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5. Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma – A DAHANCA 19 study

Author

Kristensen, Morten Horsholt, Sørensen, Mia Kristina, Tramm, Trine, Alsner, Jan, Sørensen, Brita Singers, Maare, Christian, Johansen, Jørgen, Primdahl, Hanne, Bratland, Åse, Kristensen, Claus Andrup, Andersen, Maria, Lilja-Fischer, Jacob Kinggaard, Holm, Anne Ivalu Sander, Samsøe, Eva, Hansen, Christian Rønn, Zukauskaite, Ruta, Overgaard, Jens, and Eriksen, Jesper Grau

Published
2024
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8. The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus

Author

Kaidar-Person, Orit, Pfob, André, Gentilini, Oreste Davide, Borisch, Bettina, Bosch, Ana, Cardoso, Maria João, Curigliano, Giuseppe, De Boniface, Jana, Denkert, Carsten, Hauser, Nik, Heil, Jörg, Knauer, Michael, Kühn, Thorsten, Lee, Han-Byoel, Loibl, Sibylle, Mannhart, Meinrad, Meattini, Icro, Montagna, Giacomo, Pinker, Katja, Poulakaki, Fiorita, Rubio, Isabel T., Sager, Patrizia, Steyerova, Petra, Tausch, Christoph, Tramm, Trine, Vrancken Peeters, Marie-Jeanne, Wyld, Lynda, Yu, Jong Han, Weber, Walter Paul, Poortmans, Philip, and Dubsky, Peter

Published
2023
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9. Pathology Report

Author

Tramm, Trine, Moinfar, Farid, Kaidar-Person, Orit, editor, Meattini, Icro, editor, and Poortmans, Philip, editor

Published
2022
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16. Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., Rahman, Arman, Pathologie, Cancer, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., and Rahman, Arman

Published
2024

17. Image-based multiplex immune profiling of cancer tissues:translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer

Author

Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., Rahman, Arman, Jahangir, Chowdhury Arif, Page, David B., Broeckx, Glenn, Gonzalez, Claudia A., Burke, Caoimbhe, Murphy, Clodagh, Reis-Filho, Jorge S., Ly, Amy, Harms, Paul W., Gupta, Rajarsi R., Vieth, Michael, Hida, Akira I., Kahila, Mohamed, Kos, Zuzana, van Diest, Paul J., Verbandt, Sara, Thagaard, Jeppe, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Adams, Sylvia, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Chardas, Alexandros, Cheang, Maggie Chon U., Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N., Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hewitt, Stephen, Horlings, Hugo M., Husain, Zaheed, Irshad, Sheeba, Janssen, Emiel A.M., Kataoka, Tatsuki R., Kawaguchi, Kosuke, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Akturk, Guray, Scott, Ely, Kovács, Anikó, Lænkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Kharidehal, Durga, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Ribeiro, Joana M., Rimm, David, Vincent-Salomon, Anne, Saltz, Joel, Sayed, Shahin, Hytopoulos, Evangelos, Mahon, Sarah, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, Verghese, Gregory E., Viale, Giuseppe, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Specht Stovgaard, Elisabeth, Salgado, Roberto, Gallagher, William M., and Rahman, Arman

Abstract

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer.

Published
2024

18. A Novel and Reliable Pixel Response Correction Method (DAC-Shifting) for Spectral Photon-Counting CT Imaging.

Author

Bal, Navrit Johan Singh, Chitra Ragupathy, Imaiyan, Tramm, Trine, and Nijkamp, Jasper

Subjects
DUAL energy CT (Tomography), CONE beam computed tomography, SPECTRAL sensitivity, COMPUTED tomography, SPECTRAL imaging
Abstract

