini, M, Raspagliesi, F, Benedetti Panici, P, Di Donato, V, Muzii, L, Colombo, N, Pignata, S, Scambia, G, Monk, B, Bogani, Giorgio, Ray-Coquard, Isabelle, Concin, Nicole, Ngoi, Natalie Yan Li, Morice, Philippe, Caruso, Giuseppe, Enomoto, Takayuki, Takehara, Kazuhiro, Denys, Hannelore, Lorusso, Domenica, Coleman, Robert, Vaughan, Michelle M, Takano, Masashi, Provencher, Diane Michele, Sagae, Satoru, Wimberger, Pauline, Póka, Robert, Segev, Yakir, Kim, Se Ik, Kim, Jae-Weon, Candido Dos Reis, Francisco Jose, Ramirez, Pedro T, Mariani, Andrea, Leitao, Mario, Makker, Vicky, Abu-Rustum, Nadeem R, Vergote, Ignace, Zannoni, Gianfranco, Tan, David, McCormack, Mary, Paolini, Biagio, Bini, Marta, Raspagliesi, Francesco, Benedetti Panici, Pierluigi, Di Donato, Violante, Muzii, Ludovico, Colombo, Nicoletta, Pignata, Sandro, Scambia, Giovanni, and Monk, Bradley J

Abstract

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Published
2023

16. Challenges and practical aspects of obtaining temporary protection in EU countries and the impact of obtaining protection on the right to work.

Author

Andriyiv, Vasyl M., Sevryukov, Denys H., Havrylyuk, Volodymyr O., Shal, Vita V., and Svitovenko, Daryna V.

Subjects
*RIGHT to work (Human rights), *UKRAINIANS, *TEMPORARY protection of refugees, *INTERNATIONAL law, *HUMAN rights, *EUROPEAN Union law
Abstract

In general, the situation that has developed in Ukraine on the border with the European Union shows that despite the long history of the UN and the agreement of states to resolve all conflicts through negotiations, the prohibition of the use of force and threat of force, respect for the independence of other states, there are still terrorist states in the world that do not recognize and violate international law. Thus, the states that follow the norms and principles of international law, respect the key European values, support and protect human rights and peace on the continent must unite to overcome armed aggression. That is why the granting of temporary protection to Ukrainian citizens is an important issue, as it is one of the EU's significant contributions to the protection of the identity of the Ukrainian people, who are fighting for their independence. The purpose of the article was to study the peculiarities of obtaining temporary protection in the EU, to compare it with refugee status, to analyse the approaches to this procedure in individual states, as well as to determine the impact of obtaining the relevant status on the realization of the fundamental right to work. The main method used for the research is the method of analysis and synthesis. Its application provided reliable results in many areas of research. First of all, this method was applied in the analysis of EU and international law in the context of granting refugee status and temporary protection. Also, the method of analysis and synthesis was used by the author in the study of the peculiarities of temporary protection in individual Member States. Finally, the author used this method to analyse the problems currently faced by Ukrainian citizens and their possible solutions. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

18. 592P Exposure response (ER) analysis for efficacy and safety of mirvetuximab soravtansine (MIRV) in patients with folate receptor α (FRα)-positive cancer

Author

Matulonis, U.A., primary, Moore, K.N., additional, Lorusso, D., additional, Oaknin, A., additional, Pignata, S., additional, Denys, H., additional, Colombo, N., additional, Van Gorp, T., additional, Konner, J., additional, Romeo Marin, M., additional, Harter, P., additional, Murphy, C., additional, Tu, Y., additional, Zhu, F., additional, Esteves, B., additional, Method, M., additional, Birrer, M.J., additional, Coleman, R.L., additional, and O'Malley, D., additional

Published
2022
Full Text
View/download PDF

19. 605P Population pharmacokinetic (PK) analysis of mirvetuximab soravtansine (MIRV) in patients with folate receptor α (FRα)-positive cancer

