12 results on '"Yarnold J"'
Search Results
2. Radiobiology of Breast Cancer
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Tutt, A. and Yarnold, J.
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BREAST cancer , *RADIOTHERAPY , *DNA repair , *TISSUES - Abstract
Abstract: Advances in molecular and cellular biology are transforming our understanding of breast cancer and promise the same for radiotherapy over the next few years. At the clinical level, the molecular basis of fractionation dependency and other tumour and normal tissue responses are likely to become clearer. More importantly, they will become useful in the clinic, where molecular characterisation of the patient and tumour will start to determine therapeutic options. Although many of the fundamental processes are only amenable to study in laboratory systems, the power of array-based technologies makes it possibly to address highly relevant questions in the clinic, using functional imaging and/or tissue biopsies. To help clinical oncologists exploit these opportunities in translational research, some aspects of the molecular and cellular basis of radiotherapy are described below in their relation to breast cancer. [Copyright &y& Elsevier]
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- 2006
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3. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials
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Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, J. L., Davies, C., Harvey, V. J., Holdaway, T. M., Kay, R. G., Mason, B. H., Forbes, J. F., Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, H. M. A., Focan, C., Lobelle, J. P., Peek, U., Oates, G. D., Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, M. J., Masood, M. B., Parker, D., Price, J. J., Hupperets, P. S. G. J., Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, R. B., Abu-Zahra, H. T., Portnoj, S. M., Baum, M., Cuzick, J., Houghton, J., Riley, D., Mansel, R. E., Gordon, N. H., Davis, H. L., Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, J. B., Delozier, T., Mace Lesec'h, J., Rambert, P., Petruzelka, L., Pribylova, O., Owen, J. R., Harbeck, N., Jänicke, F., Meisner, C., Meier, P., Howell, A., Ribeiro, G. C., Swindell, R., Burrett, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., Jackson, D., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Morris, P., Oulds, J., Peto, R., Taylor, C., Wang, Y., Albano, J., De Oliveira, C. F., Gervásio, H., Gordilho, J., Johansen, H., Mouridsen, H. T., Gelman, R. S., Harris, J. R., Henderson, I. C., Shapiro, C. L., Christiansen, P., Ejlertsen, B., Møller, S., Overgaard, M., Carstensen, B., Palshof, T., Trampisch, H. J., Dalesio, O., De Vries, E. G. E., Rodenhuis, S., Van Tinteren, H., Comis, R. L., Davidson, N. E., Robert, N., Sledge, G., Tormey, D. C., Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, J. G. M., Treurniet-Donker, A. D., Van Putten, W. L. J., Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Van Der Hage, J. A., Van De Velde, C. J. H., Cunningham, M. P., Catalano, R., Creech, R. H., Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Von Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., De Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, C. S., Smith, D. C., Galligioni, E., Boccardo, F., Rubagotti, A., Dent, D. M., Gudgeon, C. A., Hacking, A., Erazo, A., Medina, J. Y., Izuo, M., Morishita, Y., Takei, H., Fentiman, I. S., Hayward, J. L., Rubens, R. D., Skilton, D., Scheurlen, H., Von Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, R. J., Vilcoq, J. R., Arriagada, R., Hill, C., Laplanche, A., M. G., Lê, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, M. R., Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Van De Velde, A. O., Van Dongen, J. A., Vermorken, J. B., Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, R. D., Goldhirsch, A., Lindtner, J., Price, K. N., Rudenstam, C. M., Senn, H. J., Bliss, J. M., Chilvers, C. E. D., Coombes, R. C., Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., De Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Van Den Bogaert, W., Martin, P., Geniez, ROMAIN SYLVAIN JEAN, Hakes, T., Hudis, C. A., Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., De