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1. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors

Author

Pennel, Kathryn A. F., Hatthakarnkul, Phimmada, Wood, Colin S., Lian, Guang-Yu, Al-Badran, Sara S. F., Quinn, Jean A., Legrini, Assya, Inthagard, Jitwadee, Alexander, Peter G., van Wyk, Hester, Kurniawan, Ahmad, Hashmi, Umar, Gillespie, Michael A., Mills, Megan, Ammar, Aula, Hay, Jennifer, Andersen, Ditte, Nixon, Colin, Rebus, Selma, Chang, David K., Kelly, Caroline, Harkin, Andrea, Graham, Janet, Church, David, Tomlinson, Ian, Saunders, Mark, Iveson, Tim, Lannagan, Tamsin R. M., Jackstadt, Rene, Maka, Noori, Horgan, Paul G., Roxburgh, Campbell S. D., Sansom, Owen J., McMillan, Donald C., Steele, Colin W., Jamieson, Nigel B., Park, James H., Roseweir, Antonia K., and Edwards, Joanne

Published
2024
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2. Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer

Author

Glimelius, Bengt, Gogenur, Ismail, Jaeger, Emma, Morgan, Hannah, Orange, Clare, Palles, Claire, Roxburgh, Campbell, Nowak, Marta, Jabbar, Faiz, Rodewald, Ann-Katrin, Gneo, Luciana, Tomasevic, Tijana, Harkin, Andrea, Iveson, Tim, Saunders, Mark, Kerr, Rachel, Oein, Karin, Maka, Noori, Hay, Jennifer, Edwards, Joanne, Tomlinson, Ian, Sansom, Owen, Kelly, Caroline, Pezzella, Francesco, Kerr, David, Easton, Alistair, Domingo, Enric, Koelzer, Viktor H., and Church, David N.

Published
2024
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3. Standardizing data collection in adjuvant colon cancer trials: A consensus project from the IDEA and ACCENT international consortia and national experts

Author

Taieb, Julien, Basile, Debora, Seligmann, Jenny, Argiles, Guillem, André, Thierry, Gallois, Claire, Goldberg, Richard M., Yothers, Greg, Sobrero, Alberto, Meyerhardt, Jeffrey A., Souglakos, John, Labianca, Roberto, Iveson, Tim, Church, David N., Arnold, Dirk, Tie, Jeanne, Gill, Sharlene, Laurent-Puig, Pierre, Yoshino, Takayuki, Lonardi, Sara, and Shi, Qian

Published
2024
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4. A population-scale temporal case–control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP)

Author

Starkey, Thomas, Ionescu, Maria C., Tilby, Michael, Little, Martin, Burke, Emma, Fittall, Matthew W., Khan, Sam, Liu, Justin K. H., Platt, James R., Mew, Rosie, Tripathy, Arvind R., Watts, Isabella, Williams, Sophie Therese, Appanna, Nathan, Al-Hajji, Youssra, Barnard, Matthew, Benny, Liza, Burnett, Alexander, Bytyci, Jola, Cattell, Emma L., Cheng, Vinton, Clark, James J., Eastlake, Leonie, Gerrand, Kate, Ghafoor, Qamar, Grumett, Simon, Harper-Wynne, Catherine, Kahn, Rachel, Lee, Alvin J. X., Lomas, Oliver, Lydon, Anna, Mckenzie, Hayley, Panneerselvam, Hari, Pascoe, Jennifer S., Patel, Grisma, Patel, Vijay, Potter, Vanessa A., Randle, Amelia, Rigg, Anne S., Robinson, Tim M., Roylance, Rebecca, Roques, Tom W., Rozmanowski, Stefan, Roux, René L., Shah, Ketan, Sheehan, Remarez, Sintler, Martin, Swarup, Sanskriti, Taylor, Harriet, Tillett, Tania, Tuthill, Mark, Williams, Sarah, Ying, Yuxin, Beggs, Andrew, Iveson, Tim, Lee, Siow Ming, Middleton, Gary, Middleton, Mark, Protheroe, Andrew, Fowler, Tom, Johnson, Peter, and Lee, Lennard Y. W.

Published
2023
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5. Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II–III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis

Author

Church, David N, Domingo, Enric, Edwards, Joanne, Glimelius, Bengt, Gonegur, Ismail, Harkin, Andrea, Hay, Jen, Iveson, Timothy, Jaeger, Emma, Kelly, Caroline, Kerr, Rachel, Maka, Noori, Morgan, Hannah, Oien, Karen, Orange, Clare, Palles, Claire, Roxburgh, Campbell, Sansom, Owen, Saunders, Mark P, Tomlinson, Ian, Frei, Anja L, McGuigan, Anthony, Sinha, Ritik R A K, Jabbar, Faiz, Gneo, Luciana, Tomasevic, Tijana, Iveson, Tim, Oien, Karin A, Pezzella, Francesco, Campo, Leticia, Browne, Molly, Glaire, Mark, Kildal, Wanja, Danielsen, Havard E, Hay, Jennifer, Kerr, David, and Koelzer, Viktor H

Published
2024
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6. Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study

Author

Kinloch, Emma, Lam, Emily, Murphy, Gillian, Rhodes, Malcolm, Robinson, Kate, Lee, Lennard Y W, Starkey, Thomas, Ionescu, Maria C, Little, Martin, Tilby, Michael, Tripathy, Arvind R, Mckenzie, Hayley S, Al-Hajji, Youssra, Barnard, Matthew, Benny, Liza, Burnett, Alexander, Cattell, Emma L, Charman, Jackie, Clark, James J, Khan, Sam, Ghafoor, Qamar, Illsley, George, Harper-Wynne, Catherine, Hattersley, Rosie J, Lee, Alvin J X, Leonard, Pauline C, Liu, Justin K H, Pang, Matthew, Pascoe, Jennifer S, Platt, James R, Potter, Vanessa A, Randle, Amelia, Rigg, Anne S, Robinson, Tim M, Roques, Tom W, Roux, René L, Rozmanowski, Stefan, Tuthill, Mark H, Watts, Isabella, Williams, Sarah, Iveson, Tim, Lee, Siow Ming, Middleton, Gary, Middleton, Mark, Protheroe, Andrew, Fittall, Matthew W, Fowler, Tom, and Johnson, Peter

Published
2022
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8. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial

Author

Lamarca, Angela, Palmer, Daniel H, Wasan, Harpreet Singh, Ross, Paul J, Ma, Yuk Ting, Arora, Arvind, Falk, Stephen, Gillmore, Roopinder, Wadsley, Jonathan, Patel, Kinnari, Anthoney, Alan, Maraveyas, Anthony, Iveson, Tim, Waters, Justin S, Hobbs, Claire, Barber, Safia, Ryder, W David, Ramage, John, Davies, Linda M, Bridgewater, John A, and Valle, Juan W

Published
2021
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10. Prognostic and Predictive Value of Immunoscore in Stage III Colorectal Cancer: Pooled Analysis of Cases From the SCOT and IDEA-HORG Studies.

