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2. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy

Author

Craciun, Ligia, de Wind, Roland, Demetter, Pieter, Lucidi, Valerio, Bohlok, Ali, Michiels, Sébastien, Bouazza, Fikri, Vouche, Michael, Tancredi, Ilario, Verset, Gontran, Garaud, Soizic, Naveaux, Céline, Galdon, Maria Gomez, Gallo, Karen Willard, Hendlisz, Alain, Derijckere, Ivan Duran, Flamen, Patrick, Larsimont, Denis, and Donckier, Vincent

Published
2020
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3. Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE

Author

Delbart, Wendy, primary, Marin, Gwennaëlle, additional, Stamatopoulos, Basile, additional, de Wind, Roland, additional, Sirtaine, Nicolas, additional, Demetter, Pieter, additional, Vercruyssen, Marie, additional, Woff, Erwin, additional, Karfis, Ioannis, additional, Ghanem, Ghanem E., additional, Flamen, Patrick, additional, and Wimana, Zéna, additional

Published
2023
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4. Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

Author

Delbart, Wendy, Marin, Gwennaëlle, Stamatopoulos, Basile, De Wind, Roland, Sirtaine, Nicolas, Demetter, Pieter, Vercruyssen, Marie, Woff, Erwin, Karfis, Ioannis, Ghanem, Ghanem Elias, Flamen, Patrick, Wimana, Zéna, Delbart, Wendy, Marin, Gwennaëlle, Stamatopoulos, Basile, De Wind, Roland, Sirtaine, Nicolas, Demetter, Pieter, Vercruyssen, Marie, Woff, Erwin, Karfis, Ioannis, Ghanem, Ghanem Elias, Flamen, Patrick, and Wimana, Zéna

Abstract

Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

5. Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome

Author

Veloza, Luis, Cavalieri, Doriane, Missiaglia, Edoardo, Ledoux-Pilon, Albane, Bisig, Bettina, Pereira, Bruno, Bonnet, Christophe, Poullot, Elsa, Quintanilla-Martinez, Leticia, Dubois, Romain, Llamas-Gutierrez, Francisco, Bossard, Céline, De Wind, Roland, Drieux, Fanny, Fontaine, Juliette, Parrens, Marie, Sandrini, Jeremy, Fataccioli, Virginie, Delfau-Larue, Marie Hélène, Daniel, Adrien, Lhomme, Faustine, Clément-Filliatre, Lauriane, Lemonnier, François, Cairoli, Anne, Morel, Pierre, Glaisner, Sylvie, Joly, Bertrand, Yamani, Abderrazak El, Laribi, Kamel, Bachy, Emmanuel, Siebert, Reiner, Vallois, David, Gaulard, Philippe, Tournilhac, Olivier, de Leval, Laurence, Veloza, Luis, Cavalieri, Doriane, Missiaglia, Edoardo, Ledoux-Pilon, Albane, Bisig, Bettina, Pereira, Bruno, Bonnet, Christophe, Poullot, Elsa, Quintanilla-Martinez, Leticia, Dubois, Romain, Llamas-Gutierrez, Francisco, Bossard, Céline, De Wind, Roland, Drieux, Fanny, Fontaine, Juliette, Parrens, Marie, Sandrini, Jeremy, Fataccioli, Virginie, Delfau-Larue, Marie Hélène, Daniel, Adrien, Lhomme, Faustine, Clément-Filliatre, Lauriane, Lemonnier, François, Cairoli, Anne, Morel, Pierre, Glaisner, Sylvie, Joly, Bertrand, Yamani, Abderrazak El, Laribi, Kamel, Bachy, Emmanuel, Siebert, Reiner, Vallois, David, Gaulard, Philippe, Tournilhac, Olivier, and de Leval, Laurence

Abstract

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e. non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

6. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group

Author

Denkert, Carsten, Wienert, Stephan, Poterie, Audrey, Loibl, Sibylle, Budczies, Jan, Badve, Sunil, Bago-Horvath, Zsuzsanna, Bane, Anita, Bedri, Shahinaz, Brock, Jane, Chmielik, Ewa, Christgen, Matthias, Colpaert, Cecile, Demaria, Sandra, Van den Eynden, Gert, Floris, Giuseppe, Fox, Stephen B, Gao, Dongxia, Ingold Heppner, Barbara, Kim, S Rim, Kos, Zuzana, Kreipe, Hans H, Lakhani, Sunil R, Penault-Llorca, Frederique, Pruneri, Giancarlo, Radosevic-Robin, Nina, Rimm, David L, Schnitt, Stuart J, Sinn, Bruno V, Sinn, Peter, Sirtaine, Nicolas, O'Toole, Sandra A, Viale, Giuseppe, Van de Vijver, Koen, de Wind, Roland, von Minckwitz, Gunter, Klauschen, Frederick, Untch, Michael, Fasching, Peter A, Reimer, Toralf, Willard-Gallo, Karen, Michiels, Stefan, Loi, Sherene, and Salgado, Roberto

Published
2016
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9. Tracheal amyloidosis visualized by autofluorescence endoscopy

Author

Inthasot, V., Gabrovska, Maria, Bruyneel, Marie, De Wind, Roland, Ninane, Vincent, Inthasot, V., Gabrovska, Maria, Bruyneel, Marie, De Wind, Roland, and Ninane, Vincent

