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7. 166 Description of radiological growth patterns in screen-detected lung cancers: The ASCENT study cohort

Author

Khaw, Chuen Ryan, primary, Selway-Clarke, Hugh, additional, Hall, Helen, additional, Cheng, Daryl, additional, Davies, Kate, additional, Frazer, Zoe, additional, Percival, Charlotte, additional, Gowers, Kate, additional, Pennycuick, Adam, additional, Alhendi, Ahmed, additional, Hughes, Laura, additional, Webster, Amy, additional, Galani, Sevi, additional, Monk, Fleur, additional, Khiroya, Reena, additional, Moore, David, additional, Lawrence, David, additional, Patrini, Davide, additional, Bhakhri, Kunal, additional, de Luca, Mario, additional, Ricketts, William, additional, Lau, Kelvin, additional, Waller, David, additional, Stamenkovic, Sasha, additional, Wilson, Henrietta, additional, Giaslakiotis, Konstantinos, additional, Sheaff, Michael, additional, Teixeira, Vitor, additional, Reading, James, additional, Jacob, Joseph, additional, Thirlwell, Chrissie, additional, Hackshaw, Allan, additional, Nair, Arjun, additional, and Janes, Samuel, additional

Published
2024
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9. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma

Author

Szlosarek, P, Creelan, B, Sarkodie, T, Nolan, L, Taylor, P, Olevsky, O, Grosso, F, Cortinovis, D, Chitnis, M, Roy, A, Gilligan, D, Kindler, H, Papadatos-Pastos, D, Ceresoli, G, Mansfield, A, Tsao, A, O’Byrne, K, Nowak, A, Steele, J, Sheaff, M, Shiu, C, Kuo, C, Johnston, A, Bomalaski, J, Zauderer, M, Fennell, D, Rybkin, I, Rolfo, C, Mackean, M, Steele, N, Franks, K, Shaw, P, Lind, M, Upadhyay, S, John, T, Karapetis, C, Srivastav, R, Mencoboni, M, Chella, A, Zilembo, N, de Marinis, F, Stella, M, Chong, I, Wang, C, Null, N, Szlosarek, Peter W., Creelan, Benjamin C., Sarkodie, Thomas, Nolan, Luke, Taylor, Paul, Olevsky, Olga, Grosso, Federica, Cortinovis, Diego, Chitnis, Meenali, Roy, Amy, Gilligan, David, Kindler, Hedy, Papadatos-Pastos, Dionysis, Ceresoli, Giovanni L., Mansfield, Aaron S., Tsao, Anne, O’Byrne, Kenneth J., Nowak, Anna K., Steele, Jeremy, Sheaff, Michael, Shiu, Chiung-Fang, Kuo, Chih-Ling, Johnston, Amanda, Bomalaski, John, Zauderer, Marjorie G., Fennell, Dean A., Rybkin, Igor I., Rolfo, Christian D., MacKean, Melanie, Steele, Nicola, Franks, Kevin, Shaw, Paul, Lind, Michael J., Upadhyay, Sunil, John, Thomas, Karapetis, Christos, Srivastav, Ratnesh, Mencoboni, Manlio, Chella, Antonio, Zilembo, Nicoletta, de Marinis, Filippo, Stella, Maria Giulia, Chong, Inn-Wen, Wang, Chin-Chou, null, null, Szlosarek, P, Creelan, B, Sarkodie, T, Nolan, L, Taylor, P, Olevsky, O, Grosso, F, Cortinovis, D, Chitnis, M, Roy, A, Gilligan, D, Kindler, H, Papadatos-Pastos, D, Ceresoli, G, Mansfield, A, Tsao, A, O’Byrne, K, Nowak, A, Steele, J, Sheaff, M, Shiu, C, Kuo, C, Johnston, A, Bomalaski, J, Zauderer, M, Fennell, D, Rybkin, I, Rolfo, C, Mackean, M, Steele, N, Franks, K, Shaw, P, Lind, M, Upadhyay, S, John, T, Karapetis, C, Srivastav, R, Mencoboni, M, Chella, A, Zilembo, N, de Marinis, F, Stella, M, Chong, I, Wang, C, Null, N, Szlosarek, Peter W., Creelan, Benjamin C., Sarkodie, Thomas, Nolan, Luke, Taylor, Paul, Olevsky, Olga, Grosso, Federica, Cortinovis, Diego, Chitnis, Meenali, Roy, Amy, Gilligan, David, Kindler, Hedy, Papadatos-Pastos, Dionysis, Ceresoli, Giovanni L., Mansfield, Aaron S., Tsao, Anne, O’Byrne, Kenneth J., Nowak, Anna K., Steele, Jeremy, Sheaff, Michael, Shiu, Chiung-Fang, Kuo, Chih-Ling, Johnston, Amanda, Bomalaski, John, Zauderer, Marjorie G., Fennell, Dean A., Rybkin, Igor I., Rolfo, Christian D., MacKean, Melanie, Steele, Nicola, Franks, Kevin, Shaw, Paul, Lind, Michael J., Upadhyay, Sunil, John, Thomas, Karapetis, Christos, Srivastav, Ratnesh, Mencoboni, Manlio, Chella, Antonio, Zilembo, Nicoletta, de Marinis, Filippo, Stella, Maria Giulia, Chong, Inn-Wen, Wang, Chin-Chou, and null, null

