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1. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author

Ledermann, J.A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, D., Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A.G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., McCluggage, W.G., McNeish, I.A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J.A., Pignata, S., Ramirez, P.T., Ray-Coquard, I., Romero, I., Scambia, G., Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D.S.P., Taskiran, C., van Driel, W.J., Vergote, I., Planchamp, F., Sessa, C., and Fagotti, A.

Published
2024
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2. Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre

Author

Mosteiro, M., Azuara, D., Villatoro, S., Alay, A., Gausachs, M., Varela, M., Baixeras, N., Pijuan, L., Ajenjo-Bauza, M., Lopez-Doriga, A., Teulé, Á., Solanes, A., Palmero, R., Brenes, J., Jové, M., Padrones, S., Moreno, V., Cordero, D., Matías-Guiu, X., Lázaro, C., and Nadal, E.

Published
2023
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4. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author

Ledermann, J, Matias-Guiu, X, Amant, F, Concin, N, Davidson, B, Fotopoulou, C, González-Martin, A, Gourley, C, Leary, A, Lorusso, D, Banerjee, S, Chiva, L, Cibula, D, Colombo, N, Croce, S, Eriksson, A, Falandry, C, Fischerova, D, Harter, P, Joly, F, Lazaro, C, Lok, C, Mahner, S, Marmé, F, Marth, C, Mccluggage, W, Mcneish, I, Morice, P, Nicum, S, Oaknin, A, Pérez-Fidalgo, J, Pignata, S, Ramirez, P, Ray-Coquard, I, Romero, I, Scambia, G, Sehouli, J, Shapira-Frommer, R, Sundar, S, Tan, D, Taskiran, C, van Driel, W, Vergote, I, Planchamp, F, Sessa, C, Fagotti, A, Ledermann J. A., Matias-Guiu X., Amant F., Concin N., Davidson B., Fotopoulou C., González-Martin A., Gourley C., Leary A., Lorusso D., Banerjee S., Chiva L., Cibula D., Colombo N., Croce S., Eriksson A. G., Falandry C., Fischerova D., Harter P., Joly F., Lazaro C., Lok C., Mahner S., Marmé F., Marth C., McCluggage W. G., McNeish I. A., Morice P., Nicum S., Oaknin A., Pérez-Fidalgo J. A., Pignata S., Ramirez P. T., Ray-Coquard I., Romero I., Scambia G., Sehouli J., Shapira-Frommer R., Sundar S., Tan D. S. P., Taskiran C., van Driel W. J., Vergote I., Planchamp F., Sessa C., Fagotti A., Ledermann, J, Matias-Guiu, X, Amant, F, Concin, N, Davidson, B, Fotopoulou, C, González-Martin, A, Gourley, C, Leary, A, Lorusso, D, Banerjee, S, Chiva, L, Cibula, D, Colombo, N, Croce, S, Eriksson, A, Falandry, C, Fischerova, D, Harter, P, Joly, F, Lazaro, C, Lok, C, Mahner, S, Marmé, F, Marth, C, Mccluggage, W, Mcneish, I, Morice, P, Nicum, S, Oaknin, A, Pérez-Fidalgo, J, Pignata, S, Ramirez, P, Ray-Coquard, I, Romero, I, Scambia, G, Sehouli, J, Shapira-Frommer, R, Sundar, S, Tan, D, Taskiran, C, van Driel, W, Vergote, I, Planchamp, F, Sessa, C, Fagotti, A, Ledermann J. A., Matias-Guiu X., Amant F., Concin N., Davidson B., Fotopoulou C., González-Martin A., Gourley C., Leary A., Lorusso D., Banerjee S., Chiva L., Cibula D., Colombo N., Croce S., Eriksson A. G., Falandry C., Fischerova D., Harter P., Joly F., Lazaro C., Lok C., Mahner S., Marmé F., Marth C., McCluggage W. G., McNeish I. A., Morice P., Nicum S., Oaknin A., Pérez-Fidalgo J. A., Pignata S., Ramirez P. T., Ray-Coquard I., Romero I., Scambia G., Sehouli J., Shapira-Frommer R., Sundar S., Tan D. S. P., Taskiran C., van Driel W. J., Vergote I., Planchamp F., Sessa C., and Fagotti A.