Author

Domingo, Enric, Kelly, Caroline, Hay, Jennifer, Sansom, Owen, Maka, Noori, Oien, Karin, Iveson, Tim, Saunders, Mark, Kerr, Rachel, Tomlinson, Ian, Edwards, Joanne, Harkin, Andrea, Nowak, Marta, Koelzer, Viktor, Easton, Alistair, Boukovinas, Ioannis, Moustou, Eleni, Messaritakis, Ippokratis, Chondrozoumaki, Maria, and Karagianni, Michaela

Published
2024
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11. The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Author

Alexander, Peter G., Roseweir, Antonia K., Pennel, Kathryn A. F., van Wyk, Hester C., Powell, Arfon G. M. T., McMillan, Donald C., Horgan, Paul G., Kelly, Caroline, Hay, Jennifer, Sansom, Owen, Harkin, Andrea, Roxburgh, Campbell S. D., Graham, Janet, Church, David N., Tomlinson, Ian, Saunders, Mark, Iveson, Tim J., Edwards, Joanne, and Park, James H.

Published
2021
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12. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study

Author

Primrose, JN, Fox, RP, Morement, H, Chan, O, Rees, C, Ma, YT, Hickish, T, Falk, S, Finch-Jones, M, Pope, I, Corrie, P, Crosby, T, Sothi, S, Sharkland, K, Adamson, D, Wall, L, Evans, J, Dent, J, Hombaiah, U, Iwuji, C, Anthoney, A, Bridgewater, J, Cunningham, D, Gillmore, R, Ross, P, Slater, S, Wasan, H, Waters, J, Valle, JW, Palmer, D, Malik, H, Neoptolemos, J, Faluyi, O, Sumpter, K, Dernedde, U, Maduhusudan, S, Cogill, G, Archer, C, Iveson, T, Wadsley, J, Darby, S, Peterson, M, Mukhtar, AA, Thorpe, JG, Bateman, A, Tsang, D, Cummins, S, Nolan, L, Beaumont, E, Prasad, R, Mirza, D, Stocken, D, Praseedom, R, Davidson, B, Raftery, J, Zhu, S, Garden, J, Stubbs, C, Coxon, F, Primrose, John N, Fox, Richard P, Palmer, Daniel H, Malik, Hassan Z, Prasad, Raj, Mirza, Darius, Anthony, Alan, Corrie, Pippa, Falk, Stephen, Finch-Jones, Meg, Wasan, Harpreet, Ross, Paul, Wall, Lucy, Wadsley, Jonathan, Evans, Jeff T R, Stocken, Deborah, Praseedom, Raaj, Ma, Yuk Ting, Davidson, Brian, Neoptolemos, John P, Iveson, Tim, Raftery, James, Zhu, Shihua, Cunningham, David, Garden, O James, Stubbs, Clive, Valle, Juan W, and Bridgewater, John

Published
2019
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14. Accounting for intensity variation in image analysis of large-scale multiplexed clinical trial datasets

Author

Frei, Anja Laura, primary, McGuigan, Anthony, additional, Sinha, Ritik RAK, additional, Glaire, Mark A, additional, Jabbar, Faiz, additional, Gneo, Luciana, additional, Tomasevic, Tijana, additional, Harkin, Andrea, additional, Iveson, Tim, additional, Saunders, Mark, additional, Oien, Karin, additional, Maka, Noori, additional, Pezzella, Francesco, additional, Campo, Leticia, additional, Hay, Jennifer, additional, Edwards, Joanne, additional, Sansom, Owen, additional, Kelly, Caroline, additional, Tomlinson, Ian, additional, Kildal, Wanja, additional, Kerr, Rachel, additional, Kerr, David, additional, Danielsen, Havard Emil, additional, Domingo, Enric, additional, Church, David N, additional, and Koelzer, Viktor Hendrik, additional

Published
2023
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15. Accounting for intensity variation in image analysis of large‐scale multiplexed clinical trial datasets.

Author

Frei, Anja L, McGuigan, Anthony, Sinha, Ritik RAK, Glaire, Mark A, Jabbar, Faiz, Gneo, Luciana, Tomasevic, Tijana, Harkin, Andrea, Iveson, Tim J, Saunders, Mark, Oein, Karin, Maka, Noori, Pezella, Francesco, Campo, Leticia, Hay, Jennifer, Edwards, Joanne, Sansom, Owen J, Kelly, Caroline, Tomlinson, Ian, and Kildal, Wanja

Subjects
IMAGE analysis, CLINICAL trials, BIOMARKERS, TUMOR markers, CD8 antigen, FIDUCIAL markers (Imaging systems)
Abstract

Multiplex immunofluorescence (mIF) imaging can provide comprehensive quantitative and spatial information for multiple immune markers for tumour immunoprofiling. However, application at scale to clinical trial samples sourced from multiple institutions is challenging due to pre‐analytical heterogeneity. This study reports an analytical approach to the largest multi‐parameter immunoprofiling study of clinical trial samples to date. We analysed 12,592 tissue microarray (TMA) spots from 3,545 colorectal cancers sourced from more than 240 institutions in two clinical trials (QUASAR 2 and SCOT) stained for CD4, CD8, CD20, CD68, FoxP3, pan‐cytokeratin, and DAPI by mIF. TMA slides were multi‐spectrally imaged and analysed by cell‐based and pixel‐based marker analysis. We developed an adaptive thresholding method to account for inter‐ and intra‐slide intensity variation in TMA analysis. Applying this method effectively ameliorated inter‐ and intra‐slide intensity variation improving the image analysis results compared with methods using a single global threshold. Correlation of CD8 data derived by our mIF analysis approach with single‐plex chromogenic immunohistochemistry CD8 data derived from subsequent sections indicates the validity of our method (Spearman's rank correlation coefficients ρ between 0.63 and 0.66, p ≪ 0.01) as compared with the current gold standard analysis approach. Evaluation of correlation between cell‐based and pixel‐based analysis results confirms equivalency (ρ > 0.8, p ≪ 0.01, except for CD20 in the epithelial region) of both analytical approaches. These data suggest that our adaptive thresholding approach can enable analysis of mIF‐stained clinical trial TMA datasets by digital pathology at scale for precision immunoprofiling. [ABSTRACT FROM AUTHOR]