Abstract

IMPORTANCE Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. OBJECTIVE To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. DESIGN, SETTING, AND PARTICIPANTS Thiswas a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. INTERVENTION Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8mg/m2) or placebo. All patients received intravenous pemetrexed (500mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. MAIN OUTCOMES AND MEASURES The primary end pointwas overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. RESULTS Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95%CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95%CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95%CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (

Published
2024

10. Renal Transplant Outcomes in Plasma Cell Dyscrasias and AL Amyloidosis after Treatment with Daratumumab.

Author

Mohidin, Barian, Needleman, Amy, Fernando, Raymond, Lowe, David M., Wechalekar, Ashutosh, Sheaff, Michael, Salama, Alan, and Jones, Gareth

Subjects
PLASMA cell diseases, CHRONIC kidney failure, PLASMA cells, RENAL replacement therapy, SEROTHERAPY
Abstract

Background: The morbidity and mortality from AL amyloidosis has significantly improved with the development of novel treatments. Daratumumab is a highly effective treatment for AL amyloidosis, but end-stage kidney disease is a common complication of this condition. Kidney transplantation is the ideal form of renal replacement therapy but has historically been contraindicated in this group of patients. Methods: Given the improved survival and better treatments of both conditions, we argue that it is time to reconsider transplanting these patients. Results: We report our experience of transplanting four patients with AL amyloidosis who had achieved stable remission through treatment with daratumumab. Conclusions: We highlight the key challenges involved and discuss important clinical issues for patients receiving daratumumab, particularly the difficulties with interpreting the crossmatch in light of daratumumab and immunoglobulin therapy interference. We also discuss the complexities involved in balancing the risks of infection, relapse, rejection, and immunosuppression in such patients. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment

Author

Zhang, Min, Luo, Jin-Li, Sun, Qianqian, Harber, James, Dawson, Alan G., Nakas, Apostolos, Busacca, Sara, Sharkey, Annabel J., Waller, David, Sheaff, Michael T., Richards, Cathy, Wells-Jordan, Peter, Gaba, Aarti, Poile, Charlotte, Baitei, Essa Y., Bzura, Aleksandra, Dzialo, Joanna, Jama, Maymun, Le Quesne, John, Bajaj, Amrita, Martinson, Luke, Shaw, Jacqui A., Pritchard, Catrin, Kamata, Tamihiro, Kuse, Nathaniel, Brannan, Lee, De Philip Zhang, Pan, Yang, Hongji, Griffiths, Gareth, Wilson, Gareth, Swanton, Charles, Dudbridge, Frank, Hollox, Edward J., and Fennell, Dean A.

