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52. 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

53. 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

54. 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

55. 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

57. ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

Author

O'Dowd, Emma L, Tietzova, Ilona, Bartlett, Emily, Devaraj, Anand, Biederer, Jürgen, Brambilla, Marco, Brunelli, Alessandro, Chorostowska, Joanna, Decaluwe, Herbert, Deruysscher, Dirk, Wever, Walter De, Donoghue, Matthew, Fabre, Aurelie, Gaga, Mina, Geffen, Wouter van, Hardavella, Georgia, Kauczor, Hans-Ulrich, Kerpel-Fronius, Anna, Meerbeeck, Jan van, and Nagavci, Blin

Subjects
BRONCHIECTASIS, LUNG cancer, EARLY detection of cancer, AORTIC valve diseases, CORONARY artery calcification, MEDIASTINAL tumors
Abstract

Background Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. Methods A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. Results Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. Conclusions This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible. [ABSTRACT FROM AUTHOR]

Published
2023
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58. Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial.

Author

Woznitza, Nick, Ghimire, Bhagabati, Devaraj, Anand, Janes, Sam M., Piper, Keith, Rowe, Susan, Bhowmik, Angshu, Hayes, Natasha, Togher, Daniel, Arumalla, Nikita, Skyllberg, Erik, Au-Yong, Iain T. H., Geary, Susan, George, Bindu, Sheard, Sarah, Ellis, Stephen, Shah, Zoheb, Maughn, Sue, Duffy, Stephen W., and Baldwin, David

Subjects
LUNG cancer, RANDOMIZED controlled trials, RADIOLOGIC technologists, CAREER development, MEDICAL personnel
Abstract

The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer.Method: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter.Results: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports.Conclusions: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy.Trial Registration: International Standard Randomised Controlled Trial Number ISRCTN21818068. Registered on 20 June 2017. [ABSTRACT FROM AUTHOR]

Published
2023
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59. The SUMMIT Study: Utilising a written ‘Next Steps’ information booklet to prepare participants for potential lung cancer screening results and follow-up

Author

Bhamani, Amyn, primary, Horst, Carolyn, additional, Bojang, Fanta, additional, Quaife, Samantha L, additional, Dickson, Jennifer L, additional, Tisi, Sophie, additional, Hall, Helen, additional, Verghese, Priyam, additional, Creamer, Andrew, additional, Prendecki, Ruth, additional, McCabe, John, additional, Gyertson, Kylie, additional, Bowyer, Vicky, additional, El-Emir, Ethaar, additional, Cotton, Alice, additional, Mehta, Simranjit, additional, Levermore, Claire, additional, Mullin, Anne-Marie, additional, Teague, Jonathan, additional, Farrelly, Laura, additional, Nair, Arjun, additional, Devaraj, Anand, additional, Hackshaw, Allan, additional, and Janes, Sam M, additional

Published
2023
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62. A radiomics-based decision support tool improves lung cancer diagnosis in combination with the Herder score in large lung nodules

Author

Hunter, Benjamin, primary, Chen, Mitchell, additional, Ratnakumar, Prashanthi, additional, Alemu, Esubalew, additional, Logan, Andrew, additional, Linton-Reid, Kristofer, additional, Tong, Daniel, additional, Senthivel, Nishanthi, additional, Bhamani, Amyn, additional, Bloch, Susannah, additional, Kemp, Samuel V., additional, Boddy, Laura, additional, Jain, Sejal, additional, Gareeboo, Shafick, additional, Rawal, Bhavin, additional, Doran, Simon, additional, Navani, Neal, additional, Nair, Arjun, additional, Bunce, Catey, additional, Kaye, Stan, additional, Blackledge, Matthew, additional, Aboagye, Eric O., additional, Devaraj, Anand, additional, and Lee, Richard W., additional

Published
2022
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63. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

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

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

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

Published
2017
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67. A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae

Author

George, Peter M., primary, Reed, Anna, additional, Desai, Sujal R., additional, Devaraj, Anand, additional, Faiez, Tasnim Shahridan, additional, Laverty, Sarah, additional, Kanwal, Amama, additional, Esneau, Camille, additional, Liu, Michael K.C., additional, Kamal, Faisal, additional, Man, William D.-C., additional, Kaul, Sundeep, additional, Singh, Suveer, additional, Lamb, Georgia, additional, Faizi, Fatima K., additional, Schuliga, Michael, additional, Read, Jane, additional, Burgoyne, Thomas, additional, Pinto, Andreia L., additional, Micallef, Jake, additional, Bauwens, Emilie, additional, Candiracci, Julie, additional, Bougoussa, Mhammed, additional, Herzog, Marielle, additional, Raman, Lavanya, additional, Ahmetaj-Shala, Blerina, additional, Turville, Stuart, additional, Aggarwal, Anupriya, additional, Farne, Hugo A., additional, Dalla Pria, Alessia, additional, Aswani, Andrew D., additional, Patella, Francesca, additional, Borek, Weronika E., additional, Mitchell, Jane A., additional, Bartlett, Nathan W., additional, Dokal, Arran, additional, Xu, Xiao-Ning, additional, Kelleher, Peter, additional, Shah, Anand, additional, and Singanayagam, Aran, additional

Published
2022
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68. Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial

Author

Woznitza, Nick, primary, Ghimire, Bhagabati, additional, Devaraj, Anand, additional, Janes, Sam M, additional, Piper, Keith, additional, Rowe, Susan, additional, Bhowmik, Angshu, additional, Hayes, Natasha, additional, Togher, Daniel, additional, Arumalla, Nikita, additional, Skyllberg, Erik, additional, Au-Yong, Iain T H, additional, Geary, Susan, additional, George, Bindu, additional, Sheard, Sarah, additional, Ellis, Stephen, additional, Shah, Zoheb, additional, Maughn, Sue, additional, Duffy, Stephen W, additional, and Baldwin, David, additional

Published
2022
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69. Utilisation of primary care electronic patient records for identification and targeted invitation of individuals to a lung cancer screening programme

Author

Dickson, Jennifer L., primary, Hall, Helen, additional, Horst, Carolyn, additional, Tisi, Sophie, additional, Verghese, Priyam, additional, Worboys, Sarah, additional, Perugia, Andrew, additional, Rusius, James, additional, Mullin, Anne-Marie, additional, Teague, Jonathan, additional, Farrelly, Laura, additional, Bowyer, Vicky, additional, Gyertson, Kylie, additional, Bojang, Fanta, additional, Levermore, Claire, additional, Anastasiadis, Tania, additional, McCabe, John, additional, Devaraj, Anand, additional, Nair, Arjun, additional, Navani, Neal, additional, Hackshaw, Allan, additional, Quaife, Samantha L., additional, and Janes, Sam M., additional

Published
2022
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70. Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial

Author

Denton, Christopher P, primary, Goh, Nicole S, additional, Humphries, Stephen M, additional, Maher, Toby M, additional, Spiera, Robert, additional, Devaraj, Anand, additional, Ho, Lawrence, additional, Stock, Christian, additional, Erhardt, Elvira, additional, Alves, Margarida, additional, and Wells, Athol U, additional

Published
2022
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71. P249 Predictors of adverse outcome in sarcoidosis complicated by chronic pulmonary aspergillosis

Author

Nwankwo, Lisa, primary, Periselneris, Jimstan, additional, Gilmartin, Desmond, additional, Desai, Sujal, additional, Shah, Anand, additional, Kouranos, Vasilis, additional, Renzoni, Elisabetta, additional, Wells, Athol, additional, Molyneaux, Phil, additional, George, Peter, additional, Kokosi, M., additional, Devaraj, Anand, additional, Armstrong-James, Darius, additional, and Chua, Felix, additional

Published
2022
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75. Lung cancer screening provides an opportunity for early diagnosis and treatment of interstitial lung disease

Author

Hewitt, Richard J, primary, Bartlett, Emily C, additional, Ganatra, Rea, additional, Butt, Haroun, additional, Kouranos, Vasilis, additional, Chua, Felix, additional, Kokosi, Maria, additional, Molyneaux, Philip L, additional, Desai, Sujal R, additional, Wells, Athol U, additional, Jenkins, R Gisli, additional, Renzoni, Elisabetta A, additional, Kemp, Samuel V, additional, Devaraj, Anand, additional, and George, Peter M, additional

Published
2022
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77. The reporting of pulmonary nodule results by letter in a lung cancer screening setting

Author

Dickson, Jennifer L, primary, Bhamani, Amyn, additional, Quaife, Samantha L, additional, Horst, Carolyn, additional, Tisi, Sophie, additional, Hall, Helen, additional, Verghese, Priyam, additional, Creamer, Andrew, additional, Prendecki, Ruth, additional, McCabe, John, additional, Gyertson, Kylie, additional, Bowyer, Vicky, additional, El-Emir, Ethaar, additional, Cotton, Alice, additional, Mehta, Simranjit, additional, Bojang, Fanta, additional, Levermore, Claire, additional, Mullin, Anne-Marie, additional, Teague, Jonathan, additional, Farrelly, Laura, additional, Nair, Arjun, additional, Devaraj, Anand, additional, Hackshaw, Allan, additional, and Janes, Sam M, additional

Published
2022
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80. Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial.

