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1. Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort

Author

Anthony Edey, Neal Navani, Andrew W Creamer, Kitty Chan, Graham Robinson, Janine Zylstra, Paul Robinson, Laura Green, Anand Devaraj, Jane Rowlands, Allan Hackshaw, Carolyn Horst, Arjun Nair, Sam M Janes, Kate Davies, Jeannie Eng, Mamta Ruparel, Samantha L Quaife, Jennifer L Dickson, Magali Taylor, Angshu Bhowmik, Karen Sennett, Samantha Quaife, Samuel Janes, Hasti Robbie, Joseph Jacob, Laura Farrelly, Sophie Tisi, Andrew Creamer, Helen Hall, Samanjit Hare, Jon Teague, Thea Buchan, Stephen Ellis, Thomas Callender, Rachael Sarpong, John McCabe, Zaheer Mangera, Ethaar El-Emir, Terry O'Shaughnessy, Nick Screaton, Priyam Verghese, William M Ricketts, Anne-Marie Mullin, Vicky Bowyer, Kylie Gyertson, Fanta Bojang, Claire Levermore, Ruth Prendecki, Amyn Bhamani, Malavika Suresh, Judy Airebamen, Alice Cotton, Kaylene Phua, Elodie Murali, Simranjit Mehta, Karen Parry-Billings, Columbus Ife, April Neville, Zahra Hanif, Helen Kiconco, Ricardo McEwen, Dominique Arancon, Nicholas Beech, Derya Ovayolu, Christine Hosein, Sylvia Patricia Enes, Qin April Neville, Aashna Samson, Urja Patel, Fahmida Hoque, Hina Pervez, Sofia Nnorom, Moksud Miah, Julian McKee, Mark Clark, Anant Patel, Sara Lock, Rajesh Banka, Ugo Ekeowa, Charlotte Cash, Tunku Aziz, Alberto Villanueva, Elena Stefan, Charlie Sayer, Navinah Nundlall, Lyndsey Gallagher, Andrew Crossingham, Tanita Limani, Kate Gowers, James Rusius, Jennifer Dickson, Anne-Marie Hacker, Jonathon Teague, and Andrew Perugia TaniaAnastasiadis

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Background Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol.Methods The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT.Results In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25.Conclusions Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.

Published
2023
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2. Thoracic oncology HERMES: European curriculum recommendations for training in thoracic oncology

Author

Fernando Gamarra, Julie-Lyn Noël, Alessandro Brunelli, Anne-Marie C. Dingemans, Enriqueta Felip, Mina Gaga, Bogdan Dragos Grigoriu, Georgia Hardavella, Rudolf M. Huber, Samuel Janes, Gilbert Massard, Paul Martin Putora, Jean-Paul Sculier, Philipp A. Schnabel, Sara Ramella, Dirk Van Raemdonck, and Anne-Pascale Meert

Subjects
Diseases of the respiratory system, RC705-779
Published
2016
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3. BARD1 serum autoantibodies for the detection of lung cancer.

Author

Maxim Pilyugin, Pascaline Descloux, Pierre-Alain André, Viktoria Laszlo, Balazs Dome, Balazs Hegedus, Sylvain Sardy, Samuel Janes, Andrea Bianco, Geoffrey J Laurent, and Irmgard Irminger-Finger

