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1. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial

Author

Smith, Ian, Robertson, John, Kilburn, Lucy, Wilcox, Maggie, Evans, Abigail, Holcombe, Chris, Horgan, Kieran, Kirwan, Cliona, Mallon, Elizabeth, Sibbering, Mark, Skene, Anthony, Vidya, Raghavan, Cheang, Maggie, Banerji, Jane, Morden, James, Sidhu, Kally, Dodson, Andrew, Bliss, Judith M, and Dowsett, Mitch

Published
2020
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2. Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project

Author

Thompson, Alastair, Francis, Adele, Sibbering, Mark, Bishop, Hugh, Carpenter, Robert, George, W.D., Lee, Martin, Nicholson, Stewart, Dobson, Hilary, Evans, Andy, Maxwell, Anthony, Wallis, Matthew, Dodwell, David, Sawyer, Elinor, Adlard, Julian, Dewar, John, Ross, Gillian, Wilcox, Maggie, Hanby, Andrew, Pinder, Sarah, Speirs, Valerie, Thomas, Jeremy, Ellis, Ian, Lakhani, Sunil, Macartney, James, Tomlinson, Ian, Cheung, Shan, Lawrence, Gill, Ball, Graham, Clements, Karen, Hilton, Bridget, Kearins, Olive, Wheaton, Margot, Thompson, Alastair M., Pinder, Sarah E., Ball, Graham R., Thomas, Jeremy St J., Maxwell, Anthony J., Wallis, Matthew G., and Dodwell, David J.

Published
2018
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3. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial

Author

Al Sarakbi, Wail, Barber, Sarah, Barnett, Gillian, Bliss, Peter, Dewar, John, Eaton, David, Ebbs, Stephen, Ellis, Ian, Evans, Philip, Harris, Emma, James, Hayley, Kirwan, Cliona, Kirk, Julie, Mayles, Helen, McIntyre, Anne, Mills, Judith, Poynter, Andrew, Provenzano, Elena, Rawlings, Christine, Sculpher, Mark, Sumo, Georges, Sydenham, Mark, Tutt, Andrew, Twyman, Nicola, Venables, Karen, Winship, Anna, Winstanley, John, Wishart, Gordon, Thompson, Alastair, Coles, Charlotte E, Griffin, Clare L, Kirby, Anna M, Titley, Jenny, Agrawal, Rajiv K, Alhasso, Abdulla, Bhattacharya, Indrani S, Brunt, Adrian M, Ciurlionis, Laura, Chan, Charlie, Donovan, Ellen M, Emson, Marie A, Harnett, Adrian N, Haviland, Joanne S, Hopwood, Penelope, Jefford, Monica L, Kaggwa, Ronald, Sawyer, Elinor J, Syndikus, Isabel, Tsang, Yat M, Wheatley, Duncan A, Wilcox, Maggie, Yarnold, John R, and Bliss, Judith M

Published
2017
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5. 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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7. Six versus 12 months’ adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT

Author

Earl, Helena, primary, Hiller, Louise, additional, Vallier, Anne-Laure, additional, Loi, Shrushma, additional, McAdam, Karen, additional, Hughes-Davies, Luke, additional, Rea, Daniel, additional, Howe, Donna, additional, Raynes, Kerry, additional, Higgins, Helen B, additional, Wilcox, Maggie, additional, Plummer, Chris, additional, Mahler-Araujo, Betania, additional, Provenzano, Elena, additional, Chhabra, Anita, additional, Gasson, Sophie, additional, Balmer, Claire, additional, Abraham, Jean E, additional, Caldas, Carlos, additional, Hall, Peter, additional, Shinkins, Bethany, additional, McCabe, Christopher, additional, Hulme, Claire, additional, Miles, David, additional, Wardley, Andrew M, additional, Cameron, David A, additional, and Dunn, Janet A, additional

Published
2020
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8. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial

Author

Earl, Helena M, Hiller, Louise, Vallier, Anne-Laure, Loi, Shrushma, McAdam, Karen, Hughes-Davies, Luke, Harnett, Adrian N, Ah-See, Mei-Lin, Simcock, Richard, Rea, Daniel, Raj, Sanjay, Woodings, Pamela, Harries, Mark, Howe, Donna, Raynes, Kerry, Higgins, Helen B, Wilcox, Maggie, Plummer, Chris, Mansi, Janine, Gounaris, Ioannis, Mahler-Araujo, Betania, Provenzano, Elena, Chhabra, Anita, Abraham, Jean E, Caldas, Carlos, Hall, Peter S, McCabe, Christopher, Hulme, Claire, Miles, David, Wardley, Andrew M, Cameron, David A, Dunn, Janet A, PERSEPHONE Steering Committee And Trial Investigators, Earl, Helena [0000-0003-1549-8094], Abraham, Jean [0000-0003-0688-4807], Caldas, Carlos [0000-0003-3547-1489], and Apollo - University of Cambridge Repository

