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34 results on '"Kirtani, P"'

1. MM-PhyRLHF: Reinforcement Learning Framework for Multimodal Physics Question-Answering

Author

Anand, Avinash, Kapuriya, Janak, Kirtani, Chhavi, Singh, Apoorv, Saraf, Jay, Lal, Naman, Kumar, Jatin, Shivam, Adarsh Raj, Verma, Astha, Shah, Rajiv Ratn, and Zimmermann, Roger

Subjects
Computer Science - Artificial Intelligence
Abstract

Recent advancements in LLMs have shown their significant potential in tasks like text summarization and generation. Yet, they often encounter difficulty while solving complex physics problems that require arithmetic calculation and a good understanding of concepts. Moreover, many physics problems include images that contain important details required to understand the problem's context. We propose an LMM-based chatbot to answer multimodal physics MCQs. For domain adaptation, we utilize the MM-PhyQA dataset comprising Indian high school-level multimodal physics problems. To improve the LMM's performance, we experiment with two techniques, RLHF (Reinforcement Learning from Human Feedback) and Image Captioning. In image captioning, we add a detailed explanation of the diagram in each image, minimizing hallucinations and image processing errors. We further explore the integration of Reinforcement Learning from Human Feedback (RLHF) methodology inspired by the ranking approach in RLHF to enhance the human-like problem-solving abilities of the models. The RLHF approach incorporates human feedback into the learning process of LLMs, improving the model's problem-solving skills, truthfulness, and reasoning capabilities, minimizing the hallucinations in the answers, and improving the quality instead of using vanilla-supervised fine-tuned models. We employ the LLaVA open-source model to answer multimodal physics MCQs and compare the performance with and without using RLHF.

Published
2024

3. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, Khalid, Haynes, Harry R, Blackley, Elizabeth, Fineberg, Susan, Shear, Jeffrey, Turner, Sophia, de Freitas, Juliana Ribeiro, Sur, Daniel, Amendola, Luis Claudio, Gharib, Masoumeh, Kallala, Amine, Arun, Indu, Azmoudeh-Ardalan, Farid, Fujimoto, Luciana, Sua, Luz F, Liu, Shi-Wei, Lien, Huang-Chun, Kirtani, Pawan, Balancin, Marcelo, El Attar, Hicham, Guleria, Prerna, Yang, Wenxian, Shash, Emad, Chen, I-Chun, Bautista, Veronica, Do Prado Moura, Jose Fernando, Rapoport, Bernardo L, Castaneda, Carlos, Spengler, Eunice, Acosta-Haab, Gabriela, Frahm, Isabel, Sanchez, Joselyn, Castillo, Miluska, Bouchmaa, Najat, Md Zin, Reena R, Shui, Ruohong, Onyuma, Timothy, Yang, Wentao, Husain, Zaheed, Willard-Gallo, Karen, Coosemans, An, Perez, Edith A, Provenzano, Elena, Ericsson, Paula Gonzalez, Richardet, Eduardo, Mehrotra, Ravi, Sarancone, Sandra, Ehinger, Anna, Rimm, David L, Bartlett, John MS, Viale, Giuseppe, Denkert, Carsten, Hida, Akira I, Sotiriou, Christos, Loibl, Sibylle, Hewitt, Stephen M, Badve, Sunil, Symmans, William Fraser, Kim, Rim S, Pruneri, Giancarlo, Goel, Shom, Francis, Prudence A, Inurrigarro, Gloria, Yamaguchi, Rin, Garcia-Rivello, Hernan, Horlings, Hugo, Afqir, Said, Salgado, Roberto, Adams, Sylvia, Kok, Marleen, Dieci, Maria Vittoria, Michiels, Stefan, Demaria, Sandra, and Loi, Sherene

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Breast Cancer, Cancer, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, International Immuno-Oncology Biomarker Working Group, Clinical sciences, Oncology and carcinogenesis, Epidemiology
Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Published
2021

4. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

Khalid El Bairi, Harry R. Haynes, Elizabeth Blackley, Susan Fineberg, Jeffrey Shear, Sophia Turner, Juliana Ribeiro de Freitas, Daniel Sur, Luis Claudio Amendola, Masoumeh Gharib, Amine Kallala, Indu Arun, Farid Azmoudeh-Ardalan, Luciana Fujimoto, Luz F. Sua, Shi-Wei Liu, Huang-Chun Lien, Pawan Kirtani, Marcelo Balancin, Hicham El Attar, Prerna Guleria, Wenxian Yang, Emad Shash, I-Chun Chen, Veronica Bautista, Jose Fernando Do Prado Moura, Bernardo L. Rapoport, Carlos Castaneda, Eunice Spengler, Gabriela Acosta-Haab, Isabel Frahm, Joselyn Sanchez, Miluska Castillo, Najat Bouchmaa, Reena R. Md Zin, Ruohong Shui, Timothy Onyuma, Wentao Yang, Zaheed Husain, Karen Willard-Gallo, An Coosemans, Edith A. Perez, Elena Provenzano, Paula Gonzalez Ericsson, Eduardo Richardet, Ravi Mehrotra, Sandra Sarancone, Anna Ehinger, David L. Rimm, John M. S. Bartlett, Giuseppe Viale, Carsten Denkert, Akira I. Hida, Christos Sotiriou, Sibylle Loibl, Stephen M. Hewitt, Sunil Badve, William Fraser Symmans, Rim S. Kim, Giancarlo Pruneri, Shom Goel, Prudence A. Francis, Gloria Inurrigarro, Rin Yamaguchi, Hernan Garcia-Rivello, Hugo Horlings, Said Afqir, Roberto Salgado, Sylvia Adams, Marleen Kok, Maria Vittoria Dieci, Stefan Michiels, Sandra Demaria, Sherene Loi, and The International Immuno-Oncology Biomarker Working Group

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Published
2021
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5. 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, CA, Page, DB, Broeckx, G, Gonzalez, CA, Burke, C, Murphy, C, Reis-Filho, JS, Ly, A, Harms, PW, Gupta, RR, Vieth, M, Hida, A, Kahila, M, Kos, Z, van Diest, PJ, Verbandt, S, Thagaard, J, Khiroya, R, Abduljabbar, K, Haab, GA, Acs, B, Adams, S, Almeida, JS, Alvarado-Cabrero, I, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Fujimoto, LBM, Burgues, O, Chardas, A, Cheang, MCU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Portela, FLD, Deman, F, Demaria, S, Dudgeon, SN, Elghazawy, M, Fernandez-Martin, C, Fineberg, S, Fox, SB, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hart, SN, Hartman, J, Hewitt, S, Horlings, HM, Husain, Z, Irshad, S, Janssen, EAM, Kataoka, TR, Kawaguchi, K, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Akturk, G, Scott, E, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Madabhushi, A, Maley, SK, Narasimhamurthy, VM, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Kharidehal, D, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rajpoot, NM, Rapoport, BL, Rau, TT, Ribeiro, JM, Rimm, D, Vincent-Salomon, A, Saltz, J, Sayed, S, Hytopoulos, E, Mahon, S, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, Verghese, GE, Viale, G, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Bartlett, J, Loibl, S, Denkert, C, Savas, P, Loi, S, Stovgaard, ES, Salgado, R, Gallagher, WM, Rahman, A, Jahangir, CA, Page, DB, Broeckx, G, Gonzalez, CA, Burke, C, Murphy, C, Reis-Filho, JS, Ly, A, Harms, PW, Gupta, RR, Vieth, M, Hida, A, Kahila, M, Kos, Z, van Diest, PJ, Verbandt, S, Thagaard, J, Khiroya, R, Abduljabbar, K, Haab, GA, Acs, B, Adams, S, Almeida, JS, Alvarado-Cabrero, I, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Fujimoto, LBM, Burgues, O, Chardas, A, Cheang, MCU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Portela, FLD, Deman, F, Demaria, S, Dudgeon, SN, Elghazawy, M, Fernandez-Martin, C, Fineberg, S, Fox, SB, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hart, SN, Hartman, J, Hewitt, S, Horlings, HM, Husain, Z, Irshad, S, Janssen, EAM, Kataoka, TR, Kawaguchi, K, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Akturk, G, Scott, E, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Madabhushi, A, Maley, SK, Narasimhamurthy, VM, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Kharidehal, D, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rajpoot, NM, Rapoport, BL, Rau, TT, Ribeiro, JM, Rimm, D, Vincent-Salomon, A, Saltz, J, Sayed, S, Hytopoulos, E, Mahon, S, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, Verghese, GE, Viale, G, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Bartlett, J, Loibl, S, Denkert, C, Savas, P, Loi, S, Stovgaard, ES, Salgado, R, Gallagher, WM, and Rahman, A

Published
2024

7. PAVT: A Tool to Visualize and Teach Parsing Algorithms

Author

Sangal, Somya, Kataria, Shreya, Tyagi, Twishi, Gupta, Nidhi, Kirtani, Yukti, Agrawal, Shivli, and Chakraborty, Pinaki

Abstract

A parsing algorithm visualizer is a tool that visualizes the construction of a parser for a given context-free grammar and then illustrates the use of that parser to parse a given string. Parsing algorithm visualizers are used to teach the course on compiler construction which in invariably included in all undergraduate computer science curricula. This paper presents a new parsing algorithm visualizer that can visualize six parsing algorithms, viz. predictive parsing, simple LR parsing, canonical LR parsing, look-ahead LR parsing, Earley parsing and CYK parsing. The tool logically explains the process of parsing showing the calculations involved in each step. The output of the tool has been structured to maximize the learning outcomes and contains important constructs like FIRST and FOLLOW sets, item sets, parsing table, parse tree and leftmost or rightmost derivation depending on the algorithm being visualized. The tool has been used to teach the course on compiler construction at both undergraduate and graduate levels. An overall positive feedback was received from the students with 89% of them saying that the tool helped them in understanding the parsing algorithms. The tool is capable of visualizing multiple parsing algorithms and 88% students used it to compare the algorithms.

Published
2018
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9. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Author

Amgad, Mohamed, Stovgaard, Elisabeth Specht, Balslev, Eva, Thagaard, Jeppe, Chen, Weijie, Dudgeon, Sarah, Sharma, Ashish, Kerner, Jennifer K., Denkert, Carsten, Yuan, Yinyin, AbdulJabbar, Khalid, Wienert, Stephan, Savas, Peter, Voorwerk, Leonie, Beck, Andrew H., Madabhushi, Anant, Hartman, Johan, Sebastian, Manu M., Horlings, Hugo M., Hudeček, Jan, Ciompi, Francesco, Moore, David A., Singh, Rajendra, Roblin, Elvire, Balancin, Marcelo Luiz, Mathieu, Marie-Christine, Lennerz, Jochen K., Kirtani, Pawan, Chen, I-Chun, Braybrooke, Jeremy P., Pruneri, Giancarlo, Demaria, Sandra, Adams, Sylvia, Schnitt, Stuart J., Lakhani, Sunil R., Rojo, Federico, Comerma, Laura, Badve, Sunil S., Khojasteh, Mehrnoush, Symmans, W. Fraser, Sotiriou, Christos, Gonzalez-Ericsson, Paula, Pogue-Geile, Katherine L., Kim, Rim S., Rimm, David L., Viale, Giuseppe, Hewitt, Stephen M., Bartlett, John M. S., Penault-Llorca, Frédérique, Goel, Shom, Lien, Huang-Chun, Loibl, Sibylle, Kos, Zuzana, Loi, Sherene, Hanna, Matthew G., Michiels, Stefan, Kok, Marleen, Nielsen, Torsten O., Lazar, Alexander J., Bago-Horvath, Zsuzsanna, Kooreman, Loes F. S., van der Laak, Jeroen A. W. M., Saltz, Joel, Gallas, Brandon D., Kurkure, Uday, Barnes, Michael, Salgado, Roberto, and Cooper, Lee A. D.

