150 results on '"Coles CE"'
Search Results
2. Proton Beam Therapy in Breast Cancer Patients: The UK PARABLE Trial is Recruiting
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Kirby, AM, Haviland, JS, Mackenzie, M, Fleming, H, Anandadas, C, Wickers, S, Miles, E, Iles, N, Bliss, JM, Coles, CE, PARABLE Trial Management Group, Coles, Charlotte [0000-0003-4473-8552], and Apollo - University of Cambridge Repository
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Proton Therapy ,Humans ,Female ,Breast Neoplasms ,Radiotherapy Dosage ,United Kingdom - Published
- 2023
3. Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting
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Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili, Aristei C; Bölükbaşı Y; Kaidar-Person O; Pfeffer R; Arenas M; Boersma LJ; Ciabattoni A; Coles CE; Franco P; Krengli M; Leonardi MC; Marazzi F; Masiello V; Meattini I; Montero A; Offersen B; Trigo ML; Bourgier C; Genovesi D; Kouloulias V; Morganti AG; Meduri B; Pasinetti N; Pedretti S; Perrucci E; Rivera S; Tombolini V; Vidali C; Valentini V; Poortmans P, Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili, and Aristei C; Bölükbaşı Y; Kaidar-Person O; Pfeffer R; Arenas M; Boersma LJ; Ciabattoni A; Coles CE; Franco P; Krengli M; Leonardi MC; Marazzi F; Masiello V; Meattini I; Montero A; Offersen B; Trigo ML; Bourgier C; Genovesi D; Kouloulias V; Morganti AG; Meduri B; Pasinetti N; Pedretti S; Perrucci E; Rivera S; Tombolini V; Vidali C; Valentini V; Poortmans P
- Abstract
We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.Copyright © 2022 Elsevier B.V. All rights reserved.
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- 2022
4. Abstract DEB2-1: Pro - One Week of Whole Breast RT is the New Standard of Care
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Coles, CE, primary
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- 2022
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5. FAST-Forward phase 3 RCT of 1-week hypofractionated breast radiotherapy: 5-year results
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Brunt, AM, Haviland, JS, Wheatley, DA, Sydenham, MA, Alhasso, A, Bloomfield, D, Chan, C, Churn, M, Cleator, S, Coles, CE, Emson, M, Goodman, A, Harnett, A, Hopwood, P, Kirby, AM, Kirwan, C, Morris, C, Nabi, Z, Sawyer, E, Somaiah, N, Stones, L, Syndikus, I, Wilcox, M, Bliss, JM, and Yarnold, JR
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RA0421 ,R1 ,RA - Published
- 2020
6. Does seroma predict patient-reported adverse effects following breast radiotherapy in IMPORT HIGH?
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Bhattacharya, IS, Haviland, JS, Perotti, C, Eaton, D, Gulliford, S, Harris, E, Coles, CE, Kirwan, CC, Bliss, JM, and Kirby, AM
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32 Biomedical and Clinical Sciences ,3211 Oncology and Carcinogenesis ,51 Physical Sciences - Published
- 2019
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7. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic
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Coles, CE, Aristei, C, Bliss, J, Boersma, L, Brunt, AM, Chatterjee, S, Hanna, G, Jagsi, R, Person, OK, Kirby, A, Mjaaland, I, Meattini, I, Luis, AM, Marta, GN, Offersen, B, Poortmans, P, Rivera, S, Coles, CE, Aristei, C, Bliss, J, Boersma, L, Brunt, AM, Chatterjee, S, Hanna, G, Jagsi, R, Person, OK, Kirby, A, Mjaaland, I, Meattini, I, Luis, AM, Marta, GN, Offersen, B, Poortmans, P, and Rivera, S
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- 2020
8. A Dosimetric Comparison of Breast Radiotherapy Techniques to Treat Locoregional Lymph Nodes Including the Internal Mammary Chain
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Ranger, A, Dunlop, A, Hutchinson, K, Convery, H, Maclennan, MK, Chantler, H, Twyman, N, Rose, C, McQuaid, D, Amos, RA, Griffin, C, DeSouza, NM, Donovan, E, Harris, E, Coles, CE, Kirby, A, Coles, Charlotte [0000-0003-4473-8552], and Apollo - University of Cambridge Repository
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internal mammary chain radiotherapy ,Humans ,Heart-sparing radiotherapy ,Breast Neoplasms ,Female ,Breast ,Lymph Nodes ,proton beam therapy for breast cancer ,Middle Aged ,Radiometry - Abstract
AIMS: Radiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs). MATERIALS AND METHODS: In 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance. RESULTS: One hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB). CONCLUSIONS: Simple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics.
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- 2018
9. IMPORT LOW: in response to Vaidya et al
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Coles, CE, Haviland, JS, Kirby, AM, Titley, J, Wilcox, M, Bliss, JM, Yarnold, JR, Coles, Charlotte [0000-0003-4473-8552], and Apollo - University of Cambridge Repository
- Abstract
We reject the inference of a “survival benefit” for patients receiving partial breast irradiation (PBI) within the IMPORT LOW trial and caution against any such interpretation when the number of events reported is so small1. There is no suggestion of a difference in disease-free and overall survival across IMPORT LOW treatment groups. The TARGIT trialist’s claim of survival benefit in their own trial relates to non-breast cancer deaths and the data cited are from a selected subset of patients. In IMPORT LOW, there were 9 cardiac deaths occurring 6-36 months following randomisation, 4 after left- and 5 after right-sided breast cancer, so no suggestion of an early radiation induced effect. Lung cancer laterality in relation to the treated breast was similar for ipsilateral and contralateral tumours, with 18/19 cases developing within 5 years of randomisation. These data fail to support an increase in radiation-induced second cancers after whole breast irradiation (WBI). Therefore, the TARGIT trialist’s suggestion that WBI causes inferior survival at 5-years’ follow-up due to either cause appears unsubstantiated.
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- 2018
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10. Abstract GS4-05: Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003)
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Coles, CE, primary, Griffin, CL, additional, Kirby, AM, additional, Haviland, JS, additional, Titley, JC, additional, Benstead, K, additional, Brunt, AM, additional, Chan, C, additional, Ciurlionis, L, additional, Din, OS, additional, Donovan, EM, additional, Eaton, DJ, additional, Harnett, AN, additional, Hopwood, P, additional, Jefford, ML, additional, Jenkins, PJ, additional, Lee, CE, additional, McCormack, M, additional, Sherwin, L, additional, Syndikus, I, additional, Tsang, Y, additional, Twyman, NI, additional, Ventikaraman, R, additional, Wickers, S, additional, Wilcox, MH, additional, Bliss, JM, additional, and Yarnold, JR, additional
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- 2019
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11. ESTRO consensus guideline for target volume delineation in the setting of postmastectomy radiation therapy after implant-based immediate reconstruction for early stage breast cancer
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Universitat Rovira i Virgili, Kaidar-Person O; Vrou Offersen B; Hol S; Arenas M; Aristei C; Bourgier C; Joao Cardoso M; Chua B; Coles CE; Engberg Damsgaard T; Gabrys D; Jagsi R; Jimenez R; Kirby AM; Kirkove C; Kirova Y; Kouloulias V; Marinko T; Meattini I; Mjaaland I; Nader Marta G; Witt Nystrom P; Senkus E; Skyttä T; Tvedskov TF; Verhoeven K; Poortmans P, Universitat Rovira i Virgili, and Kaidar-Person O; Vrou Offersen B; Hol S; Arenas M; Aristei C; Bourgier C; Joao Cardoso M; Chua B; Coles CE; Engberg Damsgaard T; Gabrys D; Jagsi R; Jimenez R; Kirby AM; Kirkove C; Kirova Y; Kouloulias V; Marinko T; Meattini I; Mjaaland I; Nader Marta G; Witt Nystrom P; Senkus E; Skyttä T; Tvedskov TF; Verhoeven K; Poortmans P
- Abstract
© 2019 Elsevier B.V. Immediate breast reconstruction (IBR) rates after mastectomy are increasing. Postmastectomy radiation therapy (PMRT) contouring guidelines for target volumes in the setting of IBR are lacking. Therefore, many patients who have had IBR receive PMRT to target volumes similar to conventional simulator-based whole breast irradiation. The aim of this paper is to describe delineation guidelines for PMRT after implant-based IBR based on a thorough understanding of the surgical procedures, disease stage, patterns of recurrence and radiation techniques. They are based on a consensus endorsed by a global multidisciplinary group of breast cancer experts.