Author

Denton, Christopher P, Goh, Nicole S, Humphries, Stephen M, Maher, Toby M, Spiera, Robert, Devaraj, Anand, Ho, Lawrence, Stock, Christian, Erhardt, Elvira, Alves, Margarida, and Wells, Athol U

Subjects
LUNG physiology, CONFIDENCE intervals, ANTI-inflammatory agents, SYSTEMIC scleroderma, INTERSTITIAL lung diseases, FIBROSIS, RISK assessment, SEVERITY of illness index, VITAL capacity (Respiration), DESCRIPTIVE statistics, PULMONARY fibrosis, COMPUTED tomography, SECONDARY analysis, DISEASE risk factors, DISEASE complications
Abstract

Objective To assess associations between the extent of fibrotic interstitial lung disease (ILD) and forced vital capacity (FVC) at baseline and change in FVC over 52 weeks in patients with systemic sclerosis-associated ILD (SSc-ILD) in the SENSCIS trial. Material and methods We used generalized additive models, which involve few assumptions and allow for interaction between non-linear effects, to assess associations between the extent of fibrotic ILD on high-resolution computed tomography (HRCT), and the interplay of extent of fibrotic ILD on HRCT and FVC % predicted, at baseline and FVC decline over 52 weeks. Results In the placebo group (n  = 288), there was weak evidence of a modest association between a greater extent of fibrotic ILD at baseline and a greater decline in FVC % predicted at week 52 [r: –0.09 (95% CI –0.2, 0.03)]. Higher values of both the extent of fibrotic ILD and FVC % predicted at baseline tended to be associated with greater decline in FVC % predicted at week 52. In the nintedanib group (n  = 288), there was no evidence of an association between the extent of fibrotic ILD at baseline and decline in FVC % predicted at week 52 [r: 0.01 (95% CI: -0.11, 0.12)] or between the interplay of extent of fibrotic ILD and FVC % predicted at baseline and decline in FVC % predicted at week 52. Conclusions Data from the SENSCIS trial suggest that patients with SSc-ILD are at risk of ILD progression and benefit from nintedanib largely irrespective of their extent of fibrotic ILD at baseline. Study registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02597933. [ABSTRACT FROM AUTHOR]

Published
2023
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83. Immediate, remote smoking cessation intervention in participants undergoing a targeted lung health check: QuLIT2 a randomised controlled trial

Author

Williams, Parris J, primary, Philip, Keir EJ, additional, Gill, Navjot Kaur, additional, Flannery, Deirdre, additional, Buttery, Sara, additional, Bartlett, Emily C, additional, Devaraj, Anand, additional, Kemp, Samuel V, additional, Addis, Jamie, additional, Derbyshire, Jane, additional, Chen, Michelle, additional, Morris, Katie, additional, Laverty, Anthony A., additional, and Hopkinson, Nicholas S, additional

Published
2022
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84. Quality assurance of radiology reporting in lung cancer screening: the role of a radiology review meeting

Author

Creamer, Andrew, primary, Horst, Carolyn, additional, Dickson, Jennifer, additional, Tisi, Sophie, additional, Hall, Helen, additional, Verghese, Priyam, additional, Prendecki, Ruth, additional, Bhamani, Amyn, additional, Teague, Jonathan, additional, Farrelly, Laura, additional, Gyertson, Kylie, additional, Mullin, Anne-Marie, additional, Devaraj, Anand, additional, Nair, Arjun, additional, Hackshaw, Allan, additional, and Janes, Sam, additional

Published
2022
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86. Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease

Author

Vijayakumar, Bavithra, primary, Boustani, Karim, additional, Ogger, Patricia P., additional, Papadaki, Artemis, additional, Tonkin, James, additional, Orton, Christopher M., additional, Ghai, Poonam, additional, Suveizdyte, Kornelija, additional, Hewitt, Richard J., additional, Desai, Sujal R., additional, Devaraj, Anand, additional, Snelgrove, Robert J., additional, Molyneaux, Philip L., additional, Garner, Justin L., additional, Peters, James E., additional, Shah, Pallav L., additional, Lloyd, Clare M., additional, and Harker, James A., additional