Published
2020
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10. 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, J, Broeckx, G, Page, DB, Jahangir, CA, Verbandt, S, Kos, Z, Gupta, R, Khiroya, R, Abduljabbar, K, Acosta Haab, G, Acs, B, Akturk, G, Almeida, JS, Alvarado-Cabrero, I, Amgad, M, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Balslev, E, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Botinelly Mendonca Fujimoto, L, Bouchmaa, N, Burgues, O, Chardas, A, Cheang, MU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Dahl, AB, Dantas Portela, FL, Deman, F, Demaria, S, Dore Hansen, J, Dudgeon, SN, Ebstrup, T, Elghazawy, M, Fernandez-Martin, C, Fox, SB, Gallagher, WM, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hart, SN, Hartman, J, Hauberg, S, Hewitt, S, Hida, A, Horlings, HM, Husain, Z, Hytopoulos, E, Irshad, S, Janssen, EAM, Kahila, M, Kataoka, TR, Kawaguchi, K, Kharidehal, D, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Ly, A, Madabhushi, A, Maley, SK, Manur Narasimhamurthy, V, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rahman, A, Rajpoot, NM, Rapoport, BL, Rau, TT, Reis-Filho, JS, Ribeiro, JM, Rimm, D, Roslind, A, Vincent-Salomon, A, Salto-Tellez, M, Saltz, J, Sayed, S, Scott, E, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Fineberg, S, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, van Diest, PJ, Verghese, GE, Viale, G, Vieth, M, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Zin, RM, Adams, S, Bartlett, J, Loibl, S, Denkert, C, Savas, P, Loi, S, Salgado, R, Specht Stovgaard, E, Thagaard, J, Broeckx, G, Page, DB, Jahangir, CA, Verbandt, S, Kos, Z, Gupta, R, Khiroya, R, Abduljabbar, K, Acosta Haab, G, Acs, B, Akturk, G, Almeida, JS, Alvarado-Cabrero, I, Amgad, M, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Balslev, E, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Botinelly Mendonca Fujimoto, L, Bouchmaa, N, Burgues, O, Chardas, A, Cheang, MU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Dahl, AB, Dantas Portela, FL, Deman, F, Demaria, S, Dore Hansen, J, Dudgeon, SN, Ebstrup, T, Elghazawy, M, Fernandez-Martin, C, Fox, SB, Gallagher, WM, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hart, SN, Hartman, J, Hauberg, S, Hewitt, S, Hida, A, Horlings, HM, Husain, Z, Hytopoulos, E, Irshad, S, Janssen, EAM, Kahila, M, Kataoka, TR, Kawaguchi, K, Kharidehal, D, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Ly, A, Madabhushi, A, Maley, SK, Manur Narasimhamurthy, V, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rahman, A, Rajpoot, NM, Rapoport, BL, Rau, TT, Reis-Filho, JS, Ribeiro, JM, Rimm, D, Roslind, A, Vincent-Salomon, A, Salto-Tellez, M, Saltz, J, Sayed, S, Scott, E, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Fineberg, S, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, van Diest, PJ, Verghese, GE, Viale, G, Vieth, M, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Zin, RM, Adams, S, Bartlett, J, Loibl, S, Denkert, C, Savas, P, Loi, S, Salgado, R, and Specht Stovgaard, E

Published
2023

11. 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, DB, Broeckx, G, Jahangir, CA, Jahangir, C, Verbandt, S, Gupta, RR, Thagaard, J, Khiroya, R, Kos, Z, Abduljabbar, K, Acosta Haab, G, Acs, B, Almeida, JS, Alvarado-Cabrero, I, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Botinelly Mendonca Fujimoto, L, Burgues, O, Cheang, MCU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Dantas Portela, FL, Deman, F, Demaria, S, Dudgeon, SN, Elghazawy, M, Ely, S, Fernandez-Martin, C, Fineberg, S, Fox, SB, Gallagher, WM, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hardas, A, Hart, SN, Hartman, J, Hewitt, S, Hida, A, Horlings, HM, Husain, Z, Hytopoulos, E, Irshad, S, Janssen, EAM, Kahila, M, Kataoka, TR, Kawaguchi, K, Kharidehal, D, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Ly, A, Madabhushi, A, Maley, SK, Manur Narasimhamurthy, V, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rahman, A, Rajpoot, NM, Rapoport, BL, Rau, TT, Reis-Filho, JS, Ribeiro, JM, Rimm, D, Salomon, A-V, Salto-Tellez, M, Saltz, J, Sayed, S, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, van Diest, PJ, Verghese, GE, Viale, G, Vieth, M, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Adams, S, Bartlett, JMS, Loibl, S, Denkert, C, Savas, P, Loi, S, Salgado, R, Specht Stovgaard, E, Akturk, G, Bouchmaa, N, Page, DB, Broeckx, G, Jahangir, CA, Jahangir, C, Verbandt, S, Gupta, RR, Thagaard, J, Khiroya, R, Kos, Z, Abduljabbar, K, Acosta Haab, G, Acs, B, Almeida, JS, Alvarado-Cabrero, I, Azmoudeh-Ardalan, F, Badve, S, Baharun, NB, Bellolio, ER, Bheemaraju, V, Blenman, KRM, Botinelly Mendonca Fujimoto, L, Burgues, O, Cheang, MCU, Ciompi, F, Cooper, LAD, Coosemans, A, Corredor, G, Dantas Portela, FL, Deman, F, Demaria, S, Dudgeon, SN, Elghazawy, M, Ely, S, Fernandez-Martin, C, Fineberg, S, Fox, SB, Gallagher, WM, Giltnane, JM, Gnjatic, S, Gonzalez-Ericsson, P, Grigoriadis, A, Halama, N, Hanna, MG, Harbhajanka, A, Hardas, A, Hart, SN, Hartman, J, Hewitt, S, Hida, A, Horlings, HM, Husain, Z, Hytopoulos, E, Irshad, S, Janssen, EAM, Kahila, M, Kataoka, TR, Kawaguchi, K, Kharidehal, D, Khramtsov, A, Kiraz, U, Kirtani, P, Kodach, LL, Korski, K, Kovacs, A, Laenkholm, A-V, Lang-Schwarz, C, Larsimont, D, Lennerz, JK, Lerousseau, M, Li, X, Ly, A, Madabhushi, A, Maley, SK, Manur Narasimhamurthy, V, Marks, DK, McDonald, ES, Mehrotra, R, Michiels, S, Minhas, FUAA, Mittal, S, Moore, DA, Mushtaq, S, Nighat, H, Papathomas, T, Penault-Llorca, F, Perera, RD, Pinard, CJ, Pinto-Cardenas, JC, Pruneri, G, Pusztai, L, Rahman, A, Rajpoot, NM, Rapoport, BL, Rau, TT, Reis-Filho, JS, Ribeiro, JM, Rimm, D, Salomon, A-V, Salto-Tellez, M, Saltz, J, Sayed, S, Siziopikou, KP, Sotiriou, C, Stenzinger, A, Sughayer, MA, Sur, D, Symmans, F, Tanaka, S, Taxter, T, Tejpar, S, Teuwen, J, Thompson, EA, Tramm, T, Tran, WT, van Der Laak, J, van Diest, PJ, Verghese, GE, Viale, G, Vieth, M, Wahab, N, Walter, T, Waumans, Y, Wen, HY, Yang, W, Yuan, Y, Adams, S, Bartlett, JMS, Loibl, S, Denkert, C, Savas, P, Loi, S, Salgado, R, Specht Stovgaard, E, Akturk, G, and Bouchmaa, N