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- 2019
12. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
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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
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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
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- 2017
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13. Accelerated partial breast irradiation: the new standard?
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Coles, CE and Yarnold
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Brachytherapy ,Carcinoma, Ductal, Breast ,Humans ,Breast Neoplasms ,Female ,Carcinoma in Situ - Abstract
In The Lancet, Vratislav Strnad and colleagues present 5-year results of a large, international, randomised trial testing standard whole-breast radiotherapy against accelerated partial breast irradiation (APBI) after breast-conserving surgery, in a selected low-risk population of women. The APBI technique entailed a 4–5-day postoperative course of radiotherapy delivered via radioactive sources inserted into breast tissue surrounding the operation site, the so-called tumour bed. The study design tested for non-inferiority with a primary endpoint of local recurrence in 1184 patients recruited from 16 centres, and 5-year local recurrence was less than 2% in both arms. A predefined 3% non-inferiority margin was upheld by a difference in local relapse rates of 0·52% (95% CI −0·72 to 1·75) in favour of whole-breast irradiation. There were no statistical differences in disease-free or overall survival, and adverse effects were similarly mild in both groups.
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- 2017
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14. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial
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Coles, CE, Griffin, CL, Kirby, AM, Titley, J, Agrawal, RK, Alhasso, A, Bhattacharya, IS, Brunt, AM, Ciurlionis, L, Chan, C, Donovan, EM, Emson, MA, Harnett, AN, Haviland, JS, Hopwood, P, Jefford, ML, Kaggwa, R, Sawyer, EJ, Syndikus, I, Tsang, YM, Wheatley, DA, Wilcox, M, Yarnold, JR, Bliss, JM, and Trialists, IMPORT
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R735 ,R1 ,RA - Abstract
BACKGROUND: Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy. METHODS: IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1-3, with a tumour size of 3 cm or less (pT1-2), none to three positive axillary nodes (pN0-1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase [non-inferiority margin] at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio [HR] was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634. FINDINGS: Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7-83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5-2·3) of patients in the control group, 0·2% (0·02-1·2) in the reduced-dose group, and 0·5% (0·2-1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were -0·73% (-0·99 to 0·22) for the reduced-dose and -0·38% (-0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance [p=0·007 for partial-breast] and breast harder or firmer [p=0·002 for reduced-dose and p
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- 2017
15. The Assisi Think Tank Meeting and Survey of post MAstectomy Radiation Therapy after breast reconstruction: The ATTM-SMART report.
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Universitat Rovira i Virgili, Aristei C; Kaidar-Person O; Tagliaferri L; Arenas M; Coles CE; Offersen BV; Frezza G; Leonardi MC; Valentini V; Bourgier C; Poortmans PMP., Universitat Rovira i Virgili, and Aristei C; Kaidar-Person O; Tagliaferri L; Arenas M; Coles CE; Offersen BV; Frezza G; Leonardi MC; Valentini V; Bourgier C; Poortmans PMP.
- Abstract
PURPOSE: To describe the current European practise on post-mastectomy radiation therapy (PMRT) in relation to breast reconstruction. METHODS: A 21-item questionnaire was distributed online via Survey Monkey. Items referred to 1. general topics (country, centre, years of experience in breast cancer); 2. clinical decision making; 3. RT techniques and dosimetry; 4. dose fractionation. RESULTS: 283 responses were received from 19 countries. Most responders worked in public health services and in academic institutions and had 5-20 years experience. Although many indicated they were consulted about the timing and type of breast reconstructive surgery, final decisions were most often made by surgeons. Immediate reconstruction with expander followed by RT and subsequently permanent reconstruction with prosthesis was recommended by 61.6% of responders. Most (48.4%) adviced a boost only when margins were close or involved with an another 17.7% recommending it in the presence of high-risk features (T3-T4, lympho-vascular involvement). Intensity modulated RT was rarely used by about two-thirds of responders, except when with 3D technique the dose constraints were not achieved or when regional lymph nodes were included. Almost 60% of responders did not use bolus/tissue equivalent material (TEM). The main indication for bolus/TEM use was skin involvement. The majority of responders used 1.8-2 Gy per fraction. CONCLUSIONS: The present survey highlighted controversial areas in clinical practise, confirming the uncertainties about the scheduling of PMRT and breast reconstruction.
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- 2018
16. It's PRIMETIME. Postoperative Avoidance of Radiotherapy: Biomarker Selection of Women at Very Low Risk of Local Recurrence
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Kirwan, CC, Coles, CE, Bliss, J, PRIMETIME Protocol Working Group, and Apollo - University of Cambridge Repository
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PRIMETIME Protocol Working Group - Abstract
PRIMETIME is funded by Cancer Research UK (Grant number: C17918/A20015). C.E. Coles is supported by the Cambridge National Institute of Health Research Biomedical Research Centre. C.C. Kirwan is supported by a National Institute of Health Research Clinician Scientist Award (NIHR-CS-011014).
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- 2016
17. Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer
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Eccles, SA, Aboagye, EO, Ali, S, Anderson, AS, Armes, J, Berditchevski, F, Blaydes, JP, Brennan, K, Brown, NJ, Bryant, HE, Bundred, NJ, Burchell, JM, Campbell, AM, Carroll, JS, Clarke, RB, Coles, CE, Cook, GJR, Cox, A, Curtin, NJ, Dekker, LV, Silva, IS, Duffy, SW, Easton, DF, Eccles, DM, Edwards, DR, Edwards, J, Evans, DG, Fenlon, DF, Flanagan, JM, Foster, C, Gallagher, WM, Garcia-Closas, M, Gee, JMW, Gescher, AJ, Goh, V, Groves, AM, Harvey, AJ, Harvie, M, Hennessy, BT, Hiscox, S, Holen, I, Howell, SJ, Howell, A, Hubbard, G, Hulbert-Williams, N, Hunter, MS, Jasani, B, Jones, LJ, Key, TJ, Kirwan, CC, Kong, A, Kunkler, IH, Langdon, SP, Leach, MO, Mann, DJ, Marshall, JF, Martin, LA, Martin, SG, Macdougall, JE, Miles, DW, Miller, WR, Morris, JR, Moss, SM, Mullan, P, Natrajan, R, O’Connor, JPB, O’Connor, R, Palmieri, C, Pharoah, PDP, Rakha, EA, Reed, E, Robinson, SP, Sahai, E, Saxton, JM, Schmid, P, Smalley, MJ, Speirs, V, Stein, R, Stingl, J, Streuli, CH, Tutt, ANJ, Velikova, G, Walker, RA, Watson, CJ, Williams, KJ, Young, LS, Thompson, AM, Carroll, Jason [0000-0003-3643-0080], Coles, Charlotte [0000-0003-4473-8552], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Watson, Christine [0000-0002-8548-5902], Apollo - University of Cambridge Repository, and Cancer Research UK
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Cancer Research ,medicine.medical_specialty ,ONCOLOGY DRUG DEVELOPMENT ,Breast Neoplasms ,Translational research ,ESTROGEN-RECEPTOR-BETA ,MAMMARY-GLAND DEVELOPMENT ,Metastasis ,Translational Research, Biomedical ,RC0254 ,chemistry.chemical_compound ,Breast cancer ,QUALITY-OF-LIFE ,ADJUVANT MULTINATIONAL TRIAL ,Epidemiology of cancer ,Animals ,Humans ,Medicine ,Oncology & Carcinogenesis ,Intensive care medicine ,Translational Medical Research ,Medicine(all) ,Gynecology ,Science & Technology ,TRANSGENIC MOUSE MODELS ,business.industry ,Research ,Cancer ,RANDOMIZED CONTROLLED-TRIAL ,Luminespib ,A300 ,ONCOLOGY ,medicine.disease ,EPITHELIAL-MESENCHYMAL TRANSITION ,CIRCULATING TUMOR-CELLS ,B900 ,Oncology ,RISK PREDICTION MODEL ,chemistry ,Hormonal therapy ,Female ,Personalized medicine ,business ,Life Sciences & Biomedicine ,1112 Oncology And Carcinogenesis - Abstract
IntroductionBreast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.MethodsMore than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.ResultsThe 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.ConclusionsWith resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.