Spectral photon-counting cone-beam computed tomography (CT) imaging is challenged by individual pixel response behaviours, which lead to noisy projection images and subsequent image artefacts like rings. Existing methods to correct for this either use calibration measurements, like signal-to-thickness calibration (STC), or perform a post-processing ring artefact correction of sinogram data or scan reconstructions without taking the pixel response explicitly into account. Here, we present a novel post-processing method (digital-to-analogue converter (DAC)-shifting) which explicitly measures the current pixel response using flat-field images and subsequently corrects the projection data. The DAC-shifting method was evaluated using a repeat series of the spectral photon-counting imaging (Medipix3) of a phantom with different density inserts and iodine K-edge imaging. The method was also compared against polymethyl methacrylate (PMMA)-based STC. The DAC-shifting method was shown to be effective in correcting individual pixel responses and was robust against detector instability; it led to a 47.4% average reduction in CT-number variation in homogeneous materials, with a range of 40.7–55.6%. On the contrary, the STC correction showed varying results; a 13.7% average reduction in CT-number variation, ranging from a 43.7% increase to a 45.5% reduction. In K-edge imaging, DAC-shifting provides a sharper attenuation peak and more uniform CT values, which are expected to benefit iodine concentration quantifications. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer

Author

Jahangir, Chowdhury Arif, primary, Page, David B, additional, Broeckx, Glenn, additional, Gonzalez, Claudia A, additional, Burke, Caoimbhe, additional, Murphy, Clodagh, additional, Reis‐Filho, Jorge S, additional, Ly, Amy, additional, Harms, Paul W, additional, Gupta, Rajarsi R, additional, Vieth, Michael, additional, Hida, Akira I, additional, Kahila, Mohamed, additional, Kos, Zuzana, additional, van Diest, Paul J, additional, Verbandt, Sara, additional, Thagaard, Jeppe, additional, Khiroya, Reena, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Adams, Sylvia, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Burgues, Octavio, additional, Chardas, Alexandros, additional, Cheang, Maggie Chon U, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Dudgeon, Sarah N, additional, Elghazawy, Mahmoud, additional, Fernandez‐Martín, Claudio, additional, Fineberg, Susan, additional, Fox, Stephen B, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hewitt, Stephen, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Akturk, Guray, additional, Scott, Ely, additional, Kovács, Anikó, additional, Lænkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Kharidehal, Durga, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Vincent‐Salomon, Anne, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Hytopoulos, Evangelos, additional, Mahon, Sarah, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Bartlett, John, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Specht Stovgaard, Elisabeth, additional, Salgado, Roberto, additional, Gallagher, William M, additional, and Rahman, Arman, additional

Published
2024
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20. The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen‐receptor positive tumors

Author

Quigley, David A, Fiorito, Elisa, Nord, Silje, Van Loo, Peter, Alnæs, Grethe Grenaker, Fleischer, Thomas, Tost, Jorg, Vollan, Hans Kristian Moen, Tramm, Trine, Overgaard, Jens, Bukholm, Ida R, Hurtado, Antoni, Balmain, Allan, Børresen-Dale, Anne-Lise, and Kristensen, Vessela

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Aging, Breast Cancer, Human Genome, Estrogen, Cancer, Genetics, Prevention, 2.1 Biological and endogenous factors, Aetiology, Alleles, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasm Proteins, Quantitative Trait Loci, Receptors, Estrogen, Breast cancer, Expression Quantitative Trait Locus, chromatin, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. We conducted a genome-wide expression Quantitative Trait Locus (eQTL) study in a discovery set of 287 breast tumors and 97 normal mammary tissue samples and a replication set of 235 breast tumors. We found that the risk-associated allele of rs7716600 in the 5p12 estrogen receptor-positive (ER-positive) susceptibility locus was associated with elevated expression of the nearby gene MRPS30 exclusively in ER-positive tumors. We replicated this finding in 235 independent tumors. Further, we showed the rs7716600 risk genotype was associated with decreased MRPS30 promoter methylation exclusively in ER-positive breast tumors. In vitro studies in MCF-7 cells carrying the protective genotype showed that estrogen stimulation decreased MRPS30 promoter chromatin availability and mRNA levels. In contrast, in 600MPE cells carrying the risk genotype, estrogen increased MRPS30 expression and did not affect promoter availability. Our data suggest the 5p12 risk allele affects MRPS30 expression in estrogen-responsive tumor cells after tumor initiation by a mechanism affecting chromatin availability. These studies emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles.

