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221 results on '"Acs, Balazs"'

2. Comparing deep learning and pathologist quantification of cell-level PD-L1 expression in non-small cell lung cancer whole-slide images

Author

van Eekelen, Leander, Spronck, Joey, Looijen-Salamon, Monika, Vos, Shoko, Munari, Enrico, Girolami, Ilaria, Eccher, Albino, Acs, Balazs, Boyaci, Ceren, de Souza, Gabriel Silva, Demirel-Andishmand, Muradije, Meesters, Luca Dulce, Zegers, Daan, van der Woude, Lieke, Theelen, Willemijn, van den Heuvel, Michel, Grünberg, Katrien, van Ginneken, Bram, van der Laak, Jeroen, and Ciompi, Francesco

Published
2024
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3. Increasing the usefulness of already existing annotations through WSI registration

Author

Weitz, Philippe, Sartor, Viktoria, Acs, Balazs, Robertson, Stephanie, Budelmann, Daniel, Hartman, Johan, and Rantalainen, Mattias

Subjects
Computer Science - Computer Vision and Pattern Recognition, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

Computational pathology methods have the potential to improve access to precision medicine, as well as the reproducibility and accuracy of pathological diagnoses. Particularly the analysis of whole-slide-images (WSIs) of immunohistochemically (IHC) stained tissue sections could benefit from computational pathology methods. However, scoring biomarkers such as KI67 in IHC WSIs often necessitates the detection of areas of invasive cancer. Training cancer detection models often requires annotations, which is time-consuming and therefore costly. Currently, cancer regions are typically annotated in WSIs of haematoxylin and eosin (H&E) stained tissue sections. In this study, we investigate the possibility to register annotations that were made in H&E WSIs to their IHC counterparts. Two pathologists annotated regions of invasive cancer in WSIs of 272 breast cancer cases. For each case, a matched H&E and KI67 WSI are available, resulting in 544 WSIs with invasive cancer annotations. We find that cancer detection CNNs that were trained with annotations registered from the H&E to the KI67 WSIs only differ slightly in calibration but not in performance compared to cancer detection models trained on annotations made directly in the KI67 WSIs in a test set consisting of 54 cases. The mean slide-level AUROC is 0.974 [0.964, 0.982] for models trained with the KI67 annotations and 0.974 [0.965, 0.982] for models trained using registered annotations. This indicates that WSI registration has the potential to reduce the need for IHC-specific annotations. This could significantly increase the usefulness of already existing annotations.

Published
2023

4. Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

Author

Acs, Balazs, Leung, Samuel CY, Kidwell, Kelley M, Arun, Indu, Augulis, Renaldas, Badve, Sunil S, Bai, Yalai, Bane, Anita L, Bartlett, John MS, Bayani, Jane, Bigras, Gilbert, Blank, Annika, Buikema, Henk, Chang, Martin C, Dietz, Robin L, Dodson, Andrew, Fineberg, Susan, Focke, Cornelia M, Gao, Dongxia, Gown, Allen M, Gutierrez, Carolina, Hartman, Johan, Kos, Zuzana, Lænkholm, Anne-Vibeke, Laurinavicius, Arvydas, Levenson, Richard M, Mahboubi-Ardakani, Rustin, Mastropasqua, Mauro G, Nofech-Mozes, Sharon, Osborne, C Kent, Penault-Llorca, Frédérique M, Piper, Tammy, Quintayo, Mary Anne, Rau, Tilman T, Reinhard, Stefan, Robertson, Stephanie, Salgado, Roberto, Sugie, Tomoharu, van der Vegt, Bert, Viale, Giuseppe, Zabaglo, Lila A, Hayes, Daniel F, Dowsett, Mitch, Nielsen, Torsten O, and Rimm, David L

Subjects
Cancer, Clinical Research, Breast Cancer, Biomarkers, Tumor, Biopsy, Breast Neoplasms, Female, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Ki-67 Antigen, Receptors, Estrogen, International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group, Medical and Health Sciences, Pathology
Abstract