Abstract

SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

10. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Author

Hendry, Shona, Salgado, Roberto, Gevaert, Thomas, Russell, Prudence A., John, Tom, Thapa, Bibhusal, Christie, Michael, van de Vijver, Koen, Estrada, M.V., Gonzalez-Ericsson, Paula I., Sanders, Melinda, Solomon, Benjamin, Solinas, Cinzia, Van den Eynden, Gert G.G.M., Allory, Yves, Preusser, Matthias, Hainfellner, Johannes, Pruneri, Giancarlo, Vingiani, Andrea, Demaria, Sandra, Symmans, Fraser, Nuciforo, Paolo, Comerma, Laura, Thompson, E.A., Lakhani, Sunil, Kim, Seong-Rim, Schnitt, Stuart, Colpaert, Cecile, Sotiriou, Christos, Scherer, Stefan J., Ignatiadis, Michail, Badve, Sunil, Pierce, Robert H., Viale, Giuseppe, Sirtaine, Nicolas, Penault-Llorca, Frederique, Sugie, Tomohagu, Fineberg, Susan, Paik, Soonmyung, Srinivasan, Ashok, Richardson, Andrea, Wang, Yihong, Chmielik, Ewa, Brock, Jane, Johnson, Douglas B., Balko, Justin, Wienert, Stephan, Bossuyt, Veerle, Michiels, Stefan, Ternes, Nils, Burchardi, Nicole, Luen, Stephen J., Savas, Peter, Klauschen, Frederick, Watson, Peter H., Nelson, Brad H., Criscitiello, Carmen, O’Toole, Sandra, Larsimont, Denis, de Wind, Roland, Curigliano, Giuseppe, André, Fabrice, Lacroix-Triki, Magali, van de Vijver, Mark, Rojo, Federico, Floris, Giuseppe, Bedri, Shahinaz, Sparano, Joseph, Rimm, David, Nielsen, Torsten, Kos, Zuzana, Hewitt, Stephen, Singh, Baljit, Farshid, Gelareh, Loibl, Sibylle, Allison, Kimberly H., Tung, Nadine, Adams, Sylvia, Willard-Gallo, Karen, Horlings, Hugo M., Gandhi, Leena, Moreira, Andre, Hirsch, Fred, Dieci, Maria V., Urbanowicz, Maria, Brcic, Iva, Korski, Konstanty, Gaire, Fabien, Koeppen, Hartmut, Lo, Amy, Giltnane, Jennifer, Rebelatto, Marlon C., Steele, Keith E., Zha, Jiping, Emancipator, Kenneth, Juco, Jonathan W., Denkert, Carsten, Reis-Filho, Jorge, Loi, Sherene, and Fox, Stephen B.

Published
2017
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11. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research

Author

Hendry, Shona, Salgado, Roberto, Gevaert, Thomas, Russell, Prudence A., John, Tom, Thapa, Bibhusal, Christie, Michael, van de Vijver, Koen, Estrada, M.V., Gonzalez-Ericsson, Paula I., Sanders, Melinda, Solomon, Benjamin, Solinas, Cinzia, Van den Eynden, Gert G.G.M., Allory, Yves, Preusser, Matthias, Hainfellner, Johannes, Pruneri, Giancarlo, Vingiani, Andrea, Demaria, Sandra, Symmans, Fraser, Nuciforo, Paolo, Comerma, Laura, Thompson, E.A., Lakhani, Sunil, Kim, Seong-Rim, Schnitt, Stuart, Colpaert, Cecile, Sotiriou, Christos, Scherer, Stefan J., Ignatiadis, Michail, Badve, Sunil, Pierce, Robert H., Viale, Giuseppe, Sirtaine, Nicolas, Penault-Llorca, Frederique, Sugie, Tomohagu, Fineberg, Susan, Paik, Soonmyung, Srinivasan, Ashok, Richardson, Andrea, Wang, Yihong, Chmielik, Ewa, Brock, Jane, Johnson, Douglas B., Balko, Justin, Wienert, Stephan, Bossuyt, Veerle, Michiels, Stefan, Ternes, Nils, Burchardi, Nicole, Luen, Stephen J., Savas, Peter, Klauschen, Frederick, Watson, Peter H., Nelson, Brad H., Criscitiello, Carmen, O’Toole, Sandra, Larsimont, Denis, de Wind, Roland, Curigliano, Giuseppe, André, Fabrice, Lacroix-Triki, Magali, van de Vijver, Mark, Rojo, Federico, Floris, Giuseppe, Bedri, Shahinaz, Sparano, Joseph, Rimm, David, Nielsen, Torsten, Kos, Zuzana, Hewitt, Stephen, Singh, Baljit, Farshid, Gelareh, Loibl, Sibylle, Allison, Kimberly H., Tung, Nadine, Adams, Sylvia, Willard-Gallo, Karen, Horlings, Hugo M., Gandhi, Leena, Moreira, Andre, Hirsch, Fred, Dieci, Maria V., Urbanowicz, Maria, Brcic, Iva, Korski, Konstanty, Gaire, Fabien, Koeppen, Hartmut, Lo, Amy, Giltnane, Jennifer, Rebelatto, Marlon C., Steele, Keith E., Zha, Jiping, Emancipator, Kenneth, Juco, Jonathan W., Denkert, Carsten, Reis-Filho, Jorge, Loi, Sherene, and Fox, Stephen B.

Published
2017
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12. Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177 Lu-DOTATATE.

Author

Delbart, Wendy, Marin, Gwennaëlle, Stamatopoulos, Basile, de Wind, Roland, Sirtaine, Nicolas, Demetter, Pieter, Vercruyssen, Marie, Woff, Erwin, Karfis, Ioannis, Ghanem, Ghanem E., Flamen, Patrick, and Wimana, Zéna

Subjects
RADIOISOTOPE therapy, GLUTATHIONE, BIOLOGICAL models, IN vitro studies, IN vivo studies, XENOGRAFTS, ANIMAL experimentation, CELL receptors, OCTREOTIDE acetate, ANTIOXIDANTS, OXIDATIVE stress, NEUROENDOCRINE tumors, SOMATOSTATIN, DRUG synergism, RESEARCH funding, MULTIPLE myeloma, CELL lines, REACTIVE oxygen species, MICE, CELL death
Abstract

Simple Summary: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is an efficient treatment for patients suffering from metastasized neuroendocrine tumours. Nevertheless, suboptimal effects have been observed in the majority of patients. Hence, strategies to improve 177Lu-DOTATATE efficacy are desirable. Lu-177 induces oxidative stress, eventually leading to tumour cell death. Inhibition of the antioxidant defence mechanisms, using buthionine sulfoximine (BSO), represents an attractive strategy to increase 177Lu-DOTATATE efficacy. In cells and an animal model, the combination of 177Lu-DOTATATE and BSO was more effective than 177Lu-DOTATATE alone. In addition, it did not result in additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. [ABSTRACT FROM AUTHOR]