Published
2014

21. Factors affecting lymph node yield and density in neck dissection.

Author

Hanberg, Pelle, Tramm, Trine, Pikelis, Arunas, Schytte, Sten, Gade, Søren Dürr, and Klug, Tejs Ehlers

Subjects
*LYMPH nodes, *MOUTH tumors, *CYTODIAGNOSIS, *RADIOTHERAPY, *BODY mass index, *LYMPHADENECTOMY, *BODY weight, *MULTIVARIATE analysis, *LONGITUDINAL method, *METASTASIS, *ELECTIVE surgery, *STATISTICS, *CONFIDENCE intervals, *NECK surgery
Abstract

Background: Studies suggest that neck dissections with a minimum of 16–18 yielded nodes are associated with better overall survival compared to neck dissections with lower yields. Aims: We aimed to identify factors affecting the lymph node yield and density in patients with oral cavity cancer undergoing elective neck dissection levels 1–3. Materials and methods: Using prospectively registered data, we conducted a population-based cohort study on all patients surgically treated for oral cavity cancer including levels 1–3 neck dissection at our institution from 2018 to 2022. Uni and multivariate analyses were performed to identify factors associated with lymph node yields. Results: In total, 221 patients were included. The mean lymph nodes yield and density were 19 (95%CI 18–20) and 0.12 (95%CI 0.09–0.16), respectively. In multivariate analysis, increasing body weight (p =.034) was positively and previous radiotherapy (p =.006) were negatively correlated with the number of yielded lymph nodes. Lymph node density was positively correlated with body weight (p =.011) and body mass index (p =.032) in univariate analysis. Conclusions and significance: Increasing body weight was positively and previous radiotherapy was negatively correlated to lymph node yield. These factors should be taken into consideration when interpreting the lymph node yield as an indicator of neck dissection quality. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Antibodies toward Na+,HCO3–-cotransporter NBCn1/SLC4A7 block net acid extrusion and cause pH-dependent growth inhibition and apoptosis in breast cancer.

Author

Axelsen, Trine V., Olesen, Claus, Khan, Danish, Mohammadi, Ali, Bouzinova, Elena V., Nielsen, Christine J. F., Mele, Marco, Hauerslev, Katrine R., Pedersen, Helene L., Balling, Eva, Vahl, Pernille, Tramm, Trine, Christiansen, Peer M., and Boedtkjer, Ebbe

Abstract

Background: Na+,HCO3–-cotransporter NBCn1/Slc4a7 accelerates murine breast carcinogenesis. Lack of specific pharmacological tools previously restricted therapeutic targeting of NBCn1 and identification of NBCn1-dependent functions in human breast cancer. Methods: We develop extracellularly-targeted anti-NBCn1 antibodies, screen for functional activity on cells, and evaluate (a) mechanisms of intracellular pH regulation in human primary breast carcinomas, (b) proliferation, cell death, and tumor growth consequences of NBCn1 in triple-negative breast cancer, and (c) association of NBCn1-mediated Na+,HCO3–-cotransport with human breast cancer metastasis. Results: We identify high-affinity (KD ≈ 0.14 nM) anti-NBCn1 antibodies that block human NBCn1-mediated Na+,HCO3–-cotransport in cells, without cross-reactivity towards human NBCe1 or murine NBCn1. These anti-NBCn1 antibodies abolish Na+,HCO3–-cotransport activity in freshly isolated primary organoids from human breast carcinomas and lower net acid extrusion effectively in primary breast cancer tissue from patients with macrometastases in axillary lymph nodes. Inhibitory anti-NBCn1 antibodies decelerate tumor growth in vivo by ~50% in a patient-derived xenograft model of triple-negative breast cancer and pH-dependently reduce colony formation, cause G2/M-phase cell cycle accumulation, and increase apoptosis of metastatic triple-negative breast cancer cells in vitro. Conclusions: Inhibitory anti-NBCn1 antibodies block net acid extrusion in human breast cancer tissue, particularly from patients with disseminated disease, and pH-dependently limit triple-negative breast cancer growth. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Increased lesion detectability in patients with locally advanced breast cancer—A pilot study using dynamic whole-body [18F]FDG PET/CT.