Author

Moore, K.N., primary, Lorusso, D., additional, Oaknin, A., additional, Pignata, S., additional, Denys, H., additional, Colombo, N., additional, Van Gorp, T., additional, Konner, J., additional, Romeo Marin, M., additional, Harter, P., additional, Murphy, C., additional, Tu, Y., additional, Zhu, F., additional, Esteves, B., additional, Method, M., additional, Birrer, M.J., additional, Coleman, R.L., additional, Matulonis, U.A., additional, and O'Malley, D., additional

Published
2022
Full Text
View/download PDF

22. 712MO Final overall survival (OS) from the phase III ATALANTE/ENGOT-ov29 trial evaluating atezolizumab (Atz) versus placebo with standard chemotherapy (Cx) plus bevacizumab (bev) in ovarian cancer (OC) patients (pts) with platinum-sensitive relapse (PSR)

Author

Kurtz, J.E., Pujade-Lauraine, E., Oaknin, A., Belin, L., Grimm, C., Kocian, R., Denys, H., Rosengarten, O.S., Follana, P., Sehouli, J., Martinez-Garcia, J., Alexandre, J., Hardy-Bessard, A-C., Frenel, J-S., Sabatier, R., Gladieff, L., De La Motte Rouge, T., Lamichhane, N. Bonichon, Kalbacher, E., and Heitz, F.

Published
2024
Full Text
View/download PDF

23. Uterine serous carcinoma

Author

Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Nout, R, Lorusso, D, Vaughan, M, Bini, M, Takano, M, Provencher, D, Indini, A, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Candido dos Reis, F, Lopez, S, Mariani, A, Leitao, M, Raspagliesi, F, Panici, P, Di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Nout R. A., Lorusso D., Vaughan M. M., Bini M., Takano M., Provencher D., Indini A., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Candido dos Reis F. J., Lopez S., Mariani A., Leitao M. M., Raspagliesi F., Panici P. B., Di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., Monk B. J., Bogani, G, Ray-Coquard, I, Concin, N, Ngoi, N, Morice, P, Enomoto, T, Takehara, K, Denys, H, Nout, R, Lorusso, D, Vaughan, M, Bini, M, Takano, M, Provencher, D, Indini, A, Sagae, S, Wimberger, P, Poka, R, Segev, Y, Kim, S, Candido dos Reis, F, Lopez, S, Mariani, A, Leitao, M, Raspagliesi, F, Panici, P, Di Donato, V, Muzii, L, Colombo, N, Scambia, G, Pignata, S, Monk, B, Bogani G., Ray-Coquard I., Concin N., Ngoi N. Y. L., Morice P., Enomoto T., Takehara K., Denys H., Nout R. A., Lorusso D., Vaughan M. M., Bini M., Takano M., Provencher D., Indini A., Sagae S., Wimberger P., Poka R., Segev Y., Kim S. I., Candido dos Reis F. J., Lopez S., Mariani A., Leitao M. M., Raspagliesi F., Panici P. B., Di Donato V., Muzii L., Colombo N., Scambia G., Pignata S., and Monk B. J.

Abstract

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the “copy number high” group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous

Published
2021

26. Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer

Author

Schettini, F., Venturini, Sergio, Giuliano, M., Lambertini, M., Pinato, D. J., Onesti, C. E., De Placido, P., Harbeck, N., Luftner, D., Denys, H., Van Dam, P., Arpino, G., Zaman, K., Mustacchi, G., Gligorov, J., Awada, A., Campone, M., Wildiers, H., Gennari, Alessandro, Tjan-Heijnen, V., Bartsch, R., Cortes, J., Paris, Ida, Martin, M., De Placido, S., Del Mastro, L., Jerusalem, G., Curigliano, G., Prat, A., Generali, Daniele, Venturini S. (ORCID:0000-0002-6574-3337), Gennari A., Paris I., Generali D. (ORCID:0000-0003-2480-3855), Schettini, F., Venturini, Sergio, Giuliano, M., Lambertini, M., Pinato, D. J., Onesti, C. E., De Placido, P., Harbeck, N., Luftner, D., Denys, H., Van Dam, P., Arpino, G., Zaman, K., Mustacchi, G., Gligorov, J., Awada, A., Campone, M., Wildiers, H., Gennari, Alessandro, Tjan-Heijnen, V., Bartsch, R., Cortes, J., Paris, Ida, Martin, M., De Placido, S., Del Mastro, L., Jerusalem, G., Curigliano, G., Prat, A., Generali, Daniele, Venturini S. (ORCID:0000-0002-6574-3337), Gennari A., Paris I., and Generali D. (ORCID:0000-0003-2480-3855)