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- 2016
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18. The Cambridge Breast Intensity-modulated Radiotherapy Trial: Comparison of Clinician- versus Patient-reported Outcomes
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Mukesh, MB, Qian, W, Wah Hak, CC, Wilkinson, JS, Barnett, GC, Moody, AM, Wilson, C, Coles, CE, Qian, Wendi [0000-0002-4238-3471], Coles, Charlotte [0000-0003-4473-8552], and Apollo - University of Cambridge Repository
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concordance ,breast cancer ,late treatment toxicity ,radiotherapy - Abstract
AIMS: Breast radiotherapy-associated toxicity is often reported using clinical and photographic assessments. The addition of patient-reported outcome measures (PROMs) is becoming more common. This study investigated the concordance between clinician- and patient-reported outcomes. MATERIALS AND METHODS: The Cambridge Breast Intensity-modulated Radiotherapy (IMRT) trial prospectively collected data on clinician assessment and PROMs at 2 and 5 years after breast radiotherapy. Clinician assessment included physical examination and photographic assessment. PROMs included European Organization for Research and Treatment of Cancer (EORTC) BR23 questionnaire and four breast radiotherapy-specific questions. The correlation between patient and clinician scores were analysed on an independent patient basis using percentage agreement, Cohen's kappa coefficient (k) and Bowker's test of symmetry. The analysis was repeated after stratifying patients based on age, baseline Hospital Anxiety and Depression Score (HADS) and baseline body image score. RESULTS: At 2 and 5 years, a weak level of concordance was seen between the clinician-based assessment and PROMS for all the five toxicity end points (k = 0.05-0.21), with individual patient-based agreement of 32.9-78.3% and a highly discordant Bowker's test of symmetry (P < 0.001). The most frequently reported moderate-severe toxicity by patients was change in breast appearance (14% at both 2 and 5 years), whereas it was breast induration (36% and 25% at 2 and 5 years, respectively) by the clinicians. The lack of concordance was not affected by patient's age, baseline HADS and baseline body image score. CONCLUSIONS: This study found that moderate-severe toxicity reported by patients is low and the overall concordance between clinicians and patients is low. This could be due to methodological limitations or alternatively reflects the subjective nature of PROMs. Incorporation of a patient's perception on treatment-related toxicity will have important implications for treatment decisions and follow-up care.
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- 2016
19. Accelerated partial breast irradiation: the new standard?
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Coles, CE, Yarnold, JR, Coles, Charlotte [0000-0003-4473-8552], and Apollo - University of Cambridge Repository
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Brachytherapy ,Carcinoma, Ductal, Breast ,Humans ,Breast Neoplasms ,Female ,Carcinoma in Situ - Abstract
In The Lancet, Vratislav Strnad and colleagues present 5-year results of a large, international, randomised trial testing standard whole-breast radiotherapy against accelerated partial breast irradiation (APBI) after breast-conserving surgery, in a selected low-risk population of women. The APBI technique entailed a 4–5-day postoperative course of radiotherapy delivered via radioactive sources inserted into breast tissue surrounding the operation site, the so-called tumour bed. The study design tested for non-inferiority with a primary endpoint of local recurrence in 1184 patients recruited from 16 centres, and 5-year local recurrence was less than 2% in both arms. A predefined 3% non-inferiority margin was upheld by a difference in local relapse rates of 0·52% (95% CI −0·72 to 1·75) in favour of whole-breast irradiation. There were no statistical differences in disease-free or overall survival, and adverse effects were similarly mild in both groups.
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- 2016
20. Patients with a high polygenic risk of breast cancer do not have an increased risk of radiotherapy toxicity
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Dorling L, Barnett GC, Michailidou K, Coles CE, Burnet NG, Yarnold JR, Elliott RM, Dunning AM, Pharoah PD, West CM.
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- 2015
21. Long Term Outcome of CT-Based Image-Guided Brachytherapy for Cervix Cancer Using the Tandem-Ring Applicator
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Tan Lt, Coles Ce, and Diane Whitney D
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Brachytherapy ,Rectum ,Cancer ,medicine.disease ,Surgery ,medicine.anatomical_structure ,medicine ,Image guided brachytherapy ,Dosimetry ,Nuclear medicine ,business ,Dose rate ,Small tumors ,Cervix - Abstract
Objectives: To evaluate the long term outcome of CT-based image-guided brachytherapy (IGBT) for cervix cancer using the tandem-ring applicator. Methods: Between February 2005 and December 2008, 40 patients were treated with chemo-radiotherapy and high dose rate CT-based IGBT. A manually optimized dosimetry plan was created for each fraction. The planning aims were to deliver a point A dose ≥ 74 Gy10, D90 of the high-risk clinical target volume (HR-CTV) ≥ 74 Gy10, V100 HR-CTV ≥ 95%, D2cc rectum/sigmoid ≤ 75 Gy3 and D2cc bladder ≤ 95 Gy3. Results: Median follow-up was 61 months. The 3-year and 5-year cancer-specific survival was 80% (tumors 2-5 cm=87%, >5 cm=59%) and 74% (tumors 2-5 cm=87%, >5 cm=52%). The 3-year and 5-year local control was 89% (tumors 2-5 cm=96%, >5 cm=76%). The mean D90 for patients with and without local recurrence was 70.8 Gy10 and 85.2 Gy10 respectively. The 3-year and 5-year rate of G3 complications was 10% and 15%. Manual optimization could not improve the dosimetry in 96 (85%) fractions. Conclusions: CT-based IGBT improves local control compared to conventional BT, particularly for small tumors.
