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1. IASLC Lung Cancer Staging Project: The New Database to Inform Revisions in the Ninth Edition of the TNM Classification of Lung Cancer

Author

Hisao Asamura, Katherine K. Nishimura, Dorothy J. Giroux, Kari Chansky, Antje Hoering, Valerie Rusch, Ramón Rami-Porta, Luiz Henrique Araujo, David Beer, Pietro Bertoglio, Ricardo Beyruti, Andrea Billè, Souheil Boubia, Elisabeth Brambilla, A.K. Cangir, David Carbone, Vanessa Cilento, Casey Connolly, Gail Darling, Frank Detterbeck, Daniel Dibaba, Xavier Benoit D’Journo, Jessica Donington, Wilfried Eberhardt, John Edwards, Jeremy Erasmus, Wentao Fang, Dean Fennell, Kwun Fong, Françoise Galateau-Sallé, Oliver Gautschi, Ritu R. Gill, Dorothy Giroux, Meredith Giuliani, Jin Mo Goo, Seiki Hasegawa, Fred Hirsch, Hans Hoffman, Wayne Hofstetter, James Huang, Philippe Joubert, Kemp Kernstine, Keith Kerr, Young Tae Kim, Dong Kwan Kim, Hedy Kindler, Yolande Lievens, Hui Liu, Donald E. Low, Gustavo Lyons, Heber MacMahon, Alyson Mahar, Mirella Marino, Edith M. Marom, José-María Matilla, Jan van Meerbeeck, Luis M. Montuenga, Andrew Nicholson, Katie Nishimura, Anna Nowak, Isabelle Opitz, Meinoshin Okumura, Raymond U. Osarogiagbon, Harvey Pass, Marc de Perrot, Helmut Prosch, David Rice, Andreas Rimner, Adam Rosenthal, Enrico Ruffini, Shuji Sakai, Paul Van Schil, Navneet Singh, Francisco Suárez, Ricardo M. Terra, William D. Travis, Ming S. Tsao, Paula Ugalde, Shun-ichi Watanabe, Ignacio Wistuba, Murry Wynes, and Yasushi Yatabe

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2023
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2. The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Unresolved Issues to be Addressed for the Next Ninth Edition of the TNM Classification of Malignant Tumors

Author

Enrico Ruffini, Ramon Rami-Porta, James Huang, Usman Ahmad, Sarit Appel, Andrea Bille, Souheil Boubia, Cecilia Brambilla, Ayten Kayi Cangir, Vanessa Cilento, Frank Detterbeck, Conrad Falkson, Wentao Fang, Pier Luigi Filosso, Giuseppe Giaccone, Nicolas Girard, Francesco Guerrera, Maurizio Infante, Dong Kwan Kim, Marco Lucchi, Mirella Marino, Edith M. Marom, Andrew G. Nicholson, Meinoshin Okumura, Andreas Rimner, Charles B. Simone, Hisao Asamura, Valerie Rusch, Luiz Henrique Araujo, David Beer, Pietro Bertoglio, Ricardo Beyruti, Elisabeth Brambilla, A.K. Cangir, Casey Connolly, Gail Darling, Daniel Dibaba, Xavier Benoit D’ Journo, Wilfried Eberhardt, Jeremy Erasmus, Dean Fennell, Kwun Fong, Françoise Galateau-Salle, Ritu R. Gill, Dorothy Giroux, Meredith Giuliani, Jin Mo Goo, Fred Hirsch, Hans Hoffman, Wayne Hofstetter, Philippe Joubert, Kemp Kernstine, Keith Kerr, Young Tae Kim, Yolande Lievens, Hui Liu, Donald E. Low, Gustavo Lyons, Heber MacMahon, José-María Matilla, Jan van Meerbeeck, Luis M. Montuenga, Andrew Nicholson, Katie Nishimura, Anna Nowak, Isabelle Opitz, Raymond U. Osarogiagbon, Harvey Pass, Marc de Perrot, David Rice, Adam Rosenthal, Shuji Sakai, Paul Van Schil, Navneet Singh, Francisco Suárez, Ricardo M. Terra, William D. Travis, Ming S. Tsao, Paula Ugalde, Shun-Ichi Watanabe, Ignacio Wistuba, Murry Wynes, Yasushi Yatabe, Samuel Armato, Lawek Berzenji, Alex Brunelli, Giuseppe Cardillo, Keneng Chen, Wendy Cooper, Liyan Jiang, Mark Krasnik, Kauro Kubota, Catherine Labbe, Ho Yun Lee, Eric Lim, Geoffrey Liu, Hongxu Liu, Philip Mack, David Naidich, Mizuki Nishino, Marcin Ostrowski, Charles Powell, Carolyn Presley, Paul Martin Putora, Harry Ren, M. Patricia Rivera, Gaetano Rocco, Maria Teresa Ruiz Tzukazan, Robert Samstein, Yu Yang Soon, Kenichi Suda, Martin Tammemägi, Akif Turna, Benny Weksler, Terence Williams, Dawei Yang, Jeff Yang, Masaya Yotsukura, Conrad B. Falkson, Mark Ferguson, Jennifer Sauter, Andrea Wolf, Pier Liugi Filosso, Hong Kwan Kim, and Hong Kwuan Kim

Subjects
Pulmonary and Respiratory Medicine, Lung Neoplasms, Oncology, Humans, Neoplasms, Glandular and Epithelial, Thymus Neoplasms, Prognosis, Neoplasm Staging
Abstract

Thymic epithelial tumors are presently staged using a consistent TNM classification developed by the International Association for the Study of Lung Cancer (IASLC) and approved by the Union for International Cancer Control and the American Joint Committee on Cancer. The stage classification is incorporated in the eight edition of the TNM classification of thoracic malignancies. The IASLC Staging and Prognostic Factors Committee (SPFC)-Thymic Domain (TD) is in charge for the next (ninth) edition expected in 2024. The present article represents the midterm report of the SPFC-TD: in particular, it describes the unresolved issues identified by the group in the current stage classification which are worth being addressed and discussed for the ninth edition of the TNM classification on the basis of the available data collected in the central thymic database which will be managed and analyzed by Cancer Research And Biostatistics. These issues are grouped into issues of general importance and those specifically related to T, N, and M categories. Each issue is described in reference to the most recent reports on the subject, and the priority assigned by the IASLC SPFC-TD for the discussion of the ninth edition is provided.

Published
2022
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3. Targeting the Ubiquitin–Proteasome System Using the UBA1 Inhibitor TAK-243 is a Potential Therapeutic Strategy for Small-Cell Lung Cancer

Author

Safa Majeed, Mansi K. Aparnathi, Kevin C.J. Nixon, Vidhyasagar Venkatasubramanian, Fariha Rahman, Lifang Song, Jessica Weiss, Ranya Barayan, Vijithan Sugumar, Samir H. Barghout, Joel D. Pearson, Rod Bremner, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, and Benjamin H. Lok

Subjects
Proteasome Endopeptidase Complex, Sulfonamides, Cancer Research, Lung Neoplasms, Pyrimidines, Oncology, Ubiquitin, Cell Line, Tumor, Humans, Pyrazoles, Sulfides, Small Cell Lung Carcinoma, Xenograft Model Antitumor Assays
Abstract

Purpose: Small cell lung cancer (SCLC) is an aggressive disease with an overall 5-year survival rate of less than 10%. Treatment for SCLC with cisplatin/etoposide chemotherapy (C/E) ± radiotherapy has changed modestly over several decades. The ubiquitin-proteasome system is an underexplored therapeutic target for SCLC. We preclinically evaluated TAK-243, a first-in-class small molecule E1 inhibitor against UBA1. Experimental Design: We assessed TAK-243 in 26 SCLC cell-lines as monotherapy and combined with C/E, the PARP-inhibitor, olaparib, and with radiation using cell viability assays. We interrogated TAK-243 response with gene expression to identify candidate biomarkers. We evaluated TAK-243 alone and in combination with olaparib or radiotherapy with SCLC patient-derived xenografts (PDX). Results: Most SCLC cell lines were sensitive to TAK-243 monotherapy (EC50 median 15.8 nmol/L; range 10.2 nmol/L–367.3 nmol/L). TAK-243 sensitivity was associated with gene-sets involving the cell cycle, DNA and chromatin organization, and DNA damage repair, while resistance associated with cellular respiration, translation, and neurodevelopment. These associations were also observed in SCLC PDXs. TAK-243 synergized with C/E and olaparib in vitro across sensitive and resistant SCLC cell lines. Considerable TAK-243–olaparib synergy was observed in an SCLC PDX resistant to both drugs individually. TAK-243 radiosensitization was also observed in an SCLC PDX. Conclusions: TAK-243 displays efficacy in SCLC preclinical models. Enrichment of gene sets is associated with TAK-243 sensitivity and resistance. TAK-243 exhibits synergy when combined with genotoxic therapies in cell lines and PDXs. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes, both as a single agent and in combination with existing therapies.