Published
2023

12. 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, J., Broeckx, G., Page, D.B., Jahangir, C.A., Verbandt, S., Kos, Z., Gupta, R., Khiroya, R., AbdulJabbar, K., Haab, G.A., Acs, B., Akturk, G., Almeida, J.S., Alvarado-Cabrero, I., Amgad, M., Azmoudeh-Ardalan, F., Badve, S., Baharun, N.B., Balslev, E., Bellolio, E.R., Bheemaraju, V., Blenman, K.R., Botinelly Mendonça Fujimoto, L., Bouchmaa, N., Burgues, O., Chardas, A., Chon U Cheang, M., Ciompi, F., Cooper, L.A., Coosemans, A., Corredor, G., Dahl, A.B., Dantas Portela, F.L., Deman, F., Demaria, S., Doré Hansen, J., Dudgeon, S.N., Ebstrup, T., Elghazawy, M., Fernandez-Martín, C., Fox, S.B., Gallagher, W.M., Giltnane, J.M., Gnjatic, S., Gonzalez-Ericsson, P.I., Grigoriadis, A., Halama, N., Hanna, M.G., Harbhajanka, A., Hart, S.N., Hartman, J., Hauberg, S., Hewitt, S., Hida, A.I., Horlings, H.M., Husain, Z., Hytopoulos, E., Irshad, S., Janssen, E.a, Kahila, M., Kataoka, T.R., Kawaguchi, K., Kharidehal, D., Khramtsov, A.I., Kiraz, U., Kirtani, P., Kodach, L.L., Korski, K., Kovács, A., Laenkholm, A.V., Lang-Schwarz, C., Larsimont, D., Lennerz, J.K., Lerousseau, M., Li, Xiaoxian, Ly, Amy, Madabhushi, A., Maley, S.K., Manur Narasimhamurthy, V., Marks, D.K., McDonald, E.S., Mehrotra, R., Michiels, S., Minhas, F.U.A.A., Mittal, S., Moore, D.A., Mushtaq, S., Nighat, H., Papathomas, T., Penault-Llorca, F., Perera, R.D., Pinard, C.J., Pinto-Cardenas, J.C., Pruneri, G., Pusztai, L., Rahman, A., Rajpoot, N.M., Rapoport, B.L., Rau, T.T., Reis-Filho, J.S., Ribeiro, J.M., Rimm, D., Roslind, A., Vincent-Salomon, A., Salto-Tellez, M., Saltz, J., Sayed, S., Scott, E., Siziopikou, K.P., Sotiriou, C., Stenzinger, A., Sughayer, M.A., Sur, D., Fineberg, S., Symmans, F., Tanaka, S., Taxter, T., Tejpar, S., Teuwen, J., Thompson, E.A., Tramm, T., Tran, W.T., Laak, J.A.W.M. van der, Diest, P.J. van, Verghese, G.E., Viale, G., Vieth, M., Wahab, N., Walter, T., Waumans, Y., Wen, H.Y., Yang, W, Yuan, Y., Zin, R.M., Adams, S., Bartlett, J., Loibl, S., Denkert, C., Savas, P., Loi, S., Salgado, R., Specht Stovgaard, E., Thagaard, J., Broeckx, G., Page, D.B., Jahangir, C.A., Verbandt, S., Kos, Z., Gupta, R., Khiroya, R., AbdulJabbar, K., Haab, G.A., Acs, B., Akturk, G., Almeida, J.S., Alvarado-Cabrero, I., Amgad, M., Azmoudeh-Ardalan, F., Badve, S., Baharun, N.B., Balslev, E., Bellolio, E.R., Bheemaraju, V., Blenman, K.R., Botinelly Mendonça Fujimoto, L., Bouchmaa, N., Burgues, O., Chardas, A., Chon U Cheang, M., Ciompi, F., Cooper, L.A., Coosemans, A., Corredor, G., Dahl, A.B., Dantas Portela, F.L., Deman, F., Demaria, S., Doré Hansen, J., Dudgeon, S.N., Ebstrup, T., Elghazawy, M., Fernandez-Martín, C., Fox, S.B., Gallagher, W.M., Giltnane, J.M., Gnjatic, S., Gonzalez-Ericsson, P.I., Grigoriadis, A., Halama, N., Hanna, M.G., Harbhajanka, A., Hart, S.N., Hartman, J., Hauberg, S., Hewitt, S., Hida, A.I., Horlings, H.M., Husain, Z., Hytopoulos, E., Irshad, S., Janssen, E.a, Kahila, M., Kataoka, T.R., Kawaguchi, K., Kharidehal, D., Khramtsov, A.I., Kiraz, U., Kirtani, P., Kodach, L.L., Korski, K., Kovács, A., Laenkholm, A.V., Lang-Schwarz, C., Larsimont, D., Lennerz, J.K., Lerousseau, M., Li, Xiaoxian, Ly, Amy, Madabhushi, A., Maley, S.K., Manur Narasimhamurthy, V., Marks, D.K., McDonald, E.S., Mehrotra, R., Michiels, S., Minhas, F.U.A.A., Mittal, S., Moore, D.A., Mushtaq, S., Nighat, H., Papathomas, T., Penault-Llorca, F., Perera, R.D., Pinard, C.J., Pinto-Cardenas, J.C., Pruneri, G., Pusztai, L., Rahman, A., Rajpoot, N.M., Rapoport, B.L., Rau, T.T., Reis-Filho, J.S., Ribeiro, J.M., Rimm, D., Roslind, A., Vincent-Salomon, A., Salto-Tellez, M., Saltz, J., Sayed, S., Scott, E., Siziopikou, K.P., Sotiriou, C., Stenzinger, A., Sughayer, M.A., Sur, D., Fineberg, S., Symmans, F., Tanaka, S., Taxter, T., Tejpar, S., Teuwen, J., Thompson, E.A., Tramm, T., Tran, W.T., Laak, J.A.W.M. van der, Diest, P.J. van, Verghese, G.E., Viale, G., Vieth, M., Wahab, N., Walter, T., Waumans, Y., Wen, H.Y., Yang, W, Yuan, Y., Zin, R.M., Adams, S., Bartlett, J., Loibl, S., Denkert, C., Savas, P., Loi, S., Salgado, R., and Specht Stovgaard, E.

Abstract

01 augustus 2023, Contains fulltext : 296181.pdf (Publisher’s version ) (Open Access), 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. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Published
2023

13. 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, D.B., Broeckx, G., Jahangir, C.A., Verbandt, S., Gupta, R.R., Thagaard, J., Khiroya, R., Kos, Z., AbdulJabbar, K., Acosta Haab, G., Acs, B., Akturk, G., Almeida, J.S., Alvarado-Cabrero, I., Azmoudeh-Ardalan, F., Badve, S., Baharun, N.B., Bellolio, E.R., Bheemaraju, V., Blenman, K.R., Botinelly Mendonça Fujimoto, L., Bouchmaa, N., Burgues, O., Cheang, M.C.U., Ciompi, F., Cooper, L.A., Coosemans, A., Corredor, G., Dantas Portela, F.L., Deman, F., Demaria, S., Dudgeon, S.N., Elghazawy, M., Ely, S., Fernandez-Martín, C., Fineberg, S., Fox, S.B., Gallagher, W.M., Giltnane, J.M., Gnjatic, S., Gonzalez-Ericsson, P.I., Grigoriadis, A., Halama, N., Hanna, M.G., Harbhajanka, A., Hardas, A., Hart, S.N., Hartman, J., Hewitt, S., Hida, A.I., Horlings, H.M., Husain, Z., Hytopoulos, E., Irshad, S., Janssen, E.a, Kahila, M., Kataoka, T.R., Kawaguchi, K., Kharidehal, D., Khramtsov, A.I., Kiraz, U., Kirtani, P., Kodach, L.L., Korski, K., Kovács, A., Laenkholm, A.V., Lang-Schwarz, C., Larsimont, D., Lennerz, J.K., Lerousseau, M., Li, Xiaoxian, Ly, Amy, Madabhushi, A., Maley, S.K., Manur Narasimhamurthy, V., Marks, D.K., McDonald, E.S., Mehrotra, R., Michiels, S., Minhas, F.U.A.A., Mittal, S., Moore, D.A., Mushtaq, S., Nighat, H., Papathomas, T., Penault-Llorca, F., Perera, R.D., Pinard, C.J., Pinto-Cardenas, J.C., Pruneri, G., Pusztai, L., Rahman, A., Rajpoot, N.M., Rapoport, B.L., Rau, T.T., Reis-Filho, J.S., Ribeiro, J.M., Rimm, D., Vincent-Salomon, A., Salto-Tellez, M., Saltz, J., Sayed, S., Siziopikou, K.P., Sotiriou, C., Stenzinger, A., Sughayer, M.A., Sur, D., Symmans, F., Tanaka, S., Taxter, T., Tejpar, S., Teuwen, J., Thompson, E.A., Tramm, T., Tran, W.T., Laak, J.A.W.M. van der, Diest, P.J. van, Verghese, G.E., Viale, G., Vieth, M., Wahab, N., Walter, T., Waumans, Y., Wen, H.Y., Yang, W, Yuan, Y., Adams, S., Bartlett, J.M.S., Loibl, S., Denkert, C., Savas, P., Loi, S., Salgado, R., Specht Stovgaard, E., Page, D.B., Broeckx, G., Jahangir, C.A., Verbandt, S., Gupta, R.R., Thagaard, J., Khiroya, R., Kos, Z., AbdulJabbar, K., Acosta Haab, G., Acs, B., Akturk, G., Almeida, J.S., Alvarado-Cabrero, I., Azmoudeh-Ardalan, F., Badve, S., Baharun, N.B., Bellolio, E.R., Bheemaraju, V., Blenman, K.R., Botinelly Mendonça Fujimoto, L., Bouchmaa, N., Burgues, O., Cheang, M.C.U., Ciompi, F., Cooper, L.A., Coosemans, A., Corredor, G., Dantas Portela, F.L., Deman, F., Demaria, S., Dudgeon, S.N., Elghazawy, M., Ely, S., Fernandez-Martín, C., Fineberg, S., Fox, S.B., Gallagher, W.M., Giltnane, J.M., Gnjatic, S., Gonzalez-Ericsson, P.I., Grigoriadis, A., Halama, N., Hanna, M.G., Harbhajanka, A., Hardas, A., Hart, S.N., Hartman, J., Hewitt, S., Hida, A.I., Horlings, H.M., Husain, Z., Hytopoulos, E., Irshad, S., Janssen, E.a, Kahila, M., Kataoka, T.R., Kawaguchi, K., Kharidehal, D., Khramtsov, A.I., Kiraz, U., Kirtani, P., Kodach, L.L., Korski, K., Kovács, A., Laenkholm, A.V., Lang-Schwarz, C., Larsimont, D., Lennerz, J.K., Lerousseau, M., Li, Xiaoxian, Ly, Amy, Madabhushi, A., Maley, S.K., Manur Narasimhamurthy, V., Marks, D.K., McDonald, E.S., Mehrotra, R., Michiels, S., Minhas, F.U.A.A., Mittal, S., Moore, D.A., Mushtaq, S., Nighat, H., Papathomas, T., Penault-Llorca, F., Perera, R.D., Pinard, C.J., Pinto-Cardenas, J.C., Pruneri, G., Pusztai, L., Rahman, A., Rajpoot, N.M., Rapoport, B.L., Rau, T.T., Reis-Filho, J.S., Ribeiro, J.M., Rimm, D., Vincent-Salomon, A., Salto-Tellez, M., Saltz, J., Sayed, S., Siziopikou, K.P., Sotiriou, C., Stenzinger, A., Sughayer, M.A., Sur, D., Symmans, F., Tanaka, S., Taxter, T., Tejpar, S., Teuwen, J., Thompson, E.A., Tramm, T., Tran, W.T., Laak, J.A.W.M. van der, Diest, P.J. van, Verghese, G.E., Viale, G., Vieth, M., Wahab, N., Walter, T., Waumans, Y., Wen, H.Y., Yang, W, Yuan, Y., Adams, S., Bartlett, J.M.S., Loibl, S., Denkert, C., Savas, P., Loi, S., Salgado, R., and Specht Stovgaard, E.

Abstract

01 augustus 2023, Contains fulltext : 296131.pdf (Publisher’s version ) (Closed access), Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.