Published
2023
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16. COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Author

Lee, Lennard Y.W., primary, Ionescu, Maria C., additional, Starkey, Thomas, additional, Little, Martin, additional, Tilby, Michael, additional, Tripathy, Arvind R., additional, Mckenzie, Hayley S., additional, Al-Hajji, Youssra, additional, Appanna, Nathan, additional, Barnard, Matthew, additional, Benny, Liza, additional, Burnett, Alexander, additional, Cattell, Emma L., additional, Clark, James J., additional, Khan, Sam, additional, Ghafoor, Qamar, additional, Panneerselvam, Hari, additional, Illsley, George, additional, Harper-Wynne, Catherine, additional, Hattersley, Rosie J., additional, Lee, Alvin JX., additional, Lomas, Oliver, additional, Liu, Justin KH., additional, McCauley, Amanda, additional, Pang, Matthew, additional, Pascoe, Jennifer S., additional, Platt, James R., additional, Patel, Grisma, additional, Patel, Vijay, additional, Potter, Vanessa A., additional, Randle, Amelia, additional, Rigg, Anne S., additional, Robinson, Tim M., additional, Roques, Tom W., additional, Roux, René L., additional, Rozmanowski, Stefan, additional, Taylor, Harriet, additional, Tuthill, Mark H., additional, Watts, Isabella, additional, Williams, Sarah, additional, Beggs, Andrew, additional, Iveson, Tim, additional, Lee, Siow M., additional, Middleton, Gary, additional, Middleton, Mark, additional, Protheroe, Andrew, additional, Fittall, Matthew W., additional, Fowler, Tom, additional, Johnson, Peter, additional, Kinloch, Emma, additional, Lam, Emily, additional, Murphy, Gillian, additional, Rhodes, Malcolm, additional, Robinson, Kate, additional, Swarup, Sanskriti, additional, Bernhardt, Keeley, additional, Bytyci, Jola, additional, Ying, Yuxin, additional, Johal, Sukhmunni, additional, and Sheehan, Remarez, additional

Published
2022
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17. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Author

Middleton, Gary, Silcocks, Paul, Cox, Trevor, Valle, Juan, Wadsley, Jonathan, Propper, David, Coxon, Fareeda, Ross, Paul, Madhusudan, Srinivasan, Roques, Tom, Cunningham, David, Falk, Stephen, Wadd, Nick, Harrison, Mark, Corrie, Pippa, Iveson, Tim, Robinson, Angus, McAdam, Karen, Eatock, Martin, Evans, Jeff, Archer, Caroline, Hickish, Tamas, Garcia-Alonso, Angel, Nicolson, Marianne, Steward, William, Anthoney, Alan, Greenhalf, William, Shaw, Victoria, Costello, Eithne, Naisbitt, Dean, Rawcliffe, Charlotte, Nanson, Gemma, and Neoptolemos, John

Published
2014
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18. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial

Author

Primrose, John, Falk, Stephen, Finch-Jones, Meg, Valle, Juan, O'Reilly, Derek, Siriwardena, Ajith, Hornbuckle, Joanne, Peterson, Mark, Rees, Myrddin, Iveson, Tim, Hickish, Tamas, Butler, Rachel, Stanton, Louise, Dixon, Elizabeth, Little, Louisa, Bowers, Megan, Pugh, Siân, Garden, O James, Cunningham, David, Maughan, Tim, and Bridgewater, John

Published
2014
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19. Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Author

Lawler, Mark, Alsina, Deborah, Adams, Richard A, Anderson, Annie S, Brown, Gina, Fearnhead, Nicola S, Fenwick, Stephen W, Halloran, Stephen P, Hochhauser, Daniel, Hull, Mark A, Koelzer, Viktor H, McNair, Angus G K, Monahan, Kevin J, Näthke, Inke, Norton, Christine, Novelli, Marco R, Steele, Robert J C, Thomas, Anne L, Wilde, Lisa M, Wilson, Richard H, Tomlinson, Ian, Ahmedzai, Sam H, Andreyev, Jervoise, Arbuthnot, Nicholas, Atkin, Wendy, Bach, Simon, Berkman, Lindy, Bloor, Nicola, Boulter, Victor, Brewster, David, Brown, Karen, Burn, John, Cazier, Jean-baptiste, Chau, Ian, Cheadle, Jeremy, Cole, Ann, Coyle, Vicky, Cunningham, David, Davies, Mark, Downward, Julian, Dunlop, Malcom, Fraser, Callum, Gerlinger, Marco, Glaser, Adam, Goh, Vicky, De castro, David González, Graham, Trevor, Griffith, John, Halligan, Steve, Hamilton, Willie, Hepburn, Julie, Haynes, Rachel, Higgins, Joe, Hold, Georgina, Holden, Georgy, Houlston, Richard, Hubbard, Gill, Iqba, Tariq, Irvine, Alexandra E, Iveson, Tim, Jakowiw, Nick, Jackson, Ian, Jefford, Monica, Longley, Dan, Mcdermott, Ultan, Machesney, Michael, Maher, Jane, Marchesi, Julian, Maughan, Tim, Middleton, Gary, Moss, Barbara, Moss, Mark, Murchie, Peter, O’sullivan, Peter, Robertson, Clint, Rutter, Matt, Samuel, Leslie, Sansom, Owen, Saxton, John, Seward, Ed, Sharma, Ricky, Smith, Tracy, Sottoriva, Andrea, Steward, Will, Stocker, Phil, Sweetman, Gillian, Wagner, Christian Von, Williams, Ann, and Winton, Doug