Subjects
Adult, Aged, 80 and over, Receptor, ErbB-2, Injections, Subcutaneous, Breast Neoplasms, Middle Aged, Trastuzumab, Disease-Free Survival, Drug Administration Schedule, United Kingdom, Young Adult, Antineoplastic Agents, Immunological, Treatment Outcome, Chemotherapy, Adjuvant, Humans, Female, Prospective Studies, Infusions, Intravenous, Aged
Abstract

BACKGROUND: Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is non-inferior to the standard 12-month treatment regarding disease-free survival. METHODS: This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140). FINDINGS: Between Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6-6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9-90·7) in the 6-month group and 89·8% (88·3-91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93-1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p

Published
2019
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9. 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

10. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial

Author

Earl, Helena M, primary, Hiller, Louise, additional, Vallier, Anne-Laure, additional, Loi, Shrushma, additional, McAdam, Karen, additional, Hughes-Davies, Luke, additional, Harnett, Adrian N, additional, Ah-See, Mei-Lin, additional, Simcock, Richard, additional, Rea, Daniel, additional, Raj, Sanjay, additional, Woodings, Pamela, additional, Harries, Mark, additional, Howe, Donna, additional, Raynes, Kerry, additional, Higgins, Helen B, additional, Wilcox, Maggie, additional, Plummer, Chris, additional, Mansi, Janine, additional, Gounaris, Ioannis, additional, Mahler–Araujo, Betania, additional, Provenzano, Elena, additional, Chhabra, Anita, additional, Abraham, Jean E, additional, Caldas, Carlos, additional, Hall, Peter S, additional, McCabe, Christopher, additional, Hulme, Claire, additional, Miles, David, additional, Wardley, Andrew M, additional, Cameron, David A, additional, Dunn, Janet A, additional, Agarwal, Roshan, additional, Algurafi, Hafiz, additional, Allerton, Rozenn, additional, Archer, Caroline, additional, Armstrong, Anne, additional, Bale, Catherine, additional, Barraclough, Lisa, additional, Barthakur, Urmila, additional, Bedi, Carolyn, additional, Benstead, Kim, additional, Bloomfield, David, additional, Bowen, Rebecca, additional, Bradley, Chris, additional, Brown, Jane, additional, Butt, Mohammad, additional, Churn, Mark, additional, Cleator, Susan, additional, Cliff, Joanne, additional, Crellin, Perric, additional, Daly, Margaret, additional, De Silva-Minor, Shiroma, additional, Dhadda, Amandeep, additional, Din, Omar, additional, Down, Sue, additional, Earl, Helena, additional, Eaton, David, additional, Eichholz, Andrew, additional, Epurescu, Daniel, additional, Goh, Chee, additional, Goodman, Andrew, additional, Grieve, Robert, additional, Hadaki, Maher, additional, Harper-Wynne, Catherine, additional, Hayward, Larry, additional, Humphreys, Alison, additional, Innes, Helen, additional, Jafri, Mariam, additional, Jegannathen, Apurna, additional, Kelleher, Muireann, additional, Kristeleit, Hartmut, additional, Lee, Daniela, additional, Lupton, Susan, additional, MacGregor, Carol, additional, Malik, Zafar, additional, Marshall, Jennifer, additional, McGolick, Trevor, additional, Mehra, Rakesh, additional, Mithal, Natasha, additional, Moss, Charlotte, additional, Moss, Aian, additional, Mukesh, Mukesh, additional, Neal, Anthony, additional, Nelmes, Daniel, additional, Neville-Webbe, Helen, additional, Newby, Jacqueline, additional, O'Reilly, Susan, additional, Ostler, Peter, additional, Persic, Mojca, additional, Pettit, Laura, additional, Raja, Fharat, additional, Reed, Catherine, additional, Rigg, Anne, additional, Roe, Helen, additional, Shah, Nihal, additional, Simmonds, Peter, additional, Sims, Eliot, additional, Smith, Sarah, additional, Storey, Nicola, additional, Taylor, Wendy, additional, Thanvi, Narottam, additional, Tipples, Karen, additional, Vaidya, Jayant, additional, Varughese, Mohini, additional, Vinayan, Anup, additional, Walji, Nawaz, additional, Waters, Simon, additional, Wright, Kathryn, additional, and Yahya, Sundus, additional

Published
2019
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11. 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
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12. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial):5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial

Author

Coles, Charlotte E, Griffin, Clare L, Kirby, Anna M, Titley, Jenny, Agrawal, Rajiv K, Alhasso, Abdulla, Bhattacharya, Indrani S, Brunt, Adrian M, Ciurlionis, Laura, Chan, Charlie, Donovan, Ellen M, Emson, Marie A, Harnett, Adrian N, Haviland, Joanne S, Hopwood, Penelope, Jefford, Monica L, Kaggwa, Ronald, Sawyer, Elinor J, Syndikus, Isabel, Tsang, Yat M, Wheatley, Duncan A, Wilcox, Maggie, Yarnold, John R, Bliss, Judith M, Al Sarakbi, Wail, Barber, Sarah, Barnett, Gillian, Bliss, Peter, Dewar, John, Eaton, David, Ebbs, Stephen, Ellis, Ian, Evans, Philip, Harris, Emma, James, Hayley, Kirwan, Cliona, Kirk, Julie, Mayles, Helen, McIntyre, Anne, Mills, Judith, Poynter, Andrew, Provenzano, Elena, Rawlings, Christine, Sculpher, Mark, Sumo, Georges, Sydenham, Mark, Tutt, Andrew, Twyman, Nicola, Venables, Karen, Winship, Anna, Winstanley, John, and Wishart, Gordon

Abstract

Background: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy. Methods: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1–3, with a tumour size of 3 cm or less (pT1–2), none to three positive axillary nodes (pN0–1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634. Findings: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7–83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5–2·3) of patients in the control group, 0·2% (0·02–1·2) in the reduced-dose group, and 0·5% (0·2–1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were −0·73% (−0·99 to 0·22) for the reduced-dose and −0·38% (−0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and pInterpretation: We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide. Funding: Cancer Research UK.

Published
2017

13. 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

14. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ

Author

Maxwell, Anthony J., primary, Clements, Karen, additional, Hilton, Bridget, additional, Dodwell, David J., additional, Evans, Andrew, additional, Kearins, Olive, additional, Pinder, Sarah E., additional, Thomas, Jeremy, additional, Wallis, Matthew G., additional, Thompson, Alastair M., additional, Thompson, Alastair, additional, Dobson, Hilary, additional, Dodwell, David, additional, Hanby, Andrew, additional, Lawrence, Gill, additional, Maxwell, Anthony, additional, Pinder, Sarah, additional, Sawyer, Elinor, additional, Sibbering, Mark, additional, Speirs, Valerie, additional, Tomlinson, Ian, additional, Ball, Graham, additional, Wallis, Matthew, additional, and Wilcox, Maggie, additional

Published
2018
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16. 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
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17. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial

Author

Coles, Charlotte E, primary, Griffin, Clare L, additional, Kirby, Anna M, additional, Titley, Jenny, additional, Agrawal, Rajiv K, additional, Alhasso, Abdulla, additional, Bhattacharya, Indrani S, additional, Brunt, Adrian M, additional, Ciurlionis, Laura, additional, Chan, Charlie, additional, Donovan, Ellen M, additional, Emson, Marie A, additional, Harnett, Adrian N, additional, Haviland, Joanne S, additional, Hopwood, Penelope, additional, Jefford, Monica L, additional, Kaggwa, Ronald, additional, Sawyer, Elinor J, additional, Syndikus, Isabel, additional, Tsang, Yat M, additional, Wheatley, Duncan A, additional, Wilcox, Maggie, additional, Yarnold, John R, additional, Bliss, Judith M, additional, Al Sarakbi, Wail, additional, Barber, Sarah, additional, Barnett, Gillian, additional, Bliss, Peter, additional, Dewar, John, additional, Eaton, David, additional, Ebbs, Stephen, additional, Ellis, Ian, additional, Evans, Philip, additional, Harris, Emma, additional, James, Hayley, additional, Kirwan, Cliona, additional, Kirk, Julie, additional, Mayles, Helen, additional, McIntyre, Anne, additional, Mills, Judith, additional, Poynter, Andrew, additional, Provenzano, Elena, additional, Rawlings, Christine, additional, Sculpher, Mark, additional, Sumo, Georges, additional, Sydenham, Mark, additional, Tutt, Andrew, additional, Twyman, Nicola, additional, Venables, Karen, additional, Winship, Anna, additional, Winstanley, John, additional, Wishart, Gordon, additional, and Thompson, Alastair, additional

Published
2017
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18. Addressing overtreatment of screen detected DCIS; the LORIS trial

Author

Francis, Adele, primary, Thomas, Jeremy, additional, Fallowfield, Lesley, additional, Wallis, Matthew, additional, Bartlett, John M.S., additional, Brookes, Cassandra, additional, Roberts, Tracy, additional, Pirrie, Sarah, additional, Gaunt, Claire, additional, Young, Jennie, additional, Billingham, Lucinda, additional, Dodwell, David, additional, Hanby, Andrew, additional, Pinder, Sarah E., additional, Evans, Andrew, additional, Reed, Malcolm, additional, Jenkins, Valerie, additional, Matthews, Lucy, additional, Wilcox, Maggie, additional, Fairbrother, Patricia, additional, Bowden, Sarah, additional, and Rea, Daniel, additional