Published
2023

14. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, K., Haynes, H. R., Blackley, E., Fineberg, S., Shear, J., Turner, S., de Freitas, J. R., Sur, D., Amendola, L. C., Gharib, M., Kallala, A., Arun, I., Azmoudeh-Ardalan, F., Fujimoto, L., Sua, L. F., Liu, S. -W., Lien, H. -C., Kirtani, P., Balancin, M., El Attar, H., Guleria, P., Yang, W., Shash, E., Chen, I. -C., Bautista, V., Do Prado Moura, J. F., Rapoport, B. L., Castaneda, C., Spengler, E., Acosta-Haab, G., Frahm, I., Sanchez, J., Castillo, M., Bouchmaa, N., Md Zin, R. R., Shui, R., Onyuma, T., Husain, Z., Willard-Gallo, K., Coosemans, A., Perez, E. A., Provenzano, E., Ericsson, P. G., Richardet, E., Mehrotra, R., Sarancone, S., Ehinger, A., Rimm, D. L., Bartlett, J. M. S., Viale, G., Denkert, C., Hida, A. I., Sotiriou, C., Loibl, S., Hewitt, S. M., Badve, S., Symmans, W. F., Kim, R. S., Pruneri, G., Goel, S., Francis, P. A., Inurrigarro, G., Yamaguchi, R., Garcia-Rivello, H., Horlings, H., Afqir, S., Salgado, R., Adams, S., Kok, M., Dieci, M. V., Michiels, S., Demaria, S., Loi, S., Schelfhout, V., Arbzadeh, E., Bondanar, A., Reyes, S. A. G., Ruz, J. R., Kang, J., Xiang, L., Zimovjanova, M., Togores, P., Ozturk, T., Patil, A., Corpa, M., Whitehouse, A., Tan, B., de Paula, A., Rossetti, C., Lang-Schwarz, C., Mahon, S., Giacometti, C., Linderholm, B., Deman, F., Montagna, G., Gong, G., Pavcovich, M., Chaer, Y., Cabrero, I. A., de Brito, M. L., Ilieva, N., Fulop, A., Souza, M., Bilancia, D., Idowu, M., Johri, R., Szpor, J., Bachani, L., Schmitt, F., Giannotti, M., Kurebayashi, Y., Ramirez, B. E. A., Salido, E., Bortesi, L., Bonetto, S., Elomina, K., Lopez, P., Sharma, V., Edirisinghe, A., Mathur, D., Sahay, A., Mouloud, M. A., Giang, C. H., Mukolwe, E., Kiruka, E., Samberg, N., Abe, N., Brown, M., Millar, E., X. B., Li, Yuan, Z., Pasupathy, A., Miele, R., Luff, R., e Porfirio, M. M. A., Ajemba, O., Soni, R., Orvieto, E., Dimaio, M., Thomas, J., Merard, R., Subramaniam, M. M., Apolinario, T., Preda, O., Preda, R., Makanga, A., Maior, M. S., Li, L., Saghatchian, M., Saurine, T., Janssen, E., Cochran, J., Vlada, N., Cappellesso, R., Elfer, K., Hollick, M., Desai, S., Oner, G., Schreurs, A., Liu, S., Perera, R., Mercurio, P., Garcia, F., Hosny, K., Matsumoto, H., van Deurzen, C., Bianchini, G., Coban, I., Jahangir, A., Rahman, A., Stover, D., Luz, P., Martel, A., Waumans, Y., Stenzinger, A., Cortes, J., Dimitrova, P., Nauwelaers, I., Velasco, M., Fan, F., Akturk, G., Firer, M., Roxanis, I., Schneck, M., Wen, H., Cockenpot, V., Konstantinov, A., Calatrava, A., Vidya, M. N., Choi, H. J., Jank, P., Ciinen, A. H., Sabanathan, D., Floris, G., Hoeflmayer, D., Hamada, T., Laudus, N., Grigoriadis, A., Porcellato, I., Acs, B., Miglietta, F., Parrodi, J., Clunie, D., Calhoun, B., F. -I., Lu, Lefevre, A., Tabbarah, S., Tran, W., Garcia-murillas, I., Jelinic, P., Boeckx, C., Souza, S., Cebollero, M. C., Felip, E., Rendon, J. L. S., El Gabry, E., Saltz, J., Bria, E., Garufi, G., Hartman, J., Sebastian, M., Olofsson, H., Kooreman, L., Cucherousset, J., Mathieu, M. -C., Ballesteros-Merino, C., Siziopikou, P., Fong, J., Klein, M., Qulis, I. R. I., Wesseling, J., Bellolio, E., Araya, J. C., Naber, S., Cheang, M., Castellano, I., Ales, A., Laenkholm, A. -V., Kulka, J., Quinn, C., Sapino, A., Amendoeira, I., Marchio, C., Braybrooke, J., Vincent-Salomon, A., Korski, K. P., Sofopoulos, M., Stovgaard, E. I. S., Bianchi, S., Bago-Horvath, Z., Yu, C., Regitnig, P., Hall, S., Kos, Z., Sant, S., Tille, J. -C., Gallas, B., Bethmann, D., Savas, P., Mendes, L., Soler, T., van Seijen, M., Gruosso, T., Quintana, A., Giltnane, J., Van den Eynden, G., Duregon, E., de Cabo, R., Recamo, P. C., Gaboury, L., Zimmerman, J., Pop, C. S., Wernicke, A., Williams, D., Gill, A., Solomon, B., Thapa, B., Farshid, G., Gilham, L., Christie, M., O'Toole, S., Hendry, S., Fox, S. B., Luen, S. J., Lakhani, S. R., Fuchs, T., John, T., Brcic, I., Hainfellner, J., Sigurd, L., Preusser, M., Poortmans, P., Decaluwe, A., Carey, C., Colpaert, C., Larsimont, D., Peeters, D., Broeckx, G., van de Vijver, K., Buisseret, L., Dirix, L., Hertoghs, M., Piccart, M., Ignatiadis, M., Van Bockstal, M., Sirtaine, N., Vermeulen, P., de Wind, R., Declercq, S., Gevaert, T., Haibe-Kans, B., Nelson, B. H., Watson, P. H., Leung, S., Nielsen, T., Shi, L., Balslev, E., Thagaard, J., Almangush, A., Makitie, A., Joensuu, H., Lundin, J., Drubay, D., Roblin, E., Andre, F., Penault-Llorca, F., Lemonnier, J., Adam, J., Lacroix-Triki, M., Ternes, N., Radosevic-Robin, N., Klaushen, F., Weber, K., Harbeck, N., Gluz, O., Wienert, S., Cserni, G., Vingiani, A., Criscitiello, C., Solinas, C., Curigliano, G., Konishi, E., Suzuki, E., Yoshikawa, K., Kawaguchi, K., Takada, M., Toi, M., Ishida, M., Shibata, N., Saji, S., Kogawa, T., Sakatani, T., Okamoto, T., Moriya, T., Kataoka, T., Shimoi, T., Sugie, T., Mukohara, T., Shu, Y., Kikawa, Y., Kozuka, Y., Sayed, S., Rahayu, R., Ramsaroop, R., Senkus-Konefka, E., Chmielik, E., Cardoso, F., Ribeiro, J., Chan, J., Dent, R., Martin, M., Hagen, C., Guerrero, A., Rojo, F., Comerma, L., Nuciforo, P., Serrano, V. V., Camaea, V. P., Steenbruggen, T., Ciompi, F., Nederlof, I., Jan, Hudecek, van der Laak, J., van den Berg, J., Voorwerk, L., van de Vijver, M., de Maaker, M., Linn, S., Mckenzie, H., Somaiah, N., Tutt, A., Swanton, C., Hiley, C., Moore, D. A., Hall, J. A., Le Quesne, J., Jabbar, K. A., al Bakir, M., Hills, R., Irshad, S., Yuan, Y., Li, Z., Liu, M., Klein, J., Fadare, O., Thompson, A., Lazar, A. J., Gown, A., Lo, A., Garrido Castro, A. C., Madabhushi, A., Moreira, A., Richardson, A., Beck, A. H., Bellizzi, A. M., Wolff, A., Harbhajanka, A., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Singh, B., Chennubhotla, C. S., Chauhan, C., Dillon, D. A., Zardavas, D., Johnson, D. B., Thompson, A. E., Brogi, E., Reisenbichler, E., Huang, E., Hirsch, F. R., Mcarthur, H., Ziai, J., Brock, J., Kerner, J., Zha, J., Lennerz, J. K., Carter, J. M., Reis-Filho, J., Sparano, J., Balko, J. M., Pogue-Geile, K., Steele, K. E., Blenman, K. R. M., Allison, K. H., Pusztai, L., Cooper, L., Estrada, V. M., Flowers, M., Robson, M., Rebelatto, M. C., Hanna, M. G., Goetz, M. P., Khojasteh, M., Sanders, M. E., Regan, M. M., Misialek, M., Amgad, M., Tung, N., Singh, R., Huang, R., Pierce, R. H., Leon-Ferre, R., Swain, S., Ely, S., Kim, S. -R., Bedri, S., Paik, S., Schnitt, S., D'Alfons, T., Kurkure, U., Bossuyt, V., Tong, W., Wang, Y., Dos Anjos, C. H., Gaire, F., Van Diest, P. J., El Bairi, Khalid [0000-0002-8414-4145], de Freitas, Juliana Ribeiro [0000-0003-4978-7273], Sur, Daniel [0000-0002-0926-4614], Amendola, Luis Claudio [0000-0002-6404-450X], Azmoudeh-Ardalan, Farid [0000-0003-4701-0532], Kirtani, Pawan [0000-0002-2343-7016], Yang, Wenxian [0000-0002-5349-9680], Castillo, Miluska [0000-0002-0111-3176], Provenzano, Elena [0000-0003-3345-3965], Mehrotra, Ravi [0000-0001-9453-1408], Ehinger, Anna [0000-0001-9225-7396], Rimm, David L [0000-0001-5820-4397], Bartlett, John MS [0000-0002-0347-3888], Denkert, Carsten [0000-0002-2249-0982], Hida, Akira I [0000-0002-4486-8819], Sotiriou, Christos [0000-0002-5745-9977], Hewitt, Stephen M [0000-0001-8283-1788], Badve, Sunil [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Goel, Shom [0000-0001-8329-9084], Francis, Prudence A [0000-0002-7207-9286], Horlings, Hugo [0000-0003-4782-8828], Salgado, Roberto [0000-0002-1110-3801], Demaria, Sandra [0000-0003-4426-0499], Loi, Sherene [0000-0001-6137-9171], Apollo - University of Cambridge Repository, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), and UNICANCER

Subjects
Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], TRASTUZUMAB, Improved survival, MICROENVIRONMENT, Review Article, SUBTYPES, NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, Breast cancer, Ecology,Evolution & Ethology, PROGNOSTIC-SIGNIFICANCE, Medicine and Health Sciences, Pharmacology (medical), TUMOR-INFILTRATING LYMPHOCYTES, Stage (cooking), RC254-282, Chemical Biology & High Throughput, 0303 health sciences, Human Biology & Physiology, Genome Integrity & Repair, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, ASSOCIATION, 3. Good health, 030220 oncology & carcinogenesis, Biomarker (medicine), Life Sciences & Biomedicine, Genetics & Genomics, medicine.medical_specialty, chemical and pharmacologic phenomena, International Immuno-Oncology Biomarker Working Group, Predictive markers, 03 medical and health sciences, Signalling & Oncogenes, SDG 3 - Good Health and Well-being, Internal medicine, 692/53/2423, medicine, Radiology, Nuclear Medicine and imaging, In patient, 030304 developmental biology, Computational & Systems Biology, Science & Technology, IDENTIFICATION, business.industry, review-article, Cancer, 03.01. Általános orvostudomány, Immunotherapy, Tumour Biology, medicine.disease, PREDICTIVE-VALUE, 692/4028/67/1347, Programmed death 1, business, FREE SURVIVAL
Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

