Search

Your search keyword '"Hinsley S"' showing total 190 results
Start Over Author "Hinsley S"
190 results on '"Hinsley S"'

1. Prognostic gene expression signature for high-grade serous ovarian cancer.

Author

Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, AOCS Group, Fereday, S, Hendley, J, Traficante, N, Steed, H, Koziak, JM, Köbel, M, McNeish, IA, Goranova, T, Ennis, D, Macintyre, G, Silva De Silva, D, Ramón Y Cajal, T, García-Donas, J, Hernando Polo, S, Rodriguez, GC, Cushing-Haugen, KL, Harris, HR, Greene, CS, Zelaya, RA, Behrens, S, Fortner, RT, Sinn, P, Herpel, E, Lester, J, Lubiński, J, Oszurek, O, Tołoczko, A, Cybulski, C, Menkiszak, J, Pearce, CL, Pike, MC, Tseng, C, Alsop, J, Rhenius, V, Song, H, Jimenez-Linan, M, Piskorz, AM, Gentry-Maharaj, A, Karpinskyj, C, Widschwendter, M, Singh, N, Kennedy, CJ, Sharma, R, Harnett, PR, Gao, B, Johnatty, SE, Sayer, R, Boros, J, Winham, SJ, Keeney, GL, Kaufmann, SH, Larson, MC, Luk, H, Hernandez, BY, Thompson, PJ, Wilkens, LR, Carney, ME, Trabert, B, Lissowska, J, Brinton, L, Sherman, ME, Bodelon, C, Hinsley, S, Lewsley, LA, Glasspool, R, Banerjee, SN, Stronach, EA, Haluska, P, Ray-Coquard, I, Mahner, S, Winterhoff, B, Slamon, D, Levine, DA, Kelemen, LE, Benitez, J, and Chang-Claude, J

Subjects
AOCS Group, Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Survival Analysis, Female, Transcriptome, formalin-fixed paraffin-embedded, gene expression, high-grade serous ovarian cancer, overall survival, prognosis, Rare Diseases, Genetic Testing, Cancer, Ovarian Cancer, Genetics, 4.4 Population screening, 4.2 Evaluation of markers and technologies, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Published
2020

2. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.

Published
2020
Full Text
View/download PDF

11. Temperature synchronizes temporal variation in laying dates across European hole-nesting passerines

Author

Vriend, S. J. (Stefan J. G.), Grotan, V. (Vidar), Gamelon, M. (Marlene), Adriaensen, F. (Frank), Ahola, M. P. (Markus P.), Alvarez, E. (Elena), Bailey, L. D. (Liam D.), Barba, E. (Emilio), Bouvier, J.-C. (Jean-Charles), Burgess, M. D. (Malcolm D.), Bushuev, A. (Andrey), Camacho, C. (Carlos), Canal, D. (David), Charmantier, A. (Anne), Cole, E. F. (Ella F.), Cusimano, C. (Camillo), Doligez, B. F. (Blandine F.), Drobniak, S. M. (Szymon M.), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Erikstad, K. E. (Kjell Einar), Ferns, P. N. (Peter N.), Goodenough, A. E. (Anne E.), Hartley, I. R. (Ian R.), Hinsley, S. A. (Shelley A.), Ivankina, E. (Elena), Juskaitis, R. (Rimvydas), Kempenaers, B. (Bart), Kerimov, A. B. (Anvar B.), Kalas, J. A. (John Atle), Lavigne, C. (Claire), Leivits, A. (Agu), Mainwaring, M. C. (Mark C.), Martinez-Padilla, J. (Jesus), Matthysen, E. (Erik), van Oers, K. (Kees), Orell, M. (Markku), Pinxten, R. (Rianne), Reiertsen, T. K. (Tone Kristin), Rytkönen, S. (Seppo), Senar, J. C. (Juan Carlos), Sheldon, B. C. (Ben C.), Sorace, A. (Alberto), Torok, J. (Janos), Vatka, E. (Emma), Visser, M. E. (Marcel E.), Saether, B.-E. (Bernt-Erik), Vriend, S. J. (Stefan J. G.), Grotan, V. (Vidar), Gamelon, M. (Marlene), Adriaensen, F. (Frank), Ahola, M. P. (Markus P.), Alvarez, E. (Elena), Bailey, L. D. (Liam D.), Barba, E. (Emilio), Bouvier, J.-C. (Jean-Charles), Burgess, M. D. (Malcolm D.), Bushuev, A. (Andrey), Camacho, C. (Carlos), Canal, D. (David), Charmantier, A. (Anne), Cole, E. F. (Ella F.), Cusimano, C. (Camillo), Doligez, B. F. (Blandine F.), Drobniak, S. M. (Szymon M.), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Erikstad, K. E. (Kjell Einar), Ferns, P. N. (Peter N.), Goodenough, A. E. (Anne E.), Hartley, I. R. (Ian R.), Hinsley, S. A. (Shelley A.), Ivankina, E. (Elena), Juskaitis, R. (Rimvydas), Kempenaers, B. (Bart), Kerimov, A. B. (Anvar B.), Kalas, J. A. (John Atle), Lavigne, C. (Claire), Leivits, A. (Agu), Mainwaring, M. C. (Mark C.), Martinez-Padilla, J. (Jesus), Matthysen, E. (Erik), van Oers, K. (Kees), Orell, M. (Markku), Pinxten, R. (Rianne), Reiertsen, T. K. (Tone Kristin), Rytkönen, S. (Seppo), Senar, J. C. (Juan Carlos), Sheldon, B. C. (Ben C.), Sorace, A. (Alberto), Torok, J. (Janos), Vatka, E. (Emma), Visser, M. E. (Marcel E.), and Saether, B.-E. (Bernt-Erik)

Abstract

Identifying the environmental drivers of variation in fitness-related traits is a central objective in ecology and evolutionary biology. Temporal fluctuations of these environmental drivers are often synchronized at large spatial scales. Yet, whether synchronous environmental conditions can generate spatial synchrony in fitness-related trait values (i.e., correlated temporal trait fluctuations across populations) is poorly understood. Using data from long-term monitored populations of blue tits (Cyanistes caeruleus, n = 31), great tits (Parus major, n = 35), and pied flycatchers (Ficedula hypoleuca, n = 20) across Europe, we assessed the influence of two local climatic variables (mean temperature and mean precipitation in February-May) on spatial synchrony in three fitness-related traits: laying date, clutch size, and fledgling number. We found a high degree of spatial synchrony in laying date but a lower degree in clutch size and fledgling number for each species. Temperature strongly influenced spatial synchrony in laying date for resident blue tits and great tits but not for migratory pied flycatchers. This is a relevant finding in the context of environmental impacts on populations because spatial synchrony in fitness-related trait values among populations may influence fluctuations in vital rates or population abundances. If environmentally induced spatial synchrony in fitness-related traits increases the spatial synchrony in vital rates or population abundances, this will ultimately increase the risk of extinction for populations and species. Assessing how environmental conditions influence spatiotemporal variation in trait values improves our mechanistic understanding of environmental impacts on populations.