Published
2022
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4. The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non–Small Cell Lung Cancer

Author

John G. Edwards, Kari Chansky, Paul Van Schil, Andrew G. Nicholson, Souheil Boubia, Elisabeth Brambilla, Jessica Donington, Françoise Galateau-Sallé, Hans Hoffmann, Maurizio Infante, Mirella Marino, Edith M. Marom, Jun Nakajima, Marcin Ostrowski, William D. Travis, Ming-Sound Tsao, Yasushi Yatabe, Dorothy J. Giroux, Lynn Shemanski, John Crowley, Marc Krasnik, Hisao Asamura, Ramón Rami-Porta, Valerie Rusch, Luiz Henrique Araujo, David Beer, Pietro Bertoglio, Ricardo Beyruti, Andrea Bille, Vanessa Bolejack, James D. Brierley, A.K. Cangir, David Carbone, Gail Darling, Frank Detterbeck, Xavier Benoit D’Journo, Jessica Donnington, Wilfried Eberhardt, John Edwards, Jeremy Erasmus, Conrad Falkson, Wentao Fang, Dean Fennell, Kwun Fong, Françoise Galateau-Salle, Oliver Gautschi, Ritu Gill, Dorothy Giroux, Meredith Giuliani, Jin Mo Goo, Seiki Hasegawa, Fred Hirsch, Hans Hoffman, Wayne Hofstetter, James Huang, Philippe Joubert, Kemp Kernstine, Keith Kerr, Young Tae Kim, Hong Kwan Kim, Hedy Kindler, Yolande Lievens, Hui Liu, Donald E. Low, Gustavo Lyons, Heber MacMahon, Edith Marom, José-María Matilla, Jan van Meerbeeck, Luis M. Montuenga, Andrew Nicholson, Katie Nishimura, Anna Nowak, Isabelle Opitz, Meinoshin Okumura, Raymond U. Osarogiagbon, Harvey Pass, Marc de Perrot, Helmut Prosch, David Rice, Andreas Rimner, Enrico Ruffini, Shuji Sakai, Navneet Singh, Amy Stoll-D’Astice, Francisco Su´rez, Ricardo M. Terra, Ming S. Tsao, Paula Ugalde, David Waller, Shun-ichi Watanabe, Jacinta Wiens, Ignacio Wistuba, Liyan Jiang, Kaoru Kubota, Akif Turna, Benny Weksler, Maria Teresa Tzukazan, Martin Tammemägi, Charles Powell, David Naidich, Hongxu Liu, Samuel Armato, Alex Brunelli, Giuseppe Cardillo, Elizabeth David, Brigitte Fournier, Mark Krasnik, Kauro Kubota, Catherine Labbe, Eric Lim, Paul Martin Putora, Gaetano Rocco, Pier Luigi Filosso, Kazuya Kondo, Dong Kwan Kim, Giuseppe Giaccone, Marco Lucchi, Thomas Rice, Mark Ferguson, Prasad Adsusmilli, William Travis, Francisco Suárez, Kaura Kubota, Hisao Asamura Shun-ichi, Watanabe, Edith Marom Ramón, Rami-Porta, Ming Tsao, Ming Tsao Shun-ichi, Watanabe, Meredith Guiliani, James Brierley, Ricardo Terra, Ray Osarogiagbon, Luis Montuenga, Hongwei Wang, Françoise Galateau, Jim Mo Goo, Bill Travis, Jose Maria Matilla, Carolle St. Pierre, Ma Teresa Tzukazan, Nicholas Girard, Andreas Rimmer, Francoise Galateau, Prasad Adusumilli, Xavier D’Journo, Donald Low, Adam Rosenthal, and Int Assoc Study Lung Canc Staging

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Neoplasm, Residual, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cytology, medicine, Humans, Lung cancer, Biology, Lymph node, Neoplasm Staging, Retrospective Studies, Computer. Automation, business.industry, Carcinoma in situ, Margins of Excision, Prognosis, medicine.disease, Clinical trial, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Resection margin, Human medicine, Radiology, Non small cell, Lung cancer staging, business, Mathematics
Abstract

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2020
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5. Abstract LBA021: Immune resistance interrogation study (IRIS): Initial report of next generation sequencing (NGS) results in patients with primary versus acquired resistance to anti-PD1/L1 antibodies

Author

Sofia Genta, Farnoosh Abbas Aghababazadeh, Ming S Tsao, Aaron R Hansen, Marcus O Butler, Albiruni R Razak, Philippe L Bedard, Ben X Wang, Pugh J Trevor, Sevan Hakgor, Jeffrey Woo, Benjamin Haibe-Kains, Lillian L Siu, and Anna Spreafico

Subjects
Cancer Research, Oncology
Abstract

Background: The molecular mechanisms underlying primary versus acquired resistance to anti-PD-1/L1 antibodies have not been comprehensively evaluated across different tumor types. Methods: The Immune Resistance Interrogation Study (IRIS; NCT04243720) is a prospective, investigator-initiated study at the Princess Margaret Cancer Centre, aimed to perform extensive multi-omic characterization of solid tumors with primary resistance (disease progression on first imaging; or stable disease T mutation in 6 patients (17%), followed by TERT promoter -124C>T mutation in 5 patients (14%), FGF19/FGF4/FGF3 and CCND1 amplifications in 4 pts each (11%), and MDM2 amplification, CDK4 amplification and CDKN2A loss, detected in 3 pts each (9%). Pts with acquired resistance had a higher frequency of TP53 mutations (9/13 = 69%) compared to primary resistance pts (7/22 = 32%), p=0.04; however this was not significant when corrected for multiple testing. Interestingly, amplifications in CDK4, CCND1, FGF 19/FGF 3/FGF 4, MDM2 and mutations in NF1 were only identified in pts with primary resistant tumors. Conclusions: No significant differences in disrupted genes and variants were observed in the current analysis. However, this can be due to the small number of pts analyzed thus far. Accrual to this study is ongoing. A comparison of alterations in oncogenic pathways is planned to further define the genomic landscape of pts with primary versus acquired resistance to anti-PD1/PDL1 blockade. Citation Format: Sofia Genta, Farnoosh Abbas Aghababazadeh, Ming S Tsao, Aaron R Hansen, Marcus O Butler, Albiruni R Razak, Philippe L Bedard, Ben X Wang, Pugh J Trevor, Sevan Hakgor, Jeffrey Woo, Benjamin Haibe-Kains, Lillian L Siu, Anna Spreafico. Immune resistance interrogation study (IRIS): Initial report of next generation sequencing (NGS) results in patients with primary versus acquired resistance to anti-PD1/L1 antibodies [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA021.