Published
2015
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20. Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

Author

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

Abstract

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

Published
2014

21. Chemotherapy and Targeted Therapy for Women With Human Epidermal Growth Factor Receptor 2–Negative (or unknown) Advanced Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

Author

Partridge, Ann H., primary, Rumble, R. Bryan, additional, Carey, Lisa A., additional, Come, Steven E., additional, Davidson, Nancy E., additional, Di Leo, Angelo, additional, Gralow, Julie, additional, Hortobagyi, Gabriel N., additional, Moy, Beverly, additional, Yee, Douglas, additional, Brundage, Shelley B., additional, Danso, Michael A., additional, Wilcox, Maggie, additional, and Smith, Ian E., additional

Published
2014
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22. 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
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24. LETTERS.

Author

Moyses, Valerie, Reddaway, Stewart, King, Brian, Hitchcock, Edward, Cailliau, Robert, Reynolds, John, Robinson, Andy, Wilcox, Maggie, Constantine, Larry, Taylor, Andy, Magnusson, Trevor, Fenton, James, Thomas, Geoff, Norris, Ray, Hill, Ian, and Hayes, Sebastian

Subjects
SEX work, POPULATION forecasting, TIME, MATHEMATICAL physics
Abstract

Several letters to the editor are presented in response to previous articles, including an interview with Laura Agustin in the July 6, 2013 issue about prostitution, an article from the July 6, 2013 issue by Fred Pearce about human peak population forecasts, and a report in the June 15, 2013 issue about mathematical physics concept of time.

Published
2013

26. Endocrine Therapy, New Biologicals, and New Study Designs for Presurgical Studies in Breast Cancer

Author

Dowsett, Mitch, Smith, Ian, Robertson, John, Robison, Laura, Pinhel, Isabel, Johnson, Lindsay, Salter, Janine, Dunbier, Anita, Anderson, Helen, Ghazoui, Zara, Skene, Tony, Evans, Abigail, A'Hern, Roger, Iskender, Amanda, Wilcox, Maggie, and Bliss, Judith

Abstract

The preoperative setting is increasingly popular for the clinical investigation of hormonal agents and new biological drugs. The effectiveness of endocrine agents is well established for estrogen receptor–positive disease, and the emphasis in preoperative studies is on their combination with agents targeted at resistance mechanisms over 3 or more months. New agents are also being assessed for early evidence of clinical efficacy in shorter-term window-of-opportunity studies. The establishment of Ki67 as an intermediate marker of treatment benefit and of long-term outcome, with endocrine drugs, provides the opportunity for new trial designs with Ki67 as the primary endpoint. The PeriOperative Endocrine Therapy for Individualizing Care (POETIC) trial is randomizing (2:1) 4000 estrogen receptor–positive patients to 2 weeks presurgical treatment with a nonsteroidal aromatase inhibitor or no presurgical treatment. It provides a unique opportunity for detailed study of the determinants of response and resistance to estrogen deprivation as well as testing the role of presurgical therapy for improved biomarker-based estimates of prognosis.

Published
2011
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27. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial.

Author

EColes, Charlotte, Harnett, Adrian N., Jefford, Monica L., Sawyer, Elinor J., Syndikus, Isabel, Tsang, Yat M., Wheatley, Duncan A., Wilcox, Maggie, Yarnold, John R., Griffin, Clare L., Titley, Jenny, Bhattacharya, Indrani S., Emson, Marie A., Haviland, Joanne S., Hopwood, Penelope, Kaggwa, Ronald, Bliss, Judith M., Kirby, Anna M., Agrawal, Rajiv K., and Alhasso, Abdulla

Subjects
*MAMMOGRAMS, *BREAST surgery, *BREAST cancer patients, *BREAST cancer treatment, *RANDOMIZED controlled trials, *CANCER relapse, *BREAST, *BREAST tumors, *RADIATION doses, *RESEARCH funding, *TUMOR classification, *LUMPECTOMY, *TREATMENT effectiveness, *DUCTAL carcinoma, *PREVENTION
Abstract

Background: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy.Methods: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634.Findings: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7-83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5-2·3) of patients in the control group, 0·2% (0·02-1·2) in the reduced-dose group, and 0·5% (0·2-1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were -0·73% (-0·99 to 0·22) for the reduced-dose and -0·38% (-0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and p<0·0001 for partial-breast]) compared with whole-breast radiotherapy.Interpretation: We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide.Funding: Cancer Research UK. [ABSTRACT FROM AUTHOR]

Published
2017
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