Published
2021

15. The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Author

El Bairi, K, Haynes, HR, Blackley, E, Fineberg, S, Shear, J, Turner, S, de Freitas, JR, Sur, D, Amendola, LC, Gharib, M, Kallala, A, Arun, I, Azmoudeh-Ardalan, F, Fujimoto, L, Sua, LF, Liu, S-W, Lien, H-C, Kirtani, P, Balancin, M, El Attar, H, Guleria, P, Yang, W, Shash, E, Chen, I-C, Bautista, V, Do Prado Moura, JF, Rapoport, BL, Castaneda, C, Spengler, E, Acosta-Haab, G, Frahm, I, Sanchez, J, Castillo, M, Bouchmaa, N, Zin, RRM, Shui, R, Onyuma, T, Husain, Z, Willard-Gallo, K, Coosemans, A, Perez, EA, Provenzano, E, Ericsson, PG, Richardet, E, Mehrotra, R, Sarancone, S, Ehinger, A, Rimm, DL, Bartlett, JMS, Viale, G, Denkert, C, Hida, AI, Sotiriou, C, Loibl, S, Hewitt, SM, Badve, S, Symmans, WF, Kim, RS, Pruneri, G, Goel, S, Francis, PA, Inurrigarro, G, Yamaguchi, R, Garcia-Rivello, H, Horlings, H, Afqir, S, Salgado, R, Adams, S, Kok, M, Dieci, MV, Michiels, S, Demaria, S, Loi, S, El Bairi, K, Haynes, HR, Blackley, E, Fineberg, S, Shear, J, Turner, S, de Freitas, JR, Sur, D, Amendola, LC, Gharib, M, Kallala, A, Arun, I, Azmoudeh-Ardalan, F, Fujimoto, L, Sua, LF, Liu, S-W, Lien, H-C, Kirtani, P, Balancin, M, El Attar, H, Guleria, P, Yang, W, Shash, E, Chen, I-C, Bautista, V, Do Prado Moura, JF, Rapoport, BL, Castaneda, C, Spengler, E, Acosta-Haab, G, Frahm, I, Sanchez, J, Castillo, M, Bouchmaa, N, Zin, RRM, Shui, R, Onyuma, T, Husain, Z, Willard-Gallo, K, Coosemans, A, Perez, EA, Provenzano, E, Ericsson, PG, Richardet, E, Mehrotra, R, Sarancone, S, Ehinger, A, Rimm, DL, Bartlett, JMS, Viale, G, Denkert, C, Hida, AI, Sotiriou, C, Loibl, S, Hewitt, SM, Badve, S, Symmans, WF, Kim, RS, Pruneri, G, Goel, S, Francis, PA, Inurrigarro, G, Yamaguchi, R, Garcia-Rivello, H, Horlings, H, Afqir, S, Salgado, R, Adams, S, Kok, M, Dieci, MV, Michiels, S, Demaria, S, and Loi, S

Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Published
2021

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

Author

Kos, Z., Roblin, E., Kim, R. S., Michiels, S., Gallas, B. D., Chen, W., van de Vijver, K. K., Goel, S., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S., Denkert, C., Loibl, S., Luen, S. J., Bartlett, J. M. S., Savas, P., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kok, M., Horlings, H. M., Madabhushi, A., van der Laak, J., Ciompi, F., Laenkholm, A. -V., Bellolio, E., Gruosso, T., Fox, S. B., Araya, J. C., Floris, G., Hudecek, J., Voorwerk, L., Beck, A. H., Kerner, J., Larsimont, D., Declercq, S., Van den Eynden, G., Pusztai, L., Ehinger, A., Yang, W., Abduljabbar, K., Yuan, Y., Singh, R., Hiley, C., Bakir, M., Lazar, A. J., Naber, S., Wienert, S., Castillo, M., Curigliano, G., Dieci, M. -V., Andre, F., Swanton, C., Reis-Filho, J., Sparano, J., Balslev, E., Chen, I. -C., Stovgaard, E. I. S., Pogue-Geile, K., Blenman, K. R. M., Penault-Llorca, F., Schnitt, S., Lakhani, S. R., Vincent-Salomon, A., Rojo, F., Braybrooke, J. P., Hanna, M. G., Soler-Monso, M. T., Bethmann, D., Castaneda, C. A., Willard-Gallo, K., Sharma, A., Lien, H. -C., Fineberg, S., Thagaard, J., Comerma, L., Gonzalez-Ericsson, P., Brogi, E., Loi, S., Saltz, J., Klaushen, F., Cooper, L., Amgad, M., Moore, D. A., Salgado, R., Hyytiainen, A., Hida, A. I., Thompson, A., Lefevre, A., Gown, A., Lo, A., Sapino, A., Moreira, A. M., Richardson, A., Vingiani, A., Bellizzi, A. M., Guerrero, A., Grigoriadis, A., Garrido-Castro, A. C., Cimino-Mathews, A., Srinivasan, A., Acs, B., Singh, B., Calhoun, B., Haibe-Kans, B., Solomon, B., Thapa, B., Nelson, B. H., Ballesteroes-Merino, C., Criscitiello, C., Boeckx, C., Colpaert, C., Quinn, C., Chennubhotla, C. S., Solinas, C., Drubay, D., Sabanathan, D., Peeters, D., Zardavas, D., Hoflmayer, D., Johnson, D. B., Thompson, E. A., Perez, E., Elgabry, E. A., Blackley, E. F., Reisenbichler, E., Chmielik, E., Gaire, F., F. -I., Lu, Azmoudeh-Ardalan, F., Peale, F., Hirsch, F. R., Acosta-Haab, G., Farshid, G., Broeckx, G., Koeppen, H., Haynes, H. R., Mcarthur, H., Joensuu, H., Olofsson, H., Cree, I., Nederlof, I., Frahm, I., Brcic, I., Chan, J., Ziai, J., Brock, J., Weseling, J., Giltnane, J., Lemonnier, J., Zha, J., Ribeiro, J., Lennerz, J. K., Carter, J. M., Hartman, J., Hainfellner, J., Le Quesne, J., Juco, J. W., van den Berg, J., Sanchez, J., Cucherousset, J., Adam, J., Balko, J. M., Saeger, K., Siziopikou, K., Sikorska, K., Weber, K., Steele, K. E., Emancipator, K., El Bairi, K., Allison, K. H., Korski, K., Buisseret, L., Shi, L., Kooreman, L. F. S., Molinero, L., Estrada, M. V., Van Seijen, M., Lacroix-Triki, M., Sebastian, M. M., Balancin, M. L., Mathieu, M. -C., van de Vijver, M., Rebelatto, M. C., Piccart, M., Goetz, M. P., Preusser, M., Khojasteh, M., Sanders, M. E., Regan, M. M., Barnes, M., Christie, M., Misialek, M., Ignatiadis, M., de Maaker, M., Van Bockstal, M., Harbeck, N., Tung, N., Laudus, N., Sirtaine, N., Burchardi, N., Ternes, N., Radosevic-Robin, N., Gluz, O., Grimm, O., Nuciforo, P., Jank, P., Kirtani, P., Watson, P. H., Jelinic, P., Francis, P. A., Russell, P. A., Pierce, R. H., Hills, R., Leon-Ferre, R., de Wind, R., Shui, R., Leung, S., Tabbarah, S., Souza, S. C., O'Toole, S., Swain, S., Dudgeon, S., Willis, S., Ely, S., Bedri, S., Irshad, S., Liu, S., Hendry, S., Bianchi, S., Braganca, S., Paik, S., Luz, S., Gevaert, T., D'Alfons, T., John, T., Sugie, T., Kurkure, U., Bossuyt, V., Manem, V., Camaea, V. P., Tong, W., Tran, W. T., Wang, Y., Allory, Y., Husain, Z., Bago-Horvath, Z., Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Charité, Institute of Pathology, Translational Tumorpathology Unit, German Breast Group, University of the Sunshine Coast (USC), European Institute of Oncology [Milan] (ESMO), Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Pathology, The Netherlands Cancer Institute, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Odense University Hospital, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Breast Medical Oncology [Houston], The University of Texas M.D. Anderson Cancer Center [Houston], Helsingborg Hospital, Division of Experimental Therapeutics [Milan, Italy], Département de médecine oncologique [Gustave Roussy], Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni], University College of London [London] (UCL), Memorial Sloane Kettering Cancer Center [New York], Herlev and Gentofte Hospital, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Southern Queensland (USQ), Pharmacogenomics Unit [Paris], Department of Genetics [Paris], Institut Curie [Paris]-Institut Curie [Paris], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Ctr Biomol Struct & Org, University of Maryland [College Park], University of Maryland System-University of Maryland System, The University of Sydney, Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Int Immuno-Oncology Biomarker, Graduate School, CCA - Cancer biology and immunology, Pathology, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), German Breast Group (GBG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Gallas, Brandon D [0000-0001-7332-1620], van de Vijver, Koen K [0000-0002-2026-9790], Demaria, Sandra [0000-0003-4426-0499], Badve, Sunil S [0000-0001-8861-9980], Symmans, W Fraser [0000-0002-1526-184X], Rimm, David L [0000-0001-5820-4397], Savas, Peter [0000-0001-5999-428X], Hall, Jacqueline A [0000-0003-0708-1360], Horlings, Hugo M [0000-0003-4782-8828], van der Laak, Jeroen [0000-0001-7982-0754], Bellolio, Enrique [0000-0003-0079-5264], Araya, Juan Carlos [0000-0003-3501-8203], Floris, Giuseppe [0000-0003-2391-5425], Hudeček, Jan [0000-0003-1071-5686], Ehinger, Anna [0000-0001-9225-7396], Lazar, Alexander J [0000-0002-6395-4499], Castillo, Miluska [0000-0002-0111-3176], Curigliano, Giuseppe [0000-0003-1781-2518], Sparano, Joseph [0000-0002-9031-2010], Braybrooke, Jeremy P [0000-0003-1943-7360], Hanna, Matthew G [0000-0002-7536-1746], Willard-Gallo, Karen [0000-0002-1150-1295], Sharma, Ashish [0000-0002-1011-6504], Comerma, Laura [0000-0002-0249-4636], Gonzalez-Ericsson, Paula [0000-0002-6292-6963], Loi, Sherene [0000-0001-6137-9171], Cooper, Lee [0000-0002-3504-4965], Apollo - University of Cambridge Repository, Research Programs Unit, Heikki Joensuu / Principal Investigator, HUS Comprehensive Cancer Center, Department of Oncology, Medicum, Gallas, Brandon D. [0000-0001-7332-1620], van de Vijver, Koen K. [0000-0002-2026-9790], Badve, Sunil S. [0000-0001-8861-9980], Symmans, W. Fraser [0000-0002-1526-184X], Rimm, David L. [0000-0001-5820-4397], Hall, Jacqueline A. [0000-0003-0708-1360], Horlings, Hugo M. [0000-0003-4782-8828], Lazar, Alexander J. [0000-0002-6395-4499], Braybrooke, Jeremy P. [0000-0003-1943-7360], and Hanna, Matthew G. [0000-0002-7536-1746]

Subjects
Oncology, [SDV]Life Sciences [q-bio], THERAPY, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Prognostic markers, 0302 clinical medicine, Breast cancer, Medicine and Health Sciences, Pharmacology (medical), Lymphocytes, Stromal tumor, health care economics and organizations, 0303 health sciences, CHEMOTHERAPY, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], PROGNOSTIC VALUE, Clinical Practice, 030220 oncology & carcinogenesis, Educational resources, Immunosurveillance, medicine.medical_specialty, 3122 Cancers, [SDV.CAN]Life Sciences [q-bio]/Cancer, IMMUNITY, lcsh:RC254-282, Article, Limfòcits, Càncer de mama, 03 medical and health sciences, Gastrointestinal cancer, SDG 3 - Good Health and Well-being, Internal medicine, 692/53/2422, medicine, Radiology, Nuclear Medicine and imaging, Càncer gastrointestinal, 030304 developmental biology, Predictive biomarker, Tumor-infiltrating lymphocytes, business.industry, Médecine pathologie humaine, medicine.disease, Cancérologie, Human medicine, business, SYSTEM, 631/67/580/1884
Abstract