Abstract

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

Published
2024

6. Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer

Author

Vrede, S.W., van Weelden, W.J., Visser, N.C.M., Bulten, J., van der Putten, L.J.M., van de Vijver, K., Santacana, M., Colas, E., Gil-Moreno, A., Moiola, C.P., Mancebo, G., Krakstad, C., Trovik, J., Haldorsen, I.S., Huvila, J., Koskas, M., Weinberger, V., Bednarikova, M., Hausnerova, J., van der Wurff, A.A., Matias-Guiu, X., Amant, F., Snijders, M.P.L.M., Küsters-Vandevelde, H.V.N., Reijnen, C., and Pijnenborg, J.M.A.

Published
2021
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7. Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Author

Mateo, F, Arenas, EJ, Aguilar, H, Serra-Musach, J, de Garibay, G Ruiz, Boni, J, Maicas, M, Du, S, Iorio, F, Herranz-Ors, C, Islam, A, Prado, X, Llorente, A, Petit, A, Vidal, A, Català, I, Soler, T, Venturas, G, Rojo-Sebastian, A, Serra, H, Cuadras, D, Blanco, I, Lozano, J, Canals, F, Sieuwerts, AM, de Weerd, V, Look, MP, Puertas, S, García, N, Perkins, AS, Bonifaci, N, Skowron, M, Gómez-Baldó, L, Hernández, V, Martínez-Aranda, A, Martínez-Iniesta, M, Serrat, X, Cerón, J, Brunet, J, Barretina, MP, Gil, M, Falo, C, Fernández, A, Morilla, I, Pernas, S, Plà, MJ, Andreu, X, Seguí, MA, Ballester, R, Castellà, E, Nellist, M, Morales, S, Valls, J, Velasco, A, Matias-Guiu, X, Figueras, A, Sánchez-Mut, JV, Sánchez-Céspedes, M, Cordero, A, Gómez-Miragaya, J, Palomero, L, Gómez, A, Gajewski, TF, Cohen, EEW, Jesiotr, M, Bodnar, L, Quintela-Fandino, M, López-Bigas, N, Valdés-Mas, R, Puente, XS, Viñals, F, Casanovas, O, Graupera, M, Hernández-Losa, J, Ramón y Cajal, S, García-Alonso, L, Saez-Rodriguez, J, Esteller, M, Sierra, A, Martín-Martín, N, Matheu, A, Carracedo, A, González-Suárez, E, Nanjundan, M, Cortés, J, Lázaro, C, Odero, MD, Martens, JWM, Moreno-Bueno, G, Barcellos-Hoff, MH, Villanueva, A, Gomis, RR, and Pujana, MA

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Stem Cell Research, Adaptor Proteins, Signal Transducing, Adult, Aged, Breast Neoplasms, Carrier Proteins, Cell Proliferation, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, MCF-7 Cells, MDS1 and EVI1 Complex Locus Protein, Microfilament Proteins, Middle Aged, Neoplasm Metastasis, Osteonectin, Proto-Oncogenes, Regulatory-Associated Protein of mTOR, SOX9 Transcription Factor, Signal Transduction, TOR Serine-Threonine Kinases, Transcription Factors, Xenograft Model Antitumor Assays, Clinical Sciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Published
2017

9. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author

Ledermann, J. A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, Domenica, Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A. G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., Mccluggage, W. G., Mcneish, I. A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J. A., Pignata, S., Ramirez, P. T., Ray-Coquard, I., Romero, I., Scambia, Giovanni, Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D. S. P., Taskiran, C., van Driel, W. J., Vergote, I., Planchamp, F., Sessa, C., Fagotti, Anna, Lorusso, D., Scambia, G. (ORCID:0000-0003-2758-1063), Fagotti, A. (ORCID:0000-0001-5579-335X), Ledermann, J. A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, Domenica, Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A. G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., Mccluggage, W. G., Mcneish, I. A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J. A., Pignata, S., Ramirez, P. T., Ray-Coquard, I., Romero, I., Scambia, Giovanni, Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D. S. P., Taskiran, C., van Driel, W. J., Vergote, I., Planchamp, F., Sessa, C., Fagotti, Anna, Lorusso, D., Scambia, G. (ORCID:0000-0003-2758-1063), and Fagotti, A. (ORCID:0000-0001-5579-335X)