Subjects
Medicine, Science
Abstract

Currently the screening for lung cancer for risk groups is based on Computed Tomography (CT) or low dose CT (LDCT); however, the lung cancer death rate has not decreased significantly with people undergoing LDCT. We aimed to develop a simple reliable blood test for early detection of all types of lung cancer based on the immunogenicity of aberrant forms of BARD1 that are specifically upregulated in lung cancer.ELISA assays were performed with a panel of BARD1 epitopes to detect serum levels of antibodies against BARD1 epitopes. We tested 194 blood samples from healthy donors and lung cancer patients with a panel of 40 BARD1 antigens. Using fitted Lasso logistic regression we determined the optimal combination of BARD1 antigens to be used in ELISA for discriminating lung cancer from healthy controls. Random selection of samples for training sets or validations sets was applied to validate the accuracy of our test.Fitted Lasso logistic regression models predict high accuracy of the BARD1 autoimmune antibody test with an AUC = 0.96. Validation in independent samples provided and AUC = 0.86 and identical AUCs were obtained for combined stages 1-3 and late stage 4 lung cancers. The BARD1 antibody test is highly specific for lung cancer and not breast or ovarian cancer.The BARD1 lung cancer test shows higher sensitivity and specificity than previously published blood tests for lung cancer detection and/or diagnosis or CT scans, and it could detect all types and all stages of lung cancer. This BARD1 lung cancer test could therefore be further developed as i) screening test for early detection of lung cancers in high-risk groups, and ii) diagnostic aid in complementing CT scan.