Author

Pedersen, Mette Abildgaard, Dias, André H., Hjorthaug, Karin, Gormsen, Lars C., Fledelius, Joan, Johnsson, Anna Lyhne, Borgquist, Signe, Tramm, Trine, Munk, Ole Lajord, and Vendelbo, Mikkel Holm

Subjects
CANCER patients, MAGNETIC resonance mammography, SENTINEL lymph node biopsy, METASTATIC breast cancer, POSITRON emission tomography, COMPUTED tomography
Abstract

Background: Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning in breast cancer. Evaluation of ALN is done by ultrasound, which is limited by inter-operator variability, and by sentinel lymph node biopsy and/or ALN dissection, none of which are without risks and/or long-term complications. It is known that conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limited sensitivity for ALN metastases. However, a recently developed dynamic whole-body (D-WB) [18F]FDG PET/CT scanning protocol, allowing for imaging of tissue [18F]FDG metabolic rate (MRFDG), has been shown to have the potential to increase lesion detectability. The study purpose was to examine detectability of malignant lesions in D-WB [18F]FDG PET/CT compared to conventional [18F]FDG PET/CT. Results: This study prospectively included ten women with locally advanced breast cancer who were referred for an [18F]FDG PET/CT as part of their diagnostic work-up. They all underwent D-WB [18F]FDG PET/CT, consisting of a 6 min single bed dynamic scan over the chest region started at the time of tracer injection, a 64 min dynamic WB PET scan consisting of 16 continuous bed motion passes, and finally a contrast-enhanced CT scan, with generation of MRFDG parametric images. Lesion visibility was assessed by tumor-to-background and contrast-to-noise ratios using volumes of interest isocontouring tumors with a set limit of 50% of SUVmax and background volumes placed in the vicinity of tumors. Lesion visibility was best in the MRFDG images, with target-to-background values 2.28 (95% CI: 2.04–2.54) times higher than target-to-background values in SUV images, and contrast-to-noise values 1.23 (95% CI: 1.12–1.35) times higher than contrast-to-noise values in SUV images. Furthermore, five imaging experts visually assessed the images and three additional suspicious lesions were found in the MRFDG images compared to SUV images; one suspicious ALN, one suspicious parasternal lymph node, and one suspicious lesion located in the pelvic bone. Conclusions: D-WB [18F]FDG PET/CT with MRFDG images show potential for improved lesion detectability compared to conventional SUV images in locally advanced breast cancer. Further validation in larger cohorts is needed. Clinical trial registration: The trial is registered in clinicaltrials.gov, NCT05110443, https://www.clinicaltrials.gov/study/NCT05110443?term=NCT05110443&rank=1. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Dynamic whole-body [18F]FES PET/CT increases lesion visibility in patients with metastatic breast cancer.

Author

Pedersen, Mette A., Munk, Ole L., Dias, André H., Steffensen, Johanne H., Møller, Anders L., Johnsson, Anna Lyhne, Hansen, Kim Vang, Bender, Dirk, Jakobsen, Steen, Busk, Morten, Gormsen, Lars C., Tramm, Trine, Borgquist, Signe, and Vendelbo, Mikkel H.