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- 2014
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22. A multicentre observational study evaluating image-guided radiotherapy for more accurate partial-breast intensity-modulated radiotherapy: comparison with standard imaging technique
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Harris, E, Mukesh, M, Jena, R, Baker, A, Bartelink, H, Brooks, C, Dean, J, Donovan, E, Collette, S, Eagle, S, Fenwick, J, Graham, P, Haviland, J, Kirby, A, Mayles, H, Mitchell, RA, Perry, R, Poortmans, P, Poynter, A, Shentall, G, Titley, J, Thompson, A, Yarnold, JR, Coles, CE, Evans, PM, Harris, E, Mukesh, M, Jena, R, Baker, A, Bartelink, H, Brooks, C, Dean, J, Donovan, E, Collette, S, Eagle, S, Fenwick, J, Graham, P, Haviland, J, Kirby, A, Mayles, H, Mitchell, RA, Perry, R, Poortmans, P, Poynter, A, Shentall, G, Titley, J, Thompson, A, Yarnold, JR, Coles, CE, and Evans, PM
- Abstract
Background Whole-breast radiotherapy (WBRT) is the standard treatment for breast cancer following breast-conserving surgery. Evidence shows that tumour recurrences occur near the original cancer: the tumour bed. New treatment developments include increasing dose to the tumour bed during WBRT (synchronous integrated boost) and irradiating only the region around the tumour bed, for patients at high and low risk of tumour recurrence, respectively. Currently, standard imaging uses bony anatomy to ensure accurate delivery of WBRT. It is debatable whether or not more targeted treatments such as synchronous integrated boost and partial-breast radiotherapy require image-guided radiotherapy (IGRT) focusing on implanted tumour bed clips (clip-based IGRT). Objectives Primary – to compare accuracy of patient set-up using standard imaging compared with clip-based IGRT. Secondary – comparison of imaging techniques using (1) tumour bed radiotherapy safety margins, (2) volume of breast tissue irradiated around tumour bed, (3) estimated breast toxicity following development of a normal tissue control probability model and (4) time taken. Design Multicentre observational study embedded within a national randomised trial: IMPORT-HIGH (Intensity Modulated and Partial Organ Radiotherapy – HIGHer-risk patient group) testing synchronous integrated boost and using clip-based IGRT. Setting Five radiotherapy departments, participating in IMPORT-HIGH. Participants Two-hundred and eighteen patients receiving breast radiotherapy within IMPORT-HIGH. Interventions There was no direct intervention in patients’ treatment. Experimental and control intervention were clip-based IGRT and standard imaging, respectively. IMPORT-HIGH patients received clip-based IGRT as routine; standard imaging data were obtained from clip-based IGRT images. Main outcome measures Difference in (1) set-up errors, (2) safety margins, (3) volume of breast tissue irradiated, (4) breast toxicity and (5) time, between clip-bas
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- 2014
23. Cambridge Breast Intensity Modulated Radiotherapy Trial: dosimetry results for 1,139 patients
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Coles, CE, primary, Wilkinson, JS, additional, Wilson, CB, additional, Burnet, NG, additional, Wishart, GC, additional, Twyman, N, additional, Hoole, ACF, additional, and Moody, AM, additional
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- 2008
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24. The Cambridge breast intensity modulated radiotherapy trial
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Coles, CE, primary, Wilkinson, JS, additional, Moody, AM, additional, Hoole, ACF, additional, Twyman, N, additional, and Burnet, NG, additional
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- 2006
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25. A replicated association between polymorphisms near TNFα and risk for adverse reactions to radiotherapy.
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Talbot CJ, Tanteles GA, Barnett GC, Burnet NG, Chang-Claude J, Coles CE, Davidson S, Dunning AM, Mills J, Murray RJ, Popanda O, Seibold P, West CM, Yarnold JR, Symonds RP, Talbot, C J, Tanteles, G A, Barnett, G C, Burnet, N G, and Chang-Claude, J
- Abstract
Background: Response to radiotherapy varies between individuals both in terms of efficacy and adverse reactions. Finding genetic determinants of radiation response would allow the tailoring of the treatment, either by altering the radiation dose or by surgery. Despite a growing number of studies in radiogenomics, there are no well-replicated genetic association results.Methods: We carried out a candidate gene association study and replicated the result using three additional large cohorts, a total of 2036 women scored for adverse reactions to radiotherapy for breast cancer.Results: Genetic variation near the tumour necrosis factor alpha gene is shown to affect several clinical endpoints including breast induration, telangiectasia and overall toxicity. In the combined analysis homozygosity for the rare allele increases overall toxicity (P=0.001) and chance of being in the upper quartile of risk with odds ratio of 2.46 (95% confidence interval 1.52-3.98).Conclusion: We have identified that alleles of the class III major histocompatibility complex region associate with overall radiotherapy toxicity in breast cancer patients by using internal replication through a staged design. This is the first well-replicated report of a genetic predictor for radiotherapy reactions. [ABSTRACT FROM AUTHOR]- Published
- 2012
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26. Clinical impact of computed tomography-based image-guided brachytherapy for cervix cancer using the tandem-ring applicator - the Addenbrooke's experience.
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Tan LT, Coles CE, Hart C, and Tait E
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AIMS: We report our initial 3-year experience of chemoradiotherapy for cervical cancer with computed tomography-based image-guided high dose rate (HDR) brachytherapy using the tandem-ring applicator. MATERIALS AND METHODS: Twenty-eight patients were treated between February 2005 and December 2007. All patients received initial external beam radiotherapy (EBRT) followed by HDR brachytherapy (planned dose 21Gy to point A in three fractions over 8 days). For each insertion, a computed tomography scan was obtained with the brachytherapy applicator in situ. The cervix, uterus and organs at risk (OAR) were contoured on the computed tomography images to create an individualised dosimetry plan. The D(90) (the dose delivered to 90% of the tumour target), V(100) (the percentage of tumour target volume receiving 100% of the prescribed dose) and the minimum dose in the most exposed 2cm(3) volume (D(2cc)) of rectum, bladder and bowel were recorded. The equivalent dose in 2Gy fractions delivered by EBRT and brachytherapy was calculated. RESULTS: The 3-year cancer-specific survival was 81%, with a pelvic control rate of 96%. In 24 patients, a D(90)>/=74Gy(alpha/beta10) was achieved. The only patient with local recurrence had a D(90) of 63.8Gy(alpha/beta10). The overall actuarial risk of serious late morbidity was 14%. Seventeen patients had satisfactory OAR doses using the standard loading pattern. Seven patients had modifications to reduce the risk of toxicity, whereas two had modifications to improve the tumour dose. Comparison with a previous cohort of patients treated with chemoradiotherapy and a conventionally planned low dose rate triple source brachytherapy technique showed an improvement in local pelvic control of 20% (P=0.04). CONCLUSIONS: The implementation of a computed tomography-based tandem-ring HDR brachytherapy technique in conjunction with individual dose adaptation has resulted in a significant improvement in local control at Addenbrooke's without increasing the risk of serious toxicity, and with little effect on radiotherapy resources. [ABSTRACT FROM AUTHOR]
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- 2009
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27. Practice point. Conformal radiotherapy facilitates the delivery of concurrent chemotherapy and radiotherapy: a case of primitive neuroectodermal tumour of the chest wall.
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Coles CE, Twyman N, Earl HM, and Burnet NG
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We illustrate the principle of conformal radiotherapy by discussing the case of a patient with a primitive neuroectodermal tumour of the chest wall. Recent advances in radiotherapy planning enable precise localization of the planning target volume (PTV) and normal organs at risk of irradiation. Customized blocks are subsequently designed to produce a treatment field that 'conforms' to the PTV.The use of conformal radiotherapy (CRT) in this case facilitated the delivery of concurrent chemotherapy and radiotherapy by significantly reducing the volume of red marrow irradiated. The lack of acute and late toxicities was attributed to optimal exclusion of normal tissues from the treatment field, made possible by CRT. [ABSTRACT FROM AUTHOR]
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- 2000
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28. The Assisi think tank focus review on postoperative radiation for lobular breast cancer.
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Kaidar-Person, O., Ratosa, I, Franco, P., Masiello, V., Marazzi, F., Pedretti, S., Ciabattoni, A., Leonardi, M.C., Tramm, T., Coles, CE, Meattini, I, Arenas, M., Offersen, B.V., Boersma, L.J., Valentini, V., Dodwell, D., Poortmans, P., and Aristei, C.
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LOBULAR carcinoma , *ONCOLOGISTS , *BREAST cancer , *CANCER invasiveness , *RESEARCH institutes , *RADIOTHERAPY - Abstract
• Invasive lobular carcinoma (ILC) is the second most common breast cancer type. • There are limited data to guide locoregional therapy for ILC. • Recommendations for locoregional therapy ILC are provided according to the level of evidence. The "Assisi Think Tank Meeting" (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Longitudinal Assessment of Tumor-Infiltrating Lymphocytes in Primary Breast Cancer Following Neoadjuvant Radiation Therapy.
