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1. Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2024
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2. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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3. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Author

Gault, Abigail, Agnieszka, Michael, Bedair, Ahmed, Ghaus, Aisha, Akingboye, Akinfemi, Maynard, Alec, Pawsey, Alexander, Suwaidan, Ali Abdulnabi, Okines, Alicia, Massey, Alison, Kwan, Amy, Ferreira, Ana, Angelakas, Angelos, Wu, Anjui, Tivey, Ann, Armstrong, Anne, Madhan, Annet, Pillai, Annet, Poon-King, Ashley, Kurec, Bartlomiej, Usborne, Caroline, Dobeson, Caroline, Thirlwell, Christina, Mitchell, Christian, Sng, Christopher, Scrase, Christopher, Jingree, Christopher, Brunner, Clair, Fuller, Claire, Griffin, Clare, Barrington, Craig, Muller, Daniel, Ottaviani, Diego, Gilbert, Duncan, Tacconi, Eliana, Copson, Ellen, Renninson, Emily, Cattell, Emma, Burke, Emma, Smith, Fiona, Holt, Francesca, Soosaipillai, Gehan, Boyce, Hayley, Shaw, Heather, Hollis, Helen, Bowyer, Helen, Anil, Iris, Illingworth, Jack, Gibson, Jack, Bhosle, Jaishree, Best, James, Barrett, Jane, Noble, Jillian, Sacco, Joseph, Chacko, Joseph, Chackathayil, Julia, Banfill, Kathryn, Feeney, Laura, Horsley, Laura, Cammaert, Lauren, Mukherjee, Leena, Eastlake, Leonie, Devereaux, Louise, Melcher, Lucinda, Cook, Lucy, Teng, Mabel, Hewish, Madeleine, Bhattacharyya, Madhumita, Choudhury, Mahbuba, Baxter, Mark, Scott-Brown, Martin, Fittall, Matthew, Tilby, Michael, Rowe, Michael, Alihilali, Mohammed, Galazi, Myria, Yousaf, Nadia, Chopra, Neha, Cox, Nicola, Chan, Olivia, Sheikh, Omar, Ramage, Paul, Greaves, Paul, Leonard, Pauline, Hall, Peter S, Naksukpaiboon, Piangfan, Corrie, Pippa, Peck, Rahul, Sharkey, Rachel, Bolton, Rachel, Sargent, Rebecca, Jyothirmayi, Rema, Goldstein, Robert, Oakes, Roderick, Shotton, Rohan, Kanani, Ruhi, Board, Ruth, Pettengell, Ruth, Claydon, Ryan, Moody, Sam, Massalha, Samah, Kathirgamakarthigeyan, Sangary, Dolly, Saoirse, Derby, Sarah, Lowndes, Sarah, Benafif, Sarah, Eeckelaers, Sarah, Kingdon, Sarah, Ayers, Sarah, Brown, Sean, Ellis, Shawn, Parikh, Shefali, Pugh, Sian, Shamas, Simon, Wyatt, Simon, Grumett, Simon, Lau, Sin, Wong, Yien Ning Sophia, McGrath, Sophie, Cornthwaite, Stephanie, Hibbs, Stephen, Tillet, Tania, Rabbi, Taslima, Robinson, Tim, Roques, Tom, Angelis, Vasileios, Woodcock, Victoria, Brown, Victoria, Peng, YingYing, Drew, Yvette, Hudson, Zoe, Lee, Lennard Y W, Cazier, Jean-Baptiste, Starkey, Thomas, Briggs, Sarah E W, Arnold, Roland, Bisht, Vartika, Booth, Stephen, Campton, Naomi A, Cheng, Vinton W T, Collins, Graham, Curley, Helen M, Earwaker, Philip, Fittall, Matthew W, Gennatas, Spyridon, Goel, Anshita, Hartley, Simon, Hughes, Daniel J, Kerr, David, Lee, Alvin J X, Lee, Rebecca J, Lee, Siow Ming, Mckenzie, Hayley, Middleton, Chris P, Murugaesu, Nirupa, Newsom-Davis, Tom, Olsson-Brown, Anna C, Palles, Claire, Powles, Thomas, Protheroe, Emily A, Purshouse, Karin, Sharma-Oates, Archana, Sivakumar, Shivan, Smith, Ashley J, Topping, Oliver, Turnbull, Chris D, Várnai, Csilla, Briggs, Adam D M, Middleton, Gary, and Kerr, Rachel