Abstract

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

Published
2024

10. The WID-EC test for the detection and risk prediction of endometrial cancer

Author

Barrett, J, Jones, A, Evans, I, Herzog, C, Reisel, D, Olaitan, A, Mould, T, Macdonald, N, Doufekas, K, Newton, C, Crosbie, E, Bjorge, L, Colombo, N, Dostalek, L, Costas, L, Peremiquel-Trillas, P, Ponce, J, Matias-Guiu, X, Zikan, M, Cibula, D, Wang, J, Sundstrom, K, Dillner, J, Widschwendter, M, Barrett J. E., Jones A., Evans I., Herzog C., Reisel D., Olaitan A., Mould T., MacDonald N., Doufekas K., Newton C., Crosbie E. J., Bjorge L., Colombo N., Dostalek L., Costas L., Peremiquel-Trillas P., Ponce J., Matias-Guiu X., Zikan M., Cibula D., Wang J., Sundstrom K., Dillner J., Widschwendter M., Barrett, J, Jones, A, Evans, I, Herzog, C, Reisel, D, Olaitan, A, Mould, T, Macdonald, N, Doufekas, K, Newton, C, Crosbie, E, Bjorge, L, Colombo, N, Dostalek, L, Costas, L, Peremiquel-Trillas, P, Ponce, J, Matias-Guiu, X, Zikan, M, Cibula, D, Wang, J, Sundstrom, K, Dillner, J, Widschwendter, M, Barrett J. E., Jones A., Evans I., Herzog C., Reisel D., Olaitan A., Mould T., MacDonald N., Doufekas K., Newton C., Crosbie E. J., Bjorge L., Colombo N., Dostalek L., Costas L., Peremiquel-Trillas P., Ponce J., Matias-Guiu X., Zikan M., Cibula D., Wang J., Sundstrom K., Dillner J., and Widschwendter M.

Abstract

The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID-EC (Women's cancer risk IDentification-Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid-based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB). We validated the WID-EC test in an independent external validation set of 64 endometrial cancer cases and 225 controls. We further validated the test in 150 healthy women (prospective set) who provided a cervical sample as part of the routine Swedish cervical screening programme, 54 of whom developed endometrial cancer within 3 years of sample collection. The WID-EC test identified women with endometrial cancer with a receiver operator characteristic area under the curve (AUC) of 0.92 (95% CI: 0.88-0.97) in the external set and of 0.82 (95% CI: 0.74-0.89) in the prospective validation set. Using an optimal cutoff, cancer cases were detected with a sensitivity of 86% and a specificity of 90% in the external validation set, and a sensitivity and specificity of 52% and 98% respectively in the prospective validation set. The WID-EC test can identify women with or at risk of endometrial cancer.

Published
2023

13. High-carotenoid maize: development of plant biotechnology prototypes for human and animal health and nutrition

Author

Zhu, C., Farré, G., Zanga, D., Lloveras, J., Michelena, A., Ferrio, J. P., Voltas, J., Slafer, G., Savin, R., Albajes, R., Eizaguirre, M., Lopez, C., Cantero-Martínez, C., Díaz-Gómez, J., Nogareda, C., Moreno, J. A., Angulo, E., Estany, J., Pena, R. N., Tor, M., Portero-Otin, M., Eritja, N., Arjó, G., Serrano, J. C. E., Matias-Guiu, X., Twyman, R. M., Sandmann, G., Capell, T., and Christou, P.

Published
2018
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14. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up

Author

Colombo, N., Creutzberg, C., Amant, F., Bosse, T., González-Martín, A., Ledermann, J., Marth, C., Nout, R., Querleu, D., Mirza, M.R., Sessa, C., Abal, M., Altundag, O., van Leeuwenhoek, Antoni, Banerjee, S., Casado, A., de Agustín, L.C., Cibula, D., del Campo, J.-M., Emons, G., Goffin, F., Greggi, S., Haie-Meder, C., Katsaros, D., Kesic, V., Kurzeder, C., Lax, S., Lécuru, F., Levy, T., Lorusso, D., Mäenpää, J., Matias-Guiu, X., Morice, P., Nijman, H.W., Powell, M., Reed, N., Rodolakis, A., Salvesen, H., Sehouli, J., Taylor, A., Westermann, A., and Zeimet, A.G.