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

Published
2022

7. A Career in Football: What is Behind an Outstanding Market Value?

Author

Acs, Balazs, Toka, Laszlo, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Brefeld, Ulf, editor, Davis, Jesse, editor, Van Haaren, Jan, editor, and Zimmermann, Albrecht, editor

Published
2022
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8. Adherence to and optimization of guidelines for Risk of Recurrence/Prosigna testing using a machine learning model: a Swedish multicenter study

Author

Kjällquist, Una, primary, Tsiknakis, Nikolaos, additional, Acs, Balazs, additional, Margolin, Sara, additional, Kessler, Luisa Edman, additional, Levy, Scarlett, additional, Ekholm, Maria, additional, Lundgren, Christine, additional, Olsson, Erik, additional, Lindman, Henrik, additional, Valachis, Antonios, additional, Hartman, Johan, additional, Foukakis, Theodoros, additional, and Matikas, Alexios, additional

Published
2024
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9. Training pathologists to assess stromal tumour‐infiltrating lymphocytes in breast cancer synergises efforts in clinical care and scientific research

Author

Ly, Amy, primary, Garcia, Victor, additional, Blenman, Kim R M, additional, Ehinger, Anna, additional, Elfer, Katherine, additional, Hanna, Matthew G, additional, Li, Xiaoxian, additional, Peeters, Dieter J E, additional, Birmingham, Ryan, additional, Dudgeon, Sarah, additional, Gardecki, Emma, additional, Gupta, Rajarsi, additional, Lennerz, Jochen, additional, Pan, Tony, additional, Saltz, Joel, additional, Wharton, Keith A, additional, Ehinger, Daniel, additional, Acs, Balazs, additional, Dequeker, Elisabeth M C, additional, Salgado, Roberto, additional, and Gallas, Brandon D, additional

Published
2024
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11. Unveiling the Power of Model-Agnostic Multiscale Analysis for Enhancing Artificial Intelligence Models in Breast Cancer Histopathology Images

Author

Tsiknakis, Nikos, Manikis, Georgios, Tzoras, Evangelos, Salgkamis, Dimitrios, Vidal, Joan Martinez, Wang, Kang, Zaridis, Dimitris, Sifakis, Emmanouil, Zerdes, Ioannis, Bergh, Jonas, Hartman, Johan, Acs, Balazs, Marias, Kostas, and Foukakis, Theodoros

Abstract

Developing AI models for digital pathology has traditionally relied on single-scale analysis of histopathology slides. However, a whole slide image is a rich digital representation of the tissue, captured at various magnification levels. Limiting our analysis to a single scale overlooks critical information, spanning from intricate high-resolution cellular details to broad low-resolution tissue structures. In this study, we propose a model-agnostic multiresolution feature aggregation framework tailored for the analysis of histopathology slides in the context of breast cancer, on a multicohort dataset of 2038 patient samples. We have adapted 9 state-of-the-art multiple instance learning models on our multi-scale methodology and evaluated their performance on grade prediction, TP53 mutation status prediction and survival prediction. The results prove the dominance of the multiresolution methodology, and specifically, concatenating or linearly transforming via a learnable layer the feature vectors of image patches from a high (20x) and low (10x) magnification factors achieve improved performance for all prediction tasks across domain-specific and imagenet-based features. On the contrary, the performance of uniresolution baseline models was not consistent across domain-specific and imagenet-based features. Moreover, we shed light on the inherent inconsistencies observed in models trained on whole-tissue-sections when validated against biopsy-based datasets. Despite these challenges, our findings underscore the superiority of multiresolution analysis over uniresolution methods. Finally, cross-scale analysis also benefits the explainability aspects of attention-based architectures, since one can extract attention maps at the tissue- and cell-levels, improving the interpretation of the model's decision.