La Huerta, R., Sainz, M. G., Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O'Shaughnessy, J., Pierce, L. J., Steinberg, S., Venzon, D., Zujewski, J. A., Paradiso, A., De Lena, M., Schittulli, F., Myles, J. D., Pater, J. L., Pritchard, K. I., Whelan, T., Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, I. M., Palmer, M. K., Ingle, J. N., Suman, V. J., Bengtsson, N. O., Jonsson, H., Larsson, L. G., Lythgoe, J. P., Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, A. B., Varhaug, J. E., Gundersen, S., Hauer-Jensen, M., Høst, H., Nissen-Meyer, R., Blamey, R. W., Mitchell, A. K., Morgan, D. A. L., Robertson, J. F. R., Di Palma, M., Mathé, G., Misset, J. L., Clark, R. M., Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, M. R., Ueo, H., Falkson, C. I., A'Hern, R., Ashley, S., Powles, T. J., Smith, I. E., Yarnold, J. R., Gazet, J. C., Corcoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, A. J. S., Ewing, G. H., Firth, L. A., Krushen-Kosloski, J. L., Foster, L., George, W. D., Stewart, H. J., Stroner, P., Malmström, P., Möller, T. R., Rydén, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjöld, B., Söderberg, M., Carpenter, J. T., Albain, K., Crowley, J., Green, S., Martino, S., Osborne, C. K., Ravdin, P. M., Glas, U., Johansson, U., Rutqvist, L. E., Singnomklao, T., Wallgren, A., Maibach, R., Thürlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, A. H. G., Meakin, J. W., Panzarella, T., Shan, Y., Shao, Y. F., Wang, X., Zhao, D. B., Chen, Z. M., Pan, H. C., Bahi, J., Reid, M., Spittle, M., Deutsch, G. P., Senanayake, F., Kwong, D. L. W., Bianco, A. R., Carlomagno, C., De Laurentiis, M., De Placido, S., Buzdar, A. U., Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, C. C., Buchanan, R. B., Cross, M., Royle, G. T., Dunn, J. A., Hills, R. K., Lee, M., Morrison, J. M., Spooner, D., Litton, A., Chlebowski, R. T., Caffier, H., Clarke, M, Collins, R, Darby, S, Davies, C, Elphinstone, P, Evans, E, Godwin, J, Gray, R, Hicks, C, James, S, MacKinnon, E, McGale, P, McHugh, T, Peto, R, Taylor, C, and Wang, Y
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medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Breast Neoplasms ,Rate ratio ,Breast Conservation Treatment ,Disease-Free Survival ,Breast cancer ,Cause of Death ,Breast-conserving surgery ,Medicine ,Humans ,Lung cancer ,Aged ,Probability ,Randomized Controlled Trials as Topic ,business.industry ,Female ,Middle Aged ,Neoplasm Recurrence, Local ,Medicine (all) ,General Medicine ,medicine.disease ,Surgery ,Radiation therapy ,Unilateral Breast Neoplasms ,Neoplasm Recurrence ,Local ,business ,Mastectomy - Abstract
Background In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (10%, 25 000 women). Findings About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44·6% versus 49·5% (absolute reduction 5·0%, SE 0·8, 2p These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54·7% versus 60·1% (reduction 5·4%, SE 1·3, 2p=0·0002; overall mortality reduction 4·4%, SE 1·2, 2p=0·0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1·18, SE 0·06, 2p=0·002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1·12, SE 0·04, 2p=0·001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1·27, SE 0·07, 2p=0·0001) and lung cancer (rate ratio 1·78, SE 0·22, 2p=0·0004). Interpretation In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.
4. Accelerated partial breast irradiation: the new standard?
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Coles, C. E. and Yarnold, J. R.
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ACCELERATED partial breast irradiation , *BREAST cancer treatment , *RADIOTHERAPY , *CANCER treatment , *THERAPEUTICS , *BREAST cancer , *BREAST tumors , *RADIOISOTOPE brachytherapy , *CARCINOMA in situ , *DUCTAL carcinoma - Abstract
The article presents a comment on the study by Vratislav Strnad and colleagues on the effectiveness of accelerated partial breast irridation (APBI). Topics discussed include an overview of APBI that started in the 1980s as well as its resurgence due to advancements in radiotherapy techniques, a comparison of Strnad and colleagues' study to others who also explored APBI and the study's contribution to breast cancer treatment.