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

Published
2020

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

Author

Hudecek, J., Voorwerk, L., van Seijen, M., Nederlof, I., de Maaker, M., van den Berg, J., van de Vijver, K. K., Sikorska, K., Adams, S., Demaria, S., Viale, G., Nielsen, T. O., Badve, S. S., Michiels, S., Symmans, W. F., Sotiriou, C., Rimm, D. L., Hewitt, S. M., Denkert, C., Loibl, S., Loi, S., Bartlett, J. M. S., Pruneri, G., Dillon, D. A., Cheang, M. C. U., Tutt, A., Hall, J. A., Kos, Z., Salgado, R., Kok, M., Horlings, H. M., Hyytiainen, A., Hida, A. I., Thompson, A., Lefevre, A., Lazar, A. J., Gown, A., Lo, A., Sapino, A., Madabhushi, A., Moreira, A., Richardson, A., Vingiani, A., Beck, A. H., Bellizzi, A. M., Guerrero, A., Grigoriadis, A., Ehinger, A., Garrido-Castro, A., Vincent-Salomon, A., Laenkholm, A. -V., Sharma, A., Cimino-Mathews, A., Srinivasan, A., Acs, B., Singh, B., Calhoun, B., Haibe-Kans, B., Solomon, B., Thapa, B., Nelson, B. H., Gallas, B. D., Castaneda, C., Ballesteros-Merino, C., Criscitiello, C., Boeckx, C., Colpaert, C., Quinn, C., Chennubhotla, C. S., Swanton, C., Solinas, C., Hiley, C., Drubay, D., Bethmann, D., Moore, D. A., Larsimont, D., Sabanathan, D., Peeters, D., Zardavas, D., Hoflmayer, D., Johnson, D. B., Thompson, E. A., Brogi, E., Perez, E., Elgabry, E. A., Stovgaard, E. S., Blackley, E. F., Roblin, E., Reisenbichler, E., Bellolio, E., Balslev, E., Chmielik, E., Gaire, F., Andre, F., F. -I., Lu, Azmoudeh-Ardalan, F., Rojo, F., Gruosso, T., Ciompi, F., Peale, F., Hirsch, F. R., Klauschen, F., Penault-Llorca, F., Acosta Haab, G., Farshid, G., van den Eynden, G., Curigliano, G., Floris, G., Broeckx, G., Gonzalez-Ericsson, Koeppen, H., Haynes, H. R., Mcarthur, H., Joensuu, H., Olofsson, H., Lien, H. -C., Chen, I. -C., Cree, I., Frahm, I., Brcic, I., Chan, J., Ziai, J., Brock, J., Wesseling, J., Giltnane, J., Kerner, J. K., Thagaard, J., Braybrooke, J. P., van der Laak, J. A. W. M., Lemonnier, J., Zha, J., Ribeiro, J., Lennerz, J. K., Carter, J. M., Saltz, J., Hartman, J., Hainfellner, J., Quesne, J. L., Juco, J. W., Reis-Filho, J., Sanchez, J., Sparano, J., Cucherousset, J., Araya, J. C., Adam, J., Balko, J. M., Saeger, K., Siziopikou, K., Willard-Gallo, K., Weber, K., Pogue-Geile, K. L., Steele, K. E., Emancipator, K., Abduljabbar, K., El Bairi, K., Blenman, K. R. M., Allison, K. H., Korski, K., Pusztai, L., Comerma, L., Buisseret, L., Cooper, L. A. D., Shi, L., Kooreman, L. F. S., Molinero, L., Estrada, M. V., Lacroix-Triki, M., Al Bakir, M., Sebastian, M. M., van de Vijver, M., Balancin, M. L., Dieci, M. V., Mathieu, M. -C., Rebelatto, M. C., Piccart, M., Hanna, M. G., Goetz, M. P., Preusser, M., Khojasteh, M., Sanders, M. E., Regan, M. M., Barnes, M., Christie, M., Misialek, M., Ignatiadis, M., van Bockstal, M., Castillo, M., Amgad, M., Harbeck, N., Tung, N., Laudus, N., Sirtaine, N., Burchardi, N., Ternes, N., Radosevic-Robin, N., Gluz, O., Grimm, O., Nuciforo, P., Jank, P., Gonzalez-Ericsson, P., Kirtani, P., Jelinic, P., Watson, P. H., Savas, P., Francis, P. A., Russell, P. A., Singh, R., Kim, R. S., Pierce, R. H., Hills, R., Leon-Ferre, R., de Wind, R., Shui, R., De Clercq, S., Leung, S., Tabbarah, S., Souza, S. C., O'Toole, S., Swain, S., Dudgeon, S., Willis, S., Ely, S., Kim, S. -R., Bedri, S., Irshad, S., Liu, S. -W., Goel, S., Hendry, S., Bianchi, S., Braganca, S., Paik, S., Wienert, S., Fox, S. B., Luen, S. J., Naber, S., Schnitt, S. J., Sua, L. F., Lakhani, S. R., Fineberg, S., Soler, T., Gevaert, T., D'Alfonso, T., John, T., Sugie, T., Kurkure, U., Bossuyt, V., Manem, V., Camara, V. P., Tong, W., Chen, W., Yang, W., Tran, W. T., Wang, Y., Yuan, Y., Allory, Y., Husain, Z., Bago-Horvath, Z., Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Charité, Institute of Pathology, Translational Tumorpathology Unit, German Breast Group, Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), University of the Sunshine Coast (USC), European Institute of Oncology [Milan] (ESMO), Breakthrough Breast Cancer Centre, London Institute of Cancer, Department of Pathology, The Netherlands Cancer Institute, Division of Experimental Therapy, The Netherlands Cancer Institute NKI/AvL, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hudeček, Jan [0000-0003-1071-5686], van de Vijver, Koen K [0000-0002-2026-9790], Demaria, Sandra [0000-0003-4426-0499], Badve, Sunil S [0000-0001-8861-9980], Symmans, William Fraser [0000-0002-1526-184X], Rimm, David L [0000-0001-5820-4397], Loi, Sherene [0000-0001-6137-9171], Hall, Jacqueline A [0000-0003-0708-1360], Horlings, Hugo M [0000-0003-4782-8828], Apollo - University of Cambridge Repository, van de Vijver, Koen K. [0000-0002-2026-9790], Badve, Sunil S. [0000-0001-8861-9980], Rimm, David L. [0000-0001-5820-4397], Hall, Jacqueline A. [0000-0003-0708-1360], Horlings, Hugo M. [0000-0003-4782-8828], Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, German Breast Group (GBG), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review Article, lcsh:RC254-282, 631/67/1857, Tumour biomarkers, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 692/53, Internal medicine, Medicine and Health Sciences, medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, 692/4028/67/580, Stromal tumor, Biomarkers, Tumour immunology, business.industry, Risk management framework, review-article, Médecine pathologie humaine, 631/67/1347, Immunotherapy, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Review article, Clinical trial, Cancérologie, 030104 developmental biology, 030220 oncology & carcinogenesis, Biomarker (medicine), business
Abstract

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

Published
2020

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

Author

Amgad, M., Stovgaard, E.S., Balslev, E., Thagaard, J., Chen, W, Dudgeon, S., Sharma, A., Kerner, J.K., Denkert, C., Yuan, Y., AbdulJabbar, K., Wienert, S., Savas, P., Voorwerk, L., Beck, A.H., Madabhushi, A., Hartman, J., Sebastian, M.M., Horlings, H.M., Hudecek, J., Ciompi, F., Moore, D.A.J., Singh, R., Roblin, E., Balancin, M.L., Mathieu, M.C., Lennerz, J.K., Kirtani, P., Chen, I.C., Braybrooke, J.P., Pruneri, G., Demaria, S., Adams, S., Schnitt, S.J., Lakhani, S.R., Rojo, F., Comerma, L., Badve, S.S., Khojasteh, M., Symmans, W.F., Sotiriou, C., Gonzalez-Ericsson, P., Pogue-Geile, K.L., Kim, R.S., Rimm, D.L., Viale, G., Hewitt, S.M., Bartlett, J.M.S., Penault-Llorca, F., Goel, S., Lien, H.C., Loibl, S., Kos, Z., Loi, S., Hanna, M.G., Michiels, S., Kok, M., Nielsen, T.O., Lazar, A.J., Bago-Horvath, Z., Kooreman, L.F., Laak, J.A.W.M. van der, Saltz, J., Gallas, B.D., Kurkure, U., Barnes, M., Salgado, R., Cooper, L.A.D., Amgad, M., Stovgaard, E.S., Balslev, E., Thagaard, J., Chen, W, Dudgeon, S., Sharma, A., Kerner, J.K., Denkert, C., Yuan, Y., AbdulJabbar, K., Wienert, S., Savas, P., Voorwerk, L., Beck, A.H., Madabhushi, A., Hartman, J., Sebastian, M.M., Horlings, H.M., Hudecek, J., Ciompi, F., Moore, D.A.J., Singh, R., Roblin, E., Balancin, M.L., Mathieu, M.C., Lennerz, J.K., Kirtani, P., Chen, I.C., Braybrooke, J.P., Pruneri, G., Demaria, S., Adams, S., Schnitt, S.J., Lakhani, S.R., Rojo, F., Comerma, L., Badve, S.S., Khojasteh, M., Symmans, W.F., Sotiriou, C., Gonzalez-Ericsson, P., Pogue-Geile, K.L., Kim, R.S., Rimm, D.L., Viale, G., Hewitt, S.M., Bartlett, J.M.S., Penault-Llorca, F., Goel, S., Lien, H.C., Loibl, S., Kos, Z., Loi, S., Hanna, M.G., Michiels, S., Kok, M., Nielsen, T.O., Lazar, A.J., Bago-Horvath, Z., Kooreman, L.F., Laak, J.A.W.M. van der, Saltz, J., Gallas, B.D., Kurkure, U., Barnes, M., Salgado, R., and Cooper, L.A.D.