Abstract

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and un-certain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel +/- bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1 -positive mTNBC, performed similar to paclitaxel +/- bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, ac-cording to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Published
2022

27. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study

Author

Trillsch, F., Mahner, S., Ataseven, B., Asher, R., Aryal, N., Dubot, C., Clamp, A., Penson, R. T., Oza, A., Amit, A., Huzarski, T., Casado, A., Scambia, Giovanni, Friedlander, M., Colombo, N., Fujiwara, K., Sonke, G. S., Denys, H., Lowe, E. S., Lee, C. K., Pujade-Lauraine, E., Scambia G. (ORCID:0000-0003-2758-1063), Trillsch, F., Mahner, S., Ataseven, B., Asher, R., Aryal, N., Dubot, C., Clamp, A., Penson, R. T., Oza, A., Amit, A., Huzarski, T., Casado, A., Scambia, Giovanni, Friedlander, M., Colombo, N., Fujiwara, K., Sonke, G. S., Denys, H., Lowe, E. S., Lee, C. K., Pujade-Lauraine, E., and Scambia G. (ORCID:0000-0003-2758-1063)

Abstract

Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05). Conclusions: Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.

Published
2022

29. 1196 A randomised phase II study of combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer. FANDANGO/ENGOT-EN1/FANDANGO

Author

Mirza, M, primary, Berton, D, additional, Vergote, I, additional, Depont Christensen, R, additional, Floquet, A, additional, Maenpaa, J, additional, Braicu, I, additional, Altintas, S, additional, Follana, P, additional, Ør Knudsen, A, additional, Ataseven, B, additional, Selle, F, additional, Lundgren, C, additional, Huober, J, additional, Fabbro, M, additional, Denys, H, additional, Heudel, P, additional, Magnusson, M, additional, Lindemann, K, additional, and Sehouli, J, additional

Published
2021
Full Text
View/download PDF

30. 88P Efficacy of olaparib in advanced cancers occurring in patients with germline or somatic tumor mutations in homologous recombination (HR) genes, a Belgian Precision phase II basket study

Author

Joris, S., primary, Denys, H., additional, Martin, M., additional, t'Kint de Roodenbeke, D., additional, Duhoux, F., additional, Berchem, G., additional, Punie, K., additional, Bols, A., additional, Mebis, J., additional, Canon, J-L., additional, Decoster, L., additional, and De Grève, J., additional

Published
2021
Full Text
View/download PDF

32. Efficacy of olaparib in advanced cancers occurring in patients with germline or somatic tumor mutations in homologous recombination (HR) genes, a Belgian Precision phase II basket study

Author

Joris, S., Denys, H., Martin, M., de Roodenbeke, D. t'Kint, Duhoux, F., Berchem, G., Punie, K., Bols, A., MEBIS, Jeroen, Canon, J-L., Decoster, L., and De Greve, J.