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- 2016
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5. Fractionation in radiotherapy: results of a Canadian randomised clinical trial.
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Yarnold, J.
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Historical assumptions concerning the optimal fractionation schedules for women with breast cancer are being challenged by the early results of randomised clinical trials. Multiple small fractions of 2.0 Gy or less are optimal for squamous cell carcinomas, which are clearly less sensitive to fraction size than the surrounding dose-limiting normal tissues. Breast cancer may be different in showing comparable sensitivity to fraction size as the healthy tissues of the breast and underlying ribcage. If this is confirmed, it means that fewer, larger fractions confer the same benefit as standard 2.0 Gy schedules, provided appropriate downward corrections are made to the total dose. The approach also lends itself to tests of acceleration, shorter treatment times being of obvious interest to patients and possibly of therapeutic benefit in their own right. [ABSTRACT FROM PUBLISHER]
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- 2005
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6. Partial Breast Radiotherapy for Women with Early Breast Cancer: 10-Year Outcomes from IMPORT LOW (CRUK/06/003).
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Kirby, A., Griffin, C., Finneran, L., Sydenham, M., Alhasso, A., Brunt, A.M., Chan, H., Jefford, M., Sawyer, E., Syndikus, I., Tsang, Y.M., Wheatley, D., Yarnold, J., Coles, C., and Bliss, J.
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BREAST cancer , *CLINICAL trials , *RADIOTHERAPY , *CANCER prognosis , *LOBULAR carcinoma , *ACCELERATED partial breast irradiation , *BREAST surgery - Abstract
IMPORT LOW is a randomized, multi-center phase III trial testing partial breast radiotherapy (RT) using intensity modulated RT in women with early-stage breast cancer at lower than average risk of ipsilateral breast tumor relapse (IBTR). Five-year results concluded non-inferiority for reduced-dose & partial-breast RT with similar normal tissue effects (reduced for breast appearance & hardness as reported by patients; Lancet, 2017). Here we report outcomes after 10 years. Women age ≥50 who had breast conservation surgery, for invasive breast cancer (excluding classical lobular carcinoma) pT1-2 (≤3cm) N0-1, any grade, with microscopic margins of ≥2 mm, were eligible. Patients were randomized (1:1:1) to 40Gy/15F to whole breast (control); 36Gy/15F to whole breast & 40Gy/15Fr to partial breast (reduced-dose); or 40Gy/15F to partial breast (partial-breast). The primary endpoint is IBTR. 10-year clinician assessed adverse effects were collected. Patient assessments were not recorded at 10 years. Efficacy analysis was intention to treat. 2016 patients were recruited from 05/2007 to 09/2010 from 30 UK RT centers (674 control, 673 reduced-dose, 669 partial-breast). Median age was 63 years (IQR 57-68); 42%, 48% & 10% of patients had tumors that were grade 1, 2 & 3 respectively; 3% were node positive. Median follow-up is 121 (IQR 120-124) months. 10-year follow-up forms were received for 518, 520 & 510 whole, reduced & partial groups respectively. 