Published
2018
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20. Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study

Author

Lee, Lennard Y W, primary, Starkey, Thomas, additional, Ionescu, Maria C, additional, Little, Martin, additional, Tilby, Michael, additional, Tripathy, Arvind R, additional, Mckenzie, Hayley S, additional, Al-Hajji, Youssra, additional, Barnard, Matthew, additional, Benny, Liza, additional, Burnett, Alexander, additional, Cattell, Emma L, additional, Charman, Jackie, additional, Clark, James J, additional, Khan, Sam, additional, Ghafoor, Qamar, additional, Illsley, George, additional, Harper-Wynne, Catherine, additional, Hattersley, Rosie J, additional, Lee, Alvin J X, additional, Leonard, Pauline C, additional, Liu, Justin K H, additional, Pang, Matthew, additional, Pascoe, Jennifer S, additional, Platt, James R, additional, Potter, Vanessa A, additional, Randle, Amelia, additional, Rigg, Anne S, additional, Robinson, Tim M, additional, Roques, Tom W, additional, Roux, René L, additional, Rozmanowski, Stefan, additional, Tuthill, Mark H, additional, Watts, Isabella, additional, Williams, Sarah, additional, Iveson, Tim, additional, Lee, Siow Ming, additional, Middleton, Gary, additional, Middleton, Mark, additional, Protheroe, Andrew, additional, Fittall, Matthew W, additional, Fowler, Tom, additional, Johnson, Peter, additional, Kinloch, Emma, additional, Lam, Emily, additional, Murphy, Gillian, additional, Rhodes, Malcolm, additional, and Robinson, Kate, additional

Published
2022
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21. Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study

Author

Bridgewater, John, Fletcher, Peter, Palmer, Daniel H., Malik, Hassan Z., Prasad, Raj, Mirza, Darius, Anthony, Alan, Corrie, Pippa, Falk, Stephen, Finch-Jones, Meg, Wasan, Harpreet, Ross, Paul, Wall, Lucy, Wadsley, Jonathan, Evans, Thomas R., Stocken, Deborah, Stubbs, Clive, Praseedom, Raaj, Ma, Yuk Ting, Davidson, Brian, Neoptolemos, John, Iveson, Tim, Cunningham, David, Garden, O. James, Valle, Juan W., and Primrose, John

Subjects
Biliary Tract Neoplasms/drug therapy, Cancer Research, Adolescent, Manchester Cancer Research Centre, Oncology, Chemotherapy, Adjuvant, ResearchInstitutes_Networks_Beacons/mcrc, Humans, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Prognosis, Capecitabine
Abstract

PURPOSE The BILCAP study described a modest benefit for capecitabine as adjuvant therapy for curatively resected biliary tract cancer (BTC), and capecitabine has become the standard of care. We present the long-term data and novel exploratory subgroup analyses. METHODS This randomized, controlled, multicenter, phase III study recruited patients age 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent and an Eastern Cooperative Oncology Group performance status of < 2. Patients were randomly assigned 1:1 to receive oral capecitabine (1,250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation. The primary outcome was overall survival (OS). This study is registered with EudraCT 2005-003318-13. RESULTS Between March 15, 2006, and December 4, 2014, 447 patients were enrolled; 223 patients with BTC resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. At the data cutoff of January 21, 2021, the median follow-up for all patients was 106 months (95% CI, 98 to 108). In the intention-to-treat analysis, the median OS was 49.6 months (95% CI, 35.1 to 59.1) in the capecitabine group compared with 36.1 months (95% CI, 29.7 to 44.2) in the observation group (adjusted hazard ratio 0.84; 95% CI, 0.67 to 1.06). In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59 to 0.94). We further describe the prognostic impact of R status, grade, nodal status, and sex. CONCLUSION This long-term analysis supports the previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery and should be considered as the standard of care.

Published
2022

23. Second-line FOLFOX chemotherapy for advanced biliary tract cancer – Authors' reply

Author

Lamarca, Angela, primary, Palmer, Daniel H, additional, Wasan, Harpreet Singh, additional, Ross, Paul J, additional, Ma, Yuk Ting, additional, Arora, Arvind, additional, Falk, Stephen, additional, Gillmore, Roopinder, additional, Wadsley, Jonathan, additional, Patel, Kinnari, additional, Anthoney, Alan, additional, Maraveyas, Anthony, additional, Iveson, Tim, additional, Waters, Justin S, additional, Hobbs, Claire, additional, Barber, Safia, additional, Ryder, W David, additional, Ramage, John, additional, Davies, Linda M, additional, Bridgewater, John A, additional, and Valle, Juan W, additional

Published
2021
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24. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

Author

Valle, Juan, Wasan, Harpreet, Palmer, Daniel H., Cunningham, David, Anthoney, Alan, Maraveyas, Anthony, Madhusudan, Srinivasan, Iveson, Tim, Hughes, Sharon, Pereira, Stephen P., Roughton, Michael, and Bridgewater, John

Subjects
Cisplatin -- Dosage and administration, Cisplatin -- Comparative analysis, Drug therapy, Combination -- Evaluation, Gemcitabine -- Dosage and administration, Gemcitabine -- Comparative analysis
Abstract

The study aims to evaluate and compare the efficacy of cisplatin plus gemcitabine versus gemcitabine in the treatment of biliary tract cancer. The results indicate that cisplatin plus gemcitabine led to a significant survival advantage in such cases.