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Yoneyama M, Zormpas-Petridis K, Robinson R, Sobhani F, Provenzano E, Steel H, Lightowlers S, Towns C, Castillo SP, Anbalagan S, Lund T, Wennerberg E, Melcher A, Coles CE, Roxanis I, Yuan Y, and Somaiah N
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- Humans, Female, Longitudinal Studies, Middle Aged, Tumor Microenvironment immunology, Lymphocyte Count, Deep Learning, Lymphocytes, Tumor-Infiltrating, Breast Neoplasms radiotherapy, Breast Neoplasms pathology, Neoadjuvant Therapy methods
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Purpose: Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast cancer. Despite interest in combining radiation therapy with immunotherapy, little is known about the effect of radiation therapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of TILs and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiation therapy (NART) from PRADA and Neo-RT breast clinical trials., Methods and Materials: We manually scored stromal TILs (sTILs) from longitudinal tumor samples using standardized guidelines as well as deep learning-based scores at cell-level (cTIL) and cell- and tissue-level combination analyses (SuperTIL). In parallel, we interrogated absolute lymphocyte counts from routine blood tests at corresponding time points during treatment. Exploratory analyses studied the relationship between TILs and pathologic complete response (pCR) and long-term outcomes., Results: Patients receiving NART experienced a significant and uniform decrease in sTILs that did not recover at the time of surgery (P < .0001). This lymphodepletive effect was also mirrored in peripheral blood. Our SuperTIL deep learning score showed good concordance with manual sTILs and importantly performed comparably to manual scores in predicting pCR from diagnostic biopsies. The analysis suggested an association between baseline sTILs and pCR, as well as sTILs at surgery and relapse, in patients receiving NART., Conclusions: This study provides novel insights into TIL dynamics in the context of NART in breast cancer and demonstrates the potential for artificial intelligence to assist routine pathology. We have identified trends that warrant further interrogation and have a bearing on future radioimmunotherapy trials., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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30. Neoadjuvant Radiotherapy and Endocrine Therapy for Oestrogen Receptor Positive Breast Cancers: The Neo-RT Feasibility Study.
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Lightowlers SV, Machin A, Woitek R, Provenzano E, Allajbeu I, Al Sarakbi W, Demiris N, Forouhi P, Gilbert FJ, Kirby AM, Towns C, Somaiah N, and Coles CE
- Abstract
Aims: To establish the safety and feasibility of delivering neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor-positive breast cancers with palpable size 20mm or greater, for which radiotherapy might facilitate more conservative surgery., Materials and Methods: A single-arm feasibility study was conducted. Patients received whole breast radiotherapy with or without radiotherapy to nodal areas. Dose/fractionation was 40Gy in 15 fractions over 3 weeks, with or without either a simultaneous integrated boost to 48Gy or sequential boost to the tumour bed. This was followed by endocrine treatment for 20 weeks, then surgery. The primary endpoint of the study was the proportion of patients successfully completing neoadjuvant radiotherapy and endocrine treatment followed by breast surgery. Response and toxicity endpoints including mastectomy rate, peri/postoperative complications, and pathological response were also evaluated. The primary analysis is descriptive. The study regimen would be considered feasible if more than 70% of patients completed treatment, while it might not be considered feasible if less than 50% did so. With a one-sided 5% significance level and 80% power, a maximum of 43 patients would be required to detect a rate of ≤50% vs ≥70%., Results: 14 patients were recruited out of the planned 43. Due to slow recruitment, particularly during the COVID-19 pandemic, the decision was made to stop the trial in October 2021. One registered patient was found to be ineligible before starting treatment. 13/13 patients (100%, 90% CI: 75.3%, 100%) who received any trial treatment successfully completed all trial treatments. The lower bound of the Clopper-Pearson (exact) 90% confidence interval was 79%, indicating that the primary endpoint would have been met if the planned recruitment had been achieved. 3/13 patients underwent mastectomy. 7/13 had more conservative surgery than had been planned at baseline. 4/13 patients experienced any peri/postoperative complication. The only acute radiotherapy toxicities reported were grade 1/2 dermatitis and grade 1 fatigue. Long-term breast outcomes were clinician assessed as none/mild at all timepoints in 12/13 patients. All tumours showed evidence of some pathological response to treatment, but none had a pathological complete response., Conclusion: This treatment schedule is likely feasible. It is difficult to draw strong conclusions on safety/toxicity given the small numbers, but these seem in keeping with other recent reports of neoadjuvant breast radiotherapy., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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31. Essential requirements for reporting radiation therapy in breast cancer clinical trials: An international multi-disciplinary consensus endorsed by the European Society for Radiotherapy and Oncology (ESTRO).
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Kaidar-Person O, Meattini I, Boersma LJ, Becherini C, Cortes J, Curigliano G, de Azambuja E, Harbeck N, Rugo HS, Del Mastro L, Gennari A, Isacke CM, Vestmø Maraldo M, Marangoni E, Nader Marta G, Mjaaland I, Salvestrini V, Spanic T, Visani L, Morandi A, Lambertini M, Livi L, Coles CE, Poortmans P, and Offersen BV
- Subjects
- Humans, Female, Europe, Radiation Oncology standards, Societies, Medical, Quality Assurance, Health Care standards, Breast Neoplasms radiotherapy, Clinical Trials as Topic standards, Consensus
- Abstract
The European Society for Radiotherapy and Oncology (ESTRO) has advocated the establishment of guidelines to optimise precision radiotherapy (RT) in conjunction with contemporary therapeutics for cancer care. Quality assurance in RT (QART) plays a pivotal role in influencing treatment outcomes. Clinical trials incorporating QART protocols have demonstrated improved survival rates with minimal associated toxicity. Nonetheless, in routine clinical practice, there can be variability in the indications for RT, dosage, fractionation, and treatment planning, leading to uncertainty. In pivotal trials reporting outcomes of systemic therapy for breast cancer, there is limited information available regarding RT, and the potential interaction between modern systemic therapy and RT remains largely uncharted. This article is grounded in a consensus recommendation endorsed by ESTRO, formulated by international breast cancer experts. The consensus was reached through a modified Delphi process and was presented at an international meeting convened in Florence, Italy, in June 2023. These recommendations are regarded as both optimal and essential standards, with the latter aiming to define the minimum requirements. A template for a case report form (CRF) has been devised, which can be utilised by all clinical breast cancer trials involving RT. Optimal requirements include adherence to predefined RT planning protocols and centralised QART. Essential requirements aim to reduce variations and deviations from the guidelines in RT, even when RT is not the primary focus of the trial. These recommendations underscore the significance of implementing these practices in both clinical trials and daily clinical routines to generate high-quality data., Competing Interests: Declaration of competing interest IMe declares advisory boards supported by Eli Lilly, Novartis, Pfizer, Pierre Fabre, SeaGen, Daiichi Sankyo, Astra Zeneca. CB declares honoraria supported by declares advisory boards supported by Eli Lilly, Novartis, Pfizer, and Amgen. ML received honoraria and/or participated in advisory board from Roche, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, SeaGen, MSD, Exact Sciences, Takeda, Ipsen, Sandoz, Libbs & Knight, a travel grant from Gilead and research support to the Institution from Gilead. EdA disclosed honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca. JC disclosed consulting/advisor for Roche, Celgene, Cellestia, AstraZeneca, SeaGen, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies. NH disclosed honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sanofi, Sandoz, SeaGen. HSR disclosed institutional research support by Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Gilead Sciences Inc., GlaxoSmithKline, Lilly, Merck & Co. Inc., Novartis Pharmaceuticals Corporation, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Sermonix Pharmaceuticals Inc., Taiho Oncology Inc., and Veru Inc. GC reports personal fees for consulting, advisory role and speakers’ bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung and Daiichi Sankyo; honoraria from Ellipses Pharma and fees for travel and accommodations from Roche/Genentech and Pfizer. LV declares participation on advisory board from Daiichi Sankyo and Pfizer. ME declares advisory board supported by Pfizer and Novartis and lecture fees supported by AstraZeneca. GM declares consultancy honoraria from Roche, Novartis, AstraZeneca, Pfizer, Jensen, Lilly, and Sanofi. LDM declares consulting fees from Roche, Novartis, Eli Lilly, MSD, Daiichi Sankyo, SeaGen, Gilead, Eisai, Pierre Fabre, AstraZeneca, Stemline Menarini, Exact Sciences, Agendia, GSK, Pfizer. No other competing interests declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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32. Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.