Published
2020
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6. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Male, Proteomics, Cachexia, Lung Neoplasms, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Body Weight, Body Composition, Humans, Neoplasm Recurrence, Local, Muscle, Skeletal, Neoplasm Proteins
Abstract

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

7. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Clonal Evolution, Cohort Studies, Evolution, Molecular, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Clone Cells
Abstract

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

8. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Lung Neoplasms, Treatment Outcome, DNA Copy Number Variations, Mutagenesis, Carcinoma, Non-Small-Cell Lung, Mutation, Smoking, Humans, Adenocarcinoma of Lung, Neoplasm Recurrence, Local, Phylogeny
Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

9. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
TRACERx Consortium
Abstract

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

13. Author response

Author

Ip, Athena, primary, Black, Georgia, additional, Vindrola, Cecilia, additional, Taylor, Claire, additional, Otter, Sophie, additional, Hewish, Madeleine, additional, Bhuiya, Afsana, additional, Callin, Julie, additional, Wong, Angela, additional, Machesney, Michael, additional, Fulop, Naomi J, additional, Taylor, Cath, additional, and Whitaker, Katriina L, additional

Published
2022
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14. Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Author

Várnai, Csilla, Palles, Claire, Arnold, Roland, Curley, Helen M., Purshouse, Karin, Cheng, Vinton W. T., Booth, Stephen, Campton, Naomi A., Collins, Graham P., Hughes, Daniel J., Kulasekararaj, Austin G., Lee, Alvin J. X., Olsson-brown, Anna C., Sharma-oates, Archana, Van Hemelrijck, Mieke, Lee, Lennard Y. W., Kerr, Rachel, Middleton, Gary, Cazier, Jean-baptiste, Pugh, Sian, Corrie, Pippa, Bedair, Ahmed, Hewish, Madeleine, Leonard, Pauline, Illingworth, Jack, Hibbs, Stephen, Diamantis, Nicolaos, Massalha, Samah, Fuller, Claire, Usbourne, Caroline, Gilbert, Duncan, Davies, Jennifer, Newsom-davis, Tom, Sharkey, Rachel, Lee, Rebecca, Tivey, Ann, Shotton, Rohan, Griffin, Clare, Horsley, Laura, Shamas, Simon, Sacco, Joseph J, Choudhury, Madbuba, Noble, Jillian, Shaw, Heather, Bolton, Rachel, Ferreira, Ana, Hall, Peter, Ramage, Paul, Bhosle, Jaishree, Massey, Alison, Hill, Michaela, Mukherjee, Leena, Ghaus, Aisha, Derby, Sarah, Brown, Sean, Lowndes, Sarah, Dolly, Saorise, Russell, Beth, Moss, Charlotte, Muller, Daniel, Pillai, Annet, Lowe, Shakeel, Cook, Lucy, Scrase, Christopher, Jyothirmayi, Rema, Board, Ruth, Cornthwaite, Stephanie, Parikh, Shefail, Cattell, Emma, Cox, Nicola, Gault, Abigail, Moody, Sam, Dobeson, Caroline, Baxter, Mark, Roques, Tom, Pawsey, Alexander, Oakes, Roderick, Melcher, Lucinda, Chan, Olivia, Ayers, Sarah, Bowyer, Helen, Althohami, Mohammed, Mittal, Sajjan, Feeney, Laura, Aujayeb, Avinash, Sheikh, Omar, Kathirgamakarthigeyan, Sangary, Woodcock, Victoria, Holt, Francesca, Wyatt, Simon, Topping, Oliver, Tilby, Michael, Bhattacharyya, Madhumita, Burke, Emma, Ellis, Shawn, Chacko, Joseph, Rabbi, Taslima, Rowe, Michael, Sargent, Rebecca, Thirlwell, Christina, Gibson, Jack, Goldstein, Robert, Fittall, Mathew, Gennatas, Spyridon, Okines, Alicia, Best, James, Tillett, Tania, Renninson, Emily, Grumett, Simon, Barrington, Craig, Pettengell, Ruth, Peng, Yingyying, Chackathayil, Julia, Akingboye, Akinfemi, Hollis, Helen, Shin Chin, Ik, Bisht, Vartika, Hartley, Simon, Middleton, Christopher P, Goel, Anshita, Protheroe, Emily, Naksukpaiboon, Paingfan, Anil, Iris, Michell, Joel, D'costa, Jamie, Wu, Anjui, Ottaviani, Diego, Soosaipillai, Gehan, Galazi, Myria, Chopra, Neha, Benafif, Sarah, Sng, Christopher Ct, Wong, Sophia Yn, Scott-brown, Martin, Copson, Ellen, Robinson, Timothy, Hudson, Zoe, Smith, Fiona, Abdulnabi Mohamed, Ali-abdulnabi, Angelakas, Angelos, Eastlake, Leoni, Poon-king, Ashley, Brunner, Clair, Kwan, Amy, Maynard, Alec, Boyce, Hayley, Spurrell, Emma, Peck, Rahul, and Kurec, Bartlomiej