Published
2021
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6. The IASLC Lung Cancer Staging Project: Summary of Proposals for Revisions of the Classification of Lung Cancers with Multiple Pulmonary Sites of Involvement in the Forthcoming Eighth Edition of the TNM Classification

Author

Frank C. Detterbeck, Andrew G. Nicholson, Wilbur A. Franklin, Edith M. Marom, William D. Travis, Nicolas Girard, Douglas A. Arenberg, Vanessa Bolejack, Jessica S. Donington, Peter J. Mazzone, Lynn T. Tanoue, Valerie W. Rusch, John Crowley, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, David Ball, David G. Beer, Ricardo Beyruti, Kari Chansky, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Douglas Flieder, Myrna Godoy, Jin Mo Goo, Lawrence R. Goodman, Jim Jett, Paul de Leyn, Alberto Marchevsky, Heber MacMahon, David Naidich, Morohito Okada, Marina Perlman, Charles Powell, Paul van Schil, Arne Warth, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A.I. Blanco Orozco, M.A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M.T. González Budiño, G. González Casaurrán, J.A. Gullón Blanco, J. Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J.M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J.C. Peñalver Cuesta, J.S. Park, H. Pass, M.J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, K. Yokoi, and Nackaerts, Kristiaan

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Pathology, Lung Neoplasms, Medizin, Disease, Adenocarcinoma, 1102 Cardiovascular Medicine And Haematology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Non-small cell lung cancer, Meta-Analysis as Topic, Internal medicine, Histologic type, Non–small cell lung cancer, Humans, Medicine, Oncology & Carcinogenesis, Lung cancer staging, Multiple tumors, Lung cancer, Neoplasm Staging, Lung, business.industry, 1103 Clinical Sciences, Neoplasms, Second Primary, Prognosis, medicine.disease, TNM classification, Editorial, 030104 developmental biology, Systematic review, medicine.anatomical_structure, IASLC Staging and Prognostic Factors Committee, Advisory Boards, Multiple Pulmonary Sites Workgroup and Participating Institutions, IASLC Staging and Prognostic Factors Committee Advisory Boards Multiple Pulmonary Sites Workgroup and Participating Institutions, 030220 oncology & carcinogenesis, business
Abstract

Introduction Patients with lung cancer who harbor multiple pulmonary sites of disease have been challenging to classify; a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee was charged with developing proposals for the eighth edition of the tumor, node, and metastasis (TNM) classification to address this issue. Methods A systematic literature review and analysis of the International Association for the Study of Lung Cancer database was performed to develop proposals for revision in an iterative process involving multispecialty international input and review. Results Details of the evidence base are summarized in other articles. Four patterns of disease are recognized; the clinical presentation, pathologic correlates, and biologic behavior of these suggest specific applications of the TNM classification rules. First, it is proposed that second primary lung cancers be designated with a T, N, and M category for each tumor. Second, tumors with a separate tumor nodule of the same histologic type (either suspected or proved) should be classified according to the location of the separate nodule relative to the index tumor—T3 for a same-lobe, T4 for a same-side (different lobe), and M1a for an other-side location—with a single N and M category. Third, multiple tumors with prominent ground glass (imaging) or lepidic (histologic) features should be designated by the T category of the highest T lesion, the number or m in parentheses (#/m) to indicate the multiplicity, and a collective N and M category for all. Finally, it is proposed that diffuse pneumonic-type lung cancers be designated by size (or T3) if in one lobe, T4 if involving multiple same-side lobes, and M1a if involving both lungs with a single N and M category for all areas of involvement. Conclusion We propose to tailor TNM classification of multiple pulmonary sites of lung cancer to reflect the unique aspects of four different patterns of presentation. We hope that this will lead to more consistent classification and clarity in communication and facilitate further research in the nature and optimal treatment of these entities.

Published
2016
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7. The IASLC Lung Cancer Staging Project : a renewed call to participation

Author

Dorothy J. Giroux, Paul Van Schil, Hisao Asamura, Ramón Rami-Porta, Kari Chansky, John J. Crowley, Valerie W. Rusch, Kemp Kernstine, Valerie Rusch, Luiz Henrique Araujo, Paul Beckett, David Beer, Pietro Bertoglio, Ricardo Beyruti, Andrea Bille, Vanessa Bolejack, Souheil Boubia, Elisabeth Brambilla, James D. Brierley, A.K. Cangir, David Carbone, John Crowley, Gail Darling, Frank Detterbeck, Xavier Benoit D’Journo, Jessica Donnington, Wilfried Eberhardt, John Edwards, Jeremy Erasmus, Wentao Fang, Dean Fennell, Kwun Fong, Françoise Galateau-Salle, Oliver Gautschi, Ritu Gill, Dorothy Giroux, Jin Mo Goo, Seiki Hasegawa, Fred Hirsch, Hans Hoffman, Wayne Hofstetter, James Huang, Philippe Joubert, Keith Kerr, Young Tae Kim, Hong Kwan Kim, Hedy Kindler, Yolande Lievens, Hui Liu, Donald E. Low, Gustavo Lyons, Heber MacMahon, Mirella Marino, Edith Marom, José-María Matilla, Jan van Meerbeeck, Luis M. Montuenga, Andrew Nicholson, Anna Nowak, Isabelle Opitz, Meinoshin Okumura, Raymond U. Osarogiagbon, Harvey Pass, Marc de Perrot, Helmut Prosch, David Rice, Andreas Rimner, Enrico Ruffini, Shuji Sakai, Navneet Singh, Amy Stoll-D’Astice, Francisco Suárez, Ricardo M. Terra, William D. Travis, Ming S. Tsao, Paula Ugalde, Shun-ichi Watanabe, Jacinta Wiens, Ignacio Wistuba, Yasushi Yatabe, Liyan Jiang, Kaoru Kubota, Eric Lim, Paul Martin Putora, Akif Turna, Pier Luigi Filosso, Kazuya Kondo, Dong Kwan Kim, Giuseppe Giaccone, Marco Lucchi, Eugene Blackwell, Thomas Rice, William Travis, Andrew G. Nicholson, Ming Tsao, James Brierley, Jun Nakajima, Françoise Galateau, Bill Travis, Jim Mo Goo, Luis Montuenga, Hong Wei Wang, Katie Nishimura, Int Assoc Study Lung Canc Staging, and Eberhardt, Wilfried (Beitragende*r)

Subjects
Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Databases, Factual, Electronic data capture, Medizin, Lung cancer, Lung cancer databases, Lung cancer staging, TNM classification, Oncology, 03 medical and health sciences, 0302 clinical medicine, Cancer control, medicine, Humans, Neoplasm Staging, business.industry, Cancer, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Family medicine, Female, Human medicine, Biostatistics, business
Abstract

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Published
2018

8. The IASLC Lung Cancer Staging Project:External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer

Author

Kari Chansky, Frank C. Detterbeck, Andrew G. Nicholson, Valerie W. Rusch, Eric Vallières, Patti Groome, Catherine Kennedy, Mark Krasnik, Michael Peake, Lynn Shemanski, Vanessa Bolejack, John J. Crowley, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, David Ball, David G. Beer, Ricardo Beyruti, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, James Huang, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Anna Nowak, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A. I. Blanco Orozco, M. A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M. T. González Budiño, G. González Casaurrán, J. A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J. M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J. C. Peñalver Cuesta, J.S. Park, H. Pass, M. J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, K. Yokoi, van Meerbeeck, Jan, et al., and IASLC Staging and Prognostic Factors Committee

Subjects
Male, 0301 basic medicine, Oncology, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Lung Neoplasms, Multivariate analysis, Staging, UICC, 03 medical and health sciences, 0302 clinical medicine, International database, Internal medicine, Validation, Humans, Medicine, Stage (cooking), Lung cancer, Neoplasm Staging, AJCC, business.industry, Confounding, External validation, Reproducibility of Results, Cancer, medicine.disease, Survival Analysis, National Cancer Database, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Human medicine, Lung cancer staging, business
Abstract

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases.RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage.CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Published
2017
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9. The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma

Author

David Rice, Kari Chansky, Anna Nowak, Harvey Pass, Hedy Kindler, Lynn Shemanski, Isabelle Opitz, Sergi Call, Seiki Hasegawa, Kemp Kernstine, Cansel Atinkaya, Federico Rea, Philippe Nafteux, Valerie W. Rusch, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David Beer, Ricardo Beyruti, Vanessa Bolejack, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Kouki Inai, Lee Krug, Kristiaan Nackaerts, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Hasan Batirel, Andrea Bille, Ugo Pastorino, Ayten K. Cangir, Susana Cedres, Joseph S. Friedberg, Francoise Galateau-Salle, Seiki Hasagawa, Kemp H. Kernstine, Brian McCaughan, Cansel Atinkaya Ozturk, Marc de Perrot, David C. Rice, Robert Rintoul, Lorenzo Spaggiari, Domenico Galetta, K.N. Syrigos, Charles Thomas, Walter Weder, Masahiro Yoshimura, Nackaerts, Kristiaan, University of Zurich, Rice, David, and Eberhardt, Wilfried (Beitragende*r)