10-year rates of IBTR are 2.8% (95%CI 1.8-4.5), 1.9% (1.1-3.4) & 2.8% (1.7-4.5) in the whole-breast, reduced-dose & partial-breast groups respectively. Absolute treatment differences in IBTR compared with control for reduced-dose is -1.02% (95%CI -1.97, 0.96) & -0.02% (-1.38, 2.58) for partial-breast. 10-year overall survival rates are 87.8% (95%CI 84.9, 90.1), 87.2% (84.3, 89.6) & 90.3% (87.7, 92.4) for control, reduced-dose & partial-breast groups respectively. Clinician assessed adverse effects indicate low rates of moderate/marked events at 10 years (Table 1). At 10 years, rates of IBTR & clinician assessed moderate/marked adverse effects remain very low across all treatment groups demonstrating that reduced-dose & partial-breast RT are safe & effective RT techniques. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials
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Richard Gray, Rosie Bradley, Jeremy Braybrooke, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, William Barlow, Judith Bliss, Paolo Bruzzi, David Cameron, George Fountzilas, Sibylle Loibl, John Mackey, Miguel Martin, Lucia Del Mastro, Volker Möbus, Valentina Nekljudova, Sabino De Placido, Sandra Swain, Michael Untch, Kathleen I Pritchard, Jonas Bergh, Larry Norton, Clare Boddington, Julie Burrett, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Lucy Gettins, Jon Godwin, Robert Hills, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Yaochen Wang, Zhe Wang, Peter Fasching, Nadia Harbeck, Pascal Piedbois, Michael Gnant, Guenther Steger, Angelo Di Leo, Stella Dolci, Prue Francis, Denis Larsimont, Jean Marie Nogaret, Catherine Philippson, Martine Piccart, Sabine Linn, Petronella Peer, Vivianne Tjan-Heijnen, Sonja Vliek, Dennis Slamon, John Bartlett, Vivien H Bramwell, Bingshu Chen, Stephen Chia, Karen Gelmon, Paul Goss, Mark Levine, Wendy Parulekar, Joseph Pater, Eileen Rakovitch, Lois Shepherd, Dongsheng Tu, Tim Whelan, Don Berry, Gloria Broadwater, Constance Cirrincione, Hyman Muss, Raymond Weiss, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Harry Bartelink, Nina Bijker, Jan Bogaerts, Fatima Cardoso, Tanja Cufer, Jean-Pierre Julien, Philip Poortmans, Emiel Rutgers, Cornelis van de Velde, Eva Carrasco, Miguel Angel Segui, Jens Uwe Blohmer, Serban Costa, Bernd Gerber, Christian Jackisch, Gunter von Minckwitz, Mario Giuliano, Michele De Laurentiis, Christina Bamia, Georgia-Angeliki Koliou, Dimitris Mavroudis, Roger A'Hern, Paul Ellis, Lucy Kilburn, James Morden, John Yarnold, Mohammad Sadoon, Augustinus H Tulusan, Stewart Anderson, Gordon Bass, Joe Costantino, James Dignam, Bernard Fisher, Charles Geyer, Eleftherios P Mamounas, Soon Paik, Carol Redmond, D Lawrence Wickerham, Marco Venturini, Claudia Bighin, Simona Pastorino, Paolo Pronzato, Mario Roberto Sertoli, Theodorus Foukakis, Kathy Albain, Rodrigo Arriagada, Elizabeth Bergsten Nordström, Francesco Boccardo, Etienne Brain, Lisa Carey, Alan Coates, Robert Coleman, Candace Correa, Jack Cuzick, Nancy Davidson, Mitch Dowsett, Marianne Ewertz, John Forbes, Richard Gelber, Aron Goldhirsch, Pamela Goodwin, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Wolfgang Janni, Hirofumi Mukai, Yasuo Ohashi, Lori Pierce, Vinod Raina, Peter Ravdin, Daniel Rea, Meredith Regan, John Robertson, Joseph Sparano, Andrew Tutt, Giuseppe Viale, Nicholas Wilcken, Norman Wolmark, Wiliam Wood, Milvia