Subjects
Aged, 80 and over, Male, Lung Neoplasms, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, United Kingdom, Cohort Studies, Drug Therapy, Hematologic Neoplasms, Humans, Female, Immunotherapy, Prospective Studies, Registries, Aged
Abstract

Importance Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality.Objective To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality.Design, Setting, and Participants The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis.Exposures SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated.Main Outcomes and Measures The primary end point was all-cause mortality within the primary hospitalization.Results Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86).Conclusions and Relevance The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Published
2022

15. Supplemental Material - Healthcare Professional and Patient Perceptions of Changes in Colorectal Cancer Care Delivery During the COVID-19 Pandemic and Impact on Health Inequalities

Author

Ip, Athena, Black, Georgia, Vindrola-Padros, Cecilia, Taylor, Claire, Otter, Sophie, Hewish, Madeleine, Bhuiya, Afsana, Callin, Julie, Wong, Angela, Machesney, Michael, Green, James, Oliphant, Raymond, Fulop, Naomi J., Taylor, Cath, and Whitaker, Katriina L.

Subjects
FOS: Clinical medicine, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental Material for Healthcare Professional and Patient Perceptions of Changes in Colorectal Cancer Care Delivery During the COVID-19 Pandemic and Impact on Health Inequalities by Athena Ip, Georgia Black, Cecilia Vindrola-Padros, Claire Taylor, Sophie Otter, Madeleine Hewish, Afsana Bhuiya, Julie Callin, Angela Wong, Michael Machesney, James Green, Raymond Oliphant, Naomi J. Fulop, Cath Taylor, and Katriina L. Whitaker in Cancer Control

Published
2022
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16. Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial

Author

Smyth, Elizabeth C., Wotherspoon, Andrew, Peckitt, Clare, Gonzalez, David, Hulkki-Wilson, Sanna, Eltahir, Zakaria, Fassan, Matteo, Rugge, Massimo, Valeri, Nicola, Okines, Alicia, Hewish, Madeleine, Allum, William, Stenning, Sally, Nankivell, Matthew, Langley, Ruth, and Cunningham, David