Subjects
Oncology, Mesothelioma, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, 10255 Clinic for Thoracic Surgery, Pleural Neoplasms, education, Settore MED/21 - Chirurgia Toracica, Medizin, 610 Medicine & health, 030204 cardiovascular system & hematology, Cancer staging, Database, 03 medical and health sciences, 0302 clinical medicine, Nodal metastases, Internal medicine, Cox proportional hazards regression, Humans, Medicine, Lung cancer, Survival analysis, Neoplasm Staging, Mesothelioma, Malignant, business.industry, Pleural mesothelioma, Hazard ratio, respiratory system, medicine.disease, Surgery, respiratory tract diseases, 2740 Pulmonary and Respiratory Medicine, 030220 oncology & carcinogenesis, 2730 Oncology, Lung cancer staging, business
Abstract

Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis.There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p0.0001).A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

Published
2016

10. The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma

Author

Valerie W. Rusch, Kari Chansky, Hedy L. Kindler, Anna K. Nowak, Harvey I. Pass, David C. Rice, Lynn Shemanski, Françoise Galateau-Sallé, Brian C. McCaughan, Takashi Nakano, Enrico Ruffini, Jan P. van Meerbeeck, Masahiro Yoshimura, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David Beer, Ricardo Beyruti, Vanessa Bolejack, John Crowley, Frank C. Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Toni Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Alan Mitchell, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas W. Rice, Kenneth Rosenzweig, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William D. Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, H. Asamura, H. Batirel, A. Bille, U. Pastorino, S. Call, A. Cangir, S. Cedres, J. Friedberg, F. Galateau-Sallé, S. Hasagawa, K. Kernstine, H. Kindler, B. McCaughan, T. Nakano, A. Nowak, C. Atinkaya Ozturk, H. Pass, M. de Perrot, F. Rea, D. Rice, R. Rintoul, E. Ruffini, V. Rusch, L. Spaggiari, D. Galetta, K. Syrigos, C. Thomas, J.P. van Meerbeeck, P. Nafteux, J. Vansteenkiste, W. Weder, I. Optiz, M. Yoshimura, Nackaerts, Kristiaan, and IASLC Staging Prognostic Factors

Subjects
Oncology, Pulmonary and Respiratory Medicine, Mesothelioma, medicine.medical_specialty, Staging, Lung Neoplasms, Pleural Neoplasms, education, Locally advanced, Medizin, Recursive partitioning, Stage ii, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Stage (cooking), Lung cancer, neoplasms, Survival tree, Neoplasm Staging, business.industry, Mesothelioma, Malignant, respiratory system, medicine.disease, Staging system, Surgery, respiratory tract diseases, 030228 respiratory system, TNM stage groupings, 030220 oncology & carcinogenesis, Human medicine, Stage iv, business
Abstract

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM. Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases. The M component as it currently stands was validated by confirming sufficient discrimination (by Kaplan-Meier analysis) with respect to overall survival (OS) between the clinical MO (cM0) and cM1 categories. Candidate stage groups were developed by using a recursive partitioning and amalgamation algorithm applied to all cM0 cases. Results: Of 3519 submitted cases, 2414 were analyzable and 84 were cM1 cases. Median OS for cM1 cases was 9.7 months versus 13.4 months (p = 0.0013) for the locally advanced (T4 or N3) cM0 cases, supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggest a possible difference in OS for single- versus multiple-site cM1 cases. A recursive partitioning and amalgamation generated survival tree on the OS outcomes restricted to cM0 cases with the newly proposed (eighth edition) T and N components indicates that optimal stage groupings for the eighth edition will be as follows: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4), and stage IV (any M1). Conclusions: This first evidence-based revision of the TNM classification for MPM leads to substantial changes in the T and N components and the stage groupings. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2016

11. The IASLC Lung Cancer Staging Project: Methodology and Validation Used in the Development of Proposals for Revision of the Stage Classification of NSCLC in the Forthcoming (Eighth) Edition of the TNM Classification of Lung Cancer

Author

Frank C. Detterbeck, Kari Chansky, Patti Groome, Vanessa Bolejack, John Crowley, Lynn Shemanski, Catherine Kennedy, Mark Krasnik, Michael Peake, Ramón Rami-Porta, Peter Goldstraw, Hisao Asamura, David Ball, David G. Beer, Ricardo Beyruti, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, James Huang, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A. I. Blanco Orozco, M. A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M. T. González Budiño, G. González Casaurrán, J. A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J. M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J. C. Peñalver Cuesta, J.S. Park, M. J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, K. Yokoi, Ramon Rami-Porta, Dorothy J. Giroux, William D. Travis, Paul van Schil, Marcin Zielinski, Wilfried Eberhardt, Jan van Meeerbeeck, Andrew Nicholson, Kouru Kubota, Alex Bankier, Mary Beth Beasley, Douglas B. Flieder, Jin Mo Goo, Heber MacMahon, David Naidich, Charles A. Powell, Mathias Prokop, Yasushi Yatabe, Douglas A. Arenberg, Jessica S. Donington, Wilbur A. Franklin, Nicolas Girard, Peter J. Mazzone, Valerie W. Rusch, Lynn T. Tanoue, and Eberhardt, Wilfried (Beitragende*r)

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Stage classification, medicine.medical_specialty, Lung Neoplasms, Databases, Factual, Medizin, 1102 Cardiovascular Medicine And Haematology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, International database, Internal medicine, medicine, Histologic type, Humans, Oncology & Carcinogenesis, Stage (cooking), Lung cancer, Neoplasm Staging, business.industry, External validation, 1103 Clinical Sciences, medicine.disease, Prognosis, Surgery, 030104 developmental biology, 030220 oncology & carcinogenesis, Lung cancer staging, business
Abstract

Introduction Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017. Methods An international database of 94,708 patients with lung cancer diagnosed in 1999–2010 was assembled. This article describes the process and statistical methods used to refine the lung cancer stage classification. Results Extensive analysis allowed definition of tumor, node, and metastasis categories and stage groupings that demonstrated consistent discrimination overall and within multiple different patient cohorts (e.g., clinical or pathologic stage, R0 or R-any resection status, geographic region). Additional analyses provided evidence of applicability over time, across a spectrum of geographic regions, histologic types, evaluative approaches, and follow-up intervals. Conclusions An extensive analysis has produced stage classification proposals for lung cancer with a robust degree of discriminatory consistency and general applicability. Nevertheless, external validation is encouraged to identify areas of strength and weakness; a sound validation should have discriminatory ability and be based on an independent data set of adequate size and sufficient follow-up with enough patients for each subgroup.