Abstract

associations of EPHA3 mutations with tumor mutation burden (TMB), PD-L1 expression, microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (TILs), and clinical response to ICIs. This will be very helpful for identifying patients who may benefit from immunotherapy. Methods: The ICIs cohort from the MSKCC was used for exploring the associations between EPHA3 mutations and ICIs efficacy. The relationships between EPHA3 mutations and TMB, PD-L1 expression, and MSI-H were investigated in our Chinese cohort. The TCGA cohort was used for analyzing the link between EPHA3 mutations and TILs. Results: First, we analyzed the associations between EPHA3 mutations and overall survival (OS) after ICIs therapy. For all enrolled patients, those who harbored EPHA3 mutations had a relatively longer OS compared to those without mutations (40 vs 18 months, P ¼ 0.0102). However, EPHA3 mutations displayed divergent predictive roles in different cancer types. The median OS was significantly longer in the Mut group compared to the WT group for NSCLC (36 vs 11 months, P ¼ 0.0167). There were no associations between EPHA3 mutations and ICIs efficacy for patients with melanoma, glioma, bladder, colorectal, esophagogastric, breast, and head and neck cancers. Second, the results from our cohort showed that the median TMB was higher in the Mut group for NSCLC (14.6 vs 6.6 muts/Mb, P < 0.0001). And we did not find the associations of EPHA3 mutations with PD-L1 expression and MSI-H. Third, the analysis in the TCGA cohort revealed that NSCLC patients with EPHA3 mutations were infiltrated with increased activated natural killer cells (P ¼ 0.0131). Conclusions: Our data indicated that EPHA3 mutations were associated with prolonged OS in NSCLC, rather than other cancer types, suggesting that it might act as a predictive biomarker for ICIs therapy in NSCLC. EPHA3 mutations were also correlated with higher TMB and increased activated natural killer cells in NSCLC. Background: Dovitinib is a tyrosine kinase inhibitor that inhibits VEGFR1-3, PDGFR, FGFR1-3, c-KIT, FLT3 and topoisomerase 1 and 2. Dovitinib is in development with a tumor agnostic biomarker based on 58 genes associated with sensitivity and resistance to dovitinib. The most advanced development is in renal cell carcinoma (RCC), which is presented here. De Stichting Tegen Kanker; AstraZeneca; Kom op Tegen Kanker

Published
2021

33. Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions

Author

Vergauwen, G. (Glenn), Tulkens, J. (Joeri), Pinheiro, C. (Cláudio), Cobos, F. A. (Francisco Avila), Dedeyne, S. (Sándor), De Scheerder, M.-A. (Marie-Angélique), Vandekerckhove, L. (Linos), Impens, F. (Francis), Miinalainen, I. (Ilkka), Gevaert, K. (Kris), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), De Wever, O. (Olivier), and Hendrix, A. (An)

Subjects
separation, transcriptomics, proteomics, blood, biomarkers, exosomes, extracellular vesicles, corona, isolation, lipoprotein particles
Abstract

Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context-dependent and/or time-dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV.

Published
2021

36. 72TiP ROSALINE: A phase II, single-arm, neoadjuvant study of targeting ROS1 in combination with endocrine therapy (ET) in invAsive Lobular carcINoma of the brEast

Author

Agostinetto, E., primary, Paesmans, M., additional, Ameye, L., additional, Veys, I., additional, Buisseret, L., additional, Neven, P., additional, Taylor, D., additional, Fontaine, C., additional, Duhoux, F.P., additional, Canon, J-L., additional, Denys, H., additional, Coussy, F., additional, Chakiba, C., additional, Pistilli, B., additional, Piccart, M., additional, Ignatiadis, M., additional, and Aftimos, P.G., additional

Published
2021
Full Text
View/download PDF

37. Clinical management of first-line advanced triple-negative breast cancer patients

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Rediti, M, Punie, K, de Azambuja, E, Naert, E, Taylor, Donatienne, Duhoux, FP, Denys, H, Awada, A, Wildiers, H, Ignatiadis, M, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'oncologie médicale, Rediti, M, Punie, K, de Azambuja, E, Naert, E, Taylor, Donatienne, Duhoux, FP, Denys, H, Awada, A, Wildiers, H, and Ignatiadis, M

Abstract

Chemotherapy has represented the main treatment option for patients with advanced triple-negative breast cancer for a long time. However, due to our better understanding of tumour biology, recent clinical trials led to a change in the treatment paradigm of this disease, identifying clinically relevant subgroups with different therapeutic options. Both clinical and biological factors have become relevant and need to be considered in the treatment decision algorithm of this heterogeneous disease.