Published
2017
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17. Socioeconomic differences in help seeking for colorectal cancer symptoms during COVID-19: a UK-wide qualitative interview study

Author

Ip, Athena, primary, Black, Georgia, additional, Vindrola-Padros, Cecilia, additional, Taylor, Claire, additional, Otter, Sophie, additional, Hewish, Madeleine, additional, Bhuiya, Afsana, additional, Callin, Julie, additional, Wong, Angela, additional, Machesney, Michael, additional, Fulop, Naomi J, additional, Taylor, Cath, additional, and Whitaker, Katriina L, additional

Published
2022
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21. Healthcare Professional and Patient Perceptions of Changes in Colorectal Cancer Care Delivery During the COVID-19 Pandemic and Impact on Health Inequalities

Author

Ip, Athena, primary, Black, Georgia, additional, Vindrola-Padros, Cecilia, additional, Taylor, Claire, additional, Otter, Sophie, additional, Hewish, Madeleine, additional, Bhuiya, Afsana, additional, Callin, Julie, additional, Wong, Angela, additional, Machesney, Michael, additional, Green, James, additional, Oliphant, Raymond, additional, Fulop, Naomi J., additional, Taylor, Cath, additional, and Whitaker, Katriina L., additional

Published
2022
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22. The effect of COVID-19 on the presentation, staging, and treatment of lung cancer: a retrospective comparative audit of the ‘first wave’

Author

Evetts, Lisa, primary, Applegate, Laura, additional, Singh, Amal, additional, Johnson, Claire, additional, Wing, Sian, additional, McBride, Bernadette, additional, Dargan, Susan, additional, Dawson, Sarah, additional, Sharma, Shashank, additional, Saikia, Sujoy, additional, and Hewish, Madeleine, additional

Published
2021
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23. Digital histological markers based on routine H&E slides to predict benefit from maintenance immunotherapy in esophagogastric adenocarcinoma.

Author

Vu, Quoc Dang, primary, Fong, Caroline, additional, von Loga, Katharina, additional, Raza, Shan E Ahmed, additional, Nava Rodrigues, Daniel, additional, Patel, Bijal, additional, Peckitt, Clare, additional, Begum, Ruwaida, additional, Athauda, Avani, additional, Starling, Naureen, additional, Chau, Ian, additional, Rao, Sheela, additional, Watkins, David J., additional, Rebelatto, Marlon, additional, Waddell, Tom, additional, Wadsley, Jonathan, additional, Roques, Tom, additional, Hewish, Madeleine, additional, Cunningham, David, additional, and Rajpoot, Nasir, additional

Published
2021
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27. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Author