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Weber WP, Hanson SE, Wong DE, Heidinger M, Montagna G, Cafferty FH, Kirby AM, and Coles CE
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- Humans, Female, Radiation Dose Hypofractionation, Lymphatic Metastasis, Sentinel Lymph Node Biopsy, Combined Modality Therapy, Lymph Nodes pathology, Neoplasm Staging, Neoadjuvant Therapy, Breast Neoplasms radiotherapy, Breast Neoplasms pathology, Breast Neoplasms therapy, Axilla, Lymph Node Excision
- Abstract
The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.
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- 2024
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33. The Lancet Breast Cancer Commission.
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Coles CE, Earl H, Anderson BO, Barrios CH, Bienz M, Bliss JM, Cameron DA, Cardoso F, Cui W, Francis PA, Jagsi R, Knaul FM, McIntosh SA, Phillips KA, Radbruch L, Thompson MK, André F, Abraham JE, Bhattacharya IS, Franzoi MA, Drewett L, Fulton A, Kazmi F, Inbah Rajah D, Mutebi M, Ng D, Ng S, Olopade OI, Rosa WE, Rubasingham J, Spence D, Stobart H, Vargas Enciso V, Vaz-Luis I, and Villarreal-Garza C
- Subjects
- Humans, Female, Breast Neoplasms epidemiology
- Abstract
Competing Interests: Declaration of interests CEC reports grants from Breast Cancer Now, Cancer Research UK (CRUK), Addenbrooke's Charitable Trust, and the National Institute for Health and Care Research (NIHR); participation in the Independent Data Monitoring Committees for the UK PivotalBoost trial (chair), the PROTIS phase III sinonasal proton versus IMRT trial (member), the TORPEdO Proton Beam Therapy trial (member); and a leadership role for the Lancet Breast Cancer Commission (chair). CHB reports grants and research support from AbbVie, Nektar Therapeutics, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, Henlius, Shanghai Henlius Biotech, GSK, Janssen, OBI Pharma, Eli Lilly, Seagen, Checkpoint Therapeutics, Roche, Bristol Myers Squibb, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda Pharmaceuticals, TRIO Pharmaceuticals, PharmaMar, Celgene, Myovant, PPD, Syneos Health, DOCS, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, and Medpace; ownership or stocks in Tummi and MEDSir; and participation in advisory boards and consulting activities for Boehringer Ingelheim, GSK, Novartis, Pfizer, Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Eli Lilly, Sanofi, and Daiichi Sankyo. DAC reports research grants and support from Exact Sciences and Novartis; consulting fees from Eli Lilly, Novartis, Seagen, Daiichi Sankyo, Erytech Pharma, Carnall Farrar, Sapience, and Sanofi; payment or honoraria for lectures and presentations from Exact Sciences, Gilead, Eli Lilly, and Pfizer; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, and Grail; unremunerated leadership roles for Make Seconds Count (chair of charity trustees) and the Breast International Group (chair of board of not-for-profit research organisation); and receipt of funding for analysis and medical writing for Eli Lilly and Novartis. FC reports payment or honoraria for lectures and presentations and support for attending meetings and travel from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GSK, IQVIA, Macrogenics, Medscape, MSD, Merus, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva Pharmaceuticals, and Touch Independent Medical Education; institutional financial support for clinical trials from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Fresenius, Genentech, Gilead, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, MediGene, MedImmune, MSD, Millenium, Pfizer, Pierre Fabre, Roche, Sanofi, Sonus, Tesaro, Tigris, Wilex, and Wyeth; a leadership role for the ABC Global Alliance and ABC Consensus Conference and Guidelines (president); and membership of ESMO, ESO, EORTC-BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, and ASPIC. WC reports honoraria from AstraZeneca, Pfizer, MSD, and Eisai. PAF reports a former role in the scientific advisory committee of Breast Cancer Trials Australia and New Zealand cooperative group (chair). RJ reports support from the Susan G Komen Foundation; grants from the National Institutes of Health (NIH), the Doris Duke Charitable Foundation, the Greenwall Foundation, and the American Cancer Society; serving as an expert witness for Kleinbard and Hawks Quindel Law; roles in the Board of Directors of ASCO (former member), ASTRO's Ethics Committee (chair), and the Women in Radiation Oncology Affinity Group (chair); membership on the Medical Advisory Board for Blue Cross Blue Shield Association; stock options for their advisory board role in Equity Quotient; and personal fees from the NIH, Doris Duke Charitable Foundation, and the Greenwall Foundation. FMK reports research grants from the ABC Global Alliance, Breast Cancer Now, Merck Serono WHO, MSD, Avon Cosmetics, the US Cancer Pain Relief Committee, and the Medical Research Council; consulting fees from Merck Serono and Instituto Tecnológico y de Estudios Superiores de Monterrey Mexico; and leadership roles for the Board of Directors of Women in Global Health (unpaid member), Tómatelo a Pecho (unpaid president and founder), the Mexican Health Foundation (unpaid Senior Economist), and the Board of Directors of the International Association for Hospice and Palliative Care (unpaid member). SAMcI reports grant funding from the NIHR, CRUK, and Breast Cancer Now; honoraria from Roche, MSD, AstraZeneca, Becton, Dickinson and Company; travel and conference support from Roche, Eli Lilly, and MSD; membership of advisory boards for Eli Lilly, MSD, Roche, and Novartis; and roles for the UK National Cancer Research Institute Breast Research Group (unpaid chair) and the Royal College of Surgeons Breast Surgical Specialty Lead (unpaid). K-AP reports clinical trial funding from AstraZeneca (paid to institution) and unremunerated previous participation in AstraZeneca advisory boards. LR reports grants from the European Commission Horizon 2020 and the German Research Foundation and a role in the International Association for Hospice and Palliative Care (Chair of Board of Directors). MKT reports grants from Addenbrooke's Charitable Trust and CRUK. FA reports grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Roche and consulting fees from MedImmune, Gilead, Relay Therapeutics, and Guardant Health. JEA reports speaker honoraria from AstraZeneca, Pfizer, Novartis, and Eisai and conference travel support from AstraZeneca. ISB reports participation in the Roche advisory board for ESMO. JMB reports research grants from Breast Cancer Now, AstraZeneca, MSD, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, Eli Lilly, Roche, CRUK, and the NIHR. MAF is funded by a Conquer Cancer Breast Cancer Research Foundation Career Development Award for Diversity and Inclusion supported by the Breast Cancer Research Foundation and reports financial support from the WeShare project. AF reports consultancy work for Oxford Immune Algorithmics; grants from Addenbrooke's Charitable Trust and the Ann McLaren Building Preclinical Imaging Suite of the University of Cambridge; and travel support from the University of Cambridge. DIR reports support from the University of Chicago Center for Global Health. DN reports research support from Cepheid; a grant from the US National Cancer Institute; and an unpaid leadership role with the WHO Global Breast Cancer Initiative. WER reports grants from the Cambia Health Foundation, the Robert Wood Johnson Foundation, and the Rita and Alex Hillman Foundation; and book royalties from Springer Publishing and Jones & Bartlett Learning. JR reports funding from the NIHR and support from AstraZeneca for attendance at a teaching event. DS reports a leadership role at the Jamaica Cancer Care and Research Institute (co-director). HS reports membership of the Breast Cancer Now Tissue Bank Advisory Board and voluntary patient membership of the Independent Cancer Patients' Voice charity; an honorarium from the CRUK Precision Grand Challenge; and support for travel expenses from Breast Cancer Now, CRUK, the Association of Breast Surgeons UK, and Breast International Group. IV-L reports grants from Resilience; consulting fees from Novartis, AstraZeneca, and Amgen; payment or honoraria for lectures and presentations from Novartis, Sandoz, Amgen, AstraZeneca, and Pfizer; and support for travel and attending meetings from Novartis. CV-G reports grants from AstraZeneca and Roche; consulting fees from Roche, Novartis, Pfizer, and Eli Lilly; honoraria from Roche, Myriad Genetics, and Novartis; and support for attending meetings and travel from Roche, MSD Oncology, and Pfizer. All other authors declare no competing interests.