Published
2023

15. 1772P Characterisation of a DNA repair deficiency (DRD) biomarker phenotype in metastatic urothelial carcinoma (mUC) within the ATLANTIS clinical trial platform

Author

Crabb, S.J., primary, Dempsey, L., additional, Soulis, E., additional, Hinsley, S., additional, Song, Y.P., additional, Barber, J., additional, Frew, J., additional, Gale, J., additional, Faust, G., additional, Brock, S., additional, McGovern, U.B., additional, Parikh, O.A., additional, Enting, D., additional, Sundar, S., additional, Ratnayake, G., additional, Lees, K., additional, Hussain, S.A., additional, Powles, T.B., additional, Jones, R., additional, and Tapper, W., additional

Published
2022
Full Text
View/download PDF

17. 4P Targeting PI3K/AKT/mTOR pathway in platinum-resistant ovarian high-grade serous carcinoma: Translational analysis from the randomized phase II OCTOPUS trial

Author

Giannone, G., primary, Ennis, D., additional, Mirza, H.B., additional, Cheng, Z., additional, McDermott, J., additional, Lewsley, L-A., additional, Clamp, A.R., additional, Herbertson, R.A., additional, Glasspool, R.M., additional, Krell, J., additional, Hinsley, S., additional, Banerji, U., additional, Riisnaes, R., additional, Banerjee, S., additional, and McNeish, I., additional

Published
2022
Full Text
View/download PDF

18. Bird populations most exposed to climate change are less sensitive to climatic variation

Author

Bailey, L. D. (Liam D.), van de Pol, M. (Martijn), Adriaensen, F. (Frank), Arct, A. (Aneta), Barba, E. (Emilio), Bellamy, P. E. (Paul E.), Bonamour, S. (Suzanne), Bouvier, J.-C. (Jean-Charles), Burgess, M. D. (Malcolm D.), Charmantier, A. (Anne), Cusimano, C. (Camillo), Doligez, B. (Blandine), Drobniak, S. M. (Szymon M.), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Ferns, P. N. (Peter N.), Goodenough, A. E. (Anne E.), Hartley, I. R. (Ian R.), Hinsley, S. A. (Shelley A.), Ivankina, E. (Elena), Juskaitis, R. (Rimvydas), Kempenaers, B. (Bart), Kerimov, A. B. (Anvar B.), Lavigne, C. (Claire), Leivits, A. (Agu), Mainwaring, M. C. (Mark C.), Matthysen, E. (Erik), Nilsson, J.-A. (Jan-Ake), Orell, M. (Markku), Rytkönen, S. (Seppo), Carlos Senar, J. (Juan), Sheldon, B. C. (Ben C.), Sorace, A. (Alberto), Stenning, M. J. (Martyn J.), Torok, J. (Janos), van Oers, K. (Kees), Vatka, E. (Emma), Vriend, S. J. (Stefan J. G.), Visser, M. E. (Marcel E.), Bailey, L. D. (Liam D.), van de Pol, M. (Martijn), Adriaensen, F. (Frank), Arct, A. (Aneta), Barba, E. (Emilio), Bellamy, P. E. (Paul E.), Bonamour, S. (Suzanne), Bouvier, J.-C. (Jean-Charles), Burgess, M. D. (Malcolm D.), Charmantier, A. (Anne), Cusimano, C. (Camillo), Doligez, B. (Blandine), Drobniak, S. M. (Szymon M.), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Ferns, P. N. (Peter N.), Goodenough, A. E. (Anne E.), Hartley, I. R. (Ian R.), Hinsley, S. A. (Shelley A.), Ivankina, E. (Elena), Juskaitis, R. (Rimvydas), Kempenaers, B. (Bart), Kerimov, A. B. (Anvar B.), Lavigne, C. (Claire), Leivits, A. (Agu), Mainwaring, M. C. (Mark C.), Matthysen, E. (Erik), Nilsson, J.-A. (Jan-Ake), Orell, M. (Markku), Rytkönen, S. (Seppo), Carlos Senar, J. (Juan), Sheldon, B. C. (Ben C.), Sorace, A. (Alberto), Stenning, M. J. (Martyn J.), Torok, J. (Janos), van Oers, K. (Kees), Vatka, E. (Emma), Vriend, S. J. (Stefan J. G.), and Visser, M. E. (Marcel E.)

Abstract

The phenology of many species shows strong sensitivity to climate change; however, with few large scale intra-specific studies it is unclear how such sensitivity varies over a species’ range. We document large intra-specific variation in phenological sensitivity to temperature using laying date information from 67 populations of two co-familial European songbirds, the great tit (Parus major) and blue tit (Cyanistes caeruleus), covering a large part of their breeding range. Populations inhabiting deciduous habitats showed stronger phenological sensitivity than those in evergreen and mixed habitats. However, populations with higher sensitivity tended to have experienced less rapid change in climate over the past decades, such that populations with high phenological sensitivity will not necessarily exhibit the strongest phenological advancement. Our results show that to effectively assess the impact of climate change on phenology across a species’ range it will be necessary to account for intra-specific variation in phenological sensitivity, climate change exposure, and the ecological characteristics of a population.