Published
2010

25. Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation

Author

Lee, Lennard Y. W., Tilby, Michael, Starkey, Thomas, Ionescu, Maria C., Burnett, Alex, Hattersley, Rosie, Khan, Sam, Little, Martin, Liu, Justin K. H., Platt, James R., Tripathy, Arvind, Watts, Isabella, Williams, Sophie Therese, Appanna, Nathan, Al-Hajji, Youssra, Barnard, Matthew, Benny, Liza, Buckley, Andrew, Cattell, Emma, Cheng, Vinton, Clark, James, Eastlake, Leonie, Gerrand, Kate, Ghafoor, Qamar, Grumett, Simon, Harper-Wynne, Catherine, Kahn, Rachel, Lee, Alvin J. X., Lydon, Anna, McKenzie, Hayley, Panneerselvam, Hari, Pascoe, Jennifer, Patel, Grisma, Patel, Vijay, Potter, Vanessa, Randle, Amelia, Rigg, Anne S., Robinson, Tim, Roylance, Rebecca, Roques, Tom, Rozmanowski, Stefan, Roux, René L., Shah, Ketan, Sintler, Martin, Taylor, Harriet, Tillett, Tania, Tuthill, Mark, Williams, Sarah, Beggs, Andrew, Iveson, Tim, Lee, Siow Ming, Middleton, Gary, Middleton, Mark, Protheroe, Andrew S., Fittall, Matthew W., Fowler, Tom, and Johnson, Peter

Abstract

IMPORTANCE: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. OBJECTIVE: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK’s third-dose vaccination booster program. INTERVENTIONS: Anti–SARS-CoV-2 COV-S antibody test (Elecsys; Roche). MAIN OUTCOMES AND MEASURES: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. RESULTS: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P &lt; .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P &lt; .001) and SARS-CoV-2–related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P &lt; .001) than individuals who had a positive antibody response. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

Published
2023
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26. Single-cell AI-based detection and prognostic and predictive value of DNA mismatch repair deficiency in colorectal cancer

Author

Nowak, Marta, Jabbar, Faiz, Rodewald, Ann-Katrin, Gneo, Luciana, Tomasevic, Tijana, Harkin, Andrea, Iveson, Tim, Saunders, Mark, Kerr, Rachel, Oein, Karin, Maka, Noori, Hay, Jennifer, Edwards, Joanne, Tomlinson, Ian, Sansom, Owen, Kelly, Caroline, Pezzella, Francesco, Kerr, David, Easton, Alistair, Domingo, Enric, Glimelius, Bengt, Gogenur, Ismail, Jaeger, Emma, Morgan, Hannah, Orange, Clare, Palles, Claire, Roxburgh, Campbell, Koelzer, Viktor H., and Church, David N.

Abstract

Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRCs). Automating this would enable precision medicine, particularly if providing information on etiology not captured by deep learning (DL) methods. We present AIMMeR, an AI-based method for determination of mismatch repair (MMR) protein expression at a single-cell level in routine pathology samples. AIMMeR shows an area under the receiver-operator curve (AUROC) of 0.98, and specificity of ≥75% at 98% sensitivity against pathologist ground truth in stage II/III in two trial cohorts, with positive predictive value of ≥98% for the commonest pattern of somatic MMRd. Lower agreement with microsatellite instability (MSI) testing (AUROC 0.86) reflects discordance between MMR and MSI PCR rather than AIMMeR misclassification. Analysis of the SCOT trial confirms MMRd prognostic value in oxaliplatin-treated patients; while MMRd does not predict differential benefit of chemotherapy duration, it correlates with difference in relapse by regimen (PInteraction = 0.04). AIMMeR may help reduce pathologist workload and streamline diagnostics in CRC.

Published
2024
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29. Long Term Outcomes and Exploratory Analyses of the Randomised Phase 3 BILCAP Study

Author

Bridgewater, John, primary, Fletcher, Peter, additional, Palmer, Daniel, additional, Malik, Hassan, additional, Prasad, Raj, additional, Mirza, Darius, additional, Anthoney, Alan, additional, Corrie, Pippa, additional, Falk, Steven, additional, Finch-Jones, Meg, additional, Wasan, Harpreet, additional, Ross, Paul, additional, wall, lucy, additional, Wadsley, Jonathan, additional, Evans, Jeff, additional, Stocken, Deborah D., additional, Stubbs, Clive, additional, Praseedom, Raaj, additional, Ma, Yuk Ting, additional, Davidson, Brian, additional, Neoptolemos, John, additional, Iveson, Tim, additional, Cunningham, David, additional, Garden, James, additional, Valle, Juan, additional, and Primrose, John, additional

Published
2021
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30. Patients’ Preferences for 3 Months vs 6 Months of Adjuvant Chemotherapy for Colon Cancer

Author

Blinman, Prunella, primary, Martin, Andrew, additional, Jefford, Michael, additional, Goldstein, David, additional, Boadle, David, additional, Morris, Michelle, additional, Tebbutt, Niall, additional, Aiken, Christine, additional, Harkin, Andrea, additional, Segelov, Eva, additional, Haydon, Andrew, additional, Iveson, Tim, additional, and Stockler, Martin R, additional

Published
2020
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31. The Glasgow Microenvironment Score associates with prognosis and adjuvant chemotherapy response in colorectal cancer

Author

Alexander, Peter G., primary, Roseweir, Antonia K., additional, Pennel, Kathryn A. F., additional, van Wyk, Hester C., additional, Powell, Arfon G. M. T., additional, McMillan, Donald C., additional, Horgan, Paul G., additional, Kelly, Caroline, additional, Hay, Jennifer, additional, Sansom, Owen, additional, Harkin, Andrea, additional, Roxburgh, Campbell S. D., additional, Graham, Janet, additional, Church, David N., additional, Tomlinson, Ian, additional, Saunders, Mark, additional, Iveson, Tim J., additional, Edwards, Joanne, additional, and Park, James H., additional

Published
2020
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32. Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer

Author

Roseweir, Antonia K, primary, Park, James H, additional, Hoorn, Sanne ten, additional, Powell, Arfon GMT, additional, Aherne, Susan, additional, Roxburgh, Campbell SD, additional, McMillan, Donald C, additional, Horgan, Paul G, additional, Ryan, Elizabeth, additional, Sheahan, Kieran, additional, Vermeulen, Louis, additional, Paul, James, additional, Harkin, Andrea, additional, Graham, Janet, additional, Sansom, Owen, additional, Church, David N, additional, Tomlinson, Ian, additional, Saunders, Mark, additional, Iveson, Tim J, additional, and Edwards, Joanne, additional

Published
2020
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33. FOLFOX as Second-Line Chemotherapy for Advanced Biliary Tract Cancer

