Search

Your search keyword '"MacKenzie, Mairead"' showing total 119 results
Start Over Author "MacKenzie, Mairead"
119 results on '"MacKenzie, Mairead"'

2. Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

Author

Joharatnam-Hogan, Nalinie, Hatem, Duaa, Cafferty, Fay H., Petrucci, Giovanna, Cameron, David A., Ring, Alistair, Kynaston, Howard G., Gilbert, Duncan C., Wilson, Richard H., Hubner, Richard A., Swinson, Daniel E. B., Cleary, Siobhan, Robbins, Alex, MacKenzie, Mairead, Scott-Brown, Martin W. G., Sothi, Sharmila, Dawson, Lesley K., Capaldi, Lisa M., Churn, Mark, Cunningham, David, Khoo, Vincent, Armstrong, Anne C., Ainsworth, Nicola L., Horan, Gail, Wheatley, Duncan A., Mullen, Russell, Lofts, Fiona J., Walther, Axel, Herbertson, Rebecca A., Eaton, John D., O’Callaghan, Ann, Eichholz, Andrew, Kagzi, Mohammed M., Patterson, Daniel M., Narahari, Krishna, Bradbury, Jennifer, Stokes, Zuzana, Rizvi, Azhar J., Walker, Georgina A., Kunene, Victoria L., Srihari, Narayanan, Gentry-Maharaj, Aleksandra, Meade, Angela, Patrono, Carlo, Rocca, Bianca, and Langley, Ruth E.

Published
2023
Full Text
View/download PDF

3. Exploring locoregional treatment reporting in neoadjuvant systemic breast cancer treatment studies: A systematic review

Author

Jiang, Michael, Avery, Kerry, Ahmed, Rosina, de Boniface, Jana, Chatterjee, Sanjoy, Dodwell, David, Dubsky, Peter, Finestone, Sandy, Iwata, Hiroji, Lee, Han-Byoel, MacKenzie, Mairead, Meyn, Anne, Poulakaki, Fiorita, Richardson, Andrea L., Sepulveda, Karla, Spillane, Andrew, Thompson, Alastair M., Werutsky, Gustavo, Wright, Jean L., Zdenkowski, Nicholas, Cowan, Katherine, McIntosh, Stuart A., and Potter, Shelley

Published
2024
Full Text
View/download PDF

5. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer

Author

Meattini, Icro, Becherini, Carlotta, Boersma, Liesbeth, Kaidar-Person, Orit, Marta, Gustavo Nader, Montero, Angel, Offersen, Birgitte Vrou, Aznar, Marianne C, Belka, Claus, Brunt, Adrian Murray, Dicuonzo, Samantha, Franco, Pierfrancesco, Krause, Mechthild, MacKenzie, Mairead, Marinko, Tanja, Marrazzo, Livia, Ratosa, Ivica, Scholten, Astrid, Senkus, Elżbieta, Stobart, Hilary, Poortmans, Philip, and Coles, Charlotte E

Published
2022
Full Text
View/download PDF

7. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial

Author

Burn, John, Campbell, Sue, Capaldi, Lisa, Carse, Yvonne, Gadgil, Durga, Goldman, Arnold, Gupta, Sudeep, Leonard, Gregory, MacKenzie, Mairead, Parmar, Mahesh, Patrono, Carlo, Petty, Russell, Rothwell, Peter M., Steele, Robert J.C., Joharatnam-Hogan, Nalinie, Cafferty, Fay, Hubner, Richard, Swinson, Daniel, Sothi, Sharmila, Gupta, Kamalnayan, Falk, Stephen, Patel, Kinnari, Warner, Nicola, Kunene, Victoria, Rowley, Sam, Khabra, Komel, Underwood, Tim, Jankowski, Janusz, Bridgewater, John, Crossley, Anne, Henson, Verity, Berkman, Lindy, Gilbert, Duncan, Kynaston, Howard, Ring, Alistair, Cameron, David, Din, Farhat, Graham, Janet, Iveson, Timothy, Adams, Richard, Thomas, Anne, Wilson, Richard, Pramesh, C S, and Langley, Ruth

Published
2019
Full Text
View/download PDF

9. Long-term patient-reported outcomes of immediate breast reconstruction after mastectomy for breast cancer: population-based cohort study