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- 2024
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34. Challenges for breast radiotherapy with SIB: the IMPORT HIGH trial - Authors' reply.
- Author
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Coles CE, Haviland JS, Kirby AM, Griffin C, Sydenham M, and Bliss JM
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- Humans, Female, Breast Neoplasms radiotherapy
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- 2024
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35. Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.
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Shaitelman SF, Anderson BM, Arthur DW, Bazan JG, Bellon JR, Bradfield L, Coles CE, Gerber NK, Kathpal M, Kim L, Laronga C, Meattini I, Nichols EM, Pierce LJ, Poppe MM, Spears PA, Vinayak S, Whelan T, and Lyons JA
- Subjects
- Female, Humans, Breast, United States, Systematic Reviews as Topic, Brachytherapy, Breast Neoplasms radiotherapy, Carcinoma, Intraductal, Noninfiltrating, Radiotherapy, Conformal
- Abstract
Purpose: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ., Methods: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength., Results: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns., Conclusions: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI., Competing Interests: Disclosures All task force members’ disclosure statements were reviewed before being invited and were shared with other task force members throughout the guideline's development. Those disclosures are published within this guideline. Where potential conflicts were detected, remedial measures to address them were taken. Bethany Anderson: American Board of Radiology (ABR) (board examiner), Brachytherapy Journal (section editor), Clinical Breast Cancer Journal (associate editor), International Journal of Radiation Oncology, Biology, Physics (breast section associate editor), School of Breast Oncology (honoraria); Douglas Arthur: Advanced Radiation Therapy (consultant); Jose Bazan: ABR (board examiner), ASTRO VA Breast Panel (honoraria), International Journal of Radiation Oncology, Biology, Physics (breast section associate editor), Intraop Medical (institutional research); Jennifer Bellon: American Board of Radiology (ABR) (oral exam chair-ended 8/2023), Leidos Pharmaceutical (honoraria), National Cancer Institute (NCI) (research; BOLD task force on breast cancer co-chair), Oncoclinicas (honoraria), PER (honoraria), Prosigna (research), UpToDate (honoraria), Varian (honoraria); Charlotte Coles: Breast Cancer Now (research), Cancer Research UK (research), Lancet Breast Cancer Commission (chair), National Institutes of Health and Care Research (NIHR) (research; IMPORT LOW trial chief investigator); Naamit Gerber: Accuray (advisory board-ended 10/2023), Invus Group (consultant), John Theurer Cancer Center (consultant), Mount Sinai Icahn School of Medicine (honoraria-ended 8/2022), PreludeDX (research); Leonard Kim: American Associations of Physicists in Medicine (subcommittee/working group chair), ABR (board examiner), Elekta (MR-Linac Consortium, institutional representative), The Greeley Company (consultant-ended 5/2022); Christine Laronga (Society of Surgical Oncology [SSO]representative): SSO Breast Disease Site (chair), UpToDate (section editor); Janice Lyons (Chair): ABR (board examiner), Primum (consultant); Icro Meattini: Accuray, Eli Lily, Ipsen, Novartis, Pfizer, Seagen (all advisory board); Elizabeth Nichols: ABR (board examiner), Applied Radiation Oncology (editorial board), Xcision (research, co-chair); Lori Pierce (American Society of Clinical Oncology [ASCO] representative): ASCO (board chair), Breast Cancer Research Foundation (advisory board and travel), BMS Foundation DCIDCP National Advisory Committee (advisory board and travel), Damon Runyon Cancer Research Foundation (board of directors and travel), Exact Sciences (consultant), Michigan Radiation Oncology Quality Consortium (director), PER Educational Symposium (speakers bureau and travel), UpToDate (editor); Matthew Poppe: Agency for Healthcare Research and Quality (technical expert), Alliance for Breast Clinical Trials in Oncology (vice chair), Alliance for Breast Clinical Trials Local Regional Working Group (chair), Mevion (honoraria and travel-ended 3/2022), NIH (research), NIH/NCI (research-PI), PEEL Therapeutics (stock), UpToDate (editor); Simona Shaitelman (Vice Chair): Alpha Tau Medical (research-ended 2022), Artios Pharma (research-ended 2022), Becton, Dickinson & Co (consultant), Brachytherapy Journal (editorial board), Elekta (MR-Linac Consortium, institutional representative), Emerson Collective Foundation (research), Exact Sciences (research), NIH (research-ended 8/2023), TAE Life Sciences (research); Patti Spears (patient representative): Pfizer (advocate advisory care committee member-ended 12/2022); Shaveta Vinayak (ASCO representative): OncoSec Biotech (research and consultant), Pfizer, Puma Biotech, Seattle Genetics (all research); Timothy Whelan: Exact Sciences (research). Lisa Bradfield and Madeera Kathpal (Guideline Subcommittee representative) reported no disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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36. International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations.
- Author
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Meattini I, Becherini C, Caini S, Coles CE, Cortes J, Curigliano G, de Azambuja E, Isacke CM, Harbeck N, Kaidar-Person O, Marangoni E, Offersen BV, Rugo HS, Salvestrini V, Visani L, Morandi A, Lambertini M, Poortmans P, and Livi L
- Subjects
- Humans, Female, Consensus, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Radiation Oncology, Brachytherapy, Physicians
- Abstract
Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs., Competing Interests: Declaration of interests IMe declares participation in advisory boards supported by Eli Lilly, Novartis, Pfizer, Pierre Fabre, SeaGen, Daiichi Sankyo, and AstraZeneca. CB declares honoraria from Eli Lilly, and participation in advisory boards supported by Eli Lilly, Novartis, Pfizer, and Amgen. ML received honoraria from or participated in advisory boards for Roche, Novartis, Eli Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, SeaGen, Merck Sharp and Dohme, Exact Sciences, Takeda, Ipsen, Sandoz, Libbs, and Knight; received a travel grant from Gilead; and received research support for their institution from Gilead. EdA declares honoraria from or participation in advisory boards for Roche, Genentech, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Eli Lilly, and AstraZeneca. JC declares consulting or advisor roles supported by Roche, Celgene, Cellestia, AstraZeneca, SeaGen, Daiichi Sankyo, Erytech, Athenex, Polyphor, Eli Lilly, Merck Sharp and Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, and Expres2ion Biotechnologies. NH declares honoraria for lectures or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Eli Lilly, Merck Sharp and Dohme, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Sandoz, and SeaGen. HSR declares institutional research support from Astellas Pharma, AstraZeneca, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, Gilead Sciences, GSK, Eli Lilly, Merck & Co, Novartis Pharmaceuticals Corporation, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Sermonix Pharmaceuticals, Taiho Oncology, and Veru. GC reports personal fees for consulting, advisory roles, and speakers’ bureau from Roche, Genentech, Novartis, Pfizer, Eli Lilly, Foundation Medicine, Samsung, and Daiichi Sankyo; honoraria from Ellipses Pharma; and fees for travel and accommodations from Roche, Genentech, and Pfizer. LV declares participation in advisory boards from Daiichi Sankyo and Pfizer. ME declares participation in advisory boards supported by Pfizer and Novartis, and lecture fees supported by AstraZeneca. TS declares participation in advisory boards supported by Bristol Myers Squibb, Merck Sharp and Dohme, Novartis, and Pierre Fabre; and lecture fees supported by Astellas, AstraZeneca, and Bristol Myers Squibb. GM declares consultancy honoraria from Roche, Novartis, AstraZeneca, Pfizer, Jensen, Eli Lilly, and Sanofi. LDM declares consulting fees from Roche, Novartis, Eli Lilly, Merck Sharp and Dohme, Daiichi Sankyo, SeaGen, Gilead, Eisai, Pierre Fabre, AstraZeneca, Stemline Menarini, Exact Sciences, Agendia, GSK, and Pfizer. MM declares consulting fees from Cedilla Therapeutics and PharmEnable, and research support from PharmaMar, Eli Lilly, Pfizer, and Circle Pharma. SP-S declares consulting fees from Pfizer, Novartis, Eli Lilly, AstraZeneca, Gilead, Merck, Sharp and Dohme, and Roche. BP declares consulting fees from Astra Zeneca, SeaGen, Gilead, Eli Lilly, Merck Sharp and Dohme, Daiichi Sankyo, and Pierre Fabre. CS declares consulting fees from AstraZeneca, Daiichi Sankyo, Eisai Europe, Gilead, Novartis, Pharmalex, Pfizer, Phillips Health Works, Pierre Fabre, PintPharma, Puma Biotechnology, Roche Farma, SeaGen, Solti, Synthon Biopharmaceuticals, and Zymeworks. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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37. EUSOMA quality indicators for non-metastatic breast cancer: An update.