Published
2024
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12. Immune cell infiltrate in ductal carcinoma in situ and the risk of dying from breast cancer : case-control study

Author

Rask, Gunilla, Wadsten, Charlotta, Acs, Balazs, Hartman, Johan, Fredriksson, Irma, Garmo, Hans, Wärnberg, Fredrik, Sund, Malin, Rask, Gunilla, Wadsten, Charlotta, Acs, Balazs, Hartman, Johan, Fredriksson, Irma, Garmo, Hans, Wärnberg, Fredrik, and Sund, Malin

Abstract

Background: Studies identifying risk factors for death from breast cancer after ductal carcinoma in situ (DCIS) are rare. In this retrospective nested case-control study, clinicopathological factors in women treated for DCIS and who died from breast cancer were compared with those of patients with DCIS who were free from metastatic disease. Methods: The study included patients registered with DCIS without invasive carcinoma in Sweden between 1992 and 2012. This cohort was linked to the National Cause of Death Registry. Of 6964 women with DCIS, 96 were registered with breast cancer as cause of death (cases). For each case, up to four controls (318; women with DCIS, alive and without metastatic breast cancer at the time of death of the corresponding case) were selected randomly by incidence density sampling. Whole slides of tumour tissue were evaluated for DCIS grade, comedo necrosis, and intensity of periductal lymphocytic infiltrate. Composition of the immune cell infiltrate, expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki-67 were scored on tissue microarrays. Clinical information was obtained from medical records. Information on date, site, and histological characteristics of local and distant recurrences was obtained from medical records for both cases and controls. Results: Tumour tissue was analysed from 65 cases and 195 controls. Intense periductal lymphocytic infiltrate around DCIS was associated with an increased risk of later dying from breast cancer (OR 2.21. 95% c.i. 1.01 to 4.84). Tumours with more intense lymphocytic infiltrate had a lower T cell/B cell ratio. None of the other biomarkers correlated with increased risk of breast cancer death. Conclusion: The immune response to DCIS may influence the risk of dying from breast cancer.

Published
2024
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13. 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

14. 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

15. Quantitative assessment of PD-L1 as an analyte in immunohistochemistry diagnostic assays using a standardized cell line tissue microarray

Author

Martinez-Morilla, Sandra, McGuire, John, Gaule, Patricia, Moore, Lauren, Acs, Balazs, Cougot, Delphine, Gown, Allen M., Yaziji, Hadi, Wang, Wei-Lien, Cartun, Richard W., Hornick, Jason L., Sholl, Lynette M., Qiu, Jingxin, Mino-Kenudson, Mari, Yi, Eunhee S., Beasley, Mary Beth, Merrick, Daniel T., Ambaye, Abiy B., Zhang, Zhong J., Walker, Jill, and Rimm, David L.

Published
2020
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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

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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18. Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study

Author

Zerdes, Ioannis, Simonetti, Michele, Matikas, Alexios, Harbers, Luuk, Acs, Balazs, Boyaci, Ceren, Zhang, Ning, Salgkamis, Dimitrios, Agartz, Susanne, Moreno-Ruiz, Pablo, Bai, Yalai, Rimm, David L., Hartman, Johan, Mezheyeuski, Artur, Bergh, Jonas, Crosetto, Nicola, and Foukakis, Theodoros

Published
2021
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19. Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma

Author

Moore, Michael R., Friesner, Isabel D., Rizk, Emanuelle M., Fullerton, Benjamin T., Mondal, Manas, Trager, Megan H., Mendelson, Karen, Chikeka, Ijeuru, Kurc, Tahsin, Gupta, Rajarsi, Rohr, Bethany R., Robinson, Eric J., Acs, Balazs, Chang, Rui, Kluger, Harriet, Taback, Bret, Geskin, Larisa J., Horst, Basil, Gardner, Kevin, Niedt, George, Celebi, Julide T., Gartrell-Corrado, Robyn D., Messina, Jane, Ferringer, Tammie, Rimm, David L., Saltz, Joel, Wang, Jing, Vanguri, Rami, and Saenger, Yvonne M.