Published
2017
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4. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Orit Rozenblatt-Rosen, Aviv Regev, Philipp Oberdoerffer, Tal Nawy, Anna Hupalowska, Jennifer E. Rood, Orr Ashenberg, Ethan Cerami, Robert J. Coffey, Emek Demir, Li Ding, Edward D. Esplin, James M. Ford, Jeremy Goecks, Sharmistha Ghosh, Joe W. Gray, Justin Guinney, Sean E. Hanlon, Shannon K. Hughes, E. Shelley Hwang, Christine A. Iacobuzio-Donahue, Judit Jané-Valbuena, Bruce E. Johnson, Ken S. Lau, Tracy Lively, Sarah A. Mazzilli, Dana Pe’er, Sandro Santagata, Alex K. Shalek, Denis Schapiro, Michael P. Snyder, Peter K. Sorger, Avrum E. Spira, Sudhir Srivastava, Kai Tan, Robert B. West, Elizabeth H. Williams, Denise Aberle, Samuel I. Achilefu, Foluso O. Ademuyiwa, Andrew C. Adey, Rebecca L. Aft, Rachana Agarwal, Ruben A. Aguilar, Fatemeh Alikarami, Viola Allaj, Christopher Amos, Robert A. Anders, Michael R. Angelo, Kristen Anton, Jon C. Aster, Ozgun Babur, Amir Bahmani, Akshay Balsubramani, David Barrett, Jennifer Beane, Diane E. Bender, Kathrin Bernt, Lynne Berry, Courtney B. Betts, Julie Bletz, Katie Blise, Adrienne Boire, Genevieve Boland, Alexander Borowsky, Kristopher Bosse, Matthew Bott, Ed Boyden, James Brooks, Raphael Bueno, Erik A. Burlingame, Qiuyin Cai, Joshua Campbell, Wagma Caravan, Hassan Chaib, Joseph M. Chan, Young Hwan Chang, Deyali Chatterjee, Ojasvi Chaudhary, Alyce A. Chen, Bob Chen, Changya Chen, Chia-hui Chen, Feng Chen, Yu-An Chen, Milan G. Chheda, Koei Chin, Roxanne Chiu, Shih-Kai Chu, Rodrigo Chuaqui, Jaeyoung Chun, Luis Cisneros, Graham A. Colditz, Kristina Cole, Natalie Collins, Kevin Contrepois, Lisa M. Coussens, Allison L. Creason, Daniel Crichton, Christina Curtis, Tanja Davidsen, Sherri R. Davies, Ino de Bruijn, Laura Dellostritto, Angelo De Marzo, David G. DeNardo, Dinh Diep, Sharon Diskin, Xengie Doan, Julia Drewes, Stephen Dubinett, Michael Dyer, Jacklynn Egger, Jennifer Eng, Barbara Engelhardt, Graham Erwin, Laura Esserman, Alex Felmeister, Heidi S. Feiler, Ryan C. Fields, Stephen Fisher, Keith Flaherty, Jennifer Flournoy, Angelo Fortunato, Allison Frangieh, Jennifer L. Frye, Robert S. Fulton, Danielle Galipeau, Siting Gan, Jianjiong Gao, Long Gao, Peng Gao, Vianne R. Gao, Tim Geiger, Ajit George, Gad Getz, Marios Giannakis, David L. Gibbs, William E. Gillanders, Simon P. Goedegebuure, Alanna Gould, Kate Gowers, William Greenleaf, Jeremy Gresham, Jennifer L. Guerriero, Tuhin K. Guha, Alexander R. Guimaraes, David Gutman, Nir Hacohen, Sean Hanlon, Casey R. Hansen, Olivier Harismendy, Kathleen A. Harris, Aaron Hata, Akimasa Hayashi, Cody Heiser, Karla Helvie, John M. Herndon, Gilliam Hirst, Frank Hodi, Travis Hollmann, Aaron Horning, James J. Hsieh, Shannon Hughes, Won Jae Huh, Stephen Hunger, Shelley E. Hwang, Heba Ijaz, Benjamin Izar, Connor A. Jacobson, Samuel Janes, Reyka G. Jayasinghe, Lihua Jiang, Brett E. Johnson, Bruce Johnson, Tao Ju, Humam Kadara, Klaus Kaestner, Jacob Kagan, Lukas Kalinke, Robert Keith, Aziz Khan, Warren Kibbe, Albert H. Kim, Erika Kim, Junhyong Kim, Annette Kolodzie, Mateusz Kopytra, Eran Kotler, Robert Krueger, Kostyantyn Krysan, Anshul Kundaje, Uri Ladabaum, Blue B. Lake, Huy Lam, Rozelle Laquindanum, Ashley M. Laughney, Hayan Lee, Marc Lenburg, Carina Leonard, Ignaty Leshchiner, Rochelle Levy, Jerry Li, Christine G. Lian, Kian-Huat Lim, Jia-Ren Lin, Yiyun Lin, Qi Liu, Ruiyang Liu, William J.R. Longabaugh, Teri Longacre, Cynthia X. Ma, Mary Catherine Macedonia, Tyler Madison, Christopher A. Maher, Anirban Maitra, Netta Makinen, Danika Makowski, Carlo Maley, Zoltan Maliga, Diego Mallo, John Maris, Nick Markham, Jeffrey Marks, Daniel Martinez, Robert J. Mashl, Ignas Masilionais, Jennifer Mason, Joan Massagué, Pierre Massion, Marissa Mattar, Richard Mazurchuk, Linas Mazutis, Eliot T. McKinley, Joshua F. McMichael, Daniel Merrick, Matthew Meyerson, Julia R. Miessner, Gordon B. Mills, Meredith Mills, Suman B. Mondal, Motomi Mori, Yuriko Mori, Elizabeth Moses, Yael Mosse, Jeremy L. Muhlich, George F. Murphy, Nicholas E. Navin, Michel Nederlof, Reid Ness, Stephanie Nevins, Milen Nikolov, Ajit Johnson Nirmal, Garry Nolan, Edward Novikov, Brendan O’Connell, Michael Offin, Stephen T. Oh, Anastasiya Olson, Alex Ooms, Miguel Ossandon, Kouros Owzar, Swapnil Parmar, Tasleema Patel, Gary J. Patti, Itsik Pe'er, Tao Peng, Daniel Persson, Marvin Petty, Hanspeter Pfister, Kornelia Polyak, Kamyar Pourfarhangi, Sidharth V. Puram, Qi Qiu, Álvaro Quintanal-Villalonga, Arjun Raj, Marisol Ramirez-Solano, Rumana Rashid, Ashley N. Reeb, Mary Reid, Adam Resnick, Sheila M. Reynolds, Jessica L. Riesterer, Scott Rodig, Joseph T. Roland, Sonia Rosenfield, Asaf Rotem, Sudipta Roy, Charles M. Rudin, Marc D. Ryser, Maria Santi-Vicini, Kazuhito Sato, Deborah Schrag, Nikolaus Schultz, Cynthia L. Sears, Rosalie C. Sears, Subrata Sen, Triparna Sen, Alex Shalek, Jeff Sheng, Quanhu Sheng, Kooresh I. Shoghi, Martha J. Shrubsole, Yu Shyr, Alexander B. Sibley, Kiara Siex, Alan J. Simmons, Dinah S. Singer, Shamilene Sivagnanam, Michal Slyper, Artem Sokolov, Sheng-Kwei Song, Austin Southard-Smith, Avrum Spira, Janet Stein, Phillip Storm, Elizabeth Stover, Siri H. Strand, Timothy Su, Damir Sudar, Ryan Sullivan, Lea Surrey, Mario Suvà, Nadezhda V. Terekhanova, Luke Ternes, Lisa Thammavong, Guillaume Thibault, George V. Thomas, Vésteinn Thorsson, Ellen Todres, Linh Tran, Madison Tyler, Yasin Uzun, Anil Vachani, Eliezer Van Allen, Simon Vandekar, Deborah J. Veis, Sébastien Vigneau, Arastoo Vossough, Angela Waanders, Nikhil Wagle, Liang-Bo Wang, Michael C. Wendl, Robert West, Chi-yun Wu, Hao Wu, Hung-Yi Wu, Matthew A. Wyczalkowski, Yubin Xie, Xiaolu Yang, Clarence Yapp, Wenbao Yu, Yinyin Yuan, Dadong Zhang, Kun Zhang, Mianlei Zhang, Nancy Zhang, Yantian Zhang, Yanyan Zhao, Daniel Cui Zhou, Zilu Zhou, Houxiang Zhu, Qin Zhu, Xiangzhu Zhu, Yuankun Zhu, and Xiaowei Zhuang