Published
2023
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13. Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome

Author

Veloza, Luis, primary, Cavalieri, Doriane, additional, Missiaglia, Edoardo, additional, Ledoux-Pilon, Albane, additional, Bisig, Bettina, additional, Pereira, Bruno, additional, Bonnet, Christophe, additional, Poullot, Elsa, additional, Quintanilla-Martinez, Leticia, additional, Dubois, Romain, additional, Llamas-Gutierrez, Francisco, additional, Bossard, Céline, additional, De Wind, Roland, additional, Drieux, Fanny, additional, Fontaine, Juliette, additional, Parrens, Marie, additional, Sandrini, Jeremy, additional, Fataccioli, Virginie, additional, Delfau-Larue, Marie-Hélène, additional, Daniel, Adrien, additional, Lhomme, Faustine, additional, Clément-Filliatre, Lauriane, additional, Lemonnier, François, additional, Cairoli, Anne, additional, Morel, Pierre, additional, Glaisner, Sylvie, additional, Joly, Bertrand, additional, El Yamani, Abderrazak, additional, Laribi, Kamel, additional, Bachy, Emmanuel, additional, Siebert, Reiner, additional, Vallois, David, additional, Gaulard, Philippe, additional, Tournilhac, Olivier, additional, and De Leval, Laurence, additional

Published
2022
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14. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., van der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, Cooper, Lee A. D., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Tutt, Andrew, Guerrero-Zotano, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Anna C., Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Castaneda, Carlos, Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Dillon, Deborah A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Bellolio, Enrique, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Gruosso, Forbius Tina, Peale, Franklin, Hirsch, Fred R., Klaushen, Frederick, Acosta-Haab, Gabriela, Farshid, Gelareh, van den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Hall, Jacqueline A., Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, M. Ribeiro, Joana, Carter, Jodi M., Hainfellner, Johannes, Quesne, John Le, Juco, Jonathan W., Reis-Filho, Jorge, van den Berg, Jose, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., van de Vijver, Koen K., Korski, Konstanty, Pusztai, Lajos, Buisseret, Laurence, Shi, Leming, Shi-wei, Liu, Molinero, Luciana, Estrada, M. Valeria, van Seijen, Maartje, Lacroix-Triki, Magali, Cheang, Maggie C. U., Bakir, Maise al, van de Vijver, Marc, Dieci, Maria Vittoria, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Sanders, Melinda E., Regan, Meredith M., Christie, Michael, Misialek, Michael, Ignatiadis, Michail, de Maaker, Michiel, van Bockstal, Mieke, Castillo, Miluska, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Jelinic, Petar, Watson, Peter H., Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, de Wind, Roland, Shui, Ruohong, Declercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Willis, Scooter, Ely, Scott, Kim, Seong- Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Luz, Sua, Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, d’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Yang, Wentao, Tran, William T., Wang, Yihong, Allory, Yves, Husain, Zaheed, Amgad, Mohamed [0000-0001-7599-6162], Sharma, Ashish [0000-0002-1011-6504], Savas, Peter [0000-0001-5999-428X], Hudeček, Jan [0000-0003-1071-5686], Braybrooke, Jeremy P. [0000-0003-1943-7360], Demaria, Sandra [0000-0003-4426-0499], Comerma, Laura [0000-0002-0249-4636], Badve, Sunil S. [0000-0001-8861-9980], Symmans, W. Fraser [0000-0002-1526-184X], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Rimm, David L. [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hanna, Matthew G. [0000-0002-7536-1746], Lazar, Alexander J. [0000-0002-6395-4499], Bago-Horvath, Zsuzsanna [0000-0002-8555-7806], van der Laak, Jeroen A. W. M. [0000-0001-7982-0754], Gallas, Brandon D. [0000-0001-7332-1620], Kurkure, Uday [0000-0002-8273-7334], Cooper, Lee A. D. [0000-0002-3504-4965], and Apollo - University of Cambridge Repository

Subjects
631/67/580, 692/4028/67/1857, 631/67/2321, 692/53/2422, review-article, Review Article, 631/67/1347
Abstract

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Published
2020

15. Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer.

Author

Anciaux, Maëlle, Demetter, Pieter, De Wind, Roland, Gomez Galdon, Maria, Vande Velde, Sylvie, Lens, Gaspard, Ruscas-Craciun, Ligia Ioana, Deleruelle, Amélie, Larsimont, Denis, Lenaerts, Tom, Sclafani, Francesco, Deleporte, Amélie, Donckier, Vincent, Hendlisz, Alain, Vandeputte, Caroline, Anciaux, Maëlle, Demetter, Pieter, De Wind, Roland, Gomez Galdon, Maria, Vande Velde, Sylvie, Lens, Gaspard, Ruscas-Craciun, Ligia Ioana, Deleruelle, Amélie, Larsimont, Denis, Lenaerts, Tom, Sclafani, Francesco, Deleporte, Amélie, Donckier, Vincent, Hendlisz, Alain, and Vandeputte, Caroline

Abstract

Oesophageal cancer (OEC) is an aggressive disease with a poor survival rate. Prognostic markers are thus urgently needed. Due to the demonstrated prognostic value of histopathological growth pattern (HGP) in other cancers, we performed a retrospective assessment of HGP in patients suffering from invasive OEC., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

16. Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer

Author

Anciaux, Maelle, primary, Demetter, Pieter, additional, De Wind, Roland, additional, Gomez Galdon, Maria, additional, Vande Velde, Sylvie, additional, Lens, Gaspard, additional, Craciun, Ligia, additional, Deleruelle, Amélie, additional, Larsimont, Denis, additional, Lenaerts, Tom, additional, Sclafani, Francesco, additional, Deleporte, Amélie, additional, Donckier, Vincent, additional, Hendlisz, Alain, additional, and Vandeputte, Caroline, additional

Published
2020
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18. Primary Hepatic Lymphoma Mimicking a Hepatocellular Carcinoma in a Cirrhotic Patient: Case Report and Systematic Review of the Literature

Author

Bohlok, Ali, De Grez, Thierry, Bouazza, Fikri, De Wind, Roland, El-Khoury, Melody, Repullo, Deborah, and Donckier, Vincent