Author

Lamarca, Angela, primary, Palmer, Daniel, additional, Wasan, Harpreet, additional, Ross, Paul J., additional, Ma, Yuk Ting, additional, Arora, Arvid, additional, Falk, Stephen, additional, Gillmore, Roopinder, additional, Wadsley, Jonathan, additional, Patel, Kinnari, additional, Anthoney, Alan, additional, Maraveyas, Anthony, additional, Iveson, Tim, additional, Waters, Justin, additional, Hobbs, Claire, additional, Barber, Safia, additional, Ryder, David, additional, Ramage, John, additional, Davies, Linda, additional, Bridgewater, John, additional, Valle, Juan W., additional, and Group, Advanced Biliary Cancer (ABC) Worki, additional

Published
2020
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34. Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial

Author

Jones, Robert P, Psarelli, Eftychia-Eirini, Jackson, Richard, Ghaneh, Paula, Halloran, Christopher M, Palmer, Daniel H, Campbell, Fiona, Valle, Juan W, Faluyi, Olusola, O'Reilly, Derek A, Cunningham, David, Wadsley, Jonathan, Darby, Suzanne, Meyer, Tim, Gillmore, Roopinder, Anthoney, Alan, Lind, Pehr, Glimelius, Bengt, Falk, Stephen, Izbicki, Jakob R, Middleton, Gary William, Cummins, Sebastian, Ross, Paul J, Wasan, Harpreet, McDonald, Alec, Crosby, Tom, Ting, Yuk, Patel, Kinnari, Sherriff, David, Soomal, Rubin, Borg, David, Sothi, Sharmila, Hammel, Pascal, Lerch, Markus M, Mayerle, Julia, Tjaden, Christine, Strobel, Oliver, Hackert, Thilo, Buchler, Markus W, Neoptolemos, John P, Hill, Mark, Corrie, Pippa, Hickish, Tamas, Napier, Mark, Slater, Sarah, Valle, Juan, Shablak, Alaaeldin, Cunnell, Michelle, Guimbaud, Rosine, Roques, Tom, Iveson, Tim, Jamil, Arshad, Robinson, Angus, Garcia-Alonso, Angel, Chang, David, Tsang, David, Wadd, Nick, Wall, Lucy, Nielsen, Niels Hilmer, Lerch, Markus, Mehta, Ajay, Sivaramalingam, Muthiah, Fyfe, David, Osborne, Richard, Blesing, Claire, Bulusu, Venkata Ramesh, Rathbone, Emma, Seitz, Jean-Francois, Beaumont, Erica, Dernedde, Ulrike, McAdam, Karen, Dimopoulos, Prokopios, Cominos, Mathilda, Askill, Colin, Piwowar, Andrzej, Bachet, Jean-Baptiste, Sumpter, Kate, Raouf, Sherif, Nicoll, Jonathan, Rees, Charlotte, Dhinakaran, Kathirvelu, Haux, Johan, Bengrine-Lefevre, Leila, Terrebonne, Eric, Shankland, Catherine, Palmer, Cheryl, Medley, Louise, Toy, Elizabeth, Kaur, Jasvinder, Gupta, Kamalnayan, Cheeseman, Sue, Patterson, Daniel, Candish, Charles, Thompson, Joyce, Coxon, Fareeda, Connolly, Caroline, McPhail, Neil, Williams, Rachel, Flygare, Petra, Elmlund, Mattias, Artru, Pascal, Millat, Bertrand, and Canc, European Study Grp Pancreatic

Subjects
medicine.medical_specialty, Chemotherapy, Randomization, business.industry, medicine.medical_treatment, 030230 surgery, medicine.disease, Gastroenterology, Gemcitabine, law.invention, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, Pancreatic cancer, medicine, Carcinoma, Surgery, Prospective cohort study, business, medicine.drug
Abstract

Importance The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear. Objective To define patterns of recurrence after adjuvant chemotherapy and the association with survival. Design, Setting, and Participants Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019. Interventions Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine. Main Outcomes and Measures Overall survival, recurrence, and sites of recurrence. Results Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98;P = .03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45;P = .04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09;P = .27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P = .85 andP = .35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98;P = .03). Conclusions and Relevance There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection. Trial Registration ClinicalTrials.gov identifier:NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434.