Abstract

Contains fulltext : 220833.pdf (publisher's version ) (Open Access), Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

Published
2020

20. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice

Author

Gonzalez-Ericsson, P, Stovgaard, ES, Sua, LF, Reisenbichler, E, Kos, Z, Carter, JM, Michiels, S, Le Quesne, J, Nielsen, TO, Laenkholm, A-V, Fox, SB, Adam, J, Bartlett, JMS, Rimm, DL, Quinn, C, Peeters, D, Dieci, M, Vincent-Salomon, A, Cree, I, Hida, A, Balko, JM, Haynes, HR, Frahm, I, Acosta-Haab, G, Balancin, M, Bellolio, E, Yang, W, Kirtani, P, Sugie, T, Ehinger, A, Castaneda, CA, Kok, M, McArthur, H, Siziopikou, K, Badve, S, Fineberg, S, Gown, A, Viale, G, Schnitt, SJ, Pruneri, G, Penault-Llorca, F, Hewitt, S, Thompson, EA, Allison, KH, Symmans, WF, Bellizzi, AM, Brogi, E, Moore, DA, Larsimont, D, Dillon, DA, Lazar, A, Lien, H, Goetz, MP, Broeckx, G, El Bairi, K, Harbeck, N, Cimino-Mathews, A, Sotiriou, C, Adams, S, Liu, S-W, Loibl, S, Chen, I-C, Lakhani, SR, Juco, JW, Denkert, C, Blackley, EF, Demaria, S, Leon-Ferre, R, Gluz, O, Zardavas, D, Emancipator, K, Ely, S, Loi, S, Salgado, R, Sanders, M, Gonzalez-Ericsson, P, Stovgaard, ES, Sua, LF, Reisenbichler, E, Kos, Z, Carter, JM, Michiels, S, Le Quesne, J, Nielsen, TO, Laenkholm, A-V, Fox, SB, Adam, J, Bartlett, JMS, Rimm, DL, Quinn, C, Peeters, D, Dieci, M, Vincent-Salomon, A, Cree, I, Hida, A, Balko, JM, Haynes, HR, Frahm, I, Acosta-Haab, G, Balancin, M, Bellolio, E, Yang, W, Kirtani, P, Sugie, T, Ehinger, A, Castaneda, CA, Kok, M, McArthur, H, Siziopikou, K, Badve, S, Fineberg, S, Gown, A, Viale, G, Schnitt, SJ, Pruneri, G, Penault-Llorca, F, Hewitt, S, Thompson, EA, Allison, KH, Symmans, WF, Bellizzi, AM, Brogi, E, Moore, DA, Larsimont, D, Dillon, DA, Lazar, A, Lien, H, Goetz, MP, Broeckx, G, El Bairi, K, Harbeck, N, Cimino-Mathews, A, Sotiriou, C, Adams, S, Liu, S-W, Loibl, S, Chen, I-C, Lakhani, SR, Juco, JW, Denkert, C, Blackley, EF, Demaria, S, Leon-Ferre, R, Gluz, O, Zardavas, D, Emancipator, K, Ely, S, Loi, S, Salgado, R, and Sanders, M

Published
2020

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

Author

Amgad, M, Stovgaard, ES, Balslev, E, Thagaard, J, Chen, W, Dudgeon, S, Sharma, A, Kerner, JK, Denkert, C, Yuan, Y, AbdulJabbar, K, Wienert, S, Savas, P, Voorwerk, L, Beck, AH, Madabhushi, A, Hartman, J, Sebastian, MM, Horlings, HM, Hudecek, J, Ciompi, F, Moore, DA, Singh, R, Roblin, E, Balancin, ML, Mathieu, M-C, Lennerz, JK, Kirtani, P, Chen, I-C, Braybrooke, JP, Pruneri, G, Demaria, S, Adams, S, Schnitt, SJ, Lakhani, SR, Rojo, F, Comerma, L, Badve, SS, Khojasteh, M, Symmans, WF, Sotiriou, C, Gonzalez-Ericsson, P, Pogue-Geile, KL, Kim, RS, Rimm, DL, Viale, G, Hewitt, SM, Bartlett, JMS, Penault-Llorca, F, Goel, S, Lien, H-C, Loibl, S, Kos, Z, Loi, S, Hanna, MG, Michiels, S, Kok, M, Nielsen, TO, Lazar, AJ, Bago-Horvath, Z, Kooreman, LFS, van der Laak, JAWM, Saltz, J, Gallas, BD, Kurkure, U, Barnes, M, Salgado, R, Cooper, LAD, Amgad, M, Stovgaard, ES, Balslev, E, Thagaard, J, Chen, W, Dudgeon, S, Sharma, A, Kerner, JK, Denkert, C, Yuan, Y, AbdulJabbar, K, Wienert, S, Savas, P, Voorwerk, L, Beck, AH, Madabhushi, A, Hartman, J, Sebastian, MM, Horlings, HM, Hudecek, J, Ciompi, F, Moore, DA, Singh, R, Roblin, E, Balancin, ML, Mathieu, M-C, Lennerz, JK, Kirtani, P, Chen, I-C, Braybrooke, JP, Pruneri, G, Demaria, S, Adams, S, Schnitt, SJ, Lakhani, SR, Rojo, F, Comerma, L, Badve, SS, Khojasteh, M, Symmans, WF, Sotiriou, C, Gonzalez-Ericsson, P, Pogue-Geile, KL, Kim, RS, Rimm, DL, Viale, G, Hewitt, SM, Bartlett, JMS, Penault-Llorca, F, Goel, S, Lien, H-C, Loibl, S, Kos, Z, Loi, S, Hanna, MG, Michiels, S, Kok, M, Nielsen, TO, Lazar, AJ, Bago-Horvath, Z, Kooreman, LFS, van der Laak, JAWM, Saltz, J, Gallas, BD, Kurkure, U, Barnes, M, Salgado, R, and Cooper, LAD

Abstract

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

Published
2020

23. Project management processes are important, but are stakeholders aligned correctly?

Author

Sharma, Hemant and Kirtani, Vikas

Abstract

This paper attempts to get a perspective on key stakeholders' thinking on processes and identify possible misalignment, which can have implications on project success. The study has identified that all stakeholders want closing processes to be structured and mandated. A gap in predisposition towards initiating processes between the contractor and other stakeholders is identified. Similarly, project manager's lower priority for monitoring processes can conflict with client's expectations. Stakeholder contractor has to review their initiating processes and project manager has to understand client's expectation on monitoring processes. Bridging these gaps can set a better relationship between stakeholders.

Published
2021
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25. Glioblastoma multiforme with gliosarcoma with metastasis to lung

Author

Singal, R.K., Agarwal, Amit, Khurana, Aseem, Bhasin, Atul, Kirtani, Pawan, and Vanjara, Wasim

Abstract

A 51year old female presented with headache and projectile vomiting of 1month duration, and her systemic examination was non-contributory. Blood and urine investigations were normal. MRI brain identified a mass lesion in the right frontal lobe and anterior body of corpus callosum with areas of peri-lesional edema. Craniotomy was performed with right frontal lobectomy and tumour excised. Biopsy confirmed Glioblastoma multiforme with gliosarcomatous areas. Adjuvant external beam irradiation with concurrent temozolamide was administered followed by adjuvant temozolamide. Subject developed breathlessness 8months after surgery, and PET scan performed revealed mildly enhancing metabolically active area in genu of corpus callosum and metabolically active left sided pleural based masses with left pleural effusion. Biopsy from the pleural based lesion was consistent with metastatic disease from Glioblastoma Multiforme. Extra-cranial metastasis in a case of glioblastoma multiforme is uncommon.

Published
2018
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26. In Vitro Characterization of Platelet Dysfunction In Common Hematological Disorders Using the Verify Now® Assay

Author

D’Abreo, Nina, Kirtani, Vatsala, Eisenstein, Jennifer L. Kujawa, Nouri, Yelda, Geller, Matt, and Staszewski, Harry

Abstract

Myelodysplastic syndrome (MDS), immune thrombocytopenia purpura (ITP) and myeloproliferative disorders (MPD) are frequent diagnoses in a community hematology practice. Qualitative platelet defects are common features of these disorders but are difficult to characterize in daily practice as specialized technology is not readily available. The Verify Now® (VN) is a rapid, point-of service assay to measure platelet aggregation. VN assesses the degree of inhibition of GPIIb/IIIa mediated aggregation and uses minimal sample preparation. Its main application currently, is to determine the adequacy of anti-platelet therapy with aspirin (ASA), thienopyridines, such as clopidogrel (CPL), and GPIIb/IIIa inhibitors in patients with cardiovascular disease. (Verify Now for IIb/IIIa, aspirin, and P2Y12, Instructions for Use, Accumetrics) We used VN to detect platelet aggregation defects in patients with ITP, MDS and MPD and compared the to a platelet function analyzer PFA -100. (Francis JL; In Michelson AD, ed. Platelets, 2nded. San Diego: Elsevier/Academic Press, 2007:535-544)Subjects with MDS, ITP, and MPD were identified from our Hematology practice. Informed consent was obtained from all patients. Patients taking aspirin and /or clopidogrel were not excluded. Platelet function was determined concurrently using VN and PFA-100 using standard reference ranges. (Verify Now for IIb/IIIa, aspirin, and P2Y12, Instructions for Use, Accumetrics), (Mammen EF et al; Semin Throm Hemost. 1998; 24 (2):195-205).Thirty three patients are enrolled in the study, 21 with ITP, 6 with MDS and 6 with MPD. Assay results are available for 30 patients. Platelet counts for all patients ranged from 2 to 1206 ×103/cmm, mean platelet count being 184 ×103/cmm (SD ± 215) and median count was 120 ×103/cmm.In 15 patients with ITP and platelet count ≥ 100 ×103/cmm, 11 were not on ASA/CPL. PFA-100 and VN each detected abnormalities in 4 patients but results were non-concordant in 2 patients. In 4 patients on ASA, VN detected ASA effect in all 4 whereas the PFA-100 detected 2.In 2 patients with platelet count < 100 ×103/cmm not on ASA/CPL, VN detected abnormalities in both, whereas PFA detected only 1. (Table 1)Two patients had counts ≥ 100 ×103/cmm. One was on ASA and both assays detected ASA effect. Neither assay detected an abnormality in the patient not on ASA.In 4 patients with counts <100 ×103/cmm, 3 were not on ASA/ CPL. Both assays detected abnormalities in all 3 and ASA effect in 1 patient on ASA. (Table 2)In 4 patients with counts < 400 ×103/cmm, not on ASA/CPL, both assays detected non-concordant abnormalities in 1 patient. Both assays detected CPL and ASA effect in 1 patient taking both drugs.2 patients had count ≥400,000. In 1 patient taking CPL, VN detected CPL effect but PFA did not. In 1 patient on ASA, PFA detected abnormality but VN did not. (Table 3)In patients with MDS, ITP, and MPD, abnormal platelet function is common. These results show that VN may be as sensitive for detecting platelet dysfunction as PFA-100. Results were especially concordant in MDS patients. We plan to include 150 patients to confirm these results. We hope to define qualitative platelet defects in this population so that appropriate intervention can be recommended prior to invasive procedures.No relevant conflicts of interest to declare.

Published
2010
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28. Immunohistochemical expression of bcl-2 oncoprotein in renal cell carcinoma

Author

Mathew, Mary and Hari, Kirtani Pawan

Abstract

Bcl-2 is a proto-oncogene known to be a negative regulator of apoptosis which confers prolonged cell survival and possibly contributes to tumorigenesis. A number of studies have been carried out to estimate and analyse its expression in renal tumours but the results have been conflicting. The aim of this study was to determine the expression and intensity of Bcl-2 in renal cell carcinomas (RCCs).