Zambetti, Gray, R., Bradley, R., Braybrooke, J., Liu, Z., Peto, R., Davies, L., Dodwell, D., Mcgale, P., Pan, H., Taylor, C., Barlow, W., Bliss, J., Bruzzi, P., Cameron, D., Fountzilas, G., Loibl, S., Mackey, J., Martin, M., Del Mastro, L., Mobus, V., Nekljudova, V., De Placido, S., Swain, S., Untch, M., Pritchard, K. I., Bergh, J., Norton, L., Boddington, C., Burrett, J., Clarke, M., Davies, C., Duane, F., Evans, V., Gettins, L., Godwin, J., Hills, R., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Wang, Y., Wang, Z., Fasching, P., Harbeck, N., Piedbois, P., Gnant, M., Steger, G., Di Leo, A., Dolci, S., Francis, P., Larsimont, D., Nogaret, J. M., Philippson, C., Piccart, M., Linn, S., Peer, P., Tjan-Heijnen, V., Vliek, S., Slamon, D., Bartlett, J., Bramwell, V. H., Chen, B., Chia, S., Gelmon, K., Goss, P., Levine, M., Parulekar, W., Pater, J., Rakovitch, E., Shepherd, L., Tu, D., Whelan, T., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Weiss, R., Shan, Y., Shao, Y. F., Wang, X., Xu, B., Zhao, D. -B., Bartelink, H., Bijker, N., Bogaerts, J., Cardoso, F., Cufer, T., Julien, J. -P., Poortmans, P., Rutgers, E., van de Velde, C., Carrasco, E., Segui, M. A., Blohmer, J. U., Costa, S., Gerber, B., Jackisch, C., von Minckwitz, G., Giuliano, M., De Laurentiis, M., Bamia, C., Koliou, G. -A., Mavroudis, D., A'Hern, R., Ellis, P., Kilburn, L., Morden, J., Yarnold, J., Sadoon, M., Tulusan, A. H., Anderson, S., Bass, G., Costantino, J., Dignam, J., Fisher, B., Geyer, C., Mamounas, E. P., Paik, S., Redmond, C., Wickerham, D. L., Venturini, M., Bighin, C., Pastorino, S., Pronzato, P., Sertoli, M. R., Foukakis, T., Albain, K., Arriagada, R., Bergsten Nordstrom, E., Boccardo, F., Brain, E., Carey, L., Coates, A., Coleman, R., Correa, C., Cuzick, J., Davidson, N., Dowsett, M., Ewertz, M., Forbes, J., Gelber, R., Goldhirsch, A., Goodwin, P., Hayes, D., Hill, C., Ingle, J., Jagsi, R., Janni, W., Mukai, H., Ohashi, Y., Pierce, L., Raina, V., Ravdin, P., Rea, D., Regan, M., Robertson, J., Sparano, J., Tutt, A., Viale, G., Wilcken, N., Wolmark, N., Wood, W., and Zambetti, M.
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Oncology ,treatment schedule ,medicine.medical_specialty ,Anthracycline ,medicine.medical_treatment ,novotvorbe dojk ,Antineoplastic Agents ,Breast Neoplasms ,režim zdravljenja ,Disease ,randomized trials ,030204 cardiovascular system & hematology ,chemotherapy ,meta-analiza ,klinični protokoli ,Drug Administration Schedule ,randomizirane raziskave ,Antineoplastic Agent ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Internal medicine ,breast neoplasms ,medicine ,Humans ,clinical protocols ,terapija z zdravili ,030212 general & internal medicine ,Early breast cancer ,Chemotherapy ,Taxane ,business.industry ,rak dojk ,kemoterapija ,General Medicine ,medicine.disease ,Dose intensity ,udc:618.19-006 ,drug therapy ,meta-analysis ,Meta-analysis ,Female ,women ,ženske ,business ,Breast Neoplasm - Abstract
Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.
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- 2019
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8. Acute Toxicity and 2-year Adverse Effects of 30 Gy in Five Fractions over 15 Days to Whole Breast after Local Excision of Early Breast Cancer
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Martin, S., Mannino, M., Rostom, A., Tait, D., Donovan, E., Eagle, S., Haviland, J., and Yarnold, J.