Published
2019

35. Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial

Author

Jones, Robert P., Psarelli, Eftychia-Eirini, Jackson, Richard, Ghaneh, Paula, Halloran, Christopher M., Palmer, Daniel H., Campbell, Fiona, Valle, Juan W., Faluyi, Olusola, O'Reilly, Derek A., Cunningham, David, Wadsley, Jonathan, Darby, Suzanne, Meyer, Tim, Gillmore, Roopinder, Anthoney, Alan, Lind, Pehr, Glimelius, Bengt, Falk, Stephen, Izbicki, Jakob R., Middleton, Gary William, Cummins, Sebastian, Ross, Paul J., Wasan, Harpreet, McDonald, Alec, Crosby, Tom, Ting, Yuk, Patel, Kinnari, Sherriff, David, Soomal, Rubin, Borg, David, Sothi, Sharmila, Hammel, Pascal, Lerch, Markus M., Mayerle, Julia, Tjaden, Christine, Strobel, Oliver, Hackert, Thilo, Buchler, Markus W., Neoptolemos, John P., Hill, Mark, Corrie, Pippa, Hickish, Tamas, Napier, Mark, Slater, Sarah, Valle, Juan, Shablak, Alaaeldin, Cunnell, Michelle, Guimbaud, Rosine, Roques, Tom, Iveson, Tim, Jamil, Arshad, Robinson, Angus, Garcia-Alonso, Angel, Chang, David, Tsang, David, Wadd, Nick, Wall, Lucy, Nielsen, Niels Hilmer, Lerch, Markus, Mehta, Ajay, Sivaramalingam, Muthiah, Fyfe, David, Osborne, Richard, Blesing, Claire, Bulusu, Venkata Ramesh, Rathbone, Emma, Seitz, Jean-Francois, Beaumont, Erica, Dernedde, Ulrike, McAdam, Karen, Dimopoulos, Prokopios, Cominos, Mathilda, Askill, Colin, Piwowar, Andrzej, Bachet, Jean-Baptiste, Sumpter, Kate, Raouf, Sherif, Nicoll, Jonathan, Rees, Charlotte, Dhinakaran, Kathirvelu, Haux, Johan, Bengrine-Lefevre, Leila, Terrebonne, Eric, Shankland, Catherine, Palmer, Cheryl, Medley, Louise, Toy, Elizabeth, Kaur, Jasvinder, Gupta, Kamalnayan, Cheeseman, Sue, Patterson, Daniel, Candish, Charles, Thompson, Joyce, Coxon, Fareeda, Connolly, Caroline, McPhail, Neil, Williams, Rachel, Flygare, Petra, Elmlund, Mattias, Artru, Pascal, Millat, Bertrand, Jones, Robert P., Psarelli, Eftychia-Eirini, Jackson, Richard, Ghaneh, Paula, Halloran, Christopher M., Palmer, Daniel H., Campbell, Fiona, Valle, Juan W., Faluyi, Olusola, O'Reilly, Derek A., Cunningham, David, Wadsley, Jonathan, Darby, Suzanne, Meyer, Tim, Gillmore, Roopinder, Anthoney, Alan, Lind, Pehr, Glimelius, Bengt, Falk, Stephen, Izbicki, Jakob R., Middleton, Gary William, Cummins, Sebastian, Ross, Paul J., Wasan, Harpreet, McDonald, Alec, Crosby, Tom, Ting, Yuk, Patel, Kinnari, Sherriff, David, Soomal, Rubin, Borg, David, Sothi, Sharmila, Hammel, Pascal, Lerch, Markus M., Mayerle, Julia, Tjaden, Christine, Strobel, Oliver, Hackert, Thilo, Buchler, Markus W., Neoptolemos, John P., Hill, Mark, Corrie, Pippa, Hickish, Tamas, Napier, Mark, Slater, Sarah, Valle, Juan, Shablak, Alaaeldin, Cunnell, Michelle, Guimbaud, Rosine, Roques, Tom, Iveson, Tim, Jamil, Arshad, Robinson, Angus, Garcia-Alonso, Angel, Chang, David, Tsang, David, Wadd, Nick, Wall, Lucy, Nielsen, Niels Hilmer, Lerch, Markus, Mehta, Ajay, Sivaramalingam, Muthiah, Fyfe, David, Osborne, Richard, Blesing, Claire, Bulusu, Venkata Ramesh, Rathbone, Emma, Seitz, Jean-Francois, Beaumont, Erica, Dernedde, Ulrike, McAdam, Karen, Dimopoulos, Prokopios, Cominos, Mathilda, Askill, Colin, Piwowar, Andrzej, Bachet, Jean-Baptiste, Sumpter, Kate, Raouf, Sherif, Nicoll, Jonathan, Rees, Charlotte, Dhinakaran, Kathirvelu, Haux, Johan, Bengrine-Lefevre, Leila, Terrebonne, Eric, Shankland, Catherine, Palmer, Cheryl, Medley, Louise, Toy, Elizabeth, Kaur, Jasvinder, Gupta, Kamalnayan, Cheeseman, Sue, Patterson, Daniel, Candish, Charles, Thompson, Joyce, Coxon, Fareeda, Connolly, Caroline, McPhail, Neil, Williams, Rachel, Flygare, Petra, Elmlund, Mattias, Artru, Pascal, and Millat, Bertrand

Abstract

Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear. Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival. Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019. Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine. Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence. Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32

Published
2019
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40. Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study

Author

Pugh, Siân A, primary, Bowers, Megan, additional, Ball, Alexandre, additional, Falk, Stephen, additional, Finch-Jones, Meg, additional, Valle, Juan W, additional, O'Reilly, Derek A, additional, Siriwardena, Ajith K, additional, Hornbuckle, Joanne, additional, Rees, Myrddin, additional, Rees, Charlotte, additional, Iveson, Tim, additional, Hickish, Tamas, additional, Maishman, Tom, additional, Stanton, Louise, additional, Dixon, Elizabeth, additional, Corkhill, Andrea, additional, Radford, Mike, additional, Garden, O James, additional, Cunningham, David, additional, Maughan, Tim S, additional, Bridgewater, John A, additional, and Primrose, John N, additional

Published
2016
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42. A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

Author

Hickish, Tamas, primary, Cassidy, Jim, additional, Propper, David, additional, Chau, Ian, additional, Falk, Stephen, additional, Ford, Hugo, additional, Iveson, Tim, additional, Braun, Michael, additional, Potter, Vanessa, additional, Macpherson, Iain R., additional, Finnigan, Helen, additional, Lee, Chooi, additional, Jones, Hilary, additional, and Harrison, Mark, additional

Published
2014
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43. Add-Aspirin trial: A phase III, double blind, placebo-controlled, randomized trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumors.

Author

Langley, Ruth E, primary, Wilson, Richard H., additional, Ring, Alistair E., additional, Kynaston, Howard Gordon, additional, Cameron, David A., additional, Coyle, Christopher, additional, Gilbert, Duncan Charles, additional, Patrono, Carlo, additional, Rowley, Sam, additional, Murphy, Claire, additional, Adlam, David, additional, Hubner, Richard, additional, Iveson, Tim, additional, Steele, Robert J, additional, Thomas, Anne L., additional, Underwood, Timothy J, additional, Jankowski, Janusz, additional, Gupta, Sudeep, additional, Pramesh, Conjeevaram S, additional, and Parmar, Mahesh, additional

Published
2014
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44. Predictive cytokine biomarkers for survival in patients with advanced pancreatic cancer randomized to sequential chemoimmunotherapy comprising gemcitabine and capecitabine (GemCap) followed by the telomerase vaccine GV1001 compared to concurrent chemoimmunotherapy in the TeloVac phase III trial.

Author

Neoptolemos, John P., primary, Greenhalf, William, additional, Cox, Trevor F., additional, Costello, Eithne, additional, Shaw, Victoria, additional, Valle, Juan W., additional, Coxon, Fareeda Y., additional, Wadsley, Jonathan, additional, Propper, David, additional, Ross, Paul J., additional, Madhusudan, Srinivasan, additional, Roques, Tom, additional, Cunningham, David, additional, Eatock, Martin McKinlay, additional, Iveson, Tim, additional, Patel, Kinnari, additional, Garcia-Alonso, Angel, additional, Nanson, Gemma, additional, and Middleton, Gary, additional

Published
2014
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45. Patterns of progression, treatment of progressive disease, and postprogression survival in the new EPOC study.