Lee, Lennard Y. W., Cazier, Jean-Baptiste, Starkey, Thomas, Briggs, Sarah E. W., Arnold, Roland, Bisht, Vartika, Booth, Stephen, Campton, Naomi A., Cheng, Vinton W. T., Collins, Graham, Curley, Helen M., Earwaker, Philip, Fittall, Matthew W., Gennatas, Spyridon, Goel, Anshita, Hartley, Simon, Hughes, Daniel J., Kerr, David, Lee, Alvin J. X., Lee, Rebecca J., Lee, Siow Ming, Mckenzie, Hayley, Middleton, Chris P., Murugaesu, Nirupa, Newsom-Davis, Tom, Olsson-Brown, Anna C., Palles, Claire, Powles, Thomas, Protheroe, Emily A., Purshouse, Karin, Sharma-Oates, Archana, Sivakumar, Shivan, Smith, Ashley J., Topping, Oliver, Turnbull, Chris D., Várnai, Csilla, Briggs, Adam D. M., Middleton, Gary, Kerr, Rachel, Gault, Abigail, Agnieszka, Michael, Bedair, Ahmed, Ghaus, Aisha, Akingboye, Akinfemi, Maynard, Alec, Pawsey, Alexander, Mohamed, Ali Abdulnabi, Okines, Alicia, Massey, Alison, Kwan, Amy, Ferreira, Ana, Angelakas, Angelos, Wu, Anjui, Tivey, Ann, Armstrong, Anne, Madhan, Annet, Pillai, Annet, Poon-King, Ashley, Kurec, Bartlomiej, Usborne, Caroline, Dobeson, Caroline, Thirlwell, Christina, Mitchell, Christian, Sng, Christopher, Scrase, Christopher, Jingree, Christopher, Brunner, Clair, Fuller, Claire, Griffin, Clare, Barrington, Craig, Muller, Daniel, Ottaviani, Diego, Gilbert, Duncan, Tacconi, Eliana, Copson, Ellen, Renninson, Emily, Cattell, Emma, Burke, Emma, Smith, Fiona, Holt, Francesca, Soosaipillai, Gehan, Boyce, Hayley, Shaw, Heather, Hollis, Helen, Bowyer, Helen, Anil, Iris, Illingworth, Jack, Gibson, Jack, Bhosle, Jaishree, Best, James, Barrett, Jane, Noble, Jillian, Sacco, Joseph, Chacko, Joseph, Chackathayil, Julia, Banfill, Kathryn, Feeney, Laura, Horsley, Laura, Cammaert, Lauren, Mukherjee, Leena, Eastlake, Leonie, Devereaux, Louise, Melcher, Lucinda, Cook, Lucy, Teng, Mabel, Hewish, Madeleine, Bhattacharyya, Madhumita, Choudhury, Mahbuba, Baxter, Mark, Scott-Brown, Martin, Fittall, Matthew, Tilby, Michael, Rowe, Michael, Alihilali, Mohammed, Galazi, Myria, Yousaf, Nadia, Chopra, Neha, Cox, Nicola, Chan, Olivia, Sheikh, Omar, Ramage, Paul, Greaves, Paul, Leonard, Pauline, Hall, Peter S., Naksukpaiboon, Piangfan, Corrie, Pippa, Peck, Rahul, Sharkey, Rachel, Bolton, Rachel, Sargent, Rebecca, Jyothirmayi, Rema, Goldstein, Robert, Oakes, Roderick, Shotton, Rohan, Kanani, Ruhi, Board, Ruth, Pettengell, Ruth, Claydon, Ryan, Moody, Sam, Massalha, Samah, Kathirgamakarthigeyan, Sangary, Dolly, Saoirse, Derby, Sarah, Lowndes, Sarah, Benafif, Sarah, Eeckelaers, Sarah, Kingdon, Sarah, Ayers, Sarah, Brown, Sean, Ellis, Shawn, Parikh, Shefali, Pugh, Sian, Shamas, Simon, Wyatt, Simon, Grumett, Simon, Lau, Sin, Wong, Yien Ning Sophia, McGrath, Sophie, Cornthwaite, Stephanie, Hibbs, Stephen, Tillet, Tania, Rabbi, Taslima, Robinson, Tim, Roques, Tom, Angelis, Vasileios, Woodcock, Victoria, Brown, Victoria, Peng, YingYing, Drew, Yvette, Hudson, Zoe, and HASH(0x5651ca095ff8)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Pneumonia, Viral, Population, Risk Assessment, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Neoplasms, Internal medicine, Correspondence, Epidemiology, medicine, Humans, Prospective Studies, Lung cancer, education, Prospective cohort study, Pandemics, Aged, Cause of death, Aged, 80 and over, education.field_of_study, Manchester Cancer Research Centre, SARS-CoV-2, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, COVID-19, Cancer, Odds ratio, Middle Aged, medicine.disease, Hospitalization, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Coronavirus Infections, business, RA
Abstract