Published
2021
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13. Author Correction: Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment

Author

Zhang, Min, Luo, Jin-Li, Sun, Qianqian, Harber, James, Dawson, Alan G., Nakas, Apostolos, Busacca, Sara, Sharkey, Annabel J., Waller, David, Sheaff, Michael T., Richards, Cathy, Wells-Jordan, Peter, Gaba, Aarti, Poile, Charlotte, Baitei, Essa Y., Bzura, Aleksandra, Dzialo, Joanna, Jama, Maymun, Le Quesne, John, Bajaj, Amrita, Martinson, Luke, Shaw, Jacqui A., Pritchard, Catrin, Kamata, Tamihiro, Kuse, Nathaniel, Brannan, Lee, De Philip Zhang, Pan, Yang, Hongji, Griffiths, Gareth, Wilson, Gareth, Swanton, Charles, Dudbridge, Frank, Hollox, Edward J., and Fennell, Dean A.

Published
2021
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14. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial.

Author

Szlosarek, Peter W., Creelan, Benjamin C., Sarkodie, Thomas, Nolan, Luke, Taylor, Paul, Olevsky, Olga, Grosso, Federica, Cortinovis, Diego, Chitnis, Meenali, Roy, Amy, Gilligan, David, Kindler, Hedy, Papadatos-Pastos, Dionysis, Ceresoli, Giovanni L., Mansfield, Aaron S., Tsao, Anne, O'Byrne, Kenneth J., Nowak, Anna K., Steele, Jeremy, and Sheaff, Michael

Published
2024
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17. Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study

Author

Rosen, Lauren E, Karrison, Theodore, Ananthanarayanan, Vijayalakshmi, Gallan, Alexander J, Adusumilli, Prasad S, Alchami, Fouad S, Attanoos, Richard, Brcic, Luka, Butnor, Kelly J, Galateau-Sallé, Françoise, Hiroshima, Kenzo, Kadota, Kyuichi, Klampatsa, Astero, Stang, Nolween Le, Lindenmann, Joerg, Litzky, Leslie A, Marchevsky, Alberto, Medeiros, Filomena, Montero, M Angeles, Moore, David A, Nabeshima, Kazuki, Pavlisko, Elizabeth N, Roggli, Victor L, Sauter, Jennifer L, Sharma, Anupama, Sheaff, Michael, Travis, William D, Vigneswaran, Wickii T, Vrugt, Bart, Walts, Ann E, Tjota, Melissa Y, Krausz, Thomas, and Husain, Aliya N

Published
2018
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18. The role of platelet-derived growth factor in radiation injury to the lower urinary tract

Author

Sheaff, Michael

Subjects
615.84, Medicine
Abstract

Approximately half of all patients diagnosed with cancer will receive radiotherapy as a part of the management of their tumours. Radiotherapy allows organ sparing treatment but it is associated with a number of acute and late unwanted effects. Radiotherapy has a crucial role to play in the treatment of urothelial malignancies. However, the late non-tumoricidal consequences cause significant morbidity, particularly in relation to fibrosis of the pelvic structures. The unwanted effects of radiotherapy were originally though to be due to the result of direct cell injury, cell death and subsequent fibroatrophic changes. It is now clear that radiation initiates a series of events in cells and tissues that is primarily based upon the release of cytokines, including growth factors, which lead to the development of late radiation injury. This study investigates the changes that occur in the lower urinary tract after radiotherapy and looks for a possible role for platelet derived growth factor (PDGF) in this process. Fifty-six cystectomy specimens were retrieved from the archives of the Pathology Department of patients who had been treated with a similar schedule of radiotherapy for bladder cancer. Morphological changes were identified by routine light microscopy, focussing mainly on the bladder and prostate gland. The degree of fibrosis was measured using an image analysis system and this was related to time since irradiation. Immunohistochemistry for fibronectin, PDGFs and PDGF receptors was performed and the expression assessed by a semiquantitative scoring method. The results were compared to non-irradiated control bladders, either with or without tumours. A range of histological changes were identified including inflammatory, epithelial, stromal, vascular and neural alterations. These were either more commonly seen in the irradiated group or the normal age/physiological changes usually encountered in these organs were exaggerated in this group after irradiation. Predictably, fibrosis and fibronectin production was more obvious in the irradiated group, and this increased with time since irradiation for period of study. PDGFs and their receptors were expressed after irradiation and the levels were higher than in the non-irradiated group. The histological basis for the unwanted side effects of irradiation is described in this study. The fibrosis is progressive, with accumulation of connective tissue long after the radiation dose has been delivered. It is likely, from these results, that PDGF and its 11 receptors play a role in this process. These results pave the way for manipulation of growth factors and/or their receptors, including PDGF, in the future management of patients who are symptomatic with radiation injury.