Subjects
Article Subject
Abstract

Introduction. Primary hepatic lymphomas (PHLs) are rare liver tumors, frequently misdiagnosed preoperatively. As these tumors could be successfully treated with chemotherapy, their early recognition is essential, potentially, to avoid useless surgery. We report on the case of a cirrhotic patient with hemochromatosis who presented a PHL, initially diagnosed as a hepatocellular carcinoma (HCC), and we analyze recent data from the literature on this subject. Case Presentation and Review of the Literature. A 45 mm liver tumor was found is a 68-year-old man with alcohol cirrhosis and hemochromatosis. At imaging, the diagnosis of HCC was suspected according to vascular characteristics and the presence of cirrhosis. FDG PET scan showed a solitary hypermetabolic liver tumor. Tumor markers were negative. Surgery consisted in left lateral hepatectomy. At pathology, the diagnosis of the primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type was demonstrated. Twenty-two articles reporting 33 cases of true PHL of MALT type were found. Presentation lacked specific symptoms (70% asymptomatic). Half of patients were suspected to have other etiologies of liver mass (HCC, intrahepatic cholangiocarcinoma), and thus diagnosis was established postoperatively. In the patient, diagnosis was made by preoperative biopsy, and chemotherapy was first-line treatment. Discussion. Preoperative diagnosis of PHL, and particularly of primary hepatic MALT lymphoma, is challenging. This case illustrates that PHL remains to be considered among the differential diagnosis of isolated solid liver tumors. Further, it indicates that biopsy could be still indicated in case of suspected HCC in cirrhotic patients, particularly in the presence of unusual findings such as the combination of a FDG PET scan positive tumor in the absence of elevated alpha-fetoprotein.

Published
2018
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20. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors

Author

John, Maria, Salgado, Roberto, Gevaert, Thomas, Russell, Prudence A, John, Tom, Thapa, Bibhusal, Christie, Michael, van de Vijver, Koen, Estrada, M V, Gonzalez-Ericsson, Paula I, Sanders, Melinda, Solomon, Benjamin, Solinas, Cinzia, van den Eynden, Gert G G M, Allory, Yves, Preusser, Matthias, Hainfellner, Johannes, Pruneri, Giancarlo, Vingiani, Andre, Demaria, Sandra, Symmans, Fraser, Nuciforo, Paolo, Comerma, Laura, Thompson, E A, Lakhani, Sunil, Kim, Seong-Rim, Schnitt, Stuart, Colpaert, Cecile, Sotiriou, Christos, Scherer, Stefan, Ignatiadis, Michail, Badve, Sunil, Pierce, Robert H, Viale, Giuseppe, Sirtaine, Nicolas, Penault-Llorca, Fred, Sugie, Tomohagu, Fineberg, Susan, Paik, Soonmyung, Srinivasan, Ashok, Richardson, Andre, Wang, Yihong, Chmielik, Ewa, Brock, Jane, Johnson, Douglas B, Balko, Justin, Wienert, Stephan, Bossuyt, Veerle, Michiels, Stefan, Ternès, Nils, Burchardi, Nicole, Luen, Stephen, Savas, Peter, Klauschen, Fred, Watson, Peter H, Nelson, Brad H, Criscitiello, Carmen, O'Toole, Sandra, Larsimont, Denis, de Wind, Roland, Curigliano, Giuseppe, André, Fabrice, Lacroix-Triki, Magali, van de Vijver, Mark, Rojo, Federico, Floris, Giuseppe, Bedri, Shahinaz, Sparano, Joseph, Rimm, David, Nielsen, Torsten, Kos, Zuzana, Hewitt, Stephen, Singh, Baljit, Farshid, Gelareh, Loi, Sibylle, Allison, Kimberly H, Tung, Nadine, Adams, Sylvia, Willard-Gallo, Karen, Horlings, Hugo M, Gandhi, Leena, Moreira, Andre, Hirsch, Fred, Dieci, Maria, Urbanowicz, Maria, Brcic, Iva, Korski, Konstanty, Gaire, Fabien, Koeppen, Hartmut, Lo, Amy, Giltnane, Jennifer, Rebelatto, Marlon C, Steele, Keith E, Zha, Jiping, Emancipator, Kenneth, Juco, Jonathan W, Denkert, Carsten, Reis-Filho, Jorge, Loi, Sherene, Fox, Stephen B, Hendry, Shona, Russell, Prudence A., Estrada, M.V., Gonzalez-Ericsson, Paula I., van den Eynden, Gert G.G.M., Thompson, E.A., Pierce, Robert H., Johnson, Douglas B., Watson, Peter H., Nelson, Brad H., O’toole, Sandra, Allison, Kimberly H., Horlings, Hugo M., Rebelatto, Marlon C., Steele, Keith E., Juco, Jonathan W., Fox, Stephen B., Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Cancer Genetics Branch, National Institute of Health (NIH)-National Human Genome Research Institute (NHGRI), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Division of Pathology and Laboratory Medicine, European Institute of Oncology [Milan] (ESMO), FIRC, Institute of Molecular Oncology Foundation, Trinity College Dublin, Department of medical oncology, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Méthodologie et épidémiologie clinique en oncologie moléculaire (U1018 (Équipe 2)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Trev and Joyce Deeley Research Center, Vancouver Island Center, Division of Medical Oncology, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département de Biologie et de Pathologie, Institut Claudius Regaud, Department of Dermatology, Helsinki University Hospital-Skin and Allergy Hospital, University of Colorado Cancer Center, University of Colorado [Denver], Charité, Institute of Pathology, Translational Tumorpathology Unit, Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Experimental Pathology & Pharmacology, Vanderbilt University School of Medicine [Nashville], Department of Pathology, Peter MacCallum Cancer Center, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
hemic and immune systems, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

Published
2017
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23. Characterization of human breast cancer tissues by infrared imaging.