Published
2016
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17. Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer

Author

Lombaers, M.S., Cornel, Karlijn M.C., Visser, N.C.M., Bulten, J., Kusters-van de Velde, H.V.N., Amant, Frederic, Boll, Dorry, Bronsert, P., Colas, E., Geomini, Peggy M. A. J., Gil-Moreno, A., Hamont, D. van, Huvila, J., Krakstad, Camilla, Kraayenbrink, A.A., Koskas, M., Mancebo, G., Matias-Guiu, X., Ngo, Huy, Pijlman, B.M., Vos, Maria Caroline, Weinberger, Vit, Snijders, Marc P. L. M., Koeverden, S.W. van, Haldorsen, Ingfrid S., Reijnen, C., Pijnenborg, J.M.A., Lombaers, M.S., Cornel, Karlijn M.C., Visser, N.C.M., Bulten, J., Kusters-van de Velde, H.V.N., Amant, Frederic, Boll, Dorry, Bronsert, P., Colas, E., Geomini, Peggy M. A. J., Gil-Moreno, A., Hamont, D. van, Huvila, J., Krakstad, Camilla, Kraayenbrink, A.A., Koskas, M., Mancebo, G., Matias-Guiu, X., Ngo, Huy, Pijlman, B.M., Vos, Maria Caroline, Weinberger, Vit, Snijders, Marc P. L. M., Koeverden, S.W. van, Haldorsen, Ingfrid S., Reijnen, C., and Pijnenborg, J.M.A.

Abstract

Contains fulltext : 294914.pdf (Publisher’s version ) (Open Access)

Published
2023

19. 107P Unveiling mismatch repair deficiency (dMMR) and microsatellite-instability high (MSI-H) detection in cancer patients (pt) using a next-generation sequencing (NGS)-based molecular pre-screening program (MPP)

Author

Rincon, L. Notario, Bergamino, M.A., Ochoa de Olza Amat, M., Carcereny, E., Urbizu, A., Muñoz-Mármol, A.M., Arnaldo, L., Azuara, D., Badosa, A. Alay, Matias-Guiu, X., Jimeno, M., Hernandez, A., Balaña, D., Planas, C. Fina, Martín, M. Gil, Castillo, J.J. Soto, Martin-Liberal, J., Lazaro, C., Sanz, C., and Hierro, C.

Published
2023
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21. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

Author

Concin, N, Matias-Guiu, X, Vergote, I, Cibula, D, Mirza, M, Marnitz, S, Ledermann, J, Bosse, T, Chargari, C, Fagotti, A, Fotopoulou, C, Gonzalez Martin, A, Lax, S, Lorusso, D, Marth, C, Morice, P, Nout, R, O'Donnell, D, Querleu, D, Raspollini, M, Sehouli, J, Sturdza, A, Taylor, A, Westermann, A, Wimberger, P, Colombo, N, Planchamp, F, Creutzberg, C, Concin N., Matias-Guiu X., Vergote I., Cibula D., Mirza M. R., Marnitz S., Ledermann J., Bosse T., Chargari C., Fagotti A., Fotopoulou C., Gonzalez Martin A., Lax S., Lorusso D., Marth C., Morice P., Nout R. A., O'Donnell D., Querleu D., Raspollini M. R., Sehouli J., Sturdza A., Taylor A., Westermann A., Wimberger P., Colombo N., Planchamp F., Creutzberg C. L., Concin, N, Matias-Guiu, X, Vergote, I, Cibula, D, Mirza, M, Marnitz, S, Ledermann, J, Bosse, T, Chargari, C, Fagotti, A, Fotopoulou, C, Gonzalez Martin, A, Lax, S, Lorusso, D, Marth, C, Morice, P, Nout, R, O'Donnell, D, Querleu, D, Raspollini, M, Sehouli, J, Sturdza, A, Taylor, A, Westermann, A, Wimberger, P, Colombo, N, Planchamp, F, Creutzberg, C, Concin N., Matias-Guiu X., Vergote I., Cibula D., Mirza M. R., Marnitz S., Ledermann J., Bosse T., Chargari C., Fagotti A., Fotopoulou C., Gonzalez Martin A., Lax S., Lorusso D., Marth C., Morice P., Nout R. A., O'Donnell D., Querleu D., Raspollini M. R., Sehouli J., Sturdza A., Taylor A., Westermann A., Wimberger P., Colombo N., Planchamp F., and Creutzberg C. L.

Abstract

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.