Published
2011

19. British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders

Author

Hurst, John R., Verma, Nisha, Lowe, David, Baxendale, Helen E., Jolles, Stephen, Kelleher, Peter, Longhurst, Hilary J., Patel, Smita Y., Renzoni, Elisabetta A., Sander, Clare R., Avery, Gerard R., Babar, Judith L., Buckland, Matthew S., Burns, Siobhan, Egner, William, Gompels, Mark M., Gordins, Pavels, Haddock, Jamanda A., Hart, Simon P., Hayman, Grant R., Herriot, Richard, Hoyles, Rachel K., Huissoon, Aarnoud P., Jacob, Joseph, Nicholson, Andrew G., Rassl, Doris M., Sargur, Ravishankar B., Savic, Sinisa, Seneviratne, Suranjith L., Sheaff, Michael, Vaitla, Prashantha M., Walters, Gareth I., Whitehouse, Joanna L., Wright, Penny A., and Condliffe, Alison M.

Published
2017
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26. Lymph Nodes

Author

Sheaff, Michael T., Singh, Naveena, Sheaff, Michael T., and Singh, Naveena

Published
2013
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30. The Breast

Author

Sheaff, Michael T., Singh, Naveena, Sheaff, Michael T., and Singh, Naveena

Published
2013
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32. Abstract CT007: Phase 2-3 trial of pegargiminase plus chemotherapy versus placebo plus chemotherapy in patients with non-epithelioid pleural mesothelioma

Author

Szlosarek, Peter W., primary, Creelan, Ben, additional, Sarkodie, Thomas, additional, Nolan, Luke, additional, Taylor, Paul, additional, Olevsky, Olga, additional, Grosso, Federica, additional, Cortinovis, Diego, additional, Chitnis, Meenali, additional, Roy, Amy, additional, Gilligan, David, additional, Kindler, Hedy, additional, Papadatos-Pastos, Dionysis, additional, Ceresoli, Giovanni L., additional, Mansfield, Aaron, additional, Tsao, Anne, additional, O’Byrne, Ken, additional, Nowak, Anna K., additional, Steele, Jeremy, additional, Sheaff, Michael, additional, Johnston, Amanda, additional, Bomalaski, John, additional, Zauderer, Marjorie, additional, and Fennell, Dean A., additional

Published
2023
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33. Data from BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma

Author

Busacca, Sara, primary, O'Regan, Laura, primary, Singh, Anita, primary, Sharkey, Annabel J., primary, Dawson, Alan G., primary, Dzialo, Joanna, primary, Parsons, Aimee, primary, Kumar, Neelam, primary, Schunselaar, Laurel M., primary, Guppy, Naomi, primary, Nakas, Apostolos, primary, Sheaff, Michael, primary, Mansfield, Aaron S., primary, Janes, Sam M., primary, Baas, Paul, primary, Fry, Andrew M., primary, and Fennell, Dean A., primary

Published
2023
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34. Table S3 from BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma

Author

Busacca, Sara, primary, O'Regan, Laura, primary, Singh, Anita, primary, Sharkey, Annabel J., primary, Dawson, Alan G., primary, Dzialo, Joanna, primary, Parsons, Aimee, primary, Kumar, Neelam, primary, Schunselaar, Laurel M., primary, Guppy, Naomi, primary, Nakas, Apostolos, primary, Sheaff, Michael, primary, Mansfield, Aaron S., primary, Janes, Sam M., primary, Baas, Paul, primary, Fry, Andrew M., primary, and Fennell, Dean A., primary

Published
2023
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35. Figure S5 from BRCA1/MAD2L1 Deficiency Disrupts the Spindle Assembly Checkpoint to Confer Vinorelbine Resistance in Mesothelioma

Author

Busacca, Sara, primary, O'Regan, Laura, primary, Singh, Anita, primary, Sharkey, Annabel J., primary, Dawson, Alan G., primary, Dzialo, Joanna, primary, Parsons, Aimee, primary, Kumar, Neelam, primary, Schunselaar, Laurel M., primary, Guppy, Naomi, primary, Nakas, Apostolos, primary, Sheaff, Michael, primary, Mansfield, Aaron S., primary, Janes, Sam M., primary, Baas, Paul, primary, Fry, Andrew M., primary, and Fennell, Dean A., primary

Published
2023
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36. Figure S3 from A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

Author

Hall, Peter E., primary, Lewis, Rachel, primary, Syed, Nelofer, primary, Shaffer, Richard, primary, Evanson, Jane, primary, Ellis, Stephen, primary, Williams, Matthew, primary, Feng, Xiaoxing, primary, Johnston, Amanda, primary, Thomson, Jim A., primary, Harris, Fiona P., primary, Jena, Raj, primary, Matys, Tomasz, primary, Jefferies, Sarah, primary, Smith, Kate, primary, Wu, Bor-Wen, primary, Bomalaski, John S., primary, Crook, Timothy, primary, O'Neill, Kevin, primary, Paraskevopoulos, Dimitris, primary, Khadeir, Ramsay S., primary, Sheaff, Michael, primary, Pacey, Simon, primary, Plowman, Piers N., primary, and Szlosarek, Peter W., primary

Published
2023
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38. Restructuring health services and labour : management and union relations in an English health authority

Author

Sheaff, Michael

Subjects
658, HD Industries. Land use. Labor, R Medicine (General)
Abstract

This research explores the state of health service trade unionism in the 1980' s and considers its prospects for the future. This is located within the context of trade unionism in general and more specifically within the public services. Historically trade unions have reflected the contours of capitalist work organisations and the social relations within them. The review of British trade unionism in the 1980's therefore considers the impact of institutional factors together with broader social processes upon unions and the "models" of union behaviour which have emerged. The development of trade unionism in the health service is examined to consider how far it can be understood in similar terms. It proceeds from a review of work organisation and management in the NHS which is used to identify a continuing emphasis by the State on cost-containment in the form of efficiency gains. Attempts to introduce greater "rationality" in bureaucratic forms have confronted the influence of the medical profession in the locally negotiated order. However, more recent changes can be presented as introducing more market-oriented criteria. The possible implications of this new environment for health service trade unionism are considered. A single Health Authority case study is used to examine the types of opportunities which may be created for alternative models of trade unionism, described in terms of bargaining, professionalising and campaigning. Following some general information on the Health Authority and its context, six selected episodes are used to consider the application of alternative strategies. Each illustrates contradictory pressures to which unions may be subject. Finally, the analytical questions on the relationship of public service work to capitalist work organisation, and the consequences for trade unionism are reconsidered.