Published
2022

21. 751P Survival prognostic and surrogate values of the early modeled CA-125 KELIM in newly diagnosed advanced ovarian cancer: Data from the GCIG meta-analysis group

Author

Corbaux, P., primary, You, B., additional, Glasspool, R.M., additional, Yanaihara, N., additional, Tinker, A.V., additional, Lindemann, K., additional, Ray-Coquard, I.L., additional, Mirza, M.R., additional, Subtil, F., additional, Colomban, O., additional, Peron, J., additional, Karamouza, E., additional, McNeish, I., additional, Hinsley, S., additional, Kagimura, T., additional, Welch, S., additional, Lewsley, L-A., additional, Paoletti, X., additional, and Cook, A., additional

Published
2021
Full Text
View/download PDF

26. Identification of a Locus Near ULK1 Associated With Progression-Free Survival in Ovarian Cancer

Author

Quinn, MCJ, McCue, K, Shi, W, Johnatty, SE, Beesley, J, Civitarese, A, O'Mara, TA, Glubb, DM, Tyrer, JP, Armasu, SM, Ong, J-S, Gharahkhani, P, Lu, Y, Gao, B, Patch, A-M, Fasching, PA, Beckmann, MW, Lambrechts, D, Vergote, I, Edwards, DRV, Beeghly-Fadiel, A, Benitez, J, Garcia, MJ, Goodman, MT, Doerk, T, Duerst, M, Modugno, F, Moysich, K, du Bois, A, Pfisterer, J, Bauman, K, Karlan, BY, Lester, J, Cunningham, JM, Larson, MC, McCauley, BM, Kjaer, SK, Jensen, A, Hogdall, CK, Hogdall, E, Schildkraut, JM, Riggan, MJ, Berchuck, A, Cramer, DW, Terry, KL, Bjorge, L, Webb, PM, Friedlander, M, Pejovic, T, Moffitt, M, Glasspool, R, May, T, Ene, GE, Huntsman, DG, Woo, M, Carney, ME, Hinsley, S, Heitz, F, Fereday, S, Kennedy, CJ, Edwards, SL, Winham, SJ, deFazio, A, Pharoah, PDP, Goode, EL, MacGregor, S, Chenevix-Trench, G, Quinn, MCJ, McCue, K, Shi, W, Johnatty, SE, Beesley, J, Civitarese, A, O'Mara, TA, Glubb, DM, Tyrer, JP, Armasu, SM, Ong, J-S, Gharahkhani, P, Lu, Y, Gao, B, Patch, A-M, Fasching, PA, Beckmann, MW, Lambrechts, D, Vergote, I, Edwards, DRV, Beeghly-Fadiel, A, Benitez, J, Garcia, MJ, Goodman, MT, Doerk, T, Duerst, M, Modugno, F, Moysich, K, du Bois, A, Pfisterer, J, Bauman, K, Karlan, BY, Lester, J, Cunningham, JM, Larson, MC, McCauley, BM, Kjaer, SK, Jensen, A, Hogdall, CK, Hogdall, E, Schildkraut, JM, Riggan, MJ, Berchuck, A, Cramer, DW, Terry, KL, Bjorge, L, Webb, PM, Friedlander, M, Pejovic, T, Moffitt, M, Glasspool, R, May, T, Ene, GE, Huntsman, DG, Woo, M, Carney, ME, Hinsley, S, Heitz, F, Fereday, S, Kennedy, CJ, Edwards, SL, Winham, SJ, deFazio, A, Pharoah, PDP, Goode, EL, MacGregor, S, and Chenevix-Trench, G

Abstract

BACKGROUND: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance. METHODS: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy. RESULTS: We found seven SNPs at 12q24.33 associated with PFS (P < 5 × 10-8), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; P = 1.47 × 10-8). High expression of a nearby gene, ULK1, is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of ULK1 in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the ULK1 promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin in vitro. CONCLUSIONS: The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. ULK1 is a plausible candidate for the target of this association. IMPACT: This finding provides insight into genetic markers associated with EOC outcome and potential treatment options.See related commentary by Peres and Monteiro, p. 1604.

Published
2021

27. CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer

Author

Walls, GM, Oughton, JB, Chalmers, AJ, Brown, S, Collinson, F, Forster, MD, Franks, KN, Gilbert, A, Hanna, GG, Hannaway, N, Harrow, S, Hinsley, S, Murden, G, Phillip, R, Anderson, RJ, Salem, A, Sebag-Montefoire, D, Shaw, P, Twelves, CJ, Walker, K, Young, RJ, Faivre-Finn, C, and Greystoke, A

Abstract

Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for ‘gold standard’ treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding. Abbreviations ATM: Ataxia telangiectasia mutated ATR: Ataxia telangiectasia and Rad3 related cfDNA: Cell-free DNA CRT: Chemoradiotherapy CT: Computed tomography CTCAE: Common terminology criteria for adverse events CTRad: Clinical and Translational Radiotherapy Research Working Group DDRi: DNA damage response inhibitor DLT: Dose limiting toxicity DNA: Deoxyribonucleic acid DNA-PK: DNA-dependent protein kinase ECOG: Eastern Cooperative Oncology Group EORTC: European Organisation for Research and Treatment of Cancer ICRU: International Commission on Radiation Units and Measurements IMPs: Investigational medicinal products LA: Locally advanced MRC: Medical Research Council NCRI: National Cancer Research Institute NSCLC: Non-small cell lung cancer PARP: Poly (ADP-ribose) polymerase PET: Positron emission tomography PFS: Progression free survival PROMs: Patient-reported outcome measures RECIST: Response evaluation criteria in solid tumours RP2D: Recommended phase II dose RT: Radiotherapy SACT: Systemic anti-cancer therapy SRC: Safety review committee TiTE-CRM: Time to event continual reassessment method TNM: Tumour node metastasis

Published
2020

28. The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor

Author

Hinsley, S, Walker, K, Sherratt, D, Bailey, L, Reed, S, Flanagan, L, McKee, S, Brudenell Straw, F, Dawkins, B, Meads, D, Auner, HW, Kaiser, MF, Cook, M, Brown, S, Cook, G, Myeloma UK Clinical Trials Network, and Myeloma UK

Subjects
Boron Compounds, Oncology, medicine.medical_specialty, Cyclophosphamide, Glycine, Medicine (miscellaneous), Dexamethasone, Ixazomib, Study Protocol, 03 medical and health sciences, chemistry.chemical_compound, Clinical Trials, Phase II as Topic, 0302 clinical medicine, General & Internal Medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), Myeloma UK Clinical Trials Network, Lenalidomide, 1102 Cardiorespiratory Medicine and Haematology, Multiple myeloma, Randomized Controlled Trials as Topic, 030304 developmental biology, lcsh:R5-920, 0303 health sciences, business.industry, Bortezomib, 1103 Clinical Sciences, medicine.disease, Thalidomide, Cardiovascular System & Hematology, chemistry, 030220 oncology & carcinogenesis, Proteasome inhibitor, Multiple Myeloma, lcsh:Medicine (General), business, Proteasome Inhibitors, medicine.drug
Abstract

Background Multiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD. Methods MUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This ‘switch’ phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment. Discussion Development of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients. Further investigation of the anti-tumour effect of this drug in RRMM patients is therefore warranted, especially since no trials comparing CD with ICD have been completed at present. Trial registration ISRCTN number: ISRCTN58227268. Registered on 26 August 2015.