Author

Pugh, Sian Alexandra, primary, Ball, Alexandre, additional, Bowers, Megan, additional, Falk, Stephen, additional, Finch-Jones, Meg, additional, Valle, Juan W., additional, O'Reilly, Derek, additional, Siriwardena, Ajith K., additional, Hornbuckle, Joanne, additional, Rees, Myrddin, additional, Iveson, Tim, additional, Maishman, Tom, additional, Dixon, Elizabeth, additional, Corkhill, Andrea, additional, Radford, Mike, additional, Garden, O James, additional, Cunningham, David, additional, Maughan, Tim, additional, Bridgewater, John A., additional, and Primrose, John Neil, additional

Published
2014
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46. Analysis of progression-free survival in the new EPOC study in an “all wild-type” population.

Author

Bridgewater, John A., primary, Pugh, Sian Alexandra, additional, Moutasim, Karwan, additional, Thomas, Gareth, additional, Thiébaut, Raphaële, additional, Liebaert, Francois, additional, Falk, Stephen, additional, Finch-Jones, Meg, additional, Valle, Juan W., additional, O'Reilly, Derek, additional, Siriwardena, Ajith K., additional, Hornbuckle, Joanne, additional, Rees, Myrddin, additional, Iveson, Tim, additional, Hickish, Tamas, additional, Garden, O James, additional, Cunningham, David, additional, Maughan, Tim, additional, and Primrose, John Neil, additional

Published
2014
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47. Outcome of second-line chemotherapy for biliary tract cancer

Author

Bridgewater, John, primary, Palmer, Daniel, additional, Cunningham, David, additional, Iveson, Tim, additional, Gillmore, Roopinder, additional, Waters, Justin, additional, Harrison, Mark, additional, Wasan, Harpreet, additional, Corrie, Pippa, additional, and Valle, Juan, additional

Published
2013
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48. Quality of life, long-term survivors and long-term outcome from the ABC-02 study.

Author

Bridgewater, John, Lopes, Andre, Palmer, Daniel, Cunningham, David, Anthoney, Alan, Maraveyas, Anthony, Madhusudan, Srinivasan, Iveson, Tim, Valle, Juan, and Wasan, Harpreet

Subjects
QUALITY of life, RESEARCH funding, BILE duct tumors, TREATMENT effectiveness
Abstract

Background: The ABC-02 (Advanced Biliary Tract Cancer) study established cisplatin and gemcitabine (CisGem) as the standard first-line chemotherapy for patients with locally advanced or metastatic biliary tract cancer (BTC). We examine quality of life (QoL), describe the long-term survivors and provide a long-term outcome.Methods: A total of 410 BTC patients were randomised to receive either CisGem or gemcitabine alone (Gem); 324 patients consented to complete EORTC QLQ-C30 and EORTC QLQ-PAN26 QoL questionnaires; 268 (83%) patients returned at least one QoL questionnaire (134 in each arm). Long-term survivors were defined as those surviving over 2 years and we performed a final analysis of the primary outcome; overall survival (OS).Results: Most QoL scales showed a trend favouring the combined CisGem arm, including functional and symptomatic scales, although the differences were not statistically significant. Forty-five (11%)) patients survived at least 2 years (34 received CisGem and 11 Gem) and 21 (5%) 3 years or more (14 received CisGem and 7 Gem). After a median follow-up of 9.2 months and 398 deaths, the median OS was 11.7 months for CisGem and 8.1 months for Gem (hazard ratio (HR)=0.65, 95% CI: 0.53-0.79, P<0.001).Conclusions: The survival advantage of CisGem compared to Gem was not associated with an improvement or deterioration of QoL. Long-term survivors were more likely to have received CisGem and the long-term OS is identical to that previously described. [ABSTRACT FROM AUTHOR]

Published
2016
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49. Longitudinal quality of life and quality adjusted survival in a randomised controlled trial comparing six months of bolus fluorouracil/leucovorin vs. twelve weeks of protracted venous infusion fluorouracil as adjuvant chemotherapy for colorectal cancer

Author

Chau, Ian, primary, Norman, Andrew R., additional, Cunningham, David, additional, Iveson, Tim, additional, Hill, Mark, additional, Hickish, Tamas, additional, Lofts, Fiona, additional, Jodrell, Duncan, additional, Webb, Andrew, additional, Tait, Diana, additional, Ross, Paul J., additional, Shellito, Pat, additional, and Oates, Jacqueline R., additional

Published
2005
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50. Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II–III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis.

Author

Frei, Anja L, McGuigan, Anthony, Sinha, Ritik R A K, Jabbar, Faiz, Gneo, Luciana, Tomasevic, Tijana, Harkin, Andrea, Iveson, Tim, Saunders, Mark P, Oien, Karin A, Maka, Noori, Pezzella, Francesco, Campo, Leticia, Browne, Molly, Glaire, Mark, Kildal, Wanja, Danielsen, Havard E, Hay, Jennifer, Edwards, Joanne, and Sansom, Owen

Subjects
*COLORECTAL cancer, *TUMOR-infiltrating immune cells, *QUASARS, *PROGNOSIS, *RETROSPECTIVE studies
Abstract

Tumour-infiltrating CD8+ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8+, CD20+, FoxP3+, and CD68+ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II–III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8IE) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75 vs 25] 0·73 [95% CI 0·68–0·79], p=2·5 × 10−16), and of intrastromal FoxP3 (FoxP3IS; 0·71 [0·64–0·78], p=1·5 × 10−13) but not as strongly in the epithelium (FoxP3IE; 0·89 [0·84–0·96], p=1·5 × 10−4). Associations of other markers with recurrence-free interval were moderate. CD8IE and FoxP3IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8IE-FoxP3IS) was superior when assessed as a continuous variable (adjusted [a]HR75 vs 25 0·70 [95% CI 0·63–0·78], p=5·1 × 10−11) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29–2·20], p=1·3 × 10−4; low vs high 2·58 [1·91–3·49], p=7·9 × 10−10), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8IE-FoxP3IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR75 vs 25 0·84 [95% CI 0·73–0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17–2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89–1·88], p=0·17). Combined evaluation of CD8IE and FoxP3IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3IS cells as an immunotherapy target in colorectal cancer might be merited. Medical Research Council, National Institute for Health Research, Cancer Research UK, Swedish Cancer Society, Roche, and Promedica Foundation. [ABSTRACT FROM AUTHOR]

Published
2024
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