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TOXICITY testing , *BREAST cancer , *RADIOTHERAPY , *SURGICAL excision - Abstract
Abstract: Aims: A pilot study was undertaken with the aim of documenting acute skin reactions and 2-year late adverse effects of a five-fraction course of adjuvant whole breast radiotherapy delivered over 15 days after local tumour excision of early breast cancer. Materials and methods: Thirty women with early invasive breast cancer aged ≥50 years with a pathological tumour size <3cm, complete microscopic resection, negative axillary node status and no requirement for cytotoxic therapy were prescribed 30Gy in five fractions over 15 days to the whole breast using tangential 6–10MV X-ray beams and three-dimensional dose compensation with written informed consent. Post-surgical baseline photographs of the breasts were taken, and acute skin erythema and moist desquamation were each scored weekly for 7 weeks using four-point graded scales (grade 0=none, 1=mild, 2=moderate, 3=severe). This was followed by an annual clinical assessment, including repeat photographs at 2 years. Results: Nine patients (30%, 95% confidence interval 14.7–49.4%) developed grade 2 erythema, with the remaining 21 patients developing milder degrees of reaction. Four (13.3%, 95% confidence interval 3.7–30.7) patients developed moist desquamation, grade 1 in three women and grade 2 in the fourth. At 2 years after treatment, 23/30 (77%) patients scored no change in photographic breast appearance compared with the pre-treatment baseline; seven (23%, 95% confidence interval 9.9–42.3) scored a mild change in breast appearance, and none developed a marked change. After a mean follow-up of 3.1 years (standard deviation 0.37, range 2.1–3.9 years) there have been no ipsilateral local tumour relapses. Conclusions: Further evaluation of a five-fraction regimen of adjuvant whole breast radiotherapy in a phase III randomised trial is justified, including a regimen delivered in a total of 5 days. [Copyright &y& Elsevier]
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- 2008
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9. Matching supraclavicular fields to the extent of axillary surgery in women prescribed radiotherapy for early stage carcinoma of the breast
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Wheatley, D., Adwani, A., Ebbs, S., Hanson, J., Ross, G., Sharma, A.K., Wells, P., and Yarnold, J.
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BREAST cancer , *CANCER , *SURGERY , *ORTHOPEDICS - Abstract
Abstract: Aims: To determine (1) if the lower border of a standard anterior radiotherapy field to the supraclavicular fossa matches the upper limit of level II/III axillary dissection; and (2) whether standard lung blocks in patients prescribed axillary radiotherapy shield target axillary tissue in women with breast cancer. Materials and methods: Between 1999 and 2001, 30 women with breast cancer undergoing level II/III axillary dissection had titanium clips placed to define the upper and medial limits of surgery. At radiotherapy planning, a supraclavicular fossa field similar to that described in the UK START trial protocol was simulated, with head twist applied to position the inferior field border (50% isodose) 1cm below and parallel to the lower border of the clavicle. The field position was recorded on X-ray film. The location of the most superior axillary clip was measured in relation to this inferior field border on the X-ray film. The location of the most medial clip was measured in relation to the lung/chest wall interface. Results: The median distance between the most superior clip and the inferior border of the supraclavicular field was 3.6cm (0.8–6.9cm), representing significant underlap in all cases. In addition, five out of 30 (17%) patients had surgical clips over 2.0cm medial to the lung/chest wall interface, suggesting that medial lymph nodes in an undissected axilla would be shielded by standard lung blocks in patients prescribed axillary radiotherapy. Conclusion: Current standard radiation fields to the supraclavicular fossa, as applied in this study, leave apical axillary lymph nodes untreated in a high proportion of patients. Standard lung shielding, as applied in this study to patients simulated for axillary radiotherapy, protect medial axillary lymph nodes in a few patients. A change in practice is recommended. [Copyright &y& Elsevier]
- Published
- 2005
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10. Mature analysis of UK Taxotere as Adjuvant Chemotherapy (TACT) trial (CRUK 01/001); effects of treatment and characterisation of patterns of breast cancer relapse.