Published
2020

38. Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction

Author

Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Deun, J. (Jan), Geeurickx, E. (Edward), Dhondt, B. (Bert), Lippens, L. (Lien), De Scheerder, A. (Angélique), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), De Geest, B. G. (Bruno G.), Vandecasteele, K. (Katrien), Laukens, D. (Debby), Vandekerckhove, L. (Linos), Denys, H. (Hannelore), Vandesompele, J. (Jo), De Wever, O. (Olivier), Hendrix, A. (An), Tulkens, J. (Joeri), Vergauwen, G. (Glenn), Van Deun, J. (Jan), Geeurickx, E. (Edward), Dhondt, B. (Bert), Lippens, L. (Lien), De Scheerder, A. (Angélique), Miinalainen, I. (Ilkka), Rappu, P. (Pekka), De Geest, B. G. (Bruno G.), Vandecasteele, K. (Katrien), Laukens, D. (Debby), Vandekerckhove, L. (Linos), Denys, H. (Hannelore), Vandesompele, J. (Jo), De Wever, O. (Olivier), and Hendrix, A. (An)

Published
2020

39. 13 Efficacy on individualized starting dose (ISD) and fixed starting dose (FSD) of niraparib per investigator-assessment (IA) in newly diagnosed advanced ovarian cancer (OC)

Author

Graybill, W, primary, Mirza, M, additional, González-Martin, A, additional, O’Malley, D, additional, Gaba, L, additional, Yap, OWS, additional, Guerra, E, additional, Rose, PG, additional, Baurain, J, additional, Ghamande, S, additional, Denys, H, additional, Prendergast, E, additional, Pisano, C, additional, Follana, P, additional, Braicu, EI, additional, Calvert, PM, additional, Korach, J, additional, Li, Y, additional, Gupta, D, additional, and Monk, BJ, additional

Published
2020
Full Text
View/download PDF

40. Evaluation of an individualized starting dose of niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study

Author

Marmé, F, additional, MR, Mirza, additional, González-Martin, A, additional, Graybill, W, additional, O’Malley, DM, additional, Gaba, L, additional, OWS, Yap, additional, Guerra, E, additional, Rose, P, additional, JF, Baurain, additional, Ghamande, S, additional, Denys, H, additional, Prendergast, E, additional, Pisano, C, additional, Follana, P, additional, Baumann, K, additional, PM, Calvert, additional, Korach, J, additional, Li, Y, additional, Gupta, D, additional, and BJ, Monk, additional

Published
2020
Full Text
View/download PDF

41. Efficacy and safety of niraparib in older patients with advanced ovarian cancer (OC): results from the PRIMA/ENGOT-OV26/GOG-3012 trial

Author

Heitz, F, additional, Valabrega, G, additional, Pothuri, B, additional, Oaknin, A, additional, Graybill, W, additional, Sánchez, AB, additional, McCormick, C, additional, Baurain, JF, additional, Hoskins, P, additional, Denys, H, additional, O’Cearbhaill, RE, additional, Hietanen, S, additional, Moore, RG, additional, Knudsen, AØ, additional, de La Motte Rouge, T, additional, Levy, T, additional, Li, Y, additional, Gupta, D, additional, Monk, BJ, additional, and González-Martín, A, additional

Published
2020
Full Text
View/download PDF

42. 819P Efficacy and safety of niraparib in older patients (pts) with advanced ovarian cancer (OC): Results from the PRIMA/ENGOT-OV26/GOG-3012 trial