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O’Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, William, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2023
Full Text
View/download PDF

14. 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

15. 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

16. 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

17. 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

19. Abstract PD15-10: PD15-10 Impact of procedure type on long-term revisional surgery and secondary reconstruction following immediate breast reconstruction: The UK Brighter national population-based cohort study

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O’Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, William, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2023
Full Text
View/download PDF

20. Abstract PD15-09: PD15-09 Impact of procedure type on the long-term patient-reported outcomes of immediate breast reconstruction: The UK Brighter Study

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O’Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, William, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2023
Full Text
View/download PDF

21. Abstract P2-15-03: Impact of radiotherapy on the long-term patient-reported outcomes of immediate breast reconstruction: The UK Brighter

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O’Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, William, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2023
Full Text
View/download PDF

23. 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
Full Text
View/download PDF

24. Impact of procedure type on revisional surgery and secondary reconstruction after immediate breast reconstruction in a population-based cohort.

Author

Johnson, Leigh, White, Paul, Holcombe, Chris, O'Donoghue, Joe, Jeevan, Ranjeet, Browne, John, Fairbrother, Patricia, MacKenzie, Mairead, Gulliver-Clarke, Carmel, Mohiuddin, Syed, Hollingworth, Will, and Potter, Shelley

Subjects
MAMMAPLASTY, FREE flaps, CARCINOMA in situ, DUCTAL carcinoma, HOSPITAL statistics, SURGERY
Abstract

Background: Women considering immediate breast reconstruction require high-quality information about the likely need for secondary reconstruction and the long-term risk of revisional surgery to make fully informed decisions about different reconstructive options. Such data are currently lacking. This study aimed to explore the impact of reconstruction type on the number of revisions and secondary reconstructions performed 3, 5, and 8 years after immediate breast reconstruction in a large population-based cohort. Methods: Women undergoing unilateral mastectomy and immediate breast reconstruction for breast cancer or ductal carcinoma in situ in England between 1 April 2009 and 31 March 2015 were identified from National Health Service Hospital Episode Statistics. Numbers of revisions and secondary reconstructions in women undergoing primary definitive immediate breast reconstruction were compared by procedure type at 3, 5, and 8 years after index surgery. Results: Some 16 897 women underwent immediate breast reconstruction with at least 3 years' follow-up. Of these, 14 069 had a definitive reconstruction with an implant only (5193), latissimus dorsi flap with (3110) or without (2373) an implant, or abdominal free flap (3393). Women undergoing implant-only reconstruction were more likely to require revision, with 69.5 per cent (747 of 1075) undergoing at least one revision by 8 years compared with 49.3 per cent (1568 of 3180) in other reconstruction groups. They were also more likely to undergo secondary reconstruction, with the proportion of women having further reconstructive procedures increasing over time: 12.8 per cent (663 of 5193) at 3 years, 14.3 per cent (535 of 3752) at 5 years, and 17.6 per cent (189 of 1075) at 8 years. Conclusion: Long-term rates of revisions and secondary reconstructions were considerably higher after primary implant-based reconstruction than autologous procedures. These results should be shared with patients to support informed decision-making. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

25. GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions.

Author

Lloyd, Kelly E, Hall, Louise H, Ziegler, Lucy, Foy, Robbie, Borthwick, Gillian M, MacKenzie, Mairead, Taylor, David G, and Smith, Samuel G

Subjects
HEREDITARY nonpolyposis colorectal cancer, ASPIRIN, DRUG prescribing, CANCER treatment, FACTORIAL experiment designs
Abstract

Background: The National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing. Aim: To investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin. Design and setting: GPs in England and Wales (n = 672) were recruited to participate in an online survey with a 23 factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist. Method: Across the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated. Results: There were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P = 0.031). Conclusion: It is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

27. Long-term patient-reported outcomes of immediate breast reconstruction: Initial results from the brighter study

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O'Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, Will, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2022
Full Text
View/download PDF

28. Rates of revision and secondary reconstruction procedures 8 years following immediate breast reconstruction: Results from the brighter long-term breast reconstruction outcome study

Author

Johnson, Leigh, primary, White, Paul, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Gulliver-Clarke, Carmel, additional, O'Donoghue, Joe, additional, Mohiuddin, Syed, additional, Hollingworth, Will, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Holcombe, Chris, additional, and Potter, Shelley, additional

Published
2022
Full Text
View/download PDF

29. Additional file 1 of Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers

Author

Lloyd, Kelly E., Foy, Robbie, Hall, Louise H., Ziegler, Lucy, Green, Sophie M. C., Haider, Zainab F., Taylor, David G., MacKenzie, Mairead, and Smith, Samuel G.