Published
2009
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29. 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 CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, Reis-Filho JS, Ly A, Harms PW, Gupta RR, Vieth M, Hida AI, Kahila M, Kos Z, van Diest PJ, Verbandt S, Thagaard J, Khiroya R, Abduljabbar K, Acosta Haab G, Acs B, Adams S, Almeida JS, Alvarado-Cabrero I, Azmoudeh-Ardalan F, Badve S, Baharun NB, Bellolio ER, Bheemaraju V, Blenman KR, Botinelly Mendonça Fujimoto L, Burgues O, Chardas A, Cheang MCU, Ciompi F, Cooper LA, Coosemans A, Corredor G, Dantas Portela FL, Deman F, Demaria S, Dudgeon SN, Elghazawy M, Fernandez-Martín C, Fineberg S, Fox SB, Giltnane JM, Gnjatic S, Gonzalez-Ericsson PI, Grigoriadis A, Halama N, Hanna MG, Harbhajanka A, Hart SN, Hartman J, Hewitt S, Horlings HM, Husain Z, Irshad S, Janssen EA, Kataoka TR, Kawaguchi K, Khramtsov AI, Kiraz U, Kirtani P, Kodach LL, Korski K, Akturk G, Scott E, Kovács A, Laenkholm AV, Lang-Schwarz C, Larsimont D, Lennerz JK, Lerousseau M, Li X, Madabhushi A, Maley SK, Manur Narasimhamurthy V, Marks DK, McDonald ES, Mehrotra R, Michiels S, Kharidehal D, Minhas FUAA, Mittal S, Moore DA, Mushtaq S, Nighat H, Papathomas T, Penault-Llorca F, Perera RD, Pinard CJ, Pinto-Cardenas JC, Pruneri G, Pusztai L, Rajpoot NM, Rapoport BL, Rau TT, Ribeiro JM, Rimm D, Vincent-Salomon A, Saltz J, Sayed S, Hytopoulos E, Mahon S, Siziopikou KP, Sotiriou C, Stenzinger A, Sughayer MA, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson EA, Tramm T, Tran WT, van der Laak J, Verghese GE, Viale G, Wahab N, Walter T, Waumans Y, Wen HY, Yang W, Yuan Y, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Specht Stovgaard E, Salgado R, Gallagher WM, and Rahman A

Subjects
Humans, Female, Biomarkers, Tumor genetics, Prognosis, Phenotype, United Kingdom, Tumor Microenvironment, Breast Neoplasms
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. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Published
2024
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30. 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 DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, Khiroya R, Kos Z, Abduljabbar K, Acosta Haab G, Acs B, Akturk G, Almeida JS, Alvarado-Cabrero I, Azmoudeh-Ardalan F, Badve S, Baharun NB, Bellolio ER, Bheemaraju V, Blenman KR, Botinelly Mendonça Fujimoto L, Bouchmaa N, Burgues O, Cheang MCU, Ciompi F, Cooper LA, Coosemans A, Corredor G, Dantas Portela FL, Deman F, Demaria S, Dudgeon SN, Elghazawy M, Ely S, Fernandez-Martín C, Fineberg S, Fox SB, Gallagher WM, Giltnane JM, Gnjatic S, Gonzalez-Ericsson PI, Grigoriadis A, Halama N, Hanna MG, Harbhajanka A, Hardas A, Hart SN, Hartman J, Hewitt S, Hida AI, Horlings HM, Husain Z, Hytopoulos E, Irshad S, Janssen EA, Kahila M, Kataoka TR, Kawaguchi K, Kharidehal D, Khramtsov AI, Kiraz U, Kirtani P, Kodach LL, Korski K, Kovács A, Laenkholm AV, Lang-Schwarz C, Larsimont D, Lennerz JK, Lerousseau M, Li X, Ly A, Madabhushi A, Maley SK, Manur Narasimhamurthy V, Marks DK, McDonald ES, Mehrotra R, Michiels S, Minhas FUAA, Mittal S, Moore DA, Mushtaq S, Nighat H, Papathomas T, Penault-Llorca F, Perera RD, Pinard CJ, Pinto-Cardenas JC, Pruneri G, Pusztai L, Rahman A, Rajpoot NM, Rapoport BL, Rau TT, Reis-Filho JS, Ribeiro JM, Rimm D, Vincent-Salomon A, Salto-Tellez M, Saltz J, Sayed S, Siziopikou KP, Sotiriou C, Stenzinger A, Sughayer MA, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson EA, Tramm T, Tran WT, van der Laak J, van Diest PJ, Verghese GE, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen HY, Yang W, Yuan Y, Adams S, Bartlett JMS, Loibl S, Denkert C, Savas P, Loi S, Salgado R, and Specht Stovgaard E

Subjects
Humans, Biomarkers, Benchmarking, Lymphocytes, Tumor-Infiltrating, Spatial Analysis, Tumor Microenvironment, Colonic Neoplasms
Abstract

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Published
2023
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31. 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 J, Broeckx G, Page DB, Jahangir CA, Verbandt S, Kos Z, Gupta R, Khiroya R, Abduljabbar K, Acosta Haab G, Acs B, Akturk G, Almeida JS, Alvarado-Cabrero I, Amgad M, Azmoudeh-Ardalan F, Badve S, Baharun NB, Balslev E, Bellolio ER, Bheemaraju V, Blenman KR, Botinelly Mendonça Fujimoto L, Bouchmaa N, Burgues O, Chardas A, Chon U Cheang M, Ciompi F, Cooper LA, Coosemans A, Corredor G, Dahl AB, Dantas Portela FL, Deman F, Demaria S, Doré Hansen J, Dudgeon SN, Ebstrup T, Elghazawy M, Fernandez-Martín C, Fox SB, Gallagher WM, Giltnane JM, Gnjatic S, Gonzalez-Ericsson PI, Grigoriadis A, Halama N, Hanna MG, Harbhajanka A, Hart SN, Hartman J, Hauberg S, Hewitt S, Hida AI, Horlings HM, Husain Z, Hytopoulos E, Irshad S, Janssen EA, Kahila M, Kataoka TR, Kawaguchi K, Kharidehal D, Khramtsov AI, Kiraz U, Kirtani P, Kodach LL, Korski K, Kovács A, Laenkholm AV, Lang-Schwarz C, Larsimont D, Lennerz JK, Lerousseau M, Li X, Ly A, Madabhushi A, Maley SK, Manur Narasimhamurthy V, Marks DK, McDonald ES, Mehrotra R, Michiels S, Minhas FUAA, Mittal S, Moore DA, Mushtaq S, Nighat H, Papathomas T, Penault-Llorca F, Perera RD, Pinard CJ, Pinto-Cardenas JC, Pruneri G, Pusztai L, Rahman A, Rajpoot NM, Rapoport BL, Rau TT, Reis-Filho JS, Ribeiro JM, Rimm D, Roslind A, Vincent-Salomon A, Salto-Tellez M, Saltz J, Sayed S, Scott E, Siziopikou KP, Sotiriou C, Stenzinger A, Sughayer MA, Sur D, Fineberg S, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson EA, Tramm T, Tran WT, van der Laak J, van Diest PJ, Verghese GE, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen HY, Yang W, Yuan Y, Zin RM, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, and Specht Stovgaard E

Subjects
Humans, Animals, Lymphocytes, Tumor-Infiltrating, Biomarkers, Machine Learning, Triple Negative Breast Neoplasms, Mammary Neoplasms, Animal
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. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Published
2023
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32. Tiger Man Sign-F-18 FDG PET CT Scan Pattern in Muscular and Cutaneous Sarcoidosis: A Case Report and Literature Survey.

Author

Pruthi A, Kirtani P, Joshi P, and Kaur N

Abstract

Sarcoidosis is a chronic granulomatous disorder of unknown etiology which primarily affects the respiratory system. However, 0.5%-2.5% of patients with sarcoidosis show muscle involvement, namely sarcoid myopathy. F-18 Fluorodeoxyglucose positron-emission tomography (F-18 FDG PET) has become an important component of the diagnostic algorithm of these patients, owing to its ability to assess disease extent and identify occult sites of disease involvement and guiding sites of biopsy. Awareness of pattern of FDG uptake in sarcoid myopathy not only helps in identifying muscular involvement in already known cases but also helps in the initial diagnosis of sarcoidosis as in the present case., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Nuclear Medicine.)

Published
2020
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33. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice.

Author

Gonzalez-Ericsson PI, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, Michiels S, Le Quesne J, Nielsen TO, Laenkholm AV, Fox SB, Adam J, Bartlett JM, Rimm DL, Quinn C, Peeters D, Dieci MV, Vincent-Salomon A, Cree I, Hida AI, Balko JM, Haynes HR, Frahm I, Acosta-Haab G, Balancin M, Bellolio E, Yang W, Kirtani P, Sugie T, Ehinger A, Castaneda CA, Kok M, McArthur H, Siziopikou K, Badve S, Fineberg S, Gown A, Viale G, Schnitt SJ, Pruneri G, Penault-Llorca F, Hewitt S, Thompson EA, Allison KH, Symmans WF, Bellizzi AM, Brogi E, Moore DA, Larsimont D, Dillon DA, Lazar A, Lien H, Goetz MP, Broeckx G, El Bairi K, Harbeck N, Cimino-Mathews A, Sotiriou C, Adams S, Liu SW, Loibl S, Chen IC, Lakhani SR, Juco JW, Denkert C, Blackley EF, Demaria S, Leon-Ferre R, Gluz O, Zardavas D, Emancipator K, Ely S, Loi S, Salgado R, and Sanders M

Subjects
B7-H1 Antigen immunology, Biomarkers, Tumor immunology, Humans, Lymphocytes, Tumor-Infiltrating immunology, Risk Management, Triple Negative Breast Neoplasms immunology, B7-H1 Antigen metabolism, Biomarkers, Tumor metabolism, Lymphocytes, Tumor-Infiltrating pathology, Triple Negative Breast Neoplasms pathology
Abstract

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Published
2020
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34. Prognostic Significance of HER-2 and p53 Expression in Gallbladder Carcinoma in North Indian Patients.

Author

Singh A, Mishra PK, Saluja SS, Talikoti MA, Kirtani P, and Najmi AK

Subjects
Adult, Case-Control Studies, Female, Humans, India, Kaplan-Meier Estimate, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Prospective Studies, Sex Factors, Adenocarcinoma chemistry, Adenocarcinoma secondary, Gallbladder Neoplasms chemistry, Gallbladder Neoplasms pathology, Receptor, ErbB-2 analysis, Tumor Suppressor Protein p53 analysis
Abstract

Background/objective: Proto-oncogenes (HER-2) and tumor suppressor genes (p53) are commonly deregulated in gallbladder cancer (GBC). Available literature discloses skewed data from endemic Asian countries, especially north India. This study evaluates the prognostic significance of HER-2 and p53 in GBC patients from two major hospitals., Methods: Sixty resectable tumor and control specimens were prospectively collected from December 2012 to January 2016. Immunohistochemical staining was done using monoclonal antibodies to semiquantitatively evaluate HER-2 and p53 protein expression. The criterion for HER-2 positivity was set at >30% tumor cells showing complete, membranous staining while p53 positivity was established at <50% tumor cells showing complete nuclear staining. Clinicopathological correlations were drawn with major clinical outcomes., Results: It was observed that 36.67% (22/60) tumor cases and 5% (3/60) control cases showed strong HER-2 overexpression significantly correlating with sex, T-stage, nodal spread and distant metastasis (p < 0.05), while 33.3% (20/60) positivity was observed for p53 in tumor cases and 1.7% (1/60) in control cases. Multivariate analysis showed HER-2 (p = 0.04; hazard ratio: 2.36; 95% confidence interval: 1.04-5.33) and p53 (p = 0.03; hazard ratio: 5.63; 95% confidence interval: 1.21-26.26) expression to be independent prognostic factors., Conclusion: Our study thus suggests the plausible role of HER-2 and p53 expression in worse prognosis of GBC in a north Indian population., (© 2016 S. Karger AG, Basel.)

Published
2016
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