Subjects
METASTATIC breast cancer, POSITRON emission tomography, MAGNETIC resonance mammography, COMPUTED tomography, ESTROGEN receptors
Abstract

Background: Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images ( K i ) are quantitative and improve lesion visibility. Results: This prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. K i values from Patlak parametric images correlated with K i values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric K i images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25–2.68) and CNR 1.17 (95% CI: 1.08–1.26) times higher in K i images compared to SUV images. These quantitative differences were seen as reduced background activity in the K i images. Conclusion: [18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric K i images, with superior lesion visibility and K i values comparable to K i values found from full kinetic analyses. This may aid correct ER classification and treatment decisions. Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731 [ABSTRACT FROM AUTHOR]

Published
2024
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28. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer

Author

Page, David B, primary, Broeckx, Glenn, additional, Jahangir, Chowdhury Arif, additional, Verbandt, Sara, additional, Gupta, Rajarsi R, additional, Thagaard, Jeppe, additional, Khiroya, Reena, additional, Kos, Zuzana, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Burgues, Octavio, additional, Cheang, Maggie Chon U, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Dudgeon, Sarah N, additional, Elghazawy, Mahmoud, additional, Ely, Scott, additional, Fernandez‐Martín, Claudio, additional, Fineberg, Susan, additional, Fox, Stephen B, additional, Gallagher, William M, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hardas, Alexandros, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hewitt, Stephen, additional, Hida, Akira I, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Hytopoulos, Evangelos, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kahila, Mohamed, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Kharidehal, Durga, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Kovács, Anikó, additional, Laenkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rahman, Arman, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Reis‐Filho, Jorge S, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Salomon, Anne‐Vincent, additional, Salto‐Tellez, Manuel, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, van Diest, Paul J, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Vieth, Michael, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Adams, Sylvia, additional, Bartlett, John Mark Seaverns, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Salgado, Roberto, additional, Specht Stovgaard, Elisabeth, additional, Akturk, Guray, additional, and Bouchmaa, Najat, additional

Published
2023
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29. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