Abstract

Additional file 1. Interview schedules for Lynch syndrome and healthcare provider interviews.

Published
2022
Full Text
View/download PDF

31. Code of practice needed for samples donated by trial participants

Author

Coleman, Robert, primary, Chan, Arlene, additional, Barrios, Carlos, additional, Cameron, David, additional, Costa, Luis, additional, Dowsett, Mitch, additional, Harrison, David, additional, Howell, Anthony, additional, Lacombe, Denis, additional, MacKenzie, Mairead, additional, Martin, Miguel, additional, McIntosh, Stuart, additional, Morgan, Adrienne, additional, Piccart, Martine, additional, and Spanic, Tanja, additional

Published
2022
Full Text
View/download PDF

32. Abstract OT2-05-01: The HER2-RADiCAL study (Response ADaptive CAre pLan) - Tailoring treatment for HER2 positive early breast cancer

Author

Macpherson, Iain, primary, McIntosh, Stuart, additional, Kilburn, Lucy, additional, Tovey, Holly, additional, Kernaghan, Sarah, additional, Goddard, Katie, additional, Bhattacharya, Indrani, additional, Boyd, Clinton, additional, Coles, Charlotte, additional, Kirwan, Cliona, additional, Mackenzie, Mairead, additional, O’Brien, Ciara, additional, Ring, Alistair, additional, Snowdon, Claire, additional, Stobart, Hilary, additional, Wheatley, Duncan, additional, Wardley, Andrew, additional, Shaaban, Abeer, additional, Hall, Peter, additional, Cameron, David, additional, and Bliss, Judith, additional

Published
2022
Full Text
View/download PDF

34. Protocol for a national cohort study to explore the long-term clinical and patient-reported outcomes and cost-effectiveness of implant-based and autologous breast reconstruction after mastectomy for breast cancer: the brighter study

Author

Johnson, Leigh, primary, Holcombe, Chris, additional, O’Donoghue, Joe M, additional, Jeevan, Ranjeet, additional, Browne, John, additional, Fairbrother, Patricia, additional, MacKenzie, Mairead, additional, Gulliver-Clarke, Carmel, additional, White, Paul, additional, Mohiuddin, Syed, additional, Hollingworth, William, additional, and Potter, Shelley, additional

Published
2021
Full Text
View/download PDF

36. Aspirin as an adjuvant treatment for cancer: feasibility results from the Add-Aspirin randomised trial

Author

Joharatnam-Hogan, Nalinie, primary, Cafferty, Fay, additional, Hubner, Richard, additional, Swinson, Daniel, additional, Sothi, Sharmila, additional, Gupta, Kamalnayan, additional, Falk, Stephen, additional, Patel, Kinnari, additional, Warner, Nicola, additional, Kunene, Victoria, additional, Rowley, Sam, additional, Khabra, Komel, additional, Underwood, Tim, additional, Jankowski, Janusz, additional, Bridgewater, John, additional, Crossley, Anne, additional, Henson, Verity, additional, Berkman, Lindy, additional, Gilbert, Duncan, additional, Kynaston, Howard, additional, Ring, Alistair, additional, Cameron, David, additional, Din, Farhat, additional, Graham, Janet, additional, Iveson, Timothy, additional, Adams, Richard, additional, Thomas, Anne, additional, Wilson, Richard, additional, Pramesh, C S, additional, Langley, Ruth, additional, Burn, John, additional, Campbell, Sue, additional, Capaldi, Lisa, additional, Carse, Yvonne, additional, Gadgil, Durga, additional, Goldman, Arnold, additional, Gupta, Sudeep, additional, Leonard, Gregory, additional, MacKenzie, Mairead, additional, Parmar, Mahesh, additional, Patrono, Carlo, additional, Petty, Russell, additional, Rothwell, Peter M., additional, and Steele, Robert J.C., additional

Published
2019
Full Text
View/download PDF

37. ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours

Author

Coyle, Christopher, Cafferty, Fay H., Rowley, Samuel, MacKenzie, Mairead, Berkman, Lindy, Gupta, Sudeep, Pramesh, C S, Gilbert, Duncan, Kynaston, Howard, Cameron, David, Wilson, Richard H., Ring, Alistair, and Langley, Ruth E.