Published
2021
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22. Automated scoring of tumour infiltrating lymphocytes informs risk of death from thin melanoma: a nested case-case study

Author

Tan, Samuel X., primary, Aung, Thazin N., additional, Claeson, Magdalena, additional, Acs, Balazs, additional, Zhou, Chenhao, additional, Brown, Susan, additional, Lambie, Duncan, additional, Baade, Peter D., additional, Pandeya, Nirmala, additional, Soyer, H. Peter, additional, Smithers, B. Mark, additional, Whiteman, David C., additional, Rimm, David L., additional, and Khosrotehrani, Kiarash, additional

Published
2023
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23. 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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24. 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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30. Abstract 5432: Validation of spatial gene expression patterns predicted by deep convolutional neural networks from breast cancer histopathology images

Author

Ton, Kathy, primary, Wang, Yinxi, additional, Pan, Liuliu, additional, Kartasalo, Kimmo, additional, Acs, Balazs, additional, Weitz, Philippe, additional, Zhang, Liang, additional, Liang, Yan, additional, Hartman, Johan, additional, Volkonen, Masi, additional, Larsson, Christer, additional, Ruusuvuori, Pekka, additional, Beechem, Joseph, additional, and Rantalainen, Mattias, additional

Published
2023
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31. Supplementary Figure S2 from Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial

Author

Matikas, Alexios, primary, Johansson, Hemming, primary, Grybäck, Per, primary, Bjöhle, Judith, primary, Acs, Balazs, primary, Boyaci, Ceren, primary, Lekberg, Tobias, primary, Fredholm, Hanna, primary, Elinder, Ellinor, primary, Margolin, Sara, primary, Isaksson-Friman, Erika, primary, Bosch, Ana, primary, Lindman, Henrik, primary, Adra, Jamila, primary, Andersson, Anne, primary, Agartz, Susanne, primary, Hellström, Mats, primary, Zerdes, Ioannis, primary, Hartman, Johan, primary, Bergh, Jonas, primary, Hatschek, Thomas, primary, and Foukakis, Theodoros, primary

Published
2023
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32. Supplementary Table S1 from Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial

Author

Matikas, Alexios, primary, Johansson, Hemming, primary, Grybäck, Per, primary, Bjöhle, Judith, primary, Acs, Balazs, primary, Boyaci, Ceren, primary, Lekberg, Tobias, primary, Fredholm, Hanna, primary, Elinder, Ellinor, primary, Margolin, Sara, primary, Isaksson-Friman, Erika, primary, Bosch, Ana, primary, Lindman, Henrik, primary, Adra, Jamila, primary, Andersson, Anne, primary, Agartz, Susanne, primary, Hellström, Mats, primary, Zerdes, Ioannis, primary, Hartman, Johan, primary, Bergh, Jonas, primary, Hatschek, Thomas, primary, and Foukakis, Theodoros, primary

Published
2023
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33. Supplementary Data from Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death

Author

Kulkarni, Prathamesh M., primary, Robinson, Eric J., primary, Sarin Pradhan, Jaya, primary, Gartrell-Corrado, Robyn D., primary, Rohr, Bethany R., primary, Trager, Megan H., primary, Geskin, Larisa J., primary, Kluger, Harriet M., primary, Wong, Pok Fai, primary, Acs, Balazs, primary, Rizk, Emanuelle M., primary, Yang, Chen, primary, Mondal, Manas, primary, Moore, Michael R., primary, Osman, Iman, primary, Phelps, Robert, primary, Horst, Basil A., primary, Chen, Zhe S., primary, Ferringer, Tammie, primary, Rimm, David L., primary, Wang, Jing, primary, and Saenger, Yvonne M., primary

Published
2023
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37. Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer : Results from the Randomized PREDIX HER2 Trial

Author

Matikas, Alexios, Johansson, Hemming, Grybäck, Per, Bjöhle, Judith, Acs, Balazs, Boyaci, Ceren, Lekberg, Tobias, Fredholm, Hanna, Elinder, Ellinor, Margolin, Sara, Isaksson-Friman, Erika, Bosch, Ana, Lindman, Henrik, Adra, Jamila, Andersson, Anne, Agartz, Susanne, Hellström, Mats, Zerdes, Ioannis, Hartman, Johan, Bergh, Jonas, Hatschek, Thomas, Foukakis, Theodoros, Matikas, Alexios, Johansson, Hemming, Grybäck, Per, Bjöhle, Judith, Acs, Balazs, Boyaci, Ceren, Lekberg, Tobias, Fredholm, Hanna, Elinder, Ellinor, Margolin, Sara, Isaksson-Friman, Erika, Bosch, Ana, Lindman, Henrik, Adra, Jamila, Andersson, Anne, Agartz, Susanne, Hellström, Mats, Zerdes, Ioannis, Hartman, Johan, Bergh, Jonas, Hatschek, Thomas, and Foukakis, Theodoros