Published
1993

41. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Abbosh, Christopher, Birkbak, Nicolai J., Wilson, Gareth A., Jamal-Hanjani, Mariam, Constantin, Tudor, Salari, Raheleh, Le Quesne, John, Moore, David A., Veeriah, Selvaraju, Rosenthal, Rachel, Marafioti, Teresa, Kirkizlar, Eser, Watkins, Thomas B. K., McGranahan, Nicholas, Ward, Sophia, Martinson, Luke, Riley, Joan, Fraioli, Francesco, Al Bakir, Maise, Grnroos, Eva, Zambrana, Francisco, Endozo, Raymondo, Bi, Wenya Linda, Fennessy, Fiona M., Sponer, Nicole, Johnson, Diana, Laycock, Joanne, Shafi, Seema, Czyzewska-Khan, Justyna, Rowan, Andrew, Chambers, Tim, Matthews, Nik, Turajlic, Samra, Hiley, Crispin, Lee, Siow Ming, Forster, Martin D., Ahmad, Tanya, Falzon, Mary, Borg, Elaine, Lawrence, David, Hayward, Martin, Kolvekar, Shyam, Panagiotopoulos, Nikolaos, Janes, Sam M., Thakrar, Ricky, Ahmed, Asia, Blackhall, Fiona, Summers, Yvonne, Hafez, Dina, Naik, Ashwini, Ganguly, Apratim, Kareht, Stephanie, Shah, Rajesh, Joseph, Leena, Marie Quinn, Anne, Crosbie, Phil A., Naidu, Babu, Middleton, Gary, Langman, Gerald, Trotter, Simon, Nicolson, Marianne, Remmen, Hardy, Kerr, Keith, Chetty, Mahendran, Gomersall, Lesley, Fennell, Dean A., Nakas, Apostolos, Rathinam, Sridhar, Anand, Girija, Khan, Sajid, Russell, Peter, Ezhil, Veni, Ismail, Babikir, Irvin-Sellers, Melanie, Prakash, Vineet, Lester, Jason F., Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Oukrif, Dahmane, Akarca, Ayse U., Hartley, John A., Lowe, Helen L., Lock, Sara, Iles, Natasha, Bell, Harriet, Ngai, Yenting, Elgar, Greg, Szallasi, Zoltan, Schwarz, Roland F., Herrero, Javier, Stewart, Aengus, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Lin, C. Jimmy, Rabinowitz, Matthew, Aerts, Hugo J. W. L., Hackshaw, Allan, Shaw, Jacqui A., Zimmermann, Bernhard G., Swanton, Charles, Bosshard-Carter, Leticia, Goh, Gerald, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Horswell, Stuart, Bakir, Maise Al, Mitter, Richard, Escudero, Mickael, Xu, Hang, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Nye, Emma, Graca, Sofia, Joshi, Kroopa, Furness, Andrew, Ben Aissa, Assma, Wong, Yien Ning Sophia, Georgiou, Andy, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Taylor, Magali, Choudhary, Junaid, Califano, Raffaele, Taylor, Paul, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Moss, Stuart, Idries, Faiza, Bishop, Paul, Chaturvedi, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Rogan, Jane, Smith, Elaine, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Djearaman, Madava, Quesne, John Le, Thomas, Anne, Walter, Harriet, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Primrose, Lindsay, Amadi, Anita, Palmer, Shirley, Miller, Joy, Buchan, Keith, Edwards, Alison, Morgan, Fiona, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Cufari, Maria Elena, Ronquillo, John Carlo, Kwayie, Angela, Bhayani, Harshil, Hamilton, Morag, Bakar, Yusura, Mensah, Natalie, Ambrose, Lyn, Devaraj, Anand, Buderi, Silviu, Finch, Jonathan, Azcarate, Leire, Chavan, Hema, Green, Sophie, Mashinga, Hillaria, Nicholson, Andrew G., Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Light, Teresa, Horey, Tracey, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Fisher, Patricia, Keerio, Allah Dino, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Dentro, Stefan, and Dessimoz, Christophe

Subjects
Lung cancer -- Genetic aspects -- Development and progression, DNA sequencing -- Methods, Phylogeny -- Observations, Cancer metastasis -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies., Author(s): Christopher Abbosh [1]; Nicolai J. Birkbak [1, 2]; Gareth A. Wilson [1, 2]; Mariam Jamal-Hanjani [1]; Tudor Constantin [3]; Raheleh Salari [3]; John Le Quesne [4]; David A. Moore [...]

Published
2017
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