Published
2016

12. The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer

Author

Frank C. Detterbeck, Wilbur A. Franklin, Andrew G. Nicholson, Nicolas Girard, Douglas A. Arenberg, William D. Travis, Peter J. Mazzone, Edith M. Marom, Jessica S. Donington, Lynn T. Tanoue, Valerie W. Rusch, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, David Ball, David G. Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Douglas Flieder, Myrna Godoy, Jin Mo Goo, Lawrence R. Goodman, Jim Jett, Paul de Leyn, Alberto Marchevsky, Heber MacMahon, David Naidich, Morohito Okada, Marina Perlman, Charles Powell, Paul van Schil, Arne Warth, and Nackaerts, Kristiaan

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, Medizin, Adenocarcinoma, 1102 Cardiovascular Medicine And Haematology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Non-small cell lung cancer, Internal medicine, medicine, Humans, Non–small cell lung cancer, IASLC Staging and Prognostic Factors Committee Advisory Boards and the Multiple Pulmonary Sites Workgroup, In patient, Oncology & Carcinogenesis, Lung cancer staging, Lung cancer, Neoplasm Staging, Lung, business.industry, Background data, Cancer, Neoplasms, Second Primary, 1103 Clinical Sciences, medicine.disease, Prognosis, TNM classification, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Multiple tumors, business, IASLC Staging and Prognostic Factors Committee, Advisory Boards and the Multiple Pulmonary Sites Workgroup
Abstract

Introduction It can be difficult to distinguish between a second primary and a metastasis in patients with lung cancer who have more than one pulmonary site of cancer. Methods A systematic review of the literature was conducted by a subcommittee of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee to develop recommendations to identify second primary lung cancers. The process entailed review of knowledge relating to the mechanism of metastasis, determination of clonality, and outcomes of patients with resected tumors. Results It is easier to determine that two tumors are different than that they are the same; finding similarities does not establish that they are the same. For example, most second primary lung cancers are of the same histotype. Few criteria are reliable by themselves; these include different histologic cancer types or matching DNA breakpoints by sequencing and a comprehensive histologic assessment of resected specimens. Characteristics that are suggestive but associated with potential misclassification include the presence or absence of biomarkers, imaging characteristics, and the presence or absence of nodal involvement. Conclusions Clinical and pathologic (i.e., after resection) criteria are presented to identify two foci as separate primary lung cancers versus a metastasis. Few features are definitive; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification. Careful review by a multidisciplinary tumor board, considering all available information, is recommended.

Published
2016

13. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer

Author

Peter Goldstraw, Kari Chansky, John Crowley, Ramon Rami-Porta, Hisao Asamura, Wilfried E.E. Eberhardt, Andrew G. Nicholson, Patti Groome, Alan Mitchell, Vanessa Bolejack, Ramón Rami-Porta, David Ball, David G. Beer, Ricardo Beyruti, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Takashi Nakano, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A.I. Blanco Orozco, M.A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M.T. González Budiño, G. González Casaurrán, J.A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J.M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J.C. Peñalver Cuesta, J.S. Park, H. Pass, M.J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, and K. Yokoi

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Lung Neoplasms, Staging, Medizin, Prognostic factors, 1102 Cardiovascular Medicine And Haematology, Lung cancer, 03 medical and health sciences, 0302 clinical medicine, Seer program, medicine, Humans, Oncology & Carcinogenesis, Stage (cooking), Neoplasm Staging, business.industry, General surgery, International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions, 1103 Clinical Sciences, Prognosis, medicine.disease, International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Neoplasm staging, Biostatistics, Lung cancer staging, business, SEER Program
Abstract

The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.

Published
2016

14. The IASLC Mesothelioma Staging Project: Improving Staging of a Rare Disease Through International Participation

Author

Harvey Pass, Dorothy Giroux, Catherine Kennedy, Enrico Ruffini, Ayten K. Cangir, David Rice, Hisao Asamura, David Waller, John Edwards, Walter Weder, Hans Hoffmann, Jan P. van Meerbeeck, Anna Nowak, Valerie W. Rusch, Peter Goldstraw, Ramón Rami-Porta, David Ball, David Beer, Ricardo Beyruti, Vanessa Bolejack, Kari Chansky, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, Françoise Galateau-Sallé, Fergus Gleeson, Patti Groome, James Huang, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, H. Asamura, H. Batirel, A. Bille, U. Pastorino, S. Call, A. Cangir, S. Cedres, J. Friedberg, F. Galateau-Salle, null Hasagawa, K. Kernstine, H. Kindler, B. McCaughan, T. Nakano, A. Nowak, C. Atinkaya Ozturk, H. Pass, M. de Perrot, F. Rea, D. Rice, R. Rintoul, E. Ruffini, V. Rusch, L. Spaggiari, D. Galetta, K. Syrigos, C. Thomas, J. van Meerbeeck, J. Vansteenkiste, W. Weder, I. Opitz, M. Yoshimura, IASLC Staging Prognostic Factors, Nackaerts, Kristiaan, University of Zurich, and Pass, Harvey

Subjects
Mesothelioma, Pulmonary and Respiratory Medicine, Registry, medicine.medical_specialty, Staging, 10255 Clinic for Thoracic Surgery, education, Medizin, 610 Medicine & health, TNM staging system, TNM, Oncology, 03 medical and health sciences, 0302 clinical medicine, medicine, Lung cancer, Staging system, health care economics and organizations, business.industry, General surgery, Cancer, respiratory system, medicine.disease, Surgery, respiratory tract diseases, Clinical trial, 030228 respiratory system, 2740 Pulmonary and Respiratory Medicine, 030220 oncology & carcinogenesis, Interest group, 2730 Oncology, Human medicine, business, Rare disease
Abstract

For nearly 40 years, there was no generally accepted staging system for malignant pleural mesothelioma. In 1994, members of the International Mesothelioma Interest Group, in collaboration with the International Association for the Study of Lung Cancer, proposed a TNM staging system based on analyses of outcomes in retrospective surgical series and small clinical trials. Subsequently accepted by the American Joint Commission on Cancer and the Union for International Cancer Control for the sixth editions of their staging manuals, this system has since been the international staging standard. However, it has significant limitations, particularly with respect to clinical staging and to the categories for lymph node staging. Here we provide an overview of the development of the International Association for the Study of Lung Cancer malignant pleural mesothelioma staging database, which was designed to address these limitations through the development of a large international data set. Analyses of this database, described in papers linked to this overview, are being used to inform revisions in the eighth editions of the American Joint Commission on Cancer and Union for International Cancer Control staging systems. ispartof: Journal of Thoracic Oncology vol:11 issue:12 pages:2082-2088 ispartof: location:United States status: published

Published
2016

15. The International Association for the Study of Lung Cancer Lung Cancer Staging Project : proposals for the revision of the clinical and pathologic staging of small cell lung cancer in the forthcoming eighth edition of the TNM classification for lung cancer

Author

Andrew G. Nicholson, Kari Chansky, John Crowley, Ricardo Beyruti, Kaoru Kubota, Andrew Turrisi, Wilfried E.E. Eberhardt, Jan van Meerbeeck, Ramón Rami-Porta, Peter Goldstraw, Hisao Asamura, David Ball, David G. Beer, Vanessa Bolejack, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Toni Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Alan Mitchell, Takashi Nakano, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A.I. Blanco Orozco, M.A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M.T. González Budiño, G. González Casaurrán, J.A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J.M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J.C. Peñalver Cuesta, J.S. Park, H. Pass, M.J. Pavón Fernández, M. Rosenberg, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, K. Yokoi, and Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions

Subjects
0301 basic medicine, Oncology, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, Pleural effusion, Respiratory System, education, Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions, Medizin, Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions, 1102 Cardiovascular Medicine And Haematology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 7TH EDITION, Oncology & Carcinogenesis, Lung cancer staging, Lung cancer, Pathological, neoplasms, Survival analysis, Neoplasm Staging, Science & Technology, Small cell lung cancer, business.industry, 1103 Clinical Sciences, Prognosis, medicine.disease, Small Cell Lung Carcinoma, Survival Analysis, TNM classification, Surgery, respiratory tract diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, Non small cell, Human medicine, business, Life Sciences & Biomedicine
Abstract

Introduction Small cell lung cancer (SCLC) is commonly classified as either limited or extensive, but the Union for International Cancer Control TNM Classification of Malignant Tumours seventh edition (2009) recommended tumor, node, and metastasis (TNM) staging based on analysis of the International Association for the Study of Lung Cancer (IASLC) database. Methods Survival analyses were performed for clinically and pathologically staged patients presenting with SCLC from 1999 through 2010. Prognosis was compared in relation to the TNM seventh edition staging to serve as validation and analyzed in relation to proposed changes to the T descriptors found in the eighth edition. Results There were 5002 patients: 4848 patients with clinical and 582 with pathological stages. Among these, 428 had both. Survival differences were confirmed for T and N categories and maintained in relation to proposed revisions to T descriptors for seventh edition TNM categories and proposed changes in the eighth edition. There were also survival differences, notably at 12 months, in patients with brain-only single-site metastasis (SSM) compared to SSM at other sites, and SSM without a pleural effusion showed a better prognosis than other patients in the M1b category. Conclusion We confirm the prognostic value of clinical and pathological TNM staging in patients with SCLC, and recommend continued usage for SCLC in relation to proposed changes to T, N, and M descriptors for NSCLC in the eighth edition. However, for M descriptors, it remains uncertain whether survival differences in patients with SSM in the brain simply reflect better treatment options rather than better survival based on anatomic extent of disease.