Published
2020

29. Interaction of climate change with effects of conspecific and heterospecific density on reproduction

Author

Moller, A. P. (Anders Pape), Balbontin, J. (Javier), Dhondt, A. A. (Andre A.), Adriaensen, F. (Frank), Artemyev, A. (Alexandr), Banbura, J. (Jerzy), Barba, E. (Emilio), Biard, C. (Clotilde), Blondel, J. (Jacques), Bouvier, J.-C. (Jean-Charles), Camprodon, J. (Jordi), Cecere, F. (Francesco), Charter, M. (Motti), Cichon, M. (Mariusz), Cusimano, C. (Camillo), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Ferns, P. N. (Peter N.), Forsman, J. T. (Jukka T.), Goldshtein, A. (Aya), Goodenough, A. E. (Anne E.), Gosler, A. G. (Andrew G.), Gustafsson, L. (Lars), Harnist, I. (Iga), Hartley, I. R. (Ian R.), Heeb, P. (Philipp), Hinsley, S. A. (Shelley A.), Jacob, S. (Staffan), Jarvinen, A. (Antero), Juskaitis, R. (Rimvydas), Korpimaki, E. (Erkki), Krams, I. (Indrikis), Laaksonen, T. (Toni), Leclercq, B. (Bernard), Lehikoinen, E. (Esa), Loukola, O. (Olli), Mainwaring, M. C. (Mark C.), Mand, R. (Raivo), Massa, B. (Bruno), Matthysen, E. (Erik), Mazgajski, T. D. (Tomasz D.), Merino, S. (Santiago), Mitrus, C. (Cezary), Monkkonen, M. (Mikko), Nager, R. G. (Ruedi G.), Nilsson, J.-a. (Jan-ake), Nilsson, S. G. (Sven G.), Norte, A. C. (Ana C.), von Numers, M. (Mikael), Orell, M. (Markku), Pimentel, C. S. (Carla S.), Pinxten, R. (Rianne), Priedniece, I. (Ilze), Remes, V. (Vladimir), Richner, H. (Heinz), Robles, H. (Hugo), Rytkonen, S. (Seppo), Senar, J. C. (Juan Carlos), Seppanen, J. T. (Janne T.), da Silva, L. P. (Luis P.), Slagsvold, T. (Tore), Solonen, T. (Tapio), Sorace, A. (Alberto), Stenning, M. J. (Martyn J.), Torok, J. (Janos), Tryjanowski, P. (Piotr), van Noordwijk, A. J. (Arie J.), Walankiewicz, W. (Wieslaw), Lambrechts, M. M. (Marcel M.), Moller, A. P. (Anders Pape), Balbontin, J. (Javier), Dhondt, A. A. (Andre A.), Adriaensen, F. (Frank), Artemyev, A. (Alexandr), Banbura, J. (Jerzy), Barba, E. (Emilio), Biard, C. (Clotilde), Blondel, J. (Jacques), Bouvier, J.-C. (Jean-Charles), Camprodon, J. (Jordi), Cecere, F. (Francesco), Charter, M. (Motti), Cichon, M. (Mariusz), Cusimano, C. (Camillo), Dubiec, A. (Anna), Eens, M. (Marcel), Eeva, T. (Tapio), Ferns, P. N. (Peter N.), Forsman, J. T. (Jukka T.), Goldshtein, A. (Aya), Goodenough, A. E. (Anne E.), Gosler, A. G. (Andrew G.), Gustafsson, L. (Lars), Harnist, I. (Iga), Hartley, I. R. (Ian R.), Heeb, P. (Philipp), Hinsley, S. A. (Shelley A.), Jacob, S. (Staffan), Jarvinen, A. (Antero), Juskaitis, R. (Rimvydas), Korpimaki, E. (Erkki), Krams, I. (Indrikis), Laaksonen, T. (Toni), Leclercq, B. (Bernard), Lehikoinen, E. (Esa), Loukola, O. (Olli), Mainwaring, M. C. (Mark C.), Mand, R. (Raivo), Massa, B. (Bruno), Matthysen, E. (Erik), Mazgajski, T. D. (Tomasz D.), Merino, S. (Santiago), Mitrus, C. (Cezary), Monkkonen, M. (Mikko), Nager, R. G. (Ruedi G.), Nilsson, J.-a. (Jan-ake), Nilsson, S. G. (Sven G.), Norte, A. C. (Ana C.), von Numers, M. (Mikael), Orell, M. (Markku), Pimentel, C. S. (Carla S.), Pinxten, R. (Rianne), Priedniece, I. (Ilze), Remes, V. (Vladimir), Richner, H. (Heinz), Robles, H. (Hugo), Rytkonen, S. (Seppo), Senar, J. C. (Juan Carlos), Seppanen, J. T. (Janne T.), da Silva, L. P. (Luis P.), Slagsvold, T. (Tore), Solonen, T. (Tapio), Sorace, A. (Alberto), Stenning, M. J. (Martyn J.), Torok, J. (Janos), Tryjanowski, P. (Piotr), van Noordwijk, A. J. (Arie J.), Walankiewicz, W. (Wieslaw), and Lambrechts, M. M. (Marcel M.)

Abstract

We studied the relationship between temperature and the coexistence of great tit Parus major and blue tit Cyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density‐dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.