BACKGROUND: Patients with cancer are purported to have poor COVID-19 outcomes. However, cancer is a heterogeneous group of diseases, encompassing a spectrum of tumour subtypes. The aim of this study was to investigate COVID-19 risk according to tumour subtype and patient demographics in patients with cancer in the UK. METHODS: We compared adult patients with cancer enrolled in the UK Coronavirus Cancer Monitoring Project (UKCCMP) cohort between March 18 and May 8, 2020, with a parallel non-COVID-19 UK cancer control population from the UK Office for National Statistics (2017 data). The primary outcome of the study was the effect of primary tumour subtype, age, and sex and on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence and the case-fatality rate during hospital admission. We analysed the effect of tumour subtype and patient demographics (age and sex) on prevalence and mortality from COVID-19 using univariable and multivariable models. FINDINGS: 319 (30·6%) of 1044 patients in the UKCCMP cohort died, 295 (92·5%) of whom had a cause of death recorded as due to COVID-19. The all-cause case-fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0·10 in patients aged 40-49 years to 0·48 in those aged 80 years and older. Patients with haematological malignancies (leukaemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumours (odds ratio [OR] 1·57, 95% CI 1·15-2·15; p

Published
2020

30. Evaluating maintenance therapies in advanced oesophago-gastric adenocarcinoma (OGA): Interim analysis and biomarker results from the PLATFORM study.

Author

Cunningham, David, primary, Fong, Caroline Yean Kit, additional, Peckitt, Clare, additional, Anandappa, Gayathri, additional, Davidson, Michael, additional, Patel, Bijal, additional, Turner, Andrea, additional, Begum, Ruwaida, additional, Cafferkey, Catherine, additional, von Loga, Katharina, additional, Rebelatto, Marlon, additional, Petty, Russell D., additional, Hewish, Madeleine, additional, Roques, Tom, additional, Coxon, Fareeda Y., additional, Morgan, Carys, additional, Wadsley, Jonathan, additional, Waddell, Tom, additional, Starling, Naureen, additional, and Chau, Ian, additional

Published
2020
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34. Severe synergistic toxicity from docetaxel in a patient treated concurrently with protease inhibitors as part of HIV post-exposure prophylaxis: a case report

Author

Hewish Madeleine, Miller Rowan, Forster Martin, and Smith Ian

Subjects
Medicine
Abstract

Abstract Introduction Docetaxel is a semisynthetic taxane commonly used in solid tumour oncology. Its pharmacokinetics has been widely studied, and it is well established that it is metabolized to pharmacologically inactive products by the cytochrome P450 3A iso-enzymes. However, there have been few reports of the consequences of drug interactions between taxanes and other drugs metabolized by the cytochrome P450 pathway. To the best of our knowledge, this is the first case report of the potentially life-threatening interaction that can occur between docetaxel and the protease inhibitors lopinavir and ritonavir. Case presentation A 30-year-old Caucasian woman presented with symptoms suggestive of severe docetaxel toxicity, that is, prolonged myelosuppression, grade 4 mucositis and desquamating rash, following the commencement of post-exposure prophylaxis for a needlestick injury. She had previously received docetaxel chemotherapy with minimal side effects. Conclusion This case report highlights a probable and novel drug interaction between docetaxel and lopinavir and/or ritonavir, which is largely unreported in the medical literature. Even though these interactions may be more relevant in the field of HIV medicine, knowledge of these interactions is also beneficial to oncologists and dermatologists, as well as those providing acute medical care.

Published
2009
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36. Abstract 2931: Cancer cells deficient in DNA mismatch repair (MMR) are selectively sensitive to inhibition of the DNA dependent protein kinase (DNA-PK)

Author

Hewish, Madeleine, primary, Fontebasso, Yari, additional, Martin, Sarah A., additional, Elliott, Richard, additional, Perks, Kerry L., additional, Konde, Asha, additional, Bajrami, Ilirjana, additional, Weverwijk, Antoinette Van, additional, Cunningham, David, additional, Lord, Christopher J., additional, and Ashworth, Alan, additional

Published
2014
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38. Impact of mismatch repair (MMR) testing on colorectal cancer (CRC) oncology clinical practice.