Abstract

Purpose: PREDIX HER2 is a randomized Phase II trial that compared neoadjuvant docetaxel, trastuzumab, and pertuzumab (THP) with trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Rates of pathologic complete response (pCR) did not differ between the two groups. Here, we present the survival outcomes from PREDIX HER2 and investigate metabolic response and tumor-infiltrating lymphocytes (TIL) as prognostic factors. Patients and Methods: In total, 202 patients with HER2-positive breast cancer were enrolled and 197 patients received six cycles of either THP or T-DM1. Secondary endpoints included event-free survival (EFS), recurrence-free survival (RFS), and overall survival (OS). Assessment with PET/CT was performed at baseline, after two and six treatment cycles. TILs were assessed manually at baseline biopsies, while image-based evaluation of TILs [digital TILs (DTIL)] was performed in digitized full-face sections. Results: After a median follow-up of 5.21 years, there was no difference between the two treatment groups in terms of EFS [HR = 1.26; 95% confidence interval (CI), 0.54–2.91], RFS (HR = 0.69; 95% CI, 0.24–1.93), or OS (HR = 0.52; 95% CI, 0.09–2.82). Higher SUVmax at cycle 2 (C2) predicted lower pCR (ORadj = 0.65; 95% CI, 0.48–0.87; P = 0.005) and worse EFS (HRadj = 1.27; 95% CI, 1.12–1.41; P < 0.001). Baseline TILs and DTILs provided additional prognostic information to clinical parameters and C2 SUVmax. Conclusions: Long-term outcomes following neoadjuvant T-DM1 were similar to neoadjuvant THP. SUVmax after two cycles of neoadjuvant therapy for HER2-positive breast cancer may be an independent predictor of both short- and long-term outcomes. Combined assessment with TILs may facilitate early selection of poor responders for alternative treatment strategies.

Published
2023
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38. 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

39. 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

40. 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

41. 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

43. Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial

Author

Matikas, Alexios, primary, Johansson, Hemming, additional, Grybäck, Per, additional, Bjöhle, Judith, additional, Acs, Balazs, additional, Boyaci, Ceren, additional, Lekberg, Tobias, additional, Fredholm, Hanna, additional, Elinder, Ellinor, additional, Margolin, Sara, additional, Isaksson-Friman, Erika, additional, Bosch, Ana, additional, Lindman, Henrik, additional, Adra, Jamila, additional, Andersson, Anne, additional, Agartz, Susanne, additional, Hellström, Mats, additional, Zerdes, Ioannis, additional, Hartman, Johan, additional, Bergh, Jonas, additional, Hatschek, Thomas, additional, and Foukakis, Theodoros, additional

Published
2022
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44. External Quality Assessment 2.0: The Importance of a Standardized Implementation of TILs for Daily and Trial Practices

Author

Nauwelaers, Inne, primary, Laudus, Nele, additional, Peeters, Dieter, additional, Acs, Balazs, additional, Denkert, Carsten, additional, Michiels, Stefan, additional, Horlings, Hugo, additional, Siziopikou, Kalliopi P., additional, Ely, Scott, additional, Zardavas, Dimitrios, additional, Mustimbo, Roberts, additional, Bartlett, John, additional, Floris, Giuseppe, additional, Hartman, Johan, additional, van Deurzen, Carolien H. M., additional, Ceusters, Dorien, additional, Dequeker, Els, additional, and Salgado, Roberto, additional

Published
2022
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45. Objective assessment of tumor infiltrating lymphocytes as a prognostic marker in melanoma using machine learning algorithms