Published
2016

16. The IASLC Mesothelioma Staging Project : Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma

Author

Anna K. Nowak, Kari Chansky, David C. Rice, Harvey I. Pass, Hedy L. Kindler, Lynn Shemanski, Andrea Billé, Robert C. Rintoul, Hasan F. Batirel, Charles F. Thomas, Joseph Friedberg, Susana Cedres, Marc de Perrot, Valerie W. Rusch, Peter Goldstraw, Ramón Rami-Porta, Hisao Asamura, David Ball, David Beer, Ricardo Beyruti, Vanessa Bolejack, John Crowley, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Edith M. Marom, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Andrew G. Nicholson, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, H. Asamura, H. Batirel, A. Bille, U. Pastorino, S. Call, A. Cangir, S. Cedres, J. Friedberg, F. Galateau-Salle, S. Hasagawa, K. Kernstine, H. Kindler, B. McCaughan, T. Nakano, A. Nowak, C. Atinkaya Ozturk, H. Pass, M. de Perrot, F. Rea, D. Rice, R. Rintoul, E. Ruffini, V. Rusch, L Spaggiari, D Galetta, K. Syrigos, C. Thomas, J. van Meerbeeck, P. Nafteux, J. Vansteenkiste, W. Weder, I. Optiz, M. Yoshimura, University of Zurich, Nowak, Anna K, Nowak, Anna K., Chansky, Kari, Rice, David C., Pass, Harvey I., Kindler, Hedy L., Shemanski, Lynn, Bille, Andrea, Rintoul, Robert C., Batirel, Hasan F., Thomas, Charles F., Friedberg, Joseph, Cedres, Susana, de Perrot, Marc, Rusch, Valerie W., and Nackaerts, Kristiaan

Subjects
Mesothelioma, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Staging, Lung Neoplasms, PREDICTION, 10255 Clinic for Thoracic Surgery, Pleural Neoplasms, Settore MED/21 - Chirurgia Toracica, education, Medizin, 610 Medicine & health, THERAPY, PARAMETERS, 03 medical and health sciences, 0302 clinical medicine, Prospective, T component, Humans, Mesothelioma, Malignant, Neoplasm Staging, Medicine, Lung cancer, TUMOR THICKNESS, Staging system, Pleural mesothelioma, business.industry, General surgery, CT SCANS, ASSOCIATION, respiratory system, medicine.disease, F-18-FDG PET/CT, respiratory tract diseases, 030228 respiratory system, Oncology, 2740 Pulmonary and Respiratory Medicine, 030220 oncology & carcinogenesis, VOLUME, SURVIVAL, 2730 Oncology, business, MALIGNANT MESOTHELIOMA
Abstract

Introduction: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition. Methods: Data elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission. Results: A total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival. Conclusions: A recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2016

17. The Integrated Genomic Landscape of Thymic Epithelial Tumors

Author

Milan Radovich, Curtis R. Pickering, Ina Felau, Gavin Ha, Hailei Zhang, Heejoon Jo, Katherine A. Hoadley, Pavana Anur, Jiexin Zhang, Mike McLellan, Reanne Bowlby, Thomas Matthew, Ludmila Danilova, Apurva M. Hegde, Jaegil Kim, Mark D.M. Leiserson, Geetika Sethi, Charles Lu, Michael Ryan, Xiaoping Su, Andrew D. Cherniack, Gordon Robertson, Rehan Akbani, Paul Spellman, John N. Weinstein, D. Neil Hayes, Ben Raphael, Tara Lichtenberg, Kristen Leraas, Jean Claude Zenklusen, Junya Fujimoto, Cristovam Scapulatempo-Neto, Andre L. Moreira, David Hwang, James Huang, Mirella Marino, Robert Korst, Giuseppe Giaccone, Yesim Gokmen-Polar, Sunil Badve, Arun Rajan, Philipp Ströbel, Nicolas Girard, Ming S. Tsao, Alexander Marx, Anne S. Tsao, Patrick J. Loehrer, Adrian Ally, Elizabeth L. Appelbaum, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Madhusmita Behera, Rameen Beroukhim, Mario Berrios, Giovanni Blandino, Tom Bodenheimer, Moiz S. Bootwalla, Jay Bowen, Denise Brooks, Flavio M. Carcano, Rebecca Carlsen, Andre L. Carvalho, Patricia Castro, Lara Chalabreysse, Lynda Chin, Juok Cho, Gina Choe, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Leslie Cope, Matthew G. Cordes, Daniel Crain, Erin Curley, Timothy Defreitas, John A. Demchok, Frank Detterbeck, Noreen Dhalla, Hendrik Dienemann, W. Jeff Edenfield, Francesco Facciolo, Martin L. Ferguson, Scott Frazer, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Stacey B. Gabriel, Johanna Gardner, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, David I. Heiman, Shital Hobensack, Andrea Holbrook, Robert A. Holt, Alan P. Hoyle, Carolyn M. Hutter, Michael Ittmann, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Katayoon Kasaian, Patrick K. Kimes, Phillip H. Lai, Peter W. Laird, Michael S. Lawrence, Pei Lin, Jia Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Dennis T. Maglinte, David Mallery, Elaine R. Mardis, Marco A. Marra, Julie Martin, Michael Mayo, Sam Meier, Michael Meister, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Christopher A. Miller, Gordon B. Mills, Richard A. Moore, Scott Morris, Lisle E. Mose, Thomas Muley, Andrew J. Mungall, Karen Mungall, Rashi Naresh, Yulia Newton, Michael S. Noble, Taofeek Owonikoko, Joel S. Parker, Joseph Paulaskis, Robert Penny, Charles M. Perou, Corinne Perrin, Todd Pihl, Amie Radenbaugh, Suresh Ramalingam, Nilsa Ramirez, Ralf Rieker, Jeffrey Roach, Sara Sadeghi, Gordon Saksena, Jacqueline E. Schein, Heather K. Schmidt, Steven E. Schumacher, Candace Shelton, Troy Shelton, Yan Shi, Juliann Shih, Gabriel Sica, Henrique C.S. Silveira, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Joshua Stuart, Qiang Sun, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, David J. Van Den Berg, Mohammad A. Vasef, Umadevi Veluvolu, Doug Voet, Vonn Walter, Yunhu Wan, Zhining Wang, Arne Warth, Cleo-Aron Weis, Daniel J. Weisenberger, Matthew D. Wilkerson, Lisa Wise, Tina Wong, Hsin-Ta Wu, Ye Wu, Liming Yang, Jiashan Zhang, and Erik Zmuda

Subjects
Adult, Male, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Cancer Research, Thymoma, Adolescent, Biology, medicine.disease_cause, Article, Autoimmunity, Transcription Factors, TFII, Young Adult, 03 medical and health sciences, medicine, Humans, Neoplasms, Glandular and Epithelial, HRAS, Thymic carcinoma, Aged, Aged, 80 and over, Autoimmune disease, Oncogene, Genomics, Thymus Neoplasms, Cell Biology, Middle Aged, medicine.disease, Myasthenia gravis, 3. Good health, 030104 developmental biology, Oncology, Mutation, Cancer research, Female
Abstract

Summary Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

Published
2018
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18. The IASLC Lung Cancer Staging Project: Background Data and Proposals for the Classification of Lung Cancer with Separate Tumor Nodules in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer

Author

Frank C. Detterbeck, Vanessa Bolejack, Douglas A. Arenberg, John Crowley, Jessica S. Donington, Wilbur A. Franklin, Nicolas Girard, Edith M. Marom, Peter J. Mazzone, Andrew G. Nicholson, Valerie W. Rusch, Lynn T. Tanoue, William D. Travis, Hisao Asamura, Ramón Rami-Porta, Peter Goldstraw, David Ball, David G. Beer, Ricardo Beyruti, Kari Chansky, Frank Detterbeck, Wilfried Ernst Erich Eberhardt, John Edwards, Françoise Galateau-Sallé, Dorothy Giroux, Fergus Gleeson, Patti Groome, James Huang, Catherine Kennedy, Jhingook Kim, Young Tae Kim, Laura Kingsbury, Haruhiko Kondo, Mark Krasnik, Kaoru Kubota, Antoon Lerut, Gustavo Lyons, Mirella Marino, Jan van Meerbeeck, Alan Mitchell, Takashi Nakano, Anna Nowak, Michael Peake, Thomas Rice, Kenneth Rosenzweig, Enrico Ruffini, Valerie Rusch, Nagahiro Saijo, Paul Van Schil, Jean-Paul Sculier, Lynn Shemanski, Kelly Stratton, Kenji Suzuki, Yuji Tachimori, Charles F. Thomas, William Travis, Ming S. Tsao, Andrew Turrisi, Johan Vansteenkiste, Hirokazu Watanabe, Yi-Long Wu, Paul Baas, Jeremy Erasmus, Seiki Hasegawa, Kouki Inai, Kemp Kernstine, Hedy Kindler, Lee Krug, Kristiaan Nackaerts, Harvey Pass, David Rice, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Marco Lucchi, Meinoshin Okumura, Eugene Blackstone, Douglas Flieder, Myrna Godoy, Jin Mo Goo, Lawrence R. Goodman, Jim Jett, Paul de Leyn, Alberto Marchevsky, Heber MacMahon, David Naidich, Morohito Okada, Marina Perlman, Charles Powell, Paul van Schil, Arne Warth, F. Abad Cavaco, E. Ansótegui Barrera, J. Abal Arca, I. Parente Lamelas, A. Arnau Obrer, R. Guijarro Jorge, D. Ball, G.K. Bascom, A.I. Blanco Orozco, M.A. González Castro, M.G. Blum, D. Chimondeguy, V. Cvijanovic, S. Defranchi, B. de Olaiz Navarro, I. Escobar Campuzano, I. Macía Vidueira, E. Fernández Araujo, F. Andreo García, K.M. Fong, G. Francisco Corral, S. Cerezo González, J. Freixinet Gilart, L. García Arangüena, S. García Barajas, P. Girard, T. Goksel, M.T. González Budiño, G. González Casaurrán, J.A. Gullón Blanco, J. Hernández Hernández, H. Hernández Rodríguez, J. Herrero Collantes, M. Iglesias Heras, J.M. Izquierdo Elena, E. Jakobsen, S. Kostas, P. León Atance, A. Núñez Ares, M. Liao, M. Losanovscky, G. Lyons, R. Magaroles, L. De Esteban Júlvez, M. Mariñán Gorospe, B. McCaughan, C. Kennedy, R. Melchor Íñiguez, L. Miravet Sorribes, S. Naranjo Gozalo, C. Álvarez de Arriba, M. Núñez Delgado, J. Padilla Alarcón, J.C. Peñalver Cuesta, J.S. Park, H. Pass, M.J. Pavón Fernández, M. Rosenberg, E. Ruffini, V. Rusch, J. Sánchez de Cos Escuín, A. Saura Vinuesa, M. Serra Mitjans, T.E. Strand, D. Subotic, S. Swisher, R. Terra, C. Thomas, K. Tournoy, P. Van Schil, M. Velasquez, Y.L. Wu, and K. Yokoi

Subjects
Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Lung Neoplasms, Medizin, Adenocarcinoma, 1102 Cardiovascular Medicine And Haematology, Lung cancer, Lung cancer staging, Multiple tumors, Non-small cell lung cancer, TNM classification, Oncology, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, medicine, Humans, Non–small cell lung cancer, Oncology & Carcinogenesis, Survival rate, Neoplasm Staging, business.industry, Background data, Nodule (medicine), Neoplasms, Second Primary, 1103 Clinical Sciences, Second primary cancer, medicine.disease, Prognosis, Survival Rate, 030228 respiratory system, 030220 oncology & carcinogenesis, IASLC Staging and Prognostic Factors Committee, Advisory Boards, Multiple Pulmonary Sites Workgroup and Participating Institutions, IASLC Staging and Prognostic Factors Committee Advisory Boards Multiple Pulmonary Sites Workgroup and Participating Institutions, Neoplasm staging, medicine.symptom, business
Abstract

Introduction Separate tumor nodules with the same histologic appearance occur in the lungs in a small proportion of patients with primary lung cancer. This article addresses how such tumors can be classified to inform the eighth edition of the anatomic classification of lung cancer. Separate tumor nodules should be distinguished from second primary lung cancer, multifocal ground glass/lepidic tumors, and pneumonic-type lung cancer, which are addressed in separate analyses. Methods Survival of patients with separate tumor nodules in the International Association for the Study of Lung Cancer database were analyzed. This was compared with a systematic literature review. Results Survival of clinically staged patients decreased according to the location of the separate tumor nodule relative to the index tumor (same lobe > same side > other side) in N0 and N-any cohorts (all M0 except possible other-side nodules). However, there was also a decrease in the proportion of patients resected; among only surgically resected or among nonresected patients no survival differences were noted. There were no survival differences between patients with same-lobe nodules and those with other T3 tumors, between patients with same-side nodules and those with T4 tumors, and patients with other-side nodules and those with other M1a tumors. The data correlated with those identified in a literature review. Conclusions Tumors with same-lobe separate tumor nodules (with the same histologic appearance) are recommended to be classified as T3, same-side nodules as T4, and other-side nodules as M1a. Thus, there is no recommended change between the seventh and eighth edition of the TNM classification of lung cancer.

Published
2015

19. AB007. OS02.01. The integrated genomic landscape of thymic epithelial tumors: a report by the TCGA research network

Author

Michael C. Ryan, Charles Lu, David N. Hayes, Andrew D. Cherniack, David H. Hwang, Milan Radovich, Thomas Matthew, Mirella Marino, Xiaoping Su, John N. Weinstein, Jiexin Zhang, Katherine A. Hoadley, Arun Rajan, Heejoon Jo, Philipp Ströbel, Gavin Ha, Nicolas Girard, Pavana Anur, Tara M. Lichtenberg, Geetika Sethi, Rehan Akbani, Robert J. Korst, Cristovam Scapulatempo-Neto, Ina Felau, Gordon Robertson, Max D M Leiserson, Curtis R. Pickering, Ludmila Danilova, Jean C. Zenklusen, Yesim Gökmen-Polar, Anne S. Tsao, Alexander Marx, Paul T. Spellman, Reanne Bowlby, Michael D. McLellan, James Huang, Ben Raphael, Ming S. Tsao, Jaegil Kim, Giuseppe Giaccone, Andre L. Moreira, Kristen M. Leraas, Apurva M. Hedge, Patrick J. Loehrer, Hailei Zhang, Junya Fujimoto, and Sunil S. Badve

Subjects
Pulmonary and Respiratory Medicine, Oncology, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Radiology, Nuclear Medicine and imaging, Computational biology, Biology, Cardiology and Cardiovascular Medicine, Bioinformatics
Published
2017
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20. Abstract SY33-04: Integrated omic analysis of lung cancer reveals metabolism-proteome signatures with prognostic impact

Author

Michael F. Moran, Lei Li, Yuhong Wei, Paul Taylor, Christine To, Jiefei Tong, Vladimir Ignatchenko, Melania Pintilie, Nhu-An Pham, Wen Zhang, Lakshmi Muthuswamy, Frances A. Shepherd, Thomas Kislinger, and Ming S. Tsao

Subjects
Genetics, Cancer Research, Biology, Gene mutation, medicine.disease, Transcriptome, Oncology, Proteome, medicine, Carcinoma, Cancer research, Adenocarcinoma, Copy-number variation, Lung cancer, Gene
Abstract