- Author
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Bliss, J. M., Ellis, P., Kilburn, L., Bartlett, J., Bloomfield, D., Cameron, D., Canney, P., Coleman, R. E., Dowsett, M., Earl, H., Verril, M., Wardley, A., Yarnold, J., Ahern, R., Atkins, N., Fletcher, M., McLinden, M., and Barrett-Lee, P.
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BREAST cancer , *DOCETAXEL , *CANCER patients , *CANCER treatment , *ANTINEOPLASTIC agents - Abstract
Introduction: TACT, an investigator-led study in 4162 women with node positive (N+ve) or high risk node negative (N-ve) early breast cancer (EBC), is the largest taxane trial unconfounded by treatment (trt) duration. At principal analysis, with 5 years follow-up (fup), no evidence of improved disease-free survival (DFS) was observed by switching to 4 cycles of docetaxel (D) after 4 cycles of FEC (Ellis, Lancet 2009). Results were provocative in suggesting differential effects according to ER & HER2 status. Longer fup provides opportunity to detect emergence of late trt effects overall & within phenotypic subgroups & explore patterns of recurrence, by tumor characteristics. Patients & methods: TACT recruited women with histologically confirmed completely resected invasive EBC from 104 centers (UK (103), Belgium (1)) between 02/2001 & 07/2003 Centers chose FEC (600/60/600 mg/m² q3wk x 8) or E-CMF (E 100mg/m² q3wk x 4 →CMF 100mg/m² PO d1 -14 or 600mg/m² IV d1 &8/40/600 mg/m² q4wk x 4) as their control, reflecting standard UK practice. Patients (pts) were randomized to FEC-D (FEC q3wk x 4 → D 100 mg/m² q3wk x 4) or control. 2523 pts were from FEC centers (FEC = 1265: FEC-D = 1258) & 1639 from E-CMF centers (E-CMF = 824; FEC-D = 815). Endocrine therapy was given for 5 years. Few pts received HER2 directed therapy; 589 pts had unknown HER2 status. Median fup is now 97.5 months; this analysis updates DFS & overall survival in the ITT population. It also explores patterns of relapse by phenotypic & clinical characteristics. Analyses of trt effect are stratified by ER status due to issues of non-proportionality of hazard associated with length of fup. Results: DFS events have been reported for 1329 pts (FEC-D=640, Control=689) giving an unadjusted hazard ratio (HR) & 95%CI (stratified by control regimen & ER status) of 0.93 (0.83, 1.03) overall; p = 0.16 in favor of FEC-D & for ER+ve/HER2-ve of 0.99 (0.84, 1.17), for ER+ve/HER2+ve) 0.97 (0.73, 1.30), for ER-ve/HER2+ve 0.74 (0.53, 1.03), & ER-ve/HER2-ve 0.93 (0.73, 1.17). 1017 patients have died (FEC-D=500, Control=517); unadjusted HR=0.98 (95%CI: 0.86, 1.10); p = 0.69 with intercurrent deaths (prior to distant relapse) reported for 80 pts (FEC-D=40, Control=40). Annual event rates show different pattern of disease relapse by phenotypic subgroup Graphical representation will further explore these patterns & associated sites of relapse. Discussion: With a median fup of >8 years no clear benefit has emerged for D over standard anthracyclines within the TACT pt group. Differential effects associated with different patterns of relapse remain of interest. TACT precedes use of antiHER2 therapy which is known to have impacted on early relapse risk in HER2+ve pts. The high relapse risk observed for pts with ER-ve/HER2-ve disease remains a current clinical challenge. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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11. Possession of the ATM Codon 1853 SNP is Associated With an Increased Risk for Radiation-Induced Toxicity.
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Andreassen, C.N., Kerns, S., Rosenstein, B., Barnett, G., Fachal, L., Vega, A., Talbot, C., De Ruyck, K., Parliament, M., Koch, A., Gutiérrez-Enríquez, S., Chang-Claude, J., Yarnold, J., Bentzen, S., Elliott, R., West, C., and Alsner, J.