Author

Aung, Thazin Nwe, primary, Shafi, Saba, additional, Wilmott, James S., additional, Nourmohammadi, Saeed, additional, Vathiotis, Ioannis, additional, Gavrielatou, Niki, additional, Fernandez, Aileen, additional, Yaghoobi, Vesal, additional, Sinnberg, Tobias, additional, Amaral, Teresa, additional, Ikenberg, Kristian, additional, Khosrotehrani, Kiarash, additional, Osman, Iman, additional, Acs, Balazs, additional, Bai, Yalai, additional, Martinez-Morilla, Sandra, additional, Moutafi, Myrto, additional, Thompson, John F., additional, Scolyer, Richard A., additional, and Rimm, David L., additional

Published
2022
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48. Combined assessment of metabolic response and tumor infiltrating lymphocytes as a predictor of outcomes following neoadjuvant therapy for HER2-positive breast cancer: Results from the randomized PREDIX HER2 trial.

Author

Matikas, Alexios, primary, Johansson, Hemming, additional, Grybäck, Per, additional, Bjöhle, Judith, additional, Lekberg, Tobias, additional, Fredholm, Hanna, additional, Acs, Balazs, additional, Elinder, Ellinor, additional, Isaksson-Friman, Erika, additional, Agartz, Susanne, additional, Hellstrom, Mats, additional, Zerdes, Ioannis, additional, Hartman, Johan, additional, Bergh, Jonas C. S., additional, Hatschek, Thomas, additional, and Foukakis, Theodoros, additional

Published
2022
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49. Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study

Author

Kjällquist, Una, primary, Acs, Balazs, additional, Margolin, Sara, additional, Karlsson, Emelie, additional, Kessler, Luisa Edman, additional, Garcia Hernandez, Scarlett, additional, Ekholm, Maria, additional, Lundgren, Christine, additional, Olsson, Erik, additional, Lindman, Henrik, additional, Foukakis, Theodoros, additional, Matikas, Alexios, additional, and Hartman, Johan, additional

Published
2022
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50. Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population : A Multicenter Study

Author

Kjallquist, Una, Acs, Balazs, Margolin, Sara, Karlsson, Emelie, Kessler, Luisa Edman, Hernandez, Scarlett Garcia, Ekholm, Maria, Lundgren, Christine, Olsson, Erik, Lindman, Henrik, Foukakis, Theodoros, Matikas, Alexios, Hartman, Johan, Kjallquist, Una, Acs, Balazs, Margolin, Sara, Karlsson, Emelie, Kessler, Luisa Edman, Hernandez, Scarlett Garcia, Ekholm, Maria, Lundgren, Christine, Olsson, Erik, Lindman, Henrik, Foukakis, Theodoros, Matikas, Alexios, and Hartman, Johan

Abstract

Gene expression signatures can provide important information on the risk of recurrence in patients with hormone receptor positive early breast cancer, and they can guide post-operative treatment. We have investigated how the implementation of gene-expression-based risk signatures with the Prosigna((R)) test impacted patient management in Sweden. The two major conclusions of this study are that prognostic factors derived from routine pathology were poor predictors of the intrinsic subtype and the risk of recurrence score, and that gene-expression-based risk combined with clinicopathological biomarkers (tumor size, Ki67, tumor grade) spared patients from adjuvant chemotherapy, but also identified patients who would potentially benefit from this treatment. Molecular signatures to guide decisions for adjuvant chemotherapy are recommended in early ER-positive, HER2-negative breast cancer. The objective of this study was to assess what impact gene-expression-based risk testing has had following its recommendation by Swedish national guidelines. Postmenopausal women with ER-positive, HER2-negative and node negative breast cancer at intermediate clinical risk and eligible for chemotherapy were identified retrospectively from five Swedish hospitals. Tumor characteristics, results from Prosigna((R)) test and final treatment decision were available for all patients. Treatment recommendations were compared with the last version of regional guidelines before the introduction of routine risk signature testing. Among the 360 included patients, 41% (n = 148) had a change in decision for adjuvant treatment based on Prosigna((R)) test result. Out of the patients with clinical indication for adjuvant chemotherapy, 52% (n = 118) could avoid treatment based on results from Prosigna((R)) test. On the contrary, 23% (n = 30) of the patients with no indication were escalated to receive adjuvant chemotherapy after testing. Ki67 could not distinguish between the Prosigna((R)) risk groups or i

Published
2022
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