Published
2022
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88. Results from the randomised UKLS trial: Lung cancer mortality reduction by LDCT screening confirmed in an international meta-analysis

Author

Field, John K., Vulkan, Daniel, Davies, Micahel P.A., Baldwin, David R., Brain, Kate E., Devaraj, Anand, Eisen, Tim, Holemans, John A., Kavanagh, Terry, Kerr, Keith M., Ledson, Martin, Lifford, Kate J., McRonald, Fiona E., Nair, Arjun, Page, Richard D., Parmar, Mahesk K.B., Rassi, Doris M., Rintoul, Robert C., Wald, Nicolas J., Weler, David, Whynes, David K., Williamson, Paul R., Yadegarfar, Casham, Gabe, Rhian, and Duffy, Stephen W.

Abstract

Background\ud \ud The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.\ud Methods\ud \ud From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50–75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence.\ud Findings\ud \ud 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1–7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41–1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76–0.92) from nine eligible trials.\ud Interpretation\ud \ud The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups.\ud Funding\ud \ud NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.\ud Keywords\ud Lung Cancer\ud CT Screening\ud Lung Cancer Mortality\ud Meta-analysis

Published
2021

89. A persistent neutrophil-associated immune signature characterises post-COVID19 pulmonary sequelae

Author

George, Peter, primary, Reed, Anna, additional, Desai, Sujal, additional, Devaraj, Anand, additional, Faiez, Tasnim Shahridan, additional, Laverty, Sarah, additional, Liu, Michael, additional, Kamal, Faisal, additional, Man, William, additional, Kaul, Sundeep, additional, Singh, Suveer, additional, Lamb, Georgia, additional, Burgoyne, Thomas, additional, Pinto, Andreia, additional, Farne, Hugo, additional, Priya, Alessia Dalla, additional, Aswani, Andrew, additional, Patella, Francesca, additional, Borek, Weronika, additional, Dokal, Arran, additional, Xu, Xiao-Ning, additional, Kelleher, Peter, additional, Shah, Anand, additional, and Singanayagam, Aran, additional

Published
2022
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90. Immediate smoking cessation support versus usual care in smokers attending a targeted lung health check: the QuLIT trial

Author

Buttery, Sara C, primary, Williams, Parris, additional, Mweseli, Rebecca, additional, Philip, Keir Elmslie James, additional, Sadaka, Ahmed, additional, Bartlett, Emily Catharine, additional, Devaraj, Anand, additional, Kemp, Samuel V, additional, Addis, Jamie, additional, Derbyshire, Jane, additional, Chen, Michelle, additional, Morris, Katie, additional, Laverty, Anthony, additional, and Hopkinson, Nicholas S, additional

Published
2022
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91. Short‐term lung function changes predict mortality in patients with fibrotic hypersensitivity pneumonitis

Author

Macaluso, Claudio, primary, Boccabella, Cristina, additional, Kokosi, Maria, additional, Sivarasan, Nishanth, additional, Kouranos, Vasilis, additional, George, Peter M., additional, Margaritopoulos, George, additional, Molyneaux, Philip L., additional, Chua, Felix, additional, Maher, Toby M., additional, Jenkins, Gisli R., additional, Nicholson, Andrew G., additional, Desai, Sujal R., additional, Devaraj, Anand, additional, Wells, Athol U., additional, Renzoni, Elisabetta A., additional, and Stock, Carmel J. W., additional

Published
2022
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93. Interobserver agreement for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT

Author

Walsh, Simon L F, Calandriello, Lucio, Sverzellati, Nicola, Wells, Athol U, Hansell, David M, Jacob, Joseph, Devaraj, Anand, Gavelli, Giampaola, Nath, Hrudaya, Tashjian, Joseph, Tack, Denis, Monostori, Zsuzsanna, Johkoh, Takeshi, Davies, Anne, Zompatori, Maurizio, Polverosi, Roberta, Sassani, Ennio Vincenzo, R Ferretti, Gilbert, Zafer Karaman, Can, Sergiacomi, Gianluigi, Franquet, Tomas, Garg, Kavita, Mannion, Richard, Campos, Paula, Karl, Robert, Burrowes, Paul, Quagliarini, Franco, Norlen, Louise, Murchison, John T, Khalil, Antoine, Nayak, Sundeep M, Nchimi, Alain, Karabulut, Nevzat, Larici, Anna Rita, Matthews, Suzanne, Castañer, Eva, Arenas-Jimenez, Juan, Drosten, Ralph, Egashira, Ryoko, Lee, Hyun-Ju, Rossi, Santiago, Al-Raddadi, Mosleh, Oikonomou, Anastasia, Parkar, Anagha P, Brillet, Pierre Yves, de Paula, Wagner Diniz, Medart, Laurent, Poschenrieder, Florian, Pozek, Igor, Senbanjo, Taiwo, Marten-Engelke, Katharina, Euathrongchit, Juntima, Delaplain, Cal, Cortese, Giancarlo, Soardi, Gian Alberto, Grgic, Aleksandar, Kanne, Jeffrey, Muller, Michelle, Bruzzi, John, Jankowski, Adrien, Bozovic, Gracijela, Goncalves, Andrea, Roos, Justus, Vargas, Daniel, Elias, Mark, Bradford-Kennedy, Djenaba, Seaman, Danielle, Memauri, Brett, Chaudhary, Humera, Wong, Foong, Alegria, Julia, Guo, H Henry, Prosch, Helmut, Cantin, Luce, Serra, Goffredo, Baratella, Elisa, Silecchia, Rosalba, Icksan, Aziza, Wallis, Adam, Damani, Sidhdharth, Renapurkar, Rahul, Hare, Samanjit, Ciello, Annemilia del, Jung, Jennifer, Silva, Mario, Sonavane, Sushilkumar, Thomas, Sue, Beattie, Anna, Kislinger, Benedikt, Ca, Leo, Shroff, Girish, Gietema, Hester, Weerakkody, Yuranga, Hobbs, Stephen, Izumi, Shinyu, Kishaba, Tomoo, Shiraki, Akira, Waseda, Yuko, Castoldi, Maria Chiara, Herpels, Vincent, Pais, Antonio, Matus, Roger, Lubin, Enrico, Wilson, Ben, Mueller, Mathias, Alzubaidi, Shadha Ahmed, Ortiz, Alain, Sequeiros, lara, Bariga, Nicola Boscolo, Wills, Mark, Mak, Sze Mun, Aquaro, Giuseppe, Midia, Esin Cakmakci, Schembri, Nicola, Sheehan, Joseph A M, Farrugia, Alexia, Tomich, Jennifer, and Garcia-Hierro, J M Fernandez

Published
2016
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94. Growing small solid nodules in lung cancer screening: safety and efficacy of a 200 mm3 minimum size threshold for multidisciplinary team referral.

Author

Creamer, Andrew W., Horst, Carolyn, Dickson, Jennifer L., Tisi, Sophie, Hall, Helen, Verghese, Priyam, Prendecki, Ruth, Bhamani, Amyn, McCabe, John, Gyertson, Kylie, Mullin, Anne-Marie, Teague, Jonathan, Farrelly, Laura, Hackshaw, Allan, Nair, Arjun, Devaraj, Anand, Janes, Sam M., and SUMMIT consortium

Subjects
PULMONARY nodules, LUNG cancer, EARLY detection of cancer, COMPUTER-aided diagnosis, SMALL cell lung cancer
Abstract

The optimal management of small but growing nodules remains unclear. The SUMMIT study nodule management algorithm uses a specific threshold volume of 200 mm3 before referral of growing solid nodules to the multidisciplinary team for further investigation is advised, with growing nodules below this threshold kept under observation within the screening programme. Malignancy risk of growing solid nodules of size >200 mm3 at initial 3-month interval scan was 58.3% at a per-nodule level, compared with 13.3% in growing nodules of size ≤200 mm3 (relative risk 4.4, 95% CI 2.17 to 8.83). The positive predictive value of a combination of nodule growth (defined as percentage volume change of ≥25%), and size >200 mm3 was 65.9% (29/44) at a cancer-per-nodule basis, or 60.5% (23/38) on a cancer-per-participant basis. False negative rate of the protocol was 1.9% (95% CI 0.33% to 9.94%). These findings support the use of a 200 mm3 minimum volume threshold for referral as effective at reducing unnecessary multidisciplinary team referrals for small growing nodules, while maintaining early-stage lung cancer diagnosis. [ABSTRACT FROM AUTHOR]

Published
2023
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96. Residual Lung Disease at 6-month Follow-up CT after COVID-19: Clinical Significance Is a Key Issue