Author

Thagaard, Jeppe, primary, Broeckx, Glenn, additional, Page, David B, additional, Jahangir, Chowdhury Arif, additional, Verbandt, Sara, additional, Kos, Zuzana, additional, Gupta, Rajarsi, additional, Khiroya, Reena, additional, Abduljabbar, Khalid, additional, Acosta Haab, Gabriela, additional, Acs, Balazs, additional, Akturk, Guray, additional, Almeida, Jonas S, additional, Alvarado‐Cabrero, Isabel, additional, Amgad, Mohamed, additional, Azmoudeh‐Ardalan, Farid, additional, Badve, Sunil, additional, Baharun, Nurkhairul Bariyah, additional, Balslev, Eva, additional, Bellolio, Enrique R, additional, Bheemaraju, Vydehi, additional, Blenman, Kim RM, additional, Botinelly Mendonça Fujimoto, Luciana, additional, Bouchmaa, Najat, additional, Burgues, Octavio, additional, Chardas, Alexandros, additional, Chon U Cheang, Maggie, additional, Ciompi, Francesco, additional, Cooper, Lee AD, additional, Coosemans, An, additional, Corredor, Germán, additional, Dahl, Anders B, additional, Dantas Portela, Flavio Luis, additional, Deman, Frederik, additional, Demaria, Sandra, additional, Doré Hansen, Johan, additional, Dudgeon, Sarah N, additional, Ebstrup, Thomas, additional, Elghazawy, Mahmoud, additional, Fernandez‐Martín, Claudio, additional, Fox, Stephen B, additional, Gallagher, William M, additional, Giltnane, Jennifer M, additional, Gnjatic, Sacha, additional, Gonzalez‐Ericsson, Paula I, additional, Grigoriadis, Anita, additional, Halama, Niels, additional, Hanna, Matthew G, additional, Harbhajanka, Aparna, additional, Hart, Steven N, additional, Hartman, Johan, additional, Hauberg, Søren, additional, Hewitt, Stephen, additional, Hida, Akira I, additional, Horlings, Hugo M, additional, Husain, Zaheed, additional, Hytopoulos, Evangelos, additional, Irshad, Sheeba, additional, Janssen, Emiel AM, additional, Kahila, Mohamed, additional, Kataoka, Tatsuki R, additional, Kawaguchi, Kosuke, additional, Kharidehal, Durga, additional, Khramtsov, Andrey I, additional, Kiraz, Umay, additional, Kirtani, Pawan, additional, Kodach, Liudmila L, additional, Korski, Konstanty, additional, Kovács, Anikó, additional, Laenkholm, Anne‐Vibeke, additional, Lang‐Schwarz, Corinna, additional, Larsimont, Denis, additional, Lennerz, Jochen K, additional, Lerousseau, Marvin, additional, Li, Xiaoxian, additional, Ly, Amy, additional, Madabhushi, Anant, additional, Maley, Sai K, additional, Manur Narasimhamurthy, Vidya, additional, Marks, Douglas K, additional, McDonald, Elizabeth S, additional, Mehrotra, Ravi, additional, Michiels, Stefan, additional, Minhas, Fayyaz ul Amir Afsar, additional, Mittal, Shachi, additional, Moore, David A, additional, Mushtaq, Shamim, additional, Nighat, Hussain, additional, Papathomas, Thomas, additional, Penault‐Llorca, Frederique, additional, Perera, Rashindrie D, additional, Pinard, Christopher J, additional, Pinto‐Cardenas, Juan Carlos, additional, Pruneri, Giancarlo, additional, Pusztai, Lajos, additional, Rahman, Arman, additional, Rajpoot, Nasir Mahmood, additional, Rapoport, Bernardo Leon, additional, Rau, Tilman T, additional, Reis‐Filho, Jorge S, additional, Ribeiro, Joana M, additional, Rimm, David, additional, Roslind, Anne, additional, Vincent‐Salomon, Anne, additional, Salto‐Tellez, Manuel, additional, Saltz, Joel, additional, Sayed, Shahin, additional, Scott, Ely, additional, Siziopikou, Kalliopi P, additional, Sotiriou, Christos, additional, Stenzinger, Albrecht, additional, Sughayer, Maher A, additional, Sur, Daniel, additional, Fineberg, Susan, additional, Symmans, Fraser, additional, Tanaka, Sunao, additional, Taxter, Timothy, additional, Tejpar, Sabine, additional, Teuwen, Jonas, additional, Thompson, E Aubrey, additional, Tramm, Trine, additional, Tran, William T, additional, van der Laak, Jeroen, additional, van Diest, Paul J, additional, Verghese, Gregory E, additional, Viale, Giuseppe, additional, Vieth, Michael, additional, Wahab, Noorul, additional, Walter, Thomas, additional, Waumans, Yannick, additional, Wen, Hannah Y, additional, Yang, Wentao, additional, Yuan, Yinyin, additional, Zin, Reena Md, additional, Adams, Sylvia, additional, Bartlett, John, additional, Loibl, Sibylle, additional, Denkert, Carsten, additional, Savas, Peter, additional, Loi, Sherene, additional, Salgado, Roberto, additional, and Specht Stovgaard, Elisabeth, additional

Published
2023
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31. Supplementary Tables 1-5 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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34. Supplementary Document 1 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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35. Supplementary Figure 1 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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37. Supplementary Document 2 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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38. Supplementary Figure 3 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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39. Supplementary Figure 2 from Development and Validation of a Gene Profile Predicting Benefit of Postmastectomy Radiotherapy in Patients with High-Risk Breast Cancer: A Study of Gene Expression in the DBCG82bc Cohort

Author

Tramm, Trine, primary, Mohammed, Hayat, primary, Myhre, Simen, primary, Kyndi, Marianne, primary, Alsner, Jan, primary, Børresen-Dale, Anne-Lise, primary, Sørlie, Therese, primary, Frigessi, Arnoldo, primary, and Overgaard, Jens, primary

Published
2023
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42. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer:A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Abstract

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer.