Cancer results from processes prone to selective pressure and dysregulation acting along the sequence-to- phenotype continuum DNA→RNA→Protein→Disease. An Omics Array integrating DNA gene copy number, mRNA transcriptome, and quantified proteome was assembled into a genetic map representing non-small cell lung carcinoma (NSCLC). Data were collected from patient-matched normal lung, primary tumors, and patient tumor-derived xenograft (PDX) tumors. Dysregulated proteins not previously implicated as cancer drivers were found encoded throughout the genome including but not limited to regions of recurrent DNA amplification/deletion in NSCLC. Unsupervised clustering revealed signatures comprising metabolism proteins particularly highly recapitulated between matched primary and PDX tumors, and which distinguished between the major NSCLC histological subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Interrogation of The Cancer Genome Atlas (TCGA) revealed sizeable cohorts of NSCLC patients with DNA alterations in genes encoding the metabolism proteome signatures, and accompanied by differences in survival. Similar to the proteome signatures from which they were extrapolated, the gene mutation signatures with prognostic impact discriminated between the lung ADC and SCC subtypes. Serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in serine/glycine and folate- dependent one-carbon metabolism, is upregulated in the proteomes of NSCLC primary and PDX tumours, and is implicated as a driver of recurrent chromosome 12q14.1 amplification in NSCLC. SHMT2, along with other enzymes implicated as anti-folate targets, is also part of a metabolism proteome signature associated with poor outcome in lung ADC. The interrogation of cancer genomes and proteomes for alterations that are related products of selective pressures driving the cancer phenotype may be a general approach to uncover and group together cryptic, polygenic cancer drivers, which might represent new anti-cancer therapeutic targets. Citation Format: Michael F. Moran, Lei Li, Yuhong Wei, Paul Taylor, Christine To, Jiefei Tong, Vladimir Ignatchenko, Melania Pintilie, Nhu-An Pham, Wen Zhang, Lakshmi Muthuswamy, Frances A. Shepherd, Thomas Kislinger, Ming S. Tsao. Integrated omic analysis of lung cancer reveals metabolism-proteome signatures with prognostic impact. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY33-04. doi:10.1158/1538-7445.AM2015-SY33-04

Published
2015
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21. Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours

Author

Pamela Grenci, James A. Zwiebel, Amit M. Oza, Terrence Colgan, Jaqueline Mason, Al Covens, Ming-S. Tsao, Lisa Wang, Pnu-An Pham, James Pan, K. MacAlpine, Hal W. Hirte, and Helen Mackay

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, endocrine system diseases, medicine.drug_class, medicine.medical_treatment, Phases of clinical research, Antineoplastic Agents, Biology, Hydroxamic Acids, Article, Histones, Ovarian tumor, chemistry.chemical_compound, Internal medicine, medicine, Carcinoma, Humans, Infusions, Intravenous, Aged, Aged, 80 and over, Ovarian Neoplasms, Chemotherapy, Sulfonamides, Histone deacetylase inhibitor, Cancer, Acetylation, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, Carcinoma, Papillary, Histone Deacetylase Inhibitors, Treatment Outcome, chemistry, Drug Resistance, Neoplasm, Immunology, Female, Neoplasm Recurrence, Local, Ovarian cancer, Belinostat
Abstract

Aim Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and are intrinsically resistant to radiation and chemotherapy. Platinum resistant epithelial ovarian cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity in pre-clinical ovarian cancer models. Methods A phase II study was performed to evaluate the activity of belinostat in two patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) EOC and LMP ovarian tumours, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1000 mg/m2/d was administered iv days 1–5 of a 21 d cycle. Peripheral blood mononuclear cells (PBMCs) and tumour biopsies, where possible, for correlative studies were obtained prior to and following treatment. Results Eighteen patients with EOC and 14 patients with LMP tumours were enrolled on study. Belinostat was well tolerated with no grade four toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (3 patients), hypersensitivity (1) and elevated ALP (1). One patient with LMP tumour had a partial response (unconfirmed) and 10 had stable disease (SD), 3 were non-evaluable. Median progression-free survival (PFS) was 13.4 months (95% confidence interval (CI), 5.6 – not reached). Best response in patients with EOC was SD (nine patients) and median PFS was 2.3 months (95% CI, 1.2–5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumour tissue. Conclusions Belinostat is well tolerated in both patient groups and shows some activity in patients with micropapillary (LMP) disease.

Published
2010

22. Abstract 1191: Translational Proof-of-Concept (TransPoC), a not-for-profit research organization enabling access to large-scale translational oncology platforms: The Patient-Derived Xenograft network

Author

Peter G. Smith, David Sutton, Andrea Bertotti, Livio Trusolino, Susan Airhart, Ming S. Tsao, Bradly G. Wouters, S. Gail Eckhardt, Lai Wang, Tim Heffernan, David Verbel, Andrea Gerken, Peter Fekkes, Lihua Yu, and Markus Warmuth

Subjects
Cancer Research, Translational oncology, business.industry, Colorectal cancer, Cancer, Computational biology, medicine.disease, medicine.disease_cause, Bioinformatics, Clinical trial, Not for profit, Oncology, Proof of concept, Pharmacogenomics, medicine, KRAS, business
Abstract

TransPoC is a not-for-profit research organization that will deliver open-access, large-scale translational oncology platforms to enable greater clinical proof-of-concept success for new cancer therapies. TransPoC will comprise three platforms: 1. CPN - Cancer Cell “PoC” Network for screening compounds against 1000+ genomically-characterized cell lines; 2. MPN- Mouse “PoC” Network - a multi-site platform for mouse preclinical trials using genomically-characterized Patient-Derived Xenograft (PDX) models; 3. BioIT - analysis and integration of genomic information and pharmacological profiling data. Here we present an overview of the Mouse “PoC” Network, define a path to implementation of multi-center pre-clinical trials in mice and describe a pilot study to demonstrate the feasibility of implementing such a network. PDX models are increasingly used in pre-clinical studies as they capture and retain the histological, molecular, and genetic heterogeneity of the original tumor compared to cell line derived xenografts and are therefore a closer representation of a patient's tumor in situ. To enable transformative preclinical studies, models need to be characterized in a manner similar to tumor samples in The Cancer Genome Atlas and the International Cancer Genome Consortium, and must be assembled in sufficient quantity to capture clinically relevant major cancer (sub)types. To achieve this, TransPoC is building a global network of mouse PDX “hospitals” with genomic and metabolomic profiles characterized in a consistent manner. In addition, each mouse hospital will utilize common SOPs to generate comparable pharmacology data sets across sites that will include testing standard of care agents. BioIT will enable deep interrogation of data sets and provide pipelines for pharmacogenomics correlates of response to both standard and novel agents. To date, the network has collated over 2,000 PDX models and will enable sponsors to execute multi-center pre-clinical trials in a manner similar to those used in multi-institutional cooperative clinical trials. To demonstrate the viability of MPN, a pilot study has been initiated at 6 sites located in Canada, Italy, China and USA to evaluate the activity of MEK and RAF inhibitors against a panel of BRAF/KRAS mutant melanoma and colorectal cancer PDX models. An update on the initial tolerability, PK/PD/efficacy studies and molecular characterization of PDX models in the network will be presented. TransPoC continues to recruit new sites and characterize their PDX models for incorporation into MPN for use by TransPoC sponsors. Through this effort TransPoC enables rapid assessment of standard and novel investigational therapies to determine their therapeutic potential for translation to clinical trials with a mission to improve the chance of observing clinical proof-of-concept. Citation Format: Peter G. Smith, David Sutton, Andrea Bertotti, Livio Trusolino, Susan Airhart, Ming S. Tsao, Bradly G. Wouters, S. Gail Eckhardt, Lai Wang, Tim Heffernan, David Verbel, Andrea Gerken, Peter Fekkes, Lihua Yu, Lihua Yu, Markus Warmuth. Translational Proof-of-Concept (TransPoC), a not-for-profit research organization enabling access to large-scale translational oncology platforms: The Patient-Derived Xenograft network. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1191. doi:10.1158/1538-7445.AM2014-1191

Published
2014
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