Published
2021

22. 21MO Limited benefit of molecular profiling in patients with low-grade endometrial cancer

Author

Vrede, S., primary, Kasius, J., additional, Bulten, J., additional, Van Weelden, W.J., additional, Boll, D., additional, Vos, M.C., additional, Van Altena, A., additional, Matias-Guiu, X., additional, Asberger, J., additional, Colas, E., additional, Gil-Moreno, A., additional, Huvila, J., additional, Weinberger, V., additional, Amant, F., additional, Snijders, M., additional, Küsters-Vandevelde, H., additional, Eijkelenboom, A., additional, Kruitwagen, R., additional, Reijnen, C., additional, and Pijnenborg, J.M., additional

Published
2022
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23. Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer

Author

Vrede, S.W., Kasius, J., Bulten, J., Teerenstra, S., Huvila, J., Colas, E., Gil-Moreno, A., Boll, D., Vos, M.C., Altena, A.M. van, Asberger, J., Sweegers, Sanne, Weelden, W.J. van, Putten, L.J.M. van der, Amant, F., Visser, N.C.M., Snijders, M.P.M.L., Küsters-Vandevelde, H.V.N., Kruitwagen, R.F.P.M., Matias-Guiu, X., Weinberger, V., Reijnen, C., Pijnenborg, J.M.A., Vrede, S.W., Kasius, J., Bulten, J., Teerenstra, S., Huvila, J., Colas, E., Gil-Moreno, A., Boll, D., Vos, M.C., Altena, A.M. van, Asberger, J., Sweegers, Sanne, Weelden, W.J. van, Putten, L.J.M. van der, Amant, F., Visser, N.C.M., Snijders, M.P.M.L., Küsters-Vandevelde, H.V.N., Kruitwagen, R.F.P.M., Matias-Guiu, X., Weinberger, V., Reijnen, C., and Pijnenborg, J.M.A.

Abstract

Item does not contain fulltext, IMPORTANCE: Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. OBJECTIVE: To determine the association of molecular profiling with outcomes among patients with low-grade EC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. EXPOSURES: Molecular testing of the 4 molecular subgroups. MAIN OUTCOMES AND MEASURES: The main outcome was disease-specific survival (DSS) within the molecular subgroups. RESULTS: A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and

Published
2022

25. Response to: Are we confident treating pT1a G1 lymphovascular space invasion-negative patients (with myometrial invasion) with chemoradiotherapy on the basis of p53abn?

Author

Concin, N., Matias-Guiu, X., Creutzberg, C.L., and ESGO-ESTRO-ESP Endometrial

Subjects
Oncology, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, endometrial neoplasms, business.industry, Obstetrics and Gynecology, Chemoradiotherapy, medicine.disease, Lymphovascular, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Myometrium, medicine, Carcinoma, Humans, Female, Stage (cooking), business
Abstract

The authors have raised an interesting and relevant question. Traditionally, and supported by data from many early randomized studies, patients with endometrial carcinoma and postsurgery diagnosis of pT1A/stage IA grade 1 endometrioid endometrial carcinoma with myometrial invasion and no

Published
2021
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27. 731 Biomarker analysis of the phase 2 study of pembrolizumab in combination with doxorubicin in advanced endometrial cancer: TOPIC trial/VHIO10001

Author

Piulats, JM, primary, Fariñas-Madrid, L, additional, Santacana, M, additional, Rubio Pérez, MJ, additional, Redondo, A, additional, Villacampa, G, additional, Yubero, A, additional, Romero, I, additional, Gil-Martin, M, additional, Garcia-Donas, J, additional, Gonzalez-Martin, A, additional, Gatius, S, additional, Gallego Martínez, A, additional, Grau, F, additional, Ruiz, F, additional, Pardo Búrdalo, B, additional, Sánchez Lorenzo, L, additional, Matias Guiu, X, additional, and Oaknin, A, additional

Published
2021
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28. 466 Preoperative CA125 significantly improves risk stratification in high-grade endometrial cancer

Author

Lombaers, M, primary, Cornel, K, additional, Visser, N, additional, Amant, F, additional, Bronsert, P, additional, Geomini, P, additional, Gil-Moreno, A, additional, Van Hamont, D, additional, Huvila, J, additional, Krakstad, C, additional, Koskas, M, additional, Mancebo Moreno, G, additional, Matias-Guiu, X, additional, Pijlman, B, additional, Vos, C, additional, Weinberger, V, additional, Snijders, M, additional, Haldorsen, I, additional, Reijnen, C, additional, and Pijnenborg, J, additional

Published
2021
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34. ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer

Author

Miller, RE, Leary, A, Scott, CL, Serra, V, Lord, CJ, Bowtell, D, Chang, DK, Garsed, DW, Jonkers, J, Ledermann, JA, Nik-Zainal, S, Ray-Coquard, I, Shah, SP, Matias-Guiu, X, Swisher, EM, Yates, LR, Nik-Zainal Abidin, Serena [0000-0001-5054-1727], and Apollo - University of Cambridge Repository

Subjects
Ovarian Neoplasms, homologous recombination deficiency (HRD), genomic scar assays, poly-ADP ribose inhibitors (PARPi), BRCA, Humans, Female, Carcinoma, Ovarian Epithelial, Poly(ADP-ribose) Polymerase Inhibitors, Homologous Recombination, Biomarkers
Abstract

BACKGROUND: Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial. MATERIALS AND METHODS: To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term 'HRD test'; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC. RESULTS: A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype. CONCLUSIONS: Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.

Published
2020
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35. 773P Real-world results of homologous recombination deficiency testing: Comparison between two methods on 2,655 ovarian cancer patients in Spain

Author

Lazaro, C., Jantus Lewintre, E., Zazo, S., Pérez, S., Carvajal Garcia, N., Azuara, D., González Acosta, M., Varela, M., Torres-Martínez, S., Gallach Garcia, S., Colomar, M., Sanchez Ares, M., Perez-Becerra, R., Antunez, J.R., Orellana, M., Lencina, M., Abdulkader Nallib, I., Camps Herrero, C.J.C., Matias-Guiu, X., and Rojo, F.

Published
2023
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36. 761P A phase II trial of avelumab in combination with pegylated liposomal doxorubicin in recurrent/metastatic endometrial cancer (GEICO 70-E): analysis according to molecular classification

Author

Piulats Rodriguez, J.M., Palacio Vazquez, I., Alarcon, J.D., Gatius, S., Marin Jimenez, J.A., Gil Martín, M., Márquez Aragonés, A., Santacana, M., Manso Sanchez, L.M., Hernando Polo, S., Ruiz, N., Matias-Guiu, X., Romeo Marin, M., Navarro Garces, V., and Barbarroja, P.

Published
2023
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37. The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study

Author

Weelden, W.J. van, Reijnen, C., Kusters-vandevelde, H.V., Bulten, J., Bult, P., Leung, S., Visser, N.C.M., Santacana, M., Bronsert, P., Hirschfeld, M., Colas, E., Gil-Moreno, A., Reques, A., Mancebo, G., Huvila, J., Koskas, M., Weinberger, V., Bednarikova, M., Hausnerova, J., Snijders, M., Matias-Guiu, X., Amant, F., Weelden, W.J. van, Reijnen, C., Kusters-vandevelde, H.V., Bulten, J., Bult, P., Leung, S., Visser, N.C.M., Santacana, M., Bronsert, P., Hirschfeld, M., Colas, E., Gil-Moreno, A., Reques, A., Mancebo, G., Huvila, J., Koskas, M., Weinberger, V., Bednarikova, M., Hausnerova, J., Snijders, M., Matias-Guiu, X., and Amant, F.

Abstract

Item does not contain fulltext, There is no consensus on the cutoff for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore, we determined the cutoff value for ER and PR expression with the strongest prognostic impact on the outcome. Immunohistochemical expression of ER and PR was scored as a percentage of positive EC cell nuclei. Cutoff values were related to disease-specific survival (DSS) and disease-free survival (DFS) using sensitivity, specificity, and multivariable regression analysis. The results were validated in an independent cohort. The study cohort (n = 527) included 82% of grade 1-2 and 18% of grade 3 EC. Specificity for DSS and DFS was highest for the cutoff values of 1-30%. Sensitivity was highest for the cutoff values of 80-90%. ER and PR expression were independent markers for DSS at cutoff values of 10% and 80%. Consequently, three subgroups with distinct clinical outcomes were identified: 0-10% of ER/PR expression with, unfavorable outcome (5-year DSS = 75.9-83.3%); 20-80% of ER/PR expression with, intermediate outcome (5-year DSS = 93.0-93.9%); and 90-100% of ER/PR expression with, favorable outcome (5-year DSS = 97.8-100%). The association between ER/PR subgroups and outcomes was confirmed in the validation cohort (n = 265). We propose classification of ER and PR expression based on a high-risk (0-10%), intermediate-risk (20-80%), and low-risk (90-100%) group.