Published
2023

43. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Pathologie, Cancer, Thagaard, Jeppe, Broeckx, Glenn, Page, David B, Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dahl, Anders B, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N, Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hart, Steven N, Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Published
2023

44. Spatial analyses of immune cell infiltration in cancer: current methods and future directions. A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer

Author

Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, Bouchmaa, Najat, Pathologie, Cancer, Page, David B, Broeckx, Glenn, Jahangir, Chowdhury Arif, Verbandt, Sara, Gupta, Rajarsi R, Thagaard, Jeppe, Khiroya, Reena, Kos, Zuzana, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Almeida, Jonas S, Alvarado-Cabrero, Isabel, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Bellolio, Enrique R, Bheemaraju, Vydehi, Blenman, Kim Rm, Botinelly Mendonça Fujimoto, Luciana, Burgues, Octavio, Cheang, Maggie Chon U, Ciompi, Francesco, Cooper, Lee Ad, Coosemans, An, Corredor, Germán, Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Dudgeon, Sarah N, Elghazawy, Mahmoud, Ely, Scott, Fernandez-Martín, Claudio, Fineberg, Susan, Fox, Stephen B, Gallagher, William M, Giltnane, Jennifer M, Gnjatic, Sacha, Gonzalez-Ericsson, Paula I, Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G, Harbhajanka, Aparna, Hardas, Alexandros, Hart, Steven N, Hartman, Johan, Hewitt, Stephen, Hida, Akira I, Horlings, Hugo M, Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel Am, Kahila, Mohamed, Kataoka, Tatsuki R, Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I, Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L, Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne-Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K, Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K, Manur Narasimhamurthy, Vidya, Marks, Douglas K, McDonald, Elizabeth S, Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz Ul Amir Afsar, Mittal, Shachi, Moore, David A, Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D, Pinard, Christopher J, Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T, Reis-Filho, Jorge S, Ribeiro, Joana M, Rimm, David, Salomon, Anne-Vincent, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Siziopikou, Kalliopi P, Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A, Sur, Daniel, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E Aubrey, Tramm, Trine, Tran, William T, van der Laak, Jeroen, van Diest, Paul J, Verghese, Gregory E, Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y, Yang, Wentao, Yuan, Yinyin, Adams, Sylvia, Bartlett, John Mark Seaverns, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Akturk, Guray, and Bouchmaa, Najat

Published
2023

45. Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer:a report of the international immuno-oncology biomarker working group