Subjects
Male, Peptic Ulcer, Esophageal Neoplasms, Gastro-oesophageal cancer, India, Breast Neoplasms, Article, Disease-Free Survival, Drug Hypersensitivity, Macular Degeneration, Tinnitus, Breast cancer, SDG 3 - Good Health and Well-being, Double-Blind Method, Stomach Neoplasms, Neoplasms, Humans, Pharmacology (medical), Longitudinal Studies, Medicine(all), Randomised controlled trial, Prostate cancer, Aspirin, Anti-Inflammatory Agents, Non-Steroidal, Prostatic Neoplasms, Colorectal cancer, United Kingdom, Survival Rate, Chemotherapy, Adjuvant, Female, Neoplasm Recurrence, Local, Colorectal Neoplasms, Gastrointestinal Hemorrhage, Intracranial Hemorrhages
Abstract

Background\ud \ud There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy.\ud \ud Methods\ud \ud Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n = 3100), colorectal (n = 2600), gastro-oesophageal (n = 2100) or prostate cancer (n = 2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100 mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100 mg aspirin, 300 mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥ 75 years old are only randomised to 100 mg aspirin or placebo due to increased toxicity risk.\ud \ud Results\ud \ud The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures.\ud \ud Conclusions\ud \ud The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours.

Published
2016

38. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Litchfield, Kevin, Joshi, Kroopa, Rosenthal, Rachel, Ghorani, Ehsan, Solomon, Isabelle, Lesko, Marta H., Ruef, Nora, Roddie, Claire, Henry, Jake Y., Spain, Lavinia, Ben Aissa, Assma, Georgiou, Andrew, Wong, Yien Ning Sophia, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Nicol, David, O'Brien, Tim, Mårtensson, Linda, Ljungars, Anne, Teige, Ingrid, Frendéus, Björn, Pule, Martin, Marafioti, Teresa, Gore, Martin, Larkin, James, Turajlic, Samra, Swanton, Charles, Peggs, Karl S., Quezada, Sergio A., Harrington, Kevin, Melcher, Alan, Wotherspoon, Andrew, Francis, Nicholas, Challacombe, Ben, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Lynch, Joanna, Rudman, Sarah, Chowdhury, Simon, Harrison-Phipps, Karen, Varia, Mary, Horsfield, Catherine, Polson, Alexander, Stamp, Gordon, O'Donnell, Marie, Drake, William, Hill, Peter, Hrouda, David, Mayer, Eric, Olsburgh, Jonathan, Kooiman, Gordon, O'Connor, Kevin, Stewart, Grant, Aitchison, Michael, Tran, Maxine, Fotiadis, Nicos, Verma, Hema, Lopez, Jose, Lester, Jason, Morgan, Fiona, Kornaszewska, Malgorzata, Attanoos, Richard, Adams, Haydn, Davies, Helen, Fennell, Dean, Shaw, Jacqui, Le Quesne, John, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lock, Sara, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Novasio, Juliette, Joseph, Leena, Bishop, Paul, Chaturvedi, Anshuman, Marie Quinn, Anne, Doran, Helen, leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Brady, Ged, Rothwell, Dominic, Gulati, Sakshi, Chemie, Francesca, Tugwood, Jonathan, Pierce, Jackie, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, George, Robert, Patrini, Davide, Falzon, Mary, Borg, Elaine, Khiroya, Reena, Jamal-Hanjani, Mariam, Wilson, Gareth, Juul Birkbak, Nicolai, Watkins, Thomas, McGranahan, Nicholas, Abbosh, Christopher, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Rowan, Andrew, Hiley, Crispin, Goldman, Jacki, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Shaw, Penny, Veeriah, Raju, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Hynds, Robert, Werner Sunderland, Mariana, Reading, James, Novelli, Marco, Oukrif, Dahmane, Janes, Sam, Forster, Martin, Ahmad, Tanya, Ming Lee, Siow, van Loo, Peter, Herrero, Javier, Hartley, John, Kevin Stone, Richard, Denner, Tamara, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Ward, Sophie, Elgar, Greg, Al-Bakir, Maise, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Papadatos-Pastos, Dionysis, Scarci, Marco, Gorman, Pat, Lowe, Helen, Ensell, Leah, Moore, David, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Tavares Barbosa, Monica, Nicholson, Andrew, Bowman, Alex, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Proli, Chiara, Elena Cufari, Maria, Carlo Ronquillo, John, 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, Lau, Kelvin, Sheaff, Michael, Schmid, Peter, Conibear, John, Ezhil, Veni, Prakash, Vineet, Danson, Sarah, Bury, Jonathan, Edwards, John, Hill, Jennifer, Matthews, Sue, Kitsanta, Yota, Suvarna, Kim, Shackcloth, Michael, Gosney, John, Postmus, Pieter, Feeney, Sarah, Asante-Siaw, Julius, Russell, Peter, Light, Teresa, Horey, Tracey, Blyth, Kevin, Dick, Craig, and Kirk, Alan