Published
2021

38. Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer

Author

Velasco, A, Tokat, F, Bonde, J, Trim, N, Bauer, E, Meeney, A, de Leng, W, Chong, G, Dalstein, V, Kis, LL, Lorentzen, JA, Tomic, S, Thwaites, K, Putzova, M, Birnbaum, A, Qazi, R, Primmer, V, Dockhorn-Dworniczak, B, Hernandez-Losa, J, Soares, FA, Gertler, AA, Kalman, M, Wong, C, Carraro, DM, Sousa, AC, Reis, RM, Fox, SB, Fassan, M, Brevet, M, Merkelbach-Bruse, S, Colling, R, Soilleux, E, Teo, RYW, D'Haene, N, Nolet, S, Ristimaki, A, Vaisanen, T, Chapusot, C, Soruri, A, Unger, T, Wecgowiec, J, Biscuola, M, Frattini, M, Long, A, Campregher, P, Matias-Guiu, X, Velasco, A, Tokat, F, Bonde, J, Trim, N, Bauer, E, Meeney, A, de Leng, W, Chong, G, Dalstein, V, Kis, LL, Lorentzen, JA, Tomic, S, Thwaites, K, Putzova, M, Birnbaum, A, Qazi, R, Primmer, V, Dockhorn-Dworniczak, B, Hernandez-Losa, J, Soares, FA, Gertler, AA, Kalman, M, Wong, C, Carraro, DM, Sousa, AC, Reis, RM, Fox, SB, Fassan, M, Brevet, M, Merkelbach-Bruse, S, Colling, R, Soilleux, E, Teo, RYW, D'Haene, N, Nolet, S, Ristimaki, A, Vaisanen, T, Chapusot, C, Soruri, A, Unger, T, Wecgowiec, J, Biscuola, M, Frattini, M, Long, A, Campregher, P, and Matias-Guiu, X

Abstract

Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.

Published
2021

39. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

Author

Concin, N., Matias-Guiu, X., Vergote, I., Cibula, D., Mirza, M. R., Marnitz, S., Ledermann, J., Bosse, T., Chargari, C., Fagotti, Anna, Fotopoulou, C., Gonzalez Martin, A., Lax, S., Lorusso, Domenica, Marth, C., Morice, P., Nout, R. A., O'Donnell, D., Querleu, D., Raspollini, M. R., Sehouli, J., Sturdza, A., Taylor, Anita, Westermann, A., Wimberger, P., Colombo, N., Planchamp, F., Creutzberg, C. L., Fagotti A. (ORCID:0000-0001-5579-335X), Lorusso D., Taylor A., Concin, N., Matias-Guiu, X., Vergote, I., Cibula, D., Mirza, M. R., Marnitz, S., Ledermann, J., Bosse, T., Chargari, C., Fagotti, Anna, Fotopoulou, C., Gonzalez Martin, A., Lax, S., Lorusso, Domenica, Marth, C., Morice, P., Nout, R. A., O'Donnell, D., Querleu, D., Raspollini, M. R., Sehouli, J., Sturdza, A., Taylor, Anita, Westermann, A., Wimberger, P., Colombo, N., Planchamp, F., Creutzberg, C. L., Fagotti A. (ORCID:0000-0001-5579-335X), Lorusso D., and Taylor A.

Abstract

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.

Published
2021

50. Role ofPOLEandPOLD1in familial cancer

Author

Mur, P, Garcia-Mulero, S, del Valle, J, Magraner-Pardo, L, Vidal, A, Pineda, M, Cinnirella, G, Martin-Ramos, E, Pons, T, Lopez-Doriga, A, Belhadj, S, Feliubadalo, L, Munoz-Torres, PM, Navarro, M, Grau, E, Darder, E, Llort, G, Sanz, J, Cajal, TRY, Balmana, J, Brunet, J, Moreno, V, Piulats, JM, Matias-Guiu, X, Sanz-Pamplona, R, Aligue, R, Capella, G, Lazaro, C, and Valle, L

Subjects
hereditary colorectal cancer, ultramutated phenotype, exonuclease domain, polymerase proofreading-associated polyposis, PPAP
Abstract

Purpose Germline pathogenic variants in the exonuclease domain (ED) of polymerasesPOLEandPOLD1predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence ofPOLEandPOLD1variants in hereditary cancer are evaluated in this study. Methods POLEandPOLD1were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case-control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation. Results Twelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies

Published
2020

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