Author

Thagaard, Jeppe, Broeckx, Glenn, Page, David B., Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dahl, Anders B., Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N., Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B., Gallagher, William M., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I., Horlings, Hugo M., Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel A.M., Kahila, Mohamed, Kataoka, Tatsuki R., Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Reis-Filho, Jorge S., Ribeiro, Joana M., Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, van Diest, Paul J., Verghese, Gregory E., Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, Specht Stovgaard, Elisabeth, Thagaard, Jeppe, Broeckx, Glenn, Page, David B., Jahangir, Chowdhury Arif, Verbandt, Sara, Kos, Zuzana, Gupta, Rajarsi, Khiroya, Reena, Abduljabbar, Khalid, Acosta Haab, Gabriela, Acs, Balazs, Akturk, Guray, Almeida, Jonas S., Alvarado-Cabrero, Isabel, Amgad, Mohamed, Azmoudeh-Ardalan, Farid, Badve, Sunil, Baharun, Nurkhairul Bariyah, Balslev, Eva, Bellolio, Enrique R., Bheemaraju, Vydehi, Blenman, Kim R.M., Botinelly Mendonça Fujimoto, Luciana, Bouchmaa, Najat, Burgues, Octavio, Chardas, Alexandros, Chon U Cheang, Maggie, Ciompi, Francesco, Cooper, Lee A.D., Coosemans, An, Corredor, Germán, Dahl, Anders B., Dantas Portela, Flavio Luis, Deman, Frederik, Demaria, Sandra, Doré Hansen, Johan, Dudgeon, Sarah N., Ebstrup, Thomas, Elghazawy, Mahmoud, Fernandez-Martín, Claudio, Fox, Stephen B., Gallagher, William M., Giltnane, Jennifer M., Gnjatic, Sacha, Gonzalez-Ericsson, Paula I., Grigoriadis, Anita, Halama, Niels, Hanna, Matthew G., Harbhajanka, Aparna, Hart, Steven N., Hartman, Johan, Hauberg, Søren, Hewitt, Stephen, Hida, Akira I., Horlings, Hugo M., Husain, Zaheed, Hytopoulos, Evangelos, Irshad, Sheeba, Janssen, Emiel A.M., Kahila, Mohamed, Kataoka, Tatsuki R., Kawaguchi, Kosuke, Kharidehal, Durga, Khramtsov, Andrey I., Kiraz, Umay, Kirtani, Pawan, Kodach, Liudmila L., Korski, Konstanty, Kovács, Anikó, Laenkholm, Anne Vibeke, Lang-Schwarz, Corinna, Larsimont, Denis, Lennerz, Jochen K., Lerousseau, Marvin, Li, Xiaoxian, Ly, Amy, Madabhushi, Anant, Maley, Sai K., Manur Narasimhamurthy, Vidya, Marks, Douglas K., McDonald, Elizabeth S., Mehrotra, Ravi, Michiels, Stefan, Minhas, Fayyaz ul Amir Afsar, Mittal, Shachi, Moore, David A., Mushtaq, Shamim, Nighat, Hussain, Papathomas, Thomas, Penault-Llorca, Frederique, Perera, Rashindrie D., Pinard, Christopher J., Pinto-Cardenas, Juan Carlos, Pruneri, Giancarlo, Pusztai, Lajos, Rahman, Arman, Rajpoot, Nasir Mahmood, Rapoport, Bernardo Leon, Rau, Tilman T., Reis-Filho, Jorge S., Ribeiro, Joana M., Rimm, David, Roslind, Anne, Vincent-Salomon, Anne, Salto-Tellez, Manuel, Saltz, Joel, Sayed, Shahin, Scott, Ely, Siziopikou, Kalliopi P., Sotiriou, Christos, Stenzinger, Albrecht, Sughayer, Maher A., Sur, Daniel, Fineberg, Susan, Symmans, Fraser, Tanaka, Sunao, Taxter, Timothy, Tejpar, Sabine, Teuwen, Jonas, Thompson, E. Aubrey, Tramm, Trine, Tran, William T., van der Laak, Jeroen, van Diest, Paul J., Verghese, Gregory E., Viale, Giuseppe, Vieth, Michael, Wahab, Noorul, Walter, Thomas, Waumans, Yannick, Wen, Hannah Y., Yang, Wentao, Yuan, Yinyin, Zin, Reena Md, Adams, Sylvia, Bartlett, John, Loibl, Sibylle, Denkert, Carsten, Savas, Peter, Loi, Sherene, Salgado, Roberto, and Specht Stovgaard, Elisabeth

Abstract

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer.

Published
2023

48. HPV testing versus p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: results from the DAHANCA 19 study.

Author

Lilja-Fischer, Jacob Kinggaard, Kristensen, Morten Horsholt, Lassen, Pernille, Steiniche, Torben, Tramm, Trine, Stougaard, Magnus, Maare, Christian, Johansen, Jørgen, Primdahl, Hanne, Kristensen, Claus Andrup, Andersen, Maria, Eriksen, Jesper Grau, and Overgaard, Jens

Subjects
DNA analysis, RESEARCH, PAPILLOMAVIRUSES, CONFIDENCE intervals, IMMUNOHISTOCHEMISTRY, LOG-rank test, OROPHARYNGEAL cancer, EARLY detection of cancer, RANDOMIZED controlled trials, CANCER patients, PAPILLOMAVIRUS diseases, RESEARCH funding, DESCRIPTIVE statistics, DATA analysis software, SQUAMOUS cell carcinoma, LONGITUDINAL method
Abstract

The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected. Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator. [ABSTRACT FROM AUTHOR]

Published
2023
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