Author

Valabrega, G., primary, Pothuri, B., additional, Oaknin, A., additional, Graybill, W., additional, Sánchez, A.B., additional, Mccormick, C., additional, Baurain, J-F., additional, Hoskins, P., additional, Denys, H., additional, O’Cearbhaill, R.E., additional, Heitanen, S., additional, Moore, R.G., additional, Knudsen, A.Ø., additional, de La Motte Rouge, T., additional, Heitz, F., additional, Levy, T., additional, Li, Y., additional, Gupta, D., additional, Monk, B.J., additional, and Martín, A. González, additional

Published
2020
Full Text
View/download PDF

43. The generation and use of recombinant extracellular vesicles as biological reference material

Author

Geeurickx, E. (Edward), Tulkens, J. (Joeri), Dhondt, B. (Bert), Van Deun, J. (Jan), Lippens, L. (Lien), Vergauwen, G. (Glenn), Heyrman, E. (Elisa), De Sutter, D. (Delphine), Gevaert, K. (Kris), Impens, F. (Francis), Miinalainen, I. (Ilkka), Van Bockstal, P.-J. (Pieter-Jan), De Beer, T. (Thomas), Wauben, M. H. (Marca H. M.), Nolte-‘t-Hoen, E. N. (Esther N. M.), Bloch, K. (Katarzyna), Swinnen, J. V. (Johannes V.), van der Pol, E. (Edwin), Nieuwland, R. (Rienk), Braems, G. (Geert), Callewaert, N. (Nico), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), Eyckerman, S. (Sven), De Wever, O. (Olivier), Hendrix, A. (An), Geeurickx, E. (Edward), Tulkens, J. (Joeri), Dhondt, B. (Bert), Van Deun, J. (Jan), Lippens, L. (Lien), Vergauwen, G. (Glenn), Heyrman, E. (Elisa), De Sutter, D. (Delphine), Gevaert, K. (Kris), Impens, F. (Francis), Miinalainen, I. (Ilkka), Van Bockstal, P.-J. (Pieter-Jan), De Beer, T. (Thomas), Wauben, M. H. (Marca H. M.), Nolte-‘t-Hoen, E. N. (Esther N. M.), Bloch, K. (Katarzyna), Swinnen, J. V. (Johannes V.), van der Pol, E. (Edwin), Nieuwland, R. (Rienk), Braems, G. (Geert), Callewaert, N. (Nico), Mestdagh, P. (Pieter), Vandesompele, J. (Jo), Denys, H. (Hannelore), Eyckerman, S. (Sven), De Wever, O. (Olivier), and Hendrix, A. (An)

Abstract

Recent years have seen an increase of extracellular vesicle (EV) research geared towards biological understanding, diagnostics and therapy. However, EV data interpretation remains challenging owing to complexity of biofluids and technical variation introduced during sample preparation and analysis. To understand and mitigate these limitations, we generated trackable recombinant EV (rEV) as a biological reference material. Employing complementary characterization methods, we demonstrate that rEV are stable and bear physical and biochemical traits characteristic of sample EV. Furthermore, rEV can be quantified using fluorescence-, RNA- and protein-based technologies available in routine laboratories. Spiking rEV in biofluids allows recovery efficiencies of commonly implemented EV separation methods to be identified, intra-method and inter-user variability induced by sample handling to be defined, and to normalize and improve sensitivity of EV enumerations. We anticipate that rEV will aid EV-based sample preparation and analysis, data normalization, method development and instrument calibration in various research and biomedical applications.

Published
2019

44. Territorial transformations in agriculture of Chernihiv region in the context of climate change: the case of corn and sunflower

Author

Mykola Baranovskyi and Denys Hlushko

Subjects
climate change, transformation of agricultural production, corn, sunflower, territorial concentration index, trend modelling, chernihiv region, Physical geography, GB3-5030, Geology, QE1-996.5
Abstract