Author

Wells, Athol U and Devaraj, Anand

Subjects
Male, Editorial, SARS-CoV-2, COVID-19, Humans, Female, Tomography, X-Ray Computed, Lung, Aged, Follow-Up Studies, Retrospective Studies
Abstract

Background The long-term post-acute pulmonary sequelae of COVID-19 remain unknown. Purpose To evaluate lung injury in patients affected by COVID-19 pneumonia at the 6-month follow-up CT examination compared with the baseline chest CT examination. Materials and Methods From March 19, 2020, to May 24, 2020, patients with moderate to severe COVID-19 pneumonia who had undergone baseline chest CT were prospectively enrolled at their 6-month follow-up. The CT qualitative findings, semiquantitative Lung Severity Score (LSS), and the well-aerated lung volume at quantitative chest CT (QCCT) analysis were analyzed. The performance of the baseline LSS and QCCT findings for predicting fibrosis-like changes (reticular pattern and/or honeycombing) at the 6-month follow-up chest CT examination was tested by using receiver operating characteristic curves. Univariable and multivariable logistic regression analyses were used to test clinical and radiologic features that were predictive of fibrosis-like changes. The multivariable analysis was performed with clinical parameters alone (clinical model), radiologic parameters alone (radiologic model), and the combination of clinical and radiologic parameters (combined model). Results One hundred eighteen patients who had undergone baseline chest CT and agreed to undergo follow-up chest CT at 6 months were included in the study (62 women; mean age, 65 years ± 12 [standard deviation]). At follow-up chest CT, 85 of 118 (72%) patients showed fibrosis-like changes and 49 of 118 (42%) showed ground-glass opacities. The baseline LSS (14) and QCCT findings (≤3.75 L and ≤80%) showed excellent performance for predicting fibrosis-like changes at follow-up chest CT. In the multivariable analysis, the areas under the curve were 0.89 (95% CI: 0.77, 0.96) for the clinical model, 0.81 (95% CI: 0.68, 0.9) for the radiologic model, and 0.92 (95% CI: 0.81, 0.98) for the combined model. Conclusion At 6-month follow-up chest CT, 72% of patients showed late sequelae, in particular fibrosis-like changes. The baseline Lung Severity Score and the well-aerated lung volume at quantitative chest CT (QCCT) analysis showed excellent performance for predicting fibrosis-like changes at the 6-month chest CT (area under the curve,0.88). Male sex, cough, lymphocytosis, and the well-aerated lung volume at QCCT analysis were significant predictors of fibrosis-like changes at 6 months, demonstrating an inverse correlation (area under the curve, 0.92). © RSNA, 2021 See also the editorial by Wells and Devaraj in this issue.

Published
2021

98. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

Author

Field, John K., primary, Vulkan, Daniel, additional, Davies, Michael P.A., additional, Baldwin, David R., additional, Brain, Kate E., additional, Devaraj, Anand, additional, Eisen, Tim, additional, Gosney, John, additional, Green, Beverley A., additional, Holemans, John A., additional, Kavanagh, Terry, additional, Kerr, Keith M., additional, Ledson, Martin, additional, Lifford, Kate J., additional, McRonald, Fiona E., additional, Nair, Arjun, additional, Page, Richard D., additional, Parmar, Mahesh K.B., additional, Rassl, Doris M., additional, Rintoul, Robert C., additional, Screaton, Nicholas J., additional, Wald, Nicholas J., additional, Weller, David, additional, Whynes, David K., additional, Williamson, Paula R., additional, Yadegarfar, Gasham, additional, Gabe, Rhian, additional, and Duffy, Stephen W., additional

Published
2021
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99. Deep Learning for Lung Cancer Detection on Screening CT Scans: Results of a Large-Scale Public Competition and an Observer Study with 11 Radiologists

Author

Jacobs, Colin, primary, Setio, Arnaud A. A., additional, Scholten, Ernst T., additional, Gerke, Paul K., additional, Bhattacharya, Haimasree, additional, M. Hoesein, Firdaus A., additional, Brink, Monique, additional, Ranschaert, Erik, additional, de Jong, Pim A., additional, Silva, Mario, additional, Geurts, Bram, additional, Chung, Kaman, additional, Schalekamp, Steven, additional, Meersschaert, Joke, additional, Devaraj, Anand, additional, Pinsky, Paul F., additional, Lam, Stephen C., additional, van Ginneken, Bram, additional, and Farahani, Keyvan, additional

Published
2021
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