Published
2020

30. P258 ASTERIX: Adaptive stratification of COVID19 to facilitate endotype-directed intervention studies

Author

Ferguson, J, primary, Blyth, K, additional, McInnes, I, additional, Biankin, A, additional, Jones, R, additional, Lowe, D, additional, Murphy, M, additional, Thomson, E, additional, Scott, J, additional, Porter, D, additional, Goodyear, C, additional, Maguire, D, additional, Mark, P, additional, Hinsley, S, additional, Evans, C, additional, and Orange, C, additional

Published
2021
Full Text
View/download PDF

32. Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial

Author

Brown, J, Rathbone, E, Hinsley, S, Gregory, W, Gossiel, F, Marshall, H, Burkinshaw, R, Shulver, H, Thandar, H, Bertelli, G, Maccon, K, Bowman, A, Hanby, A, Bell, R, Cameron, D, and Coleman, R

Subjects
Bone Development, Bone Neoplasms, Breast Neoplasms, Standard of Care, Articles, Middle Aged, Prognosis, Zoledronic Acid, Bone and Bones, United Kingdom, Chemotherapy, Adjuvant, Biomarkers, Tumor, Disease Progression, Humans, Female, Bone Remodeling, Infusions, Intravenous, Early Detection of Cancer
Abstract

Background: Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis.Methods: Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided.Results: When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell’s c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid.Conclusions: Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study.

Published
2018

33. P2.01-08 Clinical Trial in Progress: CONCORDE - A Phase 1B Study of Novel Agents in Combination with Conventional Radiotherapy in NSCLC

Author

Hudson, A., primary, Brown, S., additional, Chalmers, A., additional, Dive, C., additional, Franks, K., additional, Hanna, G., additional, Hannaway, N., additional, Harrow, S., additional, Haswell, T., additional, Hiley, C., additional, Hinsley, S., additional, Krebs, M., additional, Murden, G., additional, Reed, S., additional, Ryan, A., additional, Sebag-Montefiore, D., additional, Shaw, P., additional, Smith, A., additional, Walls, G., additional, Young, R., additional, Faivre-Finn, C., additional, and Greystoke, A., additional

Published
2019
Full Text
View/download PDF

34. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years

Author

Pan, H, Gray, R, Braybrooke, J, Davies, C, Taylor, C, Mcgale, P, Peto, R, Pritchard, Ki, Bergh, J, Dowsett, M, Hayes, Df, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bartlett, J, Bergsten‐nordström, E, Bliss, J, Boccardo, F, Bradley, R, Brain, E, Cameron, D, Clarke, M, Coates, A, Coleman, R, Correa, C, Costantino, J, Cuzick, J, Davidson, N, Dodwell, D, Di Leo, A, Ewertz, M, Forbes, J, Gelber, R, Gnant, M, Goldhirsch, A, Goodwin, P, Hill, C, Ingle, J, Jagsi, R, Janni, W, Loibl, S, Mackinnon, E, Martin, M, Mukai, H, Norton, L, Ohashi, Y, Paik, S, Perez, E, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Regan, M, Robertson, J, Rutgers, E, Slamon, D, Sparano, J, Swain, S, Tutt, A, Viale, G, Von Minckwitz, G, Wang, X, Whelan, T, Wilcken, N, Winer, E, Wolmark, N, Wood, W, Zambetti, M, Alberro, Ja, Ballester, B, Deulofeu, P, Fábregas, R, Fraile, M, Gubern, Jm, Janer, J, Moral, A, De Pablo Jl, Peñalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Solà, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Garaud, P, Collett, V, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hma, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Hupperets, Psgj, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Dal, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bramwell, Vh, Chen, Be, Gelmon, K, Goss, Pe, Levine, Mn, Parulekar, W, Pater, Jl, Shepherd, Le, Tu, D, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu‐zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett‐lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec’h, J, De La Lande, B, Mouret‐fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Boddington, C, Burrett, Ja, Cutter, D, Duane, F, Evans, V, Gettins, L, Godwin, J, James, S, Kerr, A, Liu, H, Mannu, G, Mchugh, T, Morris, P, Read, S, Wang, Y, Wang, Z, Albano, J, De Oliveira Cf, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Mouridsen, Ht, Fehm, T, Trampisch, Hj, Dalesio, O, De Vries Ege, Rodenhuis, S, Van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jgm, Treurniet‐donker, Ad, Van Putten Wlj, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Van De Velde Cjh, Cunningham, Mp, Brufsky, Am, Coleman, Re, Llombart, Ha, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Carrasco, E, Segui, Ma, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Galligioni, E, Leone, B, Vallejo, Ct, Zwenger, A, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, De Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Delaloge, S, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, Van De Velde Ao, Van Dongen Ja, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Bighin, C, Bruzzi, P, Del Mastro, L, Dozin, B, Pastorino, S, Pronzato, P, Sertoli, Mr, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro Mg, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, Ah, Kohno, N, Miyashita, M, Takao, S, Ahn, Jh, Jung, Kh, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, Gj, Christiaens, R, Neven, P, Paridaens, R, Van Den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, Mg, Ro, J, Camphausen, K, Danforth, D, Lichter, A, Lippman, M, Smart, D, Steinberg, S, D’Amico, C, Lioce, M, Paradiso, A, Ohno, S, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Redmond, C, Wickerham, L, Aihara, T, Hozumi, Y, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Venturini, M, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Reinertsen, Kv, Varhaug, Je, Gundersen, S, Hauer‐jensen, M, Høst, H, Nissen‐meyer, R, Mitchell, Ak, Robertson, Jfr, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Hadji, P, A’Hern, R, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Clack, G, Van Poznak, C, Deshpande, N, Di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Ajs, Ewing, Gh, Firth, La, Krushen‐kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, Af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ahg, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Lemonnier, J, Martin, Al, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Deutsch, Gp, Kwong, Dlw, Pai, Vr, Senanayake, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Bell, R, Hinsley, S, Marshall, Hc, Pierce, Lj, Solomayer, E, Horsman, Jm, Lester, J, Winter, Mc, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Aft, R, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Other departments, CCA - Cancer Treatment and Quality of Life, Radiotherapy, Pan, Hongchao, Gray, Richard, Braybrooke, Jeremy, Davies, Christina, Taylor, Carolyn, Mcgale, Paul, Peto, Richard, Pritchard, Kathleen I, Bergh, Jona, Dowsett, Mitch, Hayes, Daniel F, De Laurentiis, Michelino, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Interne Geneeskunde