Introduction. Different crops and regions of Ukraine are characterized by unequal dependencies on climate change. This situation creates a demand for scientific research to analyse «climate-agricultural production» dependence at the regional level. Chernihiv region, whose territory is located in two environmental zones, is an ideal testing ground for assessing territorial transformations in agricultural production under the influence of climate change. The purpose of article. The purpose of the study was to identify territorial transformations in agricultural production of Chernihiv region that were formed under the influence of climate change during 2001-2020, using corn and sunflower as an example. Additionally, the impact of climate factors on the yield of the selected crops in the region was assessed. Research methods. The study was based on data on gross harvest and yields of the selected crops, corn and sunflower, in Chernihiv region during 2001-2020. Climate trends were represented by average air temperature and precipitation during the growing season for the same period. Spatial transformations of the region’s agricultural production were determined using the territorial concentration index. A number of calculations were carried out to assess the contribution of climatic factors to the dynamics of yields of the selected crops. They included the determination of 1) trend yields; 2) total and agrotechnical variance; 3) the share of the climatic factor in the total variance. Main findings. In 2001-2020, Chernihiv region observed a significant increase in heat supply, the length of the growing season, and the sum of effective temperatures. The climate trends of this period created suitable conditions for expanding of a number of heat-tolerant crops, including corn and sunflower, into the region. The study used them as selected crops to assess territorial transformations in agricultural production of this northern region of Ukraine. The analysis of statistical data showed that the sown area and gross harvest of corn and sunflower increased tenfold in Chernihiv region, and the local agroclimatic zones of their cultivation moved 125-150 km north. The main producers of corn and sunflower are still the forest-steppe areas of the region. At the same time, its Polissya part currently produces 25 to 30% of the gross harvest of these crops. Due to climate change in the region, the yield of the selected crops has increased significantly, exceeding the national average values by 37-43%. The «migration» of heat-tolerant crops to the region has considerably changed the specialization of agricultural production in this Polissya region. Based on the calculations, it was found that the contribution of the climatic factor to corn yields was maximum in 2001-2010 - 74%. The contribution of climatic trends to sunflower yield of the region was significantly lower - 53-56 % in different periods. Taking into account the results obtained, the study points out the need to develop effective measures for adapting agricultural production in Chernihiv region to climate change. Scientific novelty and practical value. The article describes for the first time the characteristics of territorial transformations in agricultural production of Chernihiv region in the context of climate change and assesses the contribution of the climatic factor to the dynamics of productivity of the selected crops in the region. The practical value of the study is the possibility of using its algorithm to conduct similar studies in other regions of Ukraine. The results of the study are important in the context of substantiating regional measures to adapt agricultural production to climate change.

Published
2023
Full Text
View/download PDF

45. P70 Description of the surgical management of patients with uterine corpus cancers in Belgium: results from a multicentric prospective observational study (EFFECT)

Author

Kakkos, A, primary, De Geyndt, A, additional, Silversmit, G, additional, Bouche, G, additional, de Jonge, E, additional, Jacomen, G, additional, Denys, H, additional, Van Limbergen, E, additional, Vandermeersch, B, additional, Kerger, J, additional, Vander Steichel, D, additional, Baldewijns, M, additional, Lauwers, E, additional, Van Damme, N, additional, Goffin, F, additional, and Amant, F, additional

Published
2019
Full Text
View/download PDF

47. Splenic metabolic activity as biomarker in cervical cancer

Author

De Jaeghere, E.A., primary, Laloo, F., additional, Lippens, L., additional, De Man, K., additional, Van Bockstal, M., additional, Van de Vijver, K., additional, Tummers, P., additional, Makar, A., additional, De Visschere, P., additional, De Wever, O., additional, Amant, F., additional, Denys, H., additional, and Vandecasteele, K., additional

Published
2019
Full Text
View/download PDF

48. RIBOB: A study on the efficacy and safety of ribociclib in combination with letrozole in older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior systemic therapy for advanced disease

Author

Kenis, C., primary, Ponde, N.F., additional, Decoster, L., additional, de Azambuja, E., additional, Jerusalem, G., additional, Neven, P., additional, Dal Lago, L., additional, Denys, H., additional, Vuylsteke, P., additional, Duhoux, F.P., additional, and Wildiers, H., additional

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results