Author

Hewish, Madeleine, primary, Stamp, Gordon, additional, Puckey, Loretto, additional, Shanley, Susan, additional, Costello, Clare, additional, Webb, Janine, additional, Hulkki Wilson, Sanna, additional, Gonzalez de Castro, David, additional, Barbachano, Yolanda, additional, Saffery, Claire, additional, Swanton, Charles, additional, Lord, Christopher J., additional, Reis-Filho, Jorge S., additional, Ashworth, Alan, additional, Chau, Ian, additional, and Cunningham, David, additional

Published
2012
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43. Genomic instability and the selection of treatments for cancer.

Author

Martin, Sarah A, Hewish, Madeleine, Lord, Christopher J, and Ashworth, Alan

Abstract

A critical link exists between DNA mutation and chromosomal rearrangements (genomic instability) and cancer development. This genomic instability can manifest itself as small changes at the nucleotide level or as gross chromosomal alterations. Mutations in the genes that encode DNA damage response proteins are responsible for a variety of genomic instability syndromes including hereditary non-polyposis colorectal carcinoma, Bloom's syndrome, ataxia-telangiectasia, BRCA-associated breast and ovarian cancers and Fanconi anaemia. Similarly, epigenetic silencing of genes associated with the maintenance of genomic stability have also been implicated in the pathogenesis of cancer. Here, we discuss how different tumours may be classified not only by tumour site but also by the type of underlying genetic instability. This type of classification may assist in the optimization of existing treatment regimens as well as informing the development of new therapeutic approaches. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2010
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45. Virtually the same? Examining the impact of the COVID-19 related shift to virtual lung cancer multidisciplinary team meetings in the UK National Health Service: a mixed methods study.

Author

Groothuizen JE, Aroyewun E, Zasada M, Harris J, Hewish M, and Taylor C

Subjects
Humans, State Medicine, Pandemics, England, Patient Care Team, COVID-19 epidemiology, Lung Neoplasms therapy
Abstract

Objectives: To evaluate the impact of the shift to virtual lung cancer multidisciplinary team meetings (MDTMs) in response to the COVID-19 pandemic, specifically in relation to the magnitude of information technology (IT) issues and distractions and MDT members'/managers' perceptions and experiences of this shift., Design: A mixed methods study comprising real-time observations of IT issues/distractions within virtual MDTM case discussions held between April and July 2021 and qualitative data from interviews/surveys., Setting: Eight hospital organisations in Southern England., Participants: Team members (respiratory physicians, surgeons, oncologists, radiologists, pathologists, palliative care professionals, nurses and MDT coordinators) and managers (n=190) across 8 local MDTs., Results: MDTM observations (n=1664) highlighted significant variation between teams regarding IT functionality. IT issues and other distractions relating to the virtual MDTM format were observed 465 times affecting 20.6% of case discussions, most of which were audio issues (18.1%). Case discussions that had audio issues were, on average, 26 s longer (t(1652)=-2.77, p<0.01). A total of 73 MDT members and managers participated in the survey and 41 participated in interviews, with all 8 teams being represented. Increased flexibility, reduced travel time and easier real-time access to patient information were seen as the main advantages of virtual MDTMs. Views regarding the impact on relational aspects and communication differed. In line with observational findings, concerns were raised in relation to IT, including having inappropriate equipment, insufficient bandwidth (impairing image sharing and video communication) and an overarching theme that virtual meeting platforms provided were not fit for purpose., Conclusions: Despite the potential benefits of virtual MDTMs, IT issues can waste valuable MDTM time. If hospital organisations plan to continue virtual MDTMs, a functioning infrastructure is required, necessitating appropriate resource and investment., Competing Interests: Competing interests: MH is co-chair for lung cancer within the regional cancer alliance through which this research was funded. No competing interests declared for any of the other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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