Abstract

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches.

Published
2018

39. Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor–Positive Early Breast Cancer: PALLET Trial

Author

Johnston, Stephen, primary, Puhalla, Shannon, additional, Wheatley, Duncan, additional, Ring, Alistair, additional, Barry, Peter, additional, Holcombe, Chris, additional, Boileau, Jean Francois, additional, Provencher, Louise, additional, Robidoux, André, additional, Rimawi, Mothaffar, additional, McIntosh, Stuart A., additional, Shalaby, Ibrahim, additional, Stein, Robert C., additional, Thirlwell, Michael, additional, Dolling, David, additional, Morden, James, additional, Snowdon, Claire, additional, Perry, Sophie, additional, Cornman, Chester, additional, Batten, Leona M., additional, Jeffs, Lisa K., additional, Dodson, Andrew, additional, Martins, Vera, additional, Modi, Arjun, additional, Osborne, C. Kent, additional, Pogue-Geile, Katherine L., additional, Cheang, Maggie Chon U, additional, Wolmark, Norman, additional, Julian, Thomas B., additional, Fisher, Kate, additional, MacKenzie, Mairead, additional, Wilcox, Maggie, additional, Huang Bartlett, Cynthia, additional, Koehler, Maria, additional, Dowsett, Mitch, additional, Bliss, Judith M., additional, and Jacobs, Samuel A., additional

Published
2019
Full Text
View/download PDF

40. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory T Cells and synergizes with PD-1 Blockade to eradicate established tumors