Subjects
Cell, Genomics, Computational biology, Tumor initiation, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Metastasis, 03 medical and health sciences, Atlases as Topic, 0302 clinical medicine, Neoplasms, Tumor Microenvironment, medicine, Humans, Precision Medicine, 030304 developmental biology, 0303 health sciences, Atlas (topology), Cancer, medicine.disease, 3. Good health, Human tumor, Cell Transformation, Neoplastic, medicine.anatomical_structure, Single-Cell Analysis, Single point, 030217 neurology & neurosurgery
Abstract

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

Published
2020

6. Epithelial ErbB2 activity determines thymus homeostasis and T cell maturation

Author

Tanvi Agrawal, Win-yan Chan, Elizabeth Sage, Krishna Kolluri, Paul Sladen, Gabrielle Sturges, Sabarinath Vallath, Samuel Janes, Mark Coles, Carrie Ambler, Jeremy Brown, and Adam Giangreco

Subjects
Immunology, Immunology and Allergy
Abstract

Thymus involution, the age-dependent loss in organ structure and functionality, promotes increased immune dysfunction in humans, causing increased susceptibility to opportunistic infections, peripheral autoimmunity and reduced vaccine efficacy. Despite this, the mechanisms that regulate thymus involution remain incompletely understood. This has resulted in a lack of clinically approved therapies capable of reversing age-associated thymus involution. Here, we identify that thymic epithelial cell (TEC) specific ErbB2 activity determines thymus homeostasis and T cell maturation. In these studies, we use a conditionally regulated bitransgenic mouse model in which a dominant-active ErbB2 transgene is expressed in keratin14 positive TECs following doxycycline administration. We show that increased ErbB2 expression causes rapid onset of thymus atrophy that resembles age-associated involution. Specific changes include destruction of thymic cortico-medullary boundaries, abnormal TEC differentiation, reduced thymus size and cellularity, and abnormal T cell differentiation. Using foetal thymus organ cultures derived from wild type and bitransgenic animals, we confirm that these phenotypes are due to TEC autonomous ErbB2 expression. Finally, we establish that treating aged mice with the clinically approved Erbb2 inhibitor Lapatinib restores thymus function, improves Streptococcus pneumoniae vaccine efficacy, and promotes infection resistance. Overall, these results demonstrate a previously unknown role for ErbB2 in adult thymus homeostasis and suggest the potential translational relevance of ErbB2 inhibition as a means to reduce or reverse age-associated thymus involution.

Published
2016

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