Subjects
0301 basic medicine, Oncology, medicine.medical_treatment, Kaplan-Meier Estimate, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Recurrence, Receptors, Neoplasm Metastasis, AMERICAN SOCIETY, Adjuvant, CLINICAL-PRACTICE GUIDELINE, Absolute risk reduction, Estrogen Antagonists, General Medicine, Estrogen Antagonist, CHEMOTHERAPY, Middle Aged, Prognosis, Neoplasm Metastasi, Local, POSTMENOPAUSAL WOMEN, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Meta-analysis, Lymphatic Metastasis, Female, Human, Estrogen Antagonists/therapeutic use, Adult, Risk, medicine.medical_specialty, Prognosi, medicine.drug_class, DISCONTINUATION, Breast Neoplasms, Article, Drug Administration Schedule, LATE DISTANT RECURRENCE, 03 medical and health sciences, Breast cancer, Breast Neoplasms/drug therapy, Internal medicine, SCORE, medicine, Humans, SURGICAL ADJUVANT BREAST, Aged, Proportional Hazards Models, Chemotherapy, business.industry, Proportional hazards model, Lymphatic Metastasi, TAMOXIFEN THERAPY, ta3122, medicine.disease, Estrogen, RANDOMIZED-TRIALS, Discontinuation, Surgery, Neoplasm Recurrence, 030104 developmental biology, Proportional Hazards Model, Neoplasm Grading, Neoplasm Recurrence, Local, business
Abstract

Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)

Published
2017

35. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author

Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited

Subjects
0301 basic medicine, Oncology, Time Factors, SURGERY, medicine.medical_treatment, menopause, chemotherapy, Mastectomy, Segmental, Rate ratio, THERAPY, aromatase inhibitors, CEA, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Breast, Neoplasm Metastasis, Randomized Controlled Trials as Topic, RISK, tamoxifen, breast tumor, CA15-3, axillary dissection, mastectomy, Middle Aged, Neoadjuvant Therapy, METHOTREXATE, 3. Good health, trastuzumab, Treatment Outcome, quadrantectomy, Chemotherapy, Adjuvant, axillary lymphnodes, 030220 oncology & carcinogenesis, Meta-analysis, SURVIVAL, Disease Progression, Female, Life Sciences & Biomedicine, axillary clearance, RADIOTHERAPY, medicine.drug, Adult, medicine.medical_specialty, Anthracycline, 3122 Cancers, Antineoplastic Agents, Breast Neoplasms, axillary nodes, sentinel node biopsy, 03 medical and health sciences, breast cancer, Breast cancer, SDG 3 - Good Health and Well-being, HER2, Internal medicine, Journal Article, medicine, cancer, Humans, Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy, Oncology & Carcinogenesis, RECURRENCE, bisphosphonates, Pathological, Neoplasm Staging, lumpectomy, Chemotherapy, Science & Technology, breast diseases, endocrine therapy, business.industry, denosumab, BRCA1, medicine.disease, BRCA2, osteoporosis, Radiation therapy, STIMULATING FACTOR, 030104 developmental biology, sentinel node, tumor marker, Methotrexate, Neoplasm Recurrence, Local, business, 1112 Oncology And Carcinogenesis, malignancy
Abstract

BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published

Published
2017

37. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Author

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Coleman, R, Powles, T, Paterson, A, Gnant, M, Anderson, S, Diel, I, Gralow, J, von Minckwitz, G, Moebus, V, Bergh, J, Pritchard, KI, Bliss, J, Cameron, D, Evans, V, Pan, H, Peto, R, Bradley, R, Gray, R, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, CF, Steger, GG, Stoger, H, Olivotto, I, Ragaz, J, Christiansen, P, Ejlertsen, B, Ewertz, M, Jensen, M-B, Moller, S, Mouridsen, HT, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, Dafni, U, Markopoulos, C, Blomqvist, C, Saarto, T, Ahn, J-H, Jung, KH, Perrone, F, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, EP, Paik, S, Redmond, C, Swain, S, Wickerham, L, Wolmark, N, Perez, E, Ingle, JN, Suman, VJ, Hadji, P, A'Hern, R, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, TJ, Smith, IE, Yarnold, JR, Clack, G, Van Poznak, C, Safra, T, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Solomayer, E, Fehm, T, Lester, J, Winter, MC, Horsman, JM, Aft, R, Brufsky, AM, and Llombart, HA

Abstract

Background Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs). Findings We received data on 18 766 women (18 206 [97%] in trials of 2–5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87–1·01; 2p=0·08), distant recurrence (0·92, 0·85–0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83–0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73–0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78–0·94; 2p=0·002), distant recurrence (0·82, 0·74–0·92; 2p=0·0003), bone recurrence (0·72, 0·60–0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73–0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75–0·97; 2p=0·02). Interpretation Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began. Funding Cancer Research UK, Medical Research Council.

Published
2015

38. Interspecific variation in the relationship between clutch size, laying date and intensity of urbanisation in four species of hole-nesting birds.