Author

Verdonck, Magali, Denayer, Amandine, Delvaux, Benjamin, Garaud, Soizic, De Wind, Roland, Desmedt, Christine, Sotiriou, Christos, Willard-Gallo, Karen, Goormaghtigh, Erik, Verdonck, Magali, Denayer, Amandine, Delvaux, Benjamin, Garaud, Soizic, De Wind, Roland, Desmedt, Christine, Sotiriou, Christos, Willard-Gallo, Karen, and Goormaghtigh, Erik

Abstract

Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

24. Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: A new mechanism of resistance to ALK inhibitors

Author

Levacq, Delphine, D'Haene, Nicky, De Wind, Roland, Remmelink, Myriam, Berghmans, Thierry, Levacq, Delphine, D'Haene, Nicky, De Wind, Roland, Remmelink, Myriam, and Berghmans, Thierry

Abstract

Various mechanisms of resistance to ALK inhibitors in ALK rearranged adenocarcinomas are reported including secondary gatekeeper mutations, bypass signaling or ALK amplifications as the commonest ones. We report a new mechanism of resistance with transformation of adenocarcinoma into small cell lung cancer. A 53-year-old non-smoker woman, experienced cancer progression after two lines of ALK inhibitors. A new biopsy showed a small cell lung cancer. FISH revealed persistent ALK rearrangement with an atypical pattern and complete loss of the 5′ region of the ALK gene., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

26. Retrospective Rescreening of Negative Cervical Cytology Samples Preceding Histologically Proven CIN2'3 and Squamous Cell Carcinoma: An Educational Opportunity to Understand and Prevent Laboratory Errors

Author

Feoli, Francesco, Renard, Christine, Abouyahia, Meryme, De Wind, Roland, Larsimont, Denis, Arbyn, Marc, Feoli, Francesco, Renard, Christine, Abouyahia, Meryme, De Wind, Roland, Larsimont, Denis, and Arbyn, Marc

Abstract

Objectives: We aimed to analyze the false-negative (FN) liquid-based cytology diagnoses from the 5 years preceding all the 2013 histologically proven cervical intraepithelial neoplasia (CIN)2-3 and squamous cell carcinoma (SCC) and to propose corrective actions. Study Design: This was a retrospective, blinded rescreening ('5-year look-back') of liquid-based cytology samples with negative categorizations, which occurred before histologically proven CIN2-3 and SCC. Results: The FN rate was 7.8% (21/256 samples preceding CIN2-3 and 0/13 samples preceding SCC). Slides confirmed as 'negative', 'interpretation error' and 'screening error', respectively, were 3.3% (9/269), 2.6% (7/269) and 1.9% (5/269). In 9/12 cases, error was associated with small atypical cells. In 7/12 cases, these diagnostic cells were less than 5/10 HPF. Inflammation and prominent reactive changes were present in 5/12 cases. Five patients had a positive clinical history. In 2 cases, there were multiple-cell-layer artifacts. Dense groups of small blue atypical cells were missed in 2 other cases. Dotting was imprecise in 6/7 samples. Conclusion: Considering the above results, we specifically reoriented our continuous education activities, focusing rapid rescreening on scanty, isolated, small, atypical cells and dense cell groups. Prior to final diagnosis, pathologists should systematically review the entire surface of the dotted slides, with special attention being devoted to slides with multiple cell layers and tridimensional groups., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

28. Breast cancer host immune and stromal biology

Author

WANG, XIAOXIAO, Buisseret, Laurence, De Wind, Roland, Duquenne, S, Gu-Trantien, Chunyan, Garaud, Soizic, Rorive, Sandrine, Paesmans, Marianne, Sotiriou, Christos, Willard-Gallo, Karen, WANG, XIAOXIAO, Buisseret, Laurence, De Wind, Roland, Duquenne, S, Gu-Trantien, Chunyan, Garaud, Soizic, Rorive, Sandrine, Paesmans, Marianne, Sotiriou, Christos, and Willard-Gallo, Karen

Abstract

Poster presentation, info:eu-repo/semantics/published

Published
2014

29. Lymphocytes infiltrating breast cancer: density, composition and organization

Author

Buisseret, Laurence, Garaud, Soizic, Duvillier, Hugues, Naveaux, Céline, Duquenne, S, De Wind, Roland, Vakili, Jalal, Sotiriou, Christos, Willard-Gallo, Karen, Buisseret, Laurence, Garaud, Soizic, Duvillier, Hugues, Naveaux, Céline, Duquenne, S, De Wind, Roland, Vakili, Jalal, Sotiriou, Christos, and Willard-Gallo, Karen

Abstract

info:eu-repo/semantics/published

Published
2014

30. CXCL13-producing extrafollicular Tfh-like CD4+ T cells in human breast cancer

Author

Gu-Trantien, Chunyan, Migliori, Edoardo, Buisseret, Laurence, Garaud, Soizic, De Wind, Roland, Lodewyckx, Jean Nicolas, Duvillier, Hugues, Naveaux, Céline, Boisson, Anaïs, Larsimont, Denis, Willard-Gallo, Karen, Gu-Trantien, Chunyan, Migliori, Edoardo, Buisseret, Laurence, Garaud, Soizic, De Wind, Roland, Lodewyckx, Jean Nicolas, Duvillier, Hugues, Naveaux, Céline, Boisson, Anaïs, Larsimont, Denis, and Willard-Gallo, Karen

Abstract

info:eu-repo/semantics/published

Published
2014

31. Characterization of tumor infiltrating lymphocytes in human breast cancer by infrared imaging

Author

Verdonck, Magali, Garaud, Soizic, Buisseret, Laurence, Duvillier, Hugues, Desmedt, Christine, De Wind, Roland, Sotiriou, Christos, Willard-Gallo, Karen, Goormaghtigh, Erik, Verdonck, Magali, Garaud, Soizic, Buisseret, Laurence, Duvillier, Hugues, Desmedt, Christine, De Wind, Roland, Sotiriou, Christos, Willard-Gallo, Karen, and Goormaghtigh, Erik