Author

Arce Vargas, Frederick, Furness, Andrew J.S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O’Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A., Spain, Lavinia, Wotherspoon, Andrew, Francis, Nicholas, Smith, Myles, Strauss, Dirk, Hayes, Andrew, Soultati, Aspasia, Stares, Mark, Lynch, Joanna, Fotiadis, Nicos, Fernando, Archana, Hazell, Steve, Chandra, Ashish, Pickering, Lisa, Rudman, Sarah, Chowdhury, Simon, Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Shafi, Seema, Czyzewska-Khan, Justyna, Johnson, Diana, Laycock, Joanne, Bosshard-Carter, Leticia, Goh, Gerald, Rosenthal, Rachel, Gorman, Pat, Murugaesu, Nirupa, Hynds, Robert E., Wilson, Gareth, Birkbak, Nicolai J., Watkins, Thomas B.K., McGranahan, Nicholas, Horswell, Stuart, Mitter, Richard, Escudero, Mickael, Stewart, Aengus, Van Loo, Peter, Rowan, Andrew, Xu, Hang, Hiley, Crispin, Abbosh, Christopher, Goldman, Jacki, Stone, Richard Kevin, Denner, Tamara, Matthews, Nik, Elgar, Greg, Ward, Sophia, Biggs, Jennifer, Costa, Marta, Begum, Sharmin, Phillimore, Ben, Chambers, Tim, Nye, Emma, Graca, Sofia, Al Bakir, Maise, Hartley, John A., Lowe, Helen L., Herrero, Javier, Lawrence, David, Hayward, Martin, Panagiotopoulos, Nikolaos, Kolvekar, Shyam, Falzon, Mary, Borg, Elaine, Simeon, Celia, Hector, Gemma, Smith, Amy, Aranda, Marie, Novelli, Marco, Oukrif, Dahmane, Janes, Sam M., Thakrar, Ricky, Forster, Martin, Ahmad, Tanya, Lee, Siow Ming, Papadatos-Pastos, Dionysis, Carnell, Dawn, Mendes, Ruheena, George, Jeremy, Navani, Neal, Ahmed, Asia, Taylor, Magali, Choudhary, Junaid, Summers, Yvonne, Califano, Raffaele, Taylor, Paul, Shah, Rajesh, Krysiak, Piotr, Rammohan, Kendadai, Fontaine, Eustace, Booton, Richard, Evison, Matthew, Crosbie, Phil, Moss, Stuart, Idries, Faiza, Joseph, Leena, Bishop, Paul, Chaturved, Anshuman, Quinn, Anne Marie, Doran, Helen, Leek, Angela, Harrison, Phil, Moore, Katrina, Waddington, Rachael, Novasio, Juliette, Blackhall, Fiona, Rogan, Jane, Smith, Elaine, Dive, Caroline, Tugwood, Jonathan, Brady, Ged, Rothwell, Dominic G., Chemi, Francesca, Pierce, Jackie, Gulati, Sakshi, Naidu, Babu, Langman, Gerald, Trotter, Simon, Bellamy, Mary, Bancroft, Hollie, Kerr, Amy, Kadiri, Salma, Webb, Joanne, Middleton, Gary, Djearaman, Madava, Fennell, Dean, Shaw, Jacqui A., Le Quesne, John, Moore, David, Nakas, Apostolos, Rathinam, Sridhar, Monteiro, William, Marshall, Hilary, Nelson, Louise, Bennett, Jonathan, Riley, Joan, Primrose, Lindsay, Martinson, Luke, Anand, Girija, Khan, Sajid, Amadi, Anita, Nicolson, Marianne, Kerr, Keith, Palmer, Shirley, Remmen, Hardy, Miller, Joy, Buchan, Keith, Chetty, Mahendran, Gomersall, Lesley, Lester, Jason, Edwards, Alison, Morgan, Fiona, Adams, Haydn, Davies, Helen, Kornaszewska, Malgorzata, Attanoos, Richard, Lock, Sara, Verjee, Azmina, MacKenzie, Mairead, Wilcox, Maggie, Bell, Harriet, Iles, Natasha, Hackshaw, Allan, Ngai, Yenting, Smith, Sean, Gower, Nicole, Ottensmeier, Christian, Chee, Serena, Johnson, Benjamin, Alzetani, Aiman, Shaw, Emily, Lim, Eric, De Sousa, Paulo, Barbosa, Monica Tavares, Bowman, Alex, Jorda, 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, Ezhil, Veni, Ismail, Babikir, Irvin-sellers, Melanie, Prakash, Vineet, Russell, Peter, 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, and Asante-Siaw, Julius

Subjects
hemic and immune systems, chemical and pharmacologic phenomena, R1
Abstract

Summary\ud \ud CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Published
2017

42. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Author

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

Published
2017
Full Text
View/download PDF

46. Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Author

Jamal-Hanjani, Mariam, primary, Hackshaw, Alan, additional, Ngai, Yenting, additional, Shaw, Jacqueline, additional, Dive, Caroline, additional, Quezada, Sergio, additional, Middleton, Gary, additional, de Bruin, Elza, additional, Le Quesne, John, additional, Shafi, Seema, additional, Falzon, Mary, additional, Horswell, Stuart, additional, Blackhall, Fiona, additional, Khan, Iftekhar, additional, Janes, Sam, additional, Nicolson, Marianne, additional, Lawrence, David, additional, Forster, Martin, additional, Fennell, Dean, additional, Lee, Siow-Ming, additional, Lester, Jason, additional, Kerr, Keith, additional, Muller, Salli, additional, Iles, Natasha, additional, Smith, Sean, additional, Murugaesu, Nirupa, additional, Mitter, Richard, additional, Salm, Max, additional, Stuart, Aengus, additional, Matthews, Nik, additional, Adams, Haydn, additional, Ahmad, Tanya, additional, Attanoos, Richard, additional, Bennett, Jonathan, additional, Birkbak, Nicolai Juul, additional, Booton, Richard, additional, Brady, Ged, additional, Buchan, Keith, additional, Capitano, Arrigo, additional, Chetty, Mahendran, additional, Cobbold, Mark, additional, Crosbie, Philip, additional, Davies, Helen, additional, Denison, Alan, additional, Djearman, Madhav, additional, Goldman, Jacki, additional, Haswell, Tom, additional, Joseph, Leena, additional, Kornaszewska, Malgorzata, additional, Krebs, Matthew, additional, Langman, Gerald, additional, MacKenzie, Mairead, additional, Millar, Joy, additional, Morgan, Bruno, additional, Naidu, Babu, additional, Nonaka, Daisuke, additional, Peggs, Karl, additional, Pritchard, Catrin, additional, Remmen, Hardy, additional, Rowan, Andrew, additional, Shah, Rajesh, additional, Smith, Elaine, additional, Summers, Yvonne, additional, Taylor, Magali, additional, Veeriah, Selvaraju, additional, Waller, David, additional, Wilcox, Ben, additional, Wilcox, Maggie, additional, Woolhouse, Ian, additional, McGranahan, Nicholas, additional, and Swanton, Charles, additional

Published
2014
Full Text
View/download PDF

49. Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

Author

Potter S, Avery K, Ahmed R, de Boniface J, Chatterjee S, Dodwell D, Dubsky P, Iwata H, Jiang M, Lee HB, MacKenzie M, Poulakaki F, Richardson AL, Sepulveda K, Spillane A, Thompson AM, Werutsky G, Wright JL, Zdenkowski N, Cowan K, and McIntosh S

Subjects
Humans, Female, Delphi Technique, Consensus, Outcome Assessment, Health Care, Breast Neoplasms therapy, Neoadjuvant Therapy, Research Design
Abstract

Introduction: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved., Methods and Analysis: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance., Ethics and Dissemination: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely., Registration: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854)., Competing Interests: Competing interests: SM reports speaker honoraria from MSD, Roche, BD and Astra Zeneca; advisory boards for Lilly, Novartis, MSD, Roche and Astra Zeneca; conference travel and support from Roche, Lilly and MSD; and institutional research funding from Novartis. HI reports consulting fees from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer and Gilead; honoraria from Daiichi Sankyo, Chugai, Astra Zeneca, Lilly, MSD, Pfizer, Taiho and Kyowa Kirin; and institutional research funding from Chugai, Daiichi Sankyo and Astra Zeneca. PD reports institutional research funding from Cepheid and Roche; consulting fees from Roche, and honoraria from Astra Zeneca and Oncoviews; and conference and travel support from Roche. H-BL reports research funding from Devicor Medical Product Inc. and is a co-founder and director of DCGen Co. Ltd. ALR reports consulting fees from Astra Zeneca and royalties from Myriad Genetics. GW reports consulting fees from Astra Zeneca, MSD, Novartis, Daiichi Sankyo and Roche; honoraria from Astra Zeneca, MSD, Novartis, Roche, Pfizer and Daiichi-Sankyo; and institutional research funding from Astra Zeneca/Medimmune, Roche/Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche, MSD, Merck, Bayer, Janssen, Astellas Pharma, Libbs and Takeda. NZ reports consulting fees from Lilly, Eisai, Astra Zeneca, MSD, Novartis and Gilead; honoraria from Roche, Pfizer, Eisai, Amgen, Gilead, Novartis, Lilly and Astra Zeneca; and conference travel and support from Novartis, Astra Zeneca and Lilly. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
Full Text
View/download PDF

50. Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population.

Author

Lloyd KE, Hall LH, Ziegler L, Foy R, Green SMC, MacKenzie M, Taylor DG, and Smith SG

Subjects
Humans, Qualitative Research, Surveys and Questionnaires, United Kingdom, Aspirin therapeutic use, Neoplasms prevention & control, Neoplasms drug therapy
Abstract

Objectives: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy., Design: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework., Setting: Online survey and remote interviews., Participants: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents., Results: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals., Conclusions: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication., Competing Interests: Competing interests: RF is a member of NICE Implementation Strategy Group. All other authors have no competing interests to declare that are relevant to the content of this article., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results