Author

VAUGOYEAU, M., ADRIAENSEN, F., ARTEMYEV, A., BAŃBURA, J., BARBA, E., BIARD, C., BLONDEL, J., BOUSLAMA, Z., BOUVIER, J-C., CAMPRODON, J., CECERE, F., CHARMANTIER, A., CHARTER, M., CICHOŃ, M., CUSIMANO, C., CZESZCZEWIK, D., DEMEYRIER, V., DOLIGEZ, B., DOUTRELANT, C., DUBIEC, A., EENS, M., EEVA, T., FAIVRE, B., FERNS, P. N., FORSMAN, J. T., GARCÍA-DEL-REY, E., GOLDSHTEIN, A., GOODENOUGH, A. E., GOSLER, A. G., GRÉGOIRE, A., GUSTAFSSON, L., HARNIST, I., HARTLEY, I. R., HEEB, P., HINSLEY, S. A., ISENMANN, P., JACOB, S., JUŠKAITIS, R., KORPIMÄKI, E., KRAMS, I., LAAKSONEN, T., LAMBRECHTS, M. M., LECLERCQ, B., LEHIKOINEN, E., LOUKOLA, O., LUNDBERG, A., MAINWARING, M. C., MÄND, R., MASSA, B., MAZGAJSKI, T. D., MERINO, S., MITRUS, C., MÖNKKÖNEN, M., MORIN, X., NAGER, R. G., NILSSON, J-Å., NILSSON, S. G., NORTE, A. C., ORELL, M., PERRET, P., PERRINS, C. M., PIMENTEL, C. S., PINXTEN, R., RICHNER, H., ROBLES, H., RYTKÖNEN, S., SENAR, J. C., SEPPÄNEN, J. T., DA SILVA, L. P., SLAGSVOLD, T., SOLONEN, T., SORACE, A., STENNING, M. J., TRYJANOWSKI, P., VON NUMERS, M., WALANKIEWICZ, W., MØLLER, A. P. and VAUGOYEAU, M., ADRIAENSEN, F., ARTEMYEV, A., BAŃBURA, J., BARBA, E., BIARD, C., BLONDEL, J., BOUSLAMA, Z., BOUVIER, J-C., CAMPRODON, J., CECERE, F., CHARMANTIER, A., CHARTER, M., CICHOŃ, M., CUSIMANO, C., CZESZCZEWIK, D., DEMEYRIER, V., DOLIGEZ, B., DOUTRELANT, C., DUBIEC, A., EENS, M., EEVA, T., FAIVRE, B., FERNS, P. N., FORSMAN, J. T., GARCÍA-DEL-REY, E., GOLDSHTEIN, A., GOODENOUGH, A. E., GOSLER, A. G., GRÉGOIRE, A., GUSTAFSSON, L., HARNIST, I., HARTLEY, I. R., HEEB, P., HINSLEY, S. A., ISENMANN, P., JACOB, S., JUŠKAITIS, R., KORPIMÄKI, E., KRAMS, I., LAAKSONEN, T., LAMBRECHTS, M. M., LECLERCQ, B., LEHIKOINEN, E., LOUKOLA, O., LUNDBERG, A., MAINWARING, M. C., MÄND, R., MASSA, B., MAZGAJSKI, T. D., MERINO, S., MITRUS, C., MÖNKKÖNEN, M., MORIN, X., NAGER, R. G., NILSSON, J-Å., NILSSON, S. G., NORTE, A. C., ORELL, M., PERRET, P., PERRINS, C. M., PIMENTEL, C. S., PINXTEN, R., RICHNER, H., ROBLES, H., RYTKÖNEN, S., SENAR, J. C., SEPPÄNEN, J. T., DA SILVA, L. P., SLAGSVOLD, T., SOLONEN, T., SORACE, A., STENNING, M. J., TRYJANOWSKI, P., VON NUMERS, M., WALANKIEWICZ, W., MØLLER, A. P.

Published
2016

39. Erratum to: The SABRTooth feasibility trial protocol: a study to determine the feasibility and acceptability of conducting a phase III randomised controlled trial comparing stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I non-small cell lung cancer (NSCLC) considered to be at higher risk of complications from surgical resection

Author

Snee, M. P., primary, McParland, L., additional, Collinson, F., additional, Lowe, C. M., additional, Striha, A., additional, Baldwin, D. R., additional, Naidu, B., additional, Sebag-Montefiore, D., additional, Gregory, W. M., additional, Bestall, J., additional, Hewison, J., additional, Hinsley, S., additional, and Franks, K. N., additional

Published
2016
Full Text
View/download PDF

40. The SABRTooth feasibility trial protocol: a study to determine the feasibility and acceptability of conducting a phase III randomised controlled trial comparing stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I non-small cell lung cancer (NSCLC) considered to be at higher risk of complications from surgical resection

Author

Snee, M. P., primary, McParland, L., additional, Collinson, F., additional, Lowe, C. M., additional, Striha, A., additional, Baldwin, D. R., additional, Naidu, B., additional, Sebag-Montefiore, D., additional, Gregory, W. M., additional, Bestall, J., additional, Hewison, J., additional, Hinsley, S., additional, and Franks, K., additional

Published
2016
Full Text
View/download PDF

41. Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials

Author

Kroep, J.R., primary, Charehbili, A., additional, Coleman, R.E., additional, Aft, R.L., additional, Hasegawa, Y., additional, Winter, M.C., additional, Weilbaecher, K., additional, Akazawa, K., additional, Hinsley, S., additional, Putter, H., additional, Liefers, G.J., additional, Nortier, J.W.R., additional, and Kohno, N., additional

Published
2016
Full Text
View/download PDF

43. Quantifying the effects of Entry Level Stewardship (ELS) on biodiversity at the farm scale: the Hillesden Experiment

Author

Heard, M.S., Botham, M., Broughton, R., Carvell, C., Hinsley, S., Woodcock, B., Pywell, R.F., Heard, M.S., Botham, M., Broughton, R., Carvell, C., Hinsley, S., Woodcock, B., and Pywell, R.F.

Abstract

The Hillesden experiment has proved to be a valuable, practical test of the effectiveness of the Entry Level Stewardship scheme for a range of taxa at the farm-scale. The experiment was a large scale, randomised block experiment with three treatments applied to replicated land areas of c. 50-60 ha: i) Cross compliance (CC, conventional intensive arable management subject to the EU rules of cross compliance), ii) Entry Level Stewardship (ELS, a small suite of options selected to replicate a ‘standard’ agreement comprising 1% area out of production), iii) Entry Level Stewardship Extra (ELS X, a more extensive selection of options targeted at farmland wildlife of conservation interest comprising 5% area out of production). The results show that over a five year period (2006-2011) the effects on (i) habitat quality and food resources, and (ii) the abundance, diversity and population dynamics of some key farmland taxa were significantly enhanced by both targeted local management and enhancements at the landscape scale. However there were clear effects of scale on the responses of different taxa (see Table 1.1). Mobile species like bumblebees, moths, birds and small mammals were more subject to the effects of wider landscape context and showed a net response to the whole farm manipulation. The response of other taxa e.g. plants and some invertebrate groups, were more influenced by local environmental effects and plot level manipulations. In general resource quality was higher in the more ‘targeted’ ELSX options. However there was high variability in results reflecting species specific responses to habitats at both local and landscape scales. Critical to the success of any ELS agreement is the quality of plot establishment and maintenance. Often if a sown option is not doing well after the first year, it will be unlikely to improve and should be abandoned. Both ground conditions at establishment and subsequent weather conditions contributed to the high plot variability obs

Published
2012

44. The impact of growing miscanthus for biomass on farmland bird populations

Author

Bellamy, P. E., Croxton, P. J., Heard, M. S., Hinsley, S. A., Hulmes, L., Hulmes, S., Nuttall, P., Pywell, R. F., Rothery, P., Bellamy, P. E., Croxton, P. J., Heard, M. S., Hinsley, S. A., Hulmes, L., Hulmes, S., Nuttall, P., Pywell, R. F., and Rothery, P.