Abstract

57P, info:eu-repo/semantics/published

Published
2014

32. Reproducibility of assessing immune infiltration in core biopsies compared to primary breast tumors.

Author

WANG, XIAOXIAO, Buisseret, Laurence, De Wind, Roland, Duquenne, S, Gu-Trantien, Chunyan, Garaud, Soizic, Rorive, Sandrine, Paesmans, Marianne, Sotiriou, Christos, Willard-Gallo, Karen, WANG, XIAOXIAO, Buisseret, Laurence, De Wind, Roland, Duquenne, S, Gu-Trantien, Chunyan, Garaud, Soizic, Rorive, Sandrine, Paesmans, Marianne, Sotiriou, Christos, and Willard-Gallo, Karen

Abstract

51P, info:eu-repo/semantics/published

Published
2014

33. Recurrent invasive thymoma with pleural dissemination: Disease management and treatment possibilities

Author

Konecna, Jana, Willemse, Esther, Lefebvre, Y., De Wind, Roland, Andry, Guy, Konecna, Jana, Willemse, Esther, Lefebvre, Y., De Wind, Roland, and Andry, Guy

Abstract

Thymoma is the most common benign neoplasm of the anterior mediastinum presenting often an agressive behaviour typical for the malignants tumors. The rate of invasive thymoma recurrency is relatively high. We present the case of a 55-year old man with a recurrent invasive thymoma with a pleural dissemination, detected on CT-imaging 2 years following his primary surgery. Since the first pre-operative imaging studies showed no invasion of the adjacent organs and a thymoma was suspected, a surgical resection was decided as a first line treatment. Per-operatively a number of adjacent structures were invaded and despite a macroscopical RO resection, the margins were microscopically positive. An invasive thymoma, WHO classification B3, Masaoka stage IVb was diagnosed and the patient received adjuvant radiotherapy. We highlight the role of multimodality treatement and disscus the potential of surgical, radiotherapeutical and systemic therapy in stage IV thymoma as well as in recurrent disease., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2014

34. Infrared imaging: a potential new tool to characterize lymphocytic infiltration in human breast cancer

Author

Verdonck, Magali, Garaud, Soizic, Duvillier, Hugues, Vermeulen, NF, Buisseret, Laurence, Desmedt, Christine, De Wind, Roland, Sotiriou, Christos, Willard-Gallo, Karen, Goormaghtigh, Erik, Verdonck, Magali, Garaud, Soizic, Duvillier, Hugues, Vermeulen, NF, Buisseret, Laurence, Desmedt, Christine, De Wind, Roland, Sotiriou, Christos, Willard-Gallo, Karen, and Goormaghtigh, Erik

Abstract

Imaging preclinical and clinical - Abstract 95P, info:eu-repo/semantics/published

Published
2013

35. La mastocytose: une maladie revisitée a la lumière des nouvelles données génétiques.

Author

Vaes, Melanie, Vereecken, Pierre, De Wind, Roland, Andry, Guy, Li, Rusheng, Bron, Dominique, Vaes, Melanie, Vereecken, Pierre, De Wind, Roland, Andry, Guy, Li, Rusheng, and Bron, Dominique

Abstract

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis., English Abstract, Journal Article, Review, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2012

36. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., Van Der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, Cooper, Lee A. D., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Tutt, Andrew, Guerrero-Zotano, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Anna C., Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Castaneda, Carlos, Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Dillon, Deborah A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Bellolio, Enrique, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Gruosso, Forbius Tina, Peale, Franklin, Hirsch, Fred R., Klaushen, Frederick, Acosta-Haab, Gabriela, Farshid, Gelareh, Van Den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Hall, Jacqueline A., Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, M. Ribeiro, Joana, Carter, Jodi M., Hainfellner, Johannes, Quesne, John Le, Juco, Jonathan W., Reis-Filho, Jorge, Van Den Berg, Jose, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., Van De Vijver, Koen K., Korski, Konstanty, Pusztai, Lajos, Buisseret, Laurence, Shi, Leming, Shi-Wei, Liu, Molinero, Luciana, Estrada, M. Valeria, Van Seijen, Maartje, Lacroix-Triki, Magali, Cheang, Maggie C. U., Bakir, Maise Al, Van De Vijver, Marc, Dieci, Maria Vittoria, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Sanders, Melinda E., Regan, Meredith M., Christie, Michael, Misialek, Michael, Ignatiadis, Michail, De Maaker, Michiel, Van Bockstal, Mieke, Castillo, Miluska, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Jelinic, Petar, Watson, Peter H., Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, Declercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Willis, Scooter, Ely, Scott, Kim, Seong- Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Luz, Sua, Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, D’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Yang, Wentao, Tran, William T., Wang, Yihong, Allory, Yves, and Husain, Zaheed

Subjects
631/67/580, 692/4028/67/1857, 631/67/2321, 692/53/2422, review-article, Review Article, 631/67/1347, humanities, 3. Good health
Abstract

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI), Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University., Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance., Funder: The Canadian Cancer Society, Funder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194, Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

37. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Author

Kos, Zuzana, Roblin, Elvire, Kim, Rim S., Michiels, Stefan, Gallas, Brandon D., Chen, Weijie, Van De Vijver, Koen K., Goel, Shom, Adams, Sylvia, Demaria, Sandra, Viale, Giuseppe, Nielsen, Torsten O., Badve, Sunil S., Symmans, W. Fraser, Sotiriou, Christos, Rimm, David L., Hewitt, Stephen, Denkert, Carsten, Loibl, Sibylle, Luen, Stephen J., Bartlett, John M. S., Savas, Peter, Pruneri, Giancarlo, Dillon, Deborah A., Cheang, Maggie Chon U., Tutt, Andrew, Hall, Jacqueline A., Kok, Marleen, Horlings, Hugo M., Madabhushi, Anant, Van Der Laak, Jeroen, Ciompi, Francesco, Laenkholm, Anne-Vibeke, Bellolio, Enrique, Gruosso, Tina, Fox, Stephen B., Araya, Juan Carlos, Floris, Giuseppe, Hudeček, Jan, Voorwerk, Leonie, Beck, Andrew H., Kerner, Jen, Larsimont, Denis, Declercq, Sabine, Van Den Eynden, Gert, Pusztai, Lajos, Ehinger, Anna, Yang, Wentao, AbdulJabbar, Khalid, Yuan, Yinyin, Singh, Rajendra, Hiley, Crispin, Bakir, Maise Al, Lazar, Alexander J., Naber, Stephen, Wienert, Stephan, Castillo, Miluska, Curigliano, Giuseppe, Dieci, Maria-Vittoria, André, Fabrice, Swanton, Charles, Reis-Filho, Jorge, Sparano, Joseph, Balslev, Eva, Chen, I-Chun, Stovgaard, Elisabeth Ida Specht, Pogue-Geile, Katherine, Blenman, Kim R. M., Penault-Llorca, Frédérique, Schnitt, Stuart, Lakhani, Sunil R., Vincent-Salomon, Anne, Rojo, Federico, Braybrooke, Jeremy P., Hanna, Matthew G., Soler-Monsó, M. Teresa, Bethmann, Daniel, Castaneda, Carlos A., Willard-Gallo, Karen, Sharma, Ashish, Lien, Huang-Chun, Fineberg, Susan, Thagaard, Jeppe, Comerma, Laura, Gonzalez-Ericsson, Paula, Brogi, Edi, Loi, Sherene, Saltz, Joel, Klaushen, Frederick, Cooper, Lee, Amgad, Mohamed, Moore, David A., Salgado, Roberto, Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Gown, Allen, Lo, Amy, Sapino, Anna, Moreira, Andre M., Richardson, Andrea, Vingiani, Andrea, Bellizzi, Andrew M., Guerrero, Angel, Grigoriadis, Anita, Garrido-Castro, Ana C., Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Ballesteroes-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Solinas, Cinzia, Drubay, Damien, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Perez, Edith, ElGabry, Ehab A., Blackley, Elizabeth F., Reisenbichler, Emily, Chmielik, Ewa, Gaire, Fabien, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Peale, Franklin, Hirsch, Fred R., Acosta-Haab, Gabriela, Farshid, Gelareh, Broeckx, Glenn, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Cree, Ian, Nederlof, Iris, Frahm, Isabel, Brcic, Iva, Chan, Jack, Ziai, James, Brock, Jane, Weseling, Jelle, Giltnane, Jennifer, Lemonnier, Jerome, Zha, Jiping, Ribeiro, Joana, Lennerz, Jochen K., Carter, Jodi M., Hartman, Johan, Hainfellner, Johannes, Le Quesne, John, Juco, Jonathan W., Van Den Berg, Jose, Sanchez, Joselyn, Cucherousset, Joël, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Sikorska, Karolina, Weber, Karsten, Steele, Keith E., Emancipator, Kenneth, El Bairi, Khalid, Allison, Kimberly H., Korski, Konstanty, Buisseret, Laurence, Shi, Leming, Kooreman, Loes F. S., Molinero, Luciana, Estrada, M. Valeria, Van Seijen, Maartje, Lacroix-Triki, Magali, Sebastian, Manu M., Balancin, Marcelo L., Mathieu, Marie-Christine, Van De Vijver, Mark, Rebelatto, Marlon C., Piccart, Martine, Goetz, Matthew P., Preusser, Matthias, Khojasteh, Mehrnoush, Sanders, Melinda E., Regan, Meredith M., Barnes, Michael, Christie, Michael, Misialek, Michael, Ignatiadis, Michail, De Maaker, Michiel, Van Bockstal, Mieke, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Kirtani, Pawan, Watson, Peter H., Jelinic, Peter, Francis, Prudence A., Russell, Prudence A., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, Leung, Samuel, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Dudgeon, Sarah, Willis, Scooter, Ely, Scott, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shiwei, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Luz, Sua, Gevaert, Thomas, D’Alfons, Timothy, John, Tom, Sugie, Tomohagu, Kurkure, Uday, Bossuyt, Veerle, Manem, Venkata, Cámaea, Vincente Peg, Tong, Weida, Tran, William T., Wang, Yihong, Allory, Yves, Husain, Zaheed, and Bago-Horvath, Zsuzsanna