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GENETIC code , *SINGLE nucleotide polymorphisms , *RADIOTHERAPY complications , *BREAST cancer , *TELANGIECTASIA - Published
- 2014
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12. The UK START (Standardisation of Breast Radiotherapy) Trials: 10-year follow-up results.
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Haviland, J. S., Agrawal, R., Aird, E., Barrett, J., Barrett-Lee, P., Brown, J., Dewar, J., Dobbs, J., Hopwood, P., Hoskin, P., Lawton, P., Magee, B., Mills, J., Morgan, D., Owen, R., Simmons, S., Sydenham, M., Venables, K., Bliss, J. M., and Yarnold, J. R.
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STANDARDS , *ADJUVANT treatment of cancer , *RADIOTHERAPY , *BREAST cancer , *RANDOMIZED controlled trials - Abstract
Background International standard adjuvant radiotherapy regimens following primary surgery for early breast cancer have historically delivered a high total dose (50Gy) in 25 small daily doses (fractions) over 5 weeks, however randomised trials, including START, indicate that a lower total dose delivered in fewer, larger fractions (Fr) is likely to be at least as safe and effective (START Trialists' Group, Lancet 2008 & Lancet Oncol 2008). With patients remaining at risk of local relapse for many years, information on long-term outcomes is needed to provide confidence in clinical practice. Here, we report 10-year follow-up of the UK START Trials testing 13- and 15-Fr regimens in terms of local cancer control and late adverse effects. Methods Between 1999 and 2002, 4451 women with completely excised invasive breast cancer (T1-3, N0-1, M0) were randomised after primary surgery to comparisons of 50Gy in 25Fr over 5 weeks vs 41⋅6Gy or 39Gy in 13Fr over 5 weeks (START A), or 50Gy in 25Fr over 5 weeks vs 40Gy in 15Fr over 3 weeks (START B). Women were eligible if aged over 18 years and did not have an immediate surgical reconstruction. Protocol-specified principal endpoints were local-regional (LR) tumour relapse and late normal tissue effects. Analysis was by intention to treat. Findings Median follow-up in survivors is now 9.3 years in START A and 9.9 years in START B, with 139 LR relapses in START A and 95 in START B. In START A, the 10-year rate of LR relapse was 7.4% (95%CI 5.5-10.0) after 50Gy, 6.3% (95%CI 4.7-8.5) after 41⋅6Gy and 8.8% (95%CI 6.7-11.4) after 39Gy. In START B, the 10-year rate of LR relapse was 5.5% (95%CI 4.2-7.2) after 50Gy and 4.3% (95%CI 3.2-5.9) after 40Gy. Clinician assessments suggested lower 10-year rates of any moderate/marked late normal tissue effects after 39Gy (43.9%; 95%CI 39.3-48.7) and similar rates after 41.6Gy (49.5%; 95%CI 44.9-54.3) compared with 50Gy (50.4%; 95%CI 45.8-55.3) in START A and lower rates after 40Gy in START B (37.9%; 95%CI 34.5-41.5) compared with 50Gy (45.3%; 95%CI 41.7-49.0). From a planned meta-analysis of START A and the START pilot trial (Owen et al, Lancet Oncol 2006), the adjusted estimate of α/β value for tumour control was 3.5Gy (95% CI 1.2-5.7) and for late change in photographic breast appearance was 3.1Gy (95% CI 2.0-4.2). Interpretation Long-term follow-up conf irms that breast cancer and the surrounding dose-limiting healthy tissues respond similarly to radiotherapy fraction size and thus that appropriately-dosed hypofractionated radiotherapy is safe and effective in treatment of patients with early breast cancer. 41⋅6Gy in 13Fr and 40Gy in 15Fr each appear comparable to 50Gy in 25Fr in terms of local-regional tumour control and late normal tissue effects. These results support the continued use of 40Gy in 15Fr as standard of care (UK NICE Guidance 2009) for women requiring adjuvant radiotherapy for early breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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