Abstract

Miscanthus is a newly introduced crop grown primarily to produce biomass for energy production and the area grown in the UK is anticipated to increase. Major differences in crop management from conventional arable crops have led to speculation that miscanthus may also have effects on farmland biodiversity. Six miscanthus fields were paired with six of a conventional crop, winter wheat, and bird diversity and abundance were compared in winter and during the breeding season along with potential food sources. Miscanthus fields had a greater abundance and diversity of birds than did wheat in winter and summer. In winter, the greater numbers of birds in miscanthus fields were probably attracted by the shelter provided by the crop and by the abundance of non-crop plants. During the breeding season, the abundance of non-crop plants in miscanthus fields, and greater numbers of insects associated with these plants, provided food resources. However, the miscanthus crop plants provided less insect food than wheat crop plants. Changes in crop structure during the breeding season influenced the breeding birds. The results from this study suggested that an increase in the area of miscanthus grown in the UK may have temporary benefits for farmland bird populations during establishment. These benefits are likely to diminish with age of crop and as crop management improves with experience. Management for wildlife will be required to maintain the diversity of features attractive to birds because many of these will be lost if miscanthus is managed solely to maximise crop yields.

Published
2009

46. Modelling the third dimension: Incorporating topography into the movement rules of an individual-based spatially explicit population model

Author

Alderman, J., Hinsley, S. A., Alderman, J., and Hinsley, S. A.

Abstract

A wide variety of topographical and environmental elements have been shown or proposed to influence the movement decisions of dispersing animals. Most real landscapes have topographical elements such as hills, valleys and urban developments, which can all act to modify a species’ perceptual range and directly influence movement behaviour. If a visual-based perceptual ability enables a dispersing individual to locate suitable habitat patches at a distance, then it is to be expected that topographical features would act to modify the overall success of this strategy. However, the majority of individual-based Spatially Explicit Population Models (SEPM) employ only two-dimensional landscapes. To investigate the effects of topographical elevation on dispersal patterns, a three-dimensional visual-based perceptual range algorithm was added to the dispersal rules of an individual-based SEPM. To explore the possible influences of a behavioural-based response to topography, an algorithm modelling valley-seeking behaviour was also developed. The performance of both algorithms was compared with that of a two-dimensional visual-based perceptual range algorithm. The overall consequences of dispersal under each algorithm were measured by recording population sizes in a target wood in the centre of a modelled, real landscape. The size of the population in the target wood, modelled using both of the three-dimensional algorithms, exhibited sensitivity to the direction of dispersal in interaction with perceptual range, which differed from that predicted by the two-dimensional approach. Population size was dependant on the spatial configuration of habitat patches and on the topography of the landscape, both of which could guide dispersers either towards or away from the target patch depending on the particular combinations of dispersal directions and perceptual ranges selected. Topography was found to have a greater effect on dispersal at shorter perceptual ranges, and thresholds in th

Published
2007

47. Woodland birds in patchy landscapes: the evidence base for strategic networks

Author

Dolman, P. M., Hinsley, S. A., Bellamy, P. E., Watts, K., Dolman, P. M., Hinsley, S. A., Bellamy, P. E., and Watts, K.

Abstract

Habitat creation and management within wooded networks is a potentially effective strategy to reduce ecological isolation and the deleterious effects of fragmentation. However, questions remain over the relative advantages of different approaches, e.g. buffering patches vs. increasing connectivity. Potential effects of woodland fragmentation include reduction in regional woodland cover, reduced patch size, edge effects with loss of core habitat, and increased isolation with disruption of dispersal and metapopulation dynamics. We adopt an evidence-based approach to review how each of these affects woodland birds with an emphasis on studies from the UK and use this to identify management priorities for mitigation. There is evidence for both patch area and composition effects: larger woodlands support more woodland bird species, and woods located within sparsely wooded landscapes are less valuable to specialist woodland species. Bird assemblages show a nested pattern with respect to area, and thus species found in small woods also occur in large woods but not vice versa. However, small woods may be preferred by a few edge species, while small woods also have greater variability in bird species composition. Consideration of the metapopulation dynamics of specialist species with poor dispersal shows that creating or buffering large woodlands is more efficient than a greater total area of small fragments. Connectivity appears most useful for widespread generalist species with almost continuous populations. Woodland structure and quality are of overwhelming importance: as well as mature woodland, young growth, scrub and edges are also key components. There is an urgent need to examine the relationship between nest predation and landscape structure within UK woodlands.

Published
2007

48. Effective and Efficient Preparation for the Unforeseeable.

Author

Hinsley, S. W., Henshaw, M. J., and Siemieniuch, C. E.

Abstract

Abstract: This paper hypothesizes that a System‐of‐Systems (SoS) that is not fit‐for‐purpose is so because it cannot implement the correct, timely and complete transfers of Material, Energy and/or Information (MEI) between its constituents and with its external environment that are necessary to achieve a particular result. This research addresses the problem of maintaining a SoS fit‐for‐purpose after unpredictable changes in operation, composition or external factors by creating a method, implemented as an engineering process and supported by an analysis technique to enhance the affordance {“Features that provide the potential for interaction by “Affording the ability to do something” [1]} of SoS constituents for MEI transfer and reveal potential undesirable transfers. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

50. The breeding birds of Monks Wood

Author

Broughton, R. K., Hinsley, S. A., Bellamy, P. E., Broughton, R. K., Hinsley, S. A., and Bellamy, P. E.

Published
2006

Catalog

Books, media, physical & digital resources
See catalog results