Subjects
692/53/2422, article, 3. Good health, 631/67/580/1884
Abstract

Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

38. Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Author

Hudeček, Jan, Voorwerk, Leonie, Van Seijen, Maartje, Nederlof, Iris, De Maaker, Michiel, Van Den Berg, Jose, Van De Vijver, Koen K., Sikorska, Karolina, Adams, Sylvia, Demaria, Sandra, Viale, Giuseppe, Nielsen, Torsten O., Badve, Sunil S., Michiels, Stefan, Symmans, William Fraser, Sotiriou, Christos, Rimm, David L., Hewitt, Stephen M., Denkert, Carsten, Loibl, Sibylle, Loi, Sherene, Bartlett, John M. S., Pruneri, Giancarlo, Dillon, Deborah A., Cheang, Maggie C. U., Tutt, Andrew, Hall, Jacqueline A., Kos, Zuzana, Salgado, Roberto, Kok, Marleen, Horlings, Hugo M., Hyytiäinen, Aini, Hida, Akira I., Thompson, Alastair, Lefevre, Alex, Lazar, Alexander J., Gown, Allen, Lo, Amy, Sapino, Anna, Madabhushi, Anant, Moreira, Andre, Richardson, Andrea, Vingiani, Andrea, Beck, Andrew H., Bellizzi, Andrew M., Guerrero, Angel, Grigoriadis, Anita, Ehinger, Anna, Garrido-Castro, Ana, Vincent-Salomon, Anne, Laenkholm, Anne-Vibeke, Sharma, Ashish, Cimino-Mathews, Ashley, Srinivasan, Ashok, Acs, Balazs, Singh, Baljit, Calhoun, Benjamin, Haibe-Kans, Benjamin, Solomon, Benjamin, Thapa, Bibhusal, Nelson, Brad H., Gallas, Brandon D., Castaneda, Carlos, Ballesteros-Merino, Carmen, Criscitiello, Carmen, Boeckx, Carolien, Colpaert, Cecile, Quinn, Cecily, Chennubhotla, Chakra S., Swanton, Charles, Solinas, Cinzia, Hiley, Crispin, Drubay, Damien, Bethmann, Daniel, Moore, David A., Larsimont, Denis, Sabanathan, Dhanusha, Peeters, Dieter, Zardavas, Dimitrios, Höflmayer, Doris, Johnson, Douglas B., Thompson, E. Aubrey, Brogi, Edi, Perez, Edith, ElGabry, Ehab A., Stovgaard, Elisabeth Specht, Blackley, Elizabeth F., Roblin, Elvire, Reisenbichler, Emily, Bellolio, Enrique, Balslev, Eva, Chmielik, Ewa, Gaire, Fabien, Andre, Fabrice, Lu, Fang-I, Azmoudeh-Ardalan, Farid, Rojo, Federico, Gruosso, Tina, Ciompi, Francesco, Peale, Franklin, Hirsch, Fred R., Klauschen, Frederick, Penault-Llorca, Frédérique, Acosta Haab, Gabriela, Farshid, Gelareh, Van Den Eynden, Gert, Curigliano, Giuseppe, Floris, Giuseppe, Broeckx, Glenn, Gonzalez-Ericsson, Koeppen, Harmut, Haynes, Harry R., McArthur, Heather, Joensuu, Heikki, Olofsson, Helena, Lien, Huang-Chun, Chen, I-Chun, Cree, Ian, Frahm, Isabel, Brcic, Iva, Chan, Jack, Ziai, James, Brock, Jane, Wesseling, Jelle, Giltnane, Jennifer, Kerner, Jennifer K., Thagaard, Jeppe, Braybrooke, Jeremy P., Van Der Laak, Jeroen A. W. M., Lemonnier, Jerome, Zha, Jiping, Ribeiro, Joana, Lennerz, Jochen K., Carter, Jodi M., Saltz, Joel, Hartman, Johan, Hainfellner, Johannes, Quesne, John Le, Juco, Jonathon W., Reis-Filho, Jorge, Sanchez, Joselyn, Sparano, Joseph, Cucherousset, Joël, Araya, Juan Carlos, Adam, Julien, Balko, Justin M., Saeger, Kai, Siziopikou, Kalliopi, Willard-Gallo, Karen, Weber, Karsten, Pogue-Geile, Katherine L., Steele, Keith E., Emancipator, Kenneth, AbdulJabbar, Khalid, El Bairi, Khalid, Blenman, Kim R. M., Allison, Kimberly H., Korski, Konstanty, Pusztai, Lajos, Comerma, Laura, Buisseret, Laurence, Cooper, Lee A. D., Shi, Leming, Kooreman, Loes F. S., Molinero, Luciana, Estrada, M. Valeria, Lacroix-Triki, Magali, Al Bakir, Maise, Sebastian, Manu M., Van De Vijver, Marc, Balancin, Marcelo Luiz, Dieci, Maria Vittoria, Mathieu, Marie-Christine, Rebelatto, Marlon C., Piccart, Martine, Hanna, Matthew G., Goetz, Matthew P., Preusser, Matthias, Khojasteh, Mehrnoush, Sanders, Melinda E., Regan, Meredith M., Barnes, Michael, Christie, Michael, Misialek, Michael, Ignatiadis, Michail, Van Bockstal, Mieke, Castillo, Miluska, Amgad, Mohamed, Harbeck, Nadia, Tung, Nadine, Laudus, Nele, Sirtaine, Nicolas, Burchardi, Nicole, Ternes, Nils, Radosevic-Robin, Nina, Gluz, Oleg, Grimm, Oliver, Nuciforo, Paolo, Jank, Paul, Gonzalez-Ericsson, Paula, Kirtani, Pawan, Jelinic, Petar, Watson, Peter H., Savas, Peter, Francis, Prudence A., Russell, Prudence A., Singh, Rajendra, Kim, Rim S., Pierce, Robert H., Hills, Robert, Leon-Ferre, Roberto, De Wind, Roland, Shui, Ruohong, De Clercq, Sabine, Leung, Sam, Tabbarah, Sami, Souza, Sandra C., O’Toole, Sandra, Swain, Sandra, Dudgeon, Sarah, Willis, Scooter, Ely, Scott, Kim, Seong-Rim, Bedri, Shahinaz, Irshad, Sheeba, Liu, Shi-Wei, Goel, Shom, Hendry, Shona, Bianchi, Simonetta, Bragança, Sofia, Paik, Soonmyung, Wienert, Stephan, Fox, Stephen B., Luen, Stephen J., Naber, Stephen, Schnitt, Stuart J., Sua, Luz F., Lakhani, Sunil R., Fineberg, Susan, Soler, Teresa, Gevaert, Thomas, D’Alfonso, Timothy, John, Tom, Sugie, Tomohagu, Kurkure, Uday, Bossuyt, Veerle, Manem, Venkata, Cámara, Vincente Peg, Tong, Weida, Chen, Weijie, Yang, Wentao, Tran, William T., Wang, Yihong, Yuan, Yinyin, Allory, Yves, Husain, Zaheed, and Bago-Horvath, Zsuzsanna

Subjects
692/53, review-article, Review Article, 631/67/1347, 692/4028/67/580, 631/67/1857, 3. Good health
Abstract

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006, Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting.

39. Monomorphic epitheliotropic intestinal T-cell lymphoma comprises morphologic and genomic heterogeneity impacting outcome.

Author

Veloza L, Cavalieri D, Missiaglia E, Ledoux-Pilon A, Bisig B, Pereira B, Bonnet C, Poullot E, Quintanilla-Martinez L, Dubois R, Llamas-Gutierrez F, Bossard C, De Wind R, Drieux F, Fontaine J, Parrens M, Sandrini J, Fataccioli V, Delfau-Larue MH, Daniel A, Lhomme F, Clément-Filliatre L, Lemonnier F, Cairoli A, Morel P, Glaisner S, Joly B, El Yamani A, Laribi K, Bachy E, Siebert R, Vallois D, Gaulard P, Tournilhac O, and De Leval L

Subjects
Male, Female, Humans, Aged, Genomics, Mutation, Signal Transduction, Enteropathy-Associated T-Cell Lymphoma genetics, Enteropathy-Associated T-Cell Lymphoma metabolism, Enteropathy-Associated T-Cell Lymphoma pathology
Abstract

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.

Published
2023
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