- Author
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Rubio IT, Marotti L, Biganzoli L, Aristei C, Athanasiou A, Campbell C, Cardoso F, Cardoso MJ, Coles CE, Eicher M, Harbeck N, Karakatsanis A, Offersen BV, Pijnappel R, Ponti A, Regitnig P, Santini D, Sardanelli F, Spanic T, Varga Z, Vrancken Peeters MJTFD, Wengström Y, Wyld L, and Curigliano G
- Subjects
- Humans, Female, Quality of Health Care, Quality Indicators, Health Care, Breast Neoplasms diagnostic imaging, Breast Neoplasms therapy
- Abstract
Introduction: Quality care in breast cancer is higher if patients are treated in a Breast Center with a dedicated and specialized multidisciplinary team. Quality control is an essential activity to ensure quality care, which has to be based on the monitoring of specific quality indicators. Eusoma has proceeded with the up-dating of the 2017 Quality indicators for non-metastatic breast cancer based on the new diagnostic, locoregional and systemic treatment modalities., Methods: To proceed with the updating, EUSOMA setup a multidisciplinary working group of BC experts and patients' representatives. It is a comprehensive set of QIs for early breast cancer care, which are classified as mandatory, recommended, or observational. For the first time patient reported outcomes (PROMs) have been included. As used in the 2017 EUSOMA QIs, evidence levels were based on the short version of the US Agency for Healthcare Research and Quality., Results: This is a set of quality indicators representative for the different steps of the patient pathway in non-metastatic setting, which allow Breast Centres to monitor their performance with referring standards, i.e minimum standard and target., Conclusions: Monitoring these Quality Indicators, within the Eusoma datacentre will allow to have a state of the art picture at European Breast Centres level and the development of challenging research projects., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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38. Publisher's Note to Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline (Pract Radiat Oncol. 2024;14:xxx-xxx. Epub ahead of print November 14, 2023.).
- Author
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Shaitelman SF, Anderson BM, Arthur DW, Bazan JG, Bellon JR, Bradfield L, Coles CE, Gerber NK, Kathpal M, Kim L, Laronga C, Meattini I, Nichols EM, Pierce LJ, Poppe MM, Spears PA, Vinayak S, Whelan T, and Lyons JA
- Published
- 2023
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39. Proton Beam Therapy for Early Breast Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes.
- Author
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Holt F, Probert J, Darby SC, Haviland JS, Coles CE, Kirby AM, Liu Z, Dodwell D, Ntentas G, Duane F, and Taylor C
- Subjects
- Humans, Female, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Breast Neoplasms etiology, Proton Therapy adverse effects, Proton Therapy methods
- Abstract
Purpose: Adjuvant proton beam therapy (PBT) is increasingly available to patients with breast cancer. It achieves better planned dose distributions than standard photon radiation therapy and therefore may reduce the risks. However, clinical evidence is lacking., Methods and Materials: A systematic review of clinical outcomes from studies of adjuvant PBT for early breast cancer published in 2000 to 2022 was undertaken. Early breast cancer was defined as when all detected invasive cancer cells are in the breast or nearby lymph nodes and can be removed surgically. Adverse outcomes were summarized quantitatively, and the prevalence of the most common ones were estimated using meta-analysis., Results: Thirty-two studies (1452 patients) reported clinical outcomes after adjuvant PBT for early breast cancer. Median follow-up ranged from 2 to 59 months. There were no published randomized trials comparing PBT with photon radiation therapy. Scattering PBT was delivered in 7 studies (258 patients) starting 2003 to 2015 and scanning PBT in 22 studies (1041 patients) starting 2000 to 2019. Two studies (123 patients) starting 2011 used both PBT types. For 1 study (30 patients), PBT type was unspecified. Adverse events were less severe after scanning than after scattering PBT. They also varied by clinical target. For partial breast PBT, 498 adverse events were reported (8 studies, 358 patients). None were categorized as severe after scanning PBT. For whole breast or chest wall ± regional lymph nodes PBT, 1344 adverse events were reported (19 studies, 933 patients). After scanning PBT, 4% (44/1026) of events were severe. The most prevalent severe outcome after scanning PBT was dermatitis, which occurred in 5.7% (95% confidence interval, 4.2-7.6) of patients. Other severe adverse outcomes included infection, pain, and pneumonitis (each ≤1%). Of the 141 reconstruction events reported (13 studies, 459 patients), the most prevalent after scanning PBT was prosthetic implant removal (34/181, 19%)., Conclusions: This is a quantitative summary of all published clinical outcomes after adjuvant PBT for early breast cancer. Ongoing randomized trials will provide information on its longer-term safety compared with standard photon radiation therapy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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40. One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT.
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Brunt AM, Haviland JS, Wheatley DA, Sydenham MA, Bloomfield DJ, Chan C, Cleator S, Coles CE, Donovan E, Fleming H, Glynn D, Goodman A, Griffin S, Hopwood P, Kirby AM, Kirwan CC, Nabi Z, Patel J, Sawyer E, Somaiah N, Syndikus I, Venables K, Yarnold JR, and Bliss JM
- Subjects
- Female, Humans, Mastectomy, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Radiation Dose Hypofractionation, Recurrence, Treatment Outcome, Breast Neoplasms radiotherapy, Breast Neoplasms pathology
- Abstract
Background: FAST-Forward aimed to identify a 5-fraction schedule of adjuvant radiotherapy delivered in 1 week that was non-inferior in terms of local cancer control and as safe as the standard 15-fraction regimen after primary surgery for early breast cancer. Published acute toxicity and 5-year results are presented here with other aspects of the trial., Design: Multicentre phase III non-inferiority trial. Patients with invasive carcinoma of the breast (pT1-3pN0-1M0) after breast conservation surgery or mastectomy randomised (1 : 1 : 1) to 40 Gy in 15 fractions (3 weeks), 27 Gy or 26 Gy in 5 fractions (1 week) whole breast/chest wall (Main Trial). Primary endpoint was ipsilateral breast tumour relapse; assuming 2% 5-year incidence for 40 Gy, non-inferiority pre-defined as < 1.6% excess for 5-fraction schedules (critical hazard ratio = 1.81). Normal tissue effects were assessed independently by clinicians, patients and photographs., Sub-Studies: Two acute skin toxicity sub-studies were undertaken to confirm safety of the test schedules. Primary endpoint was proportion of patients with grade ≥ 3 acute breast skin toxicity at any time from the start of radiotherapy to 4 weeks after completion. Nodal Sub-Study patients had breast/chest wall plus axillary radiotherapy testing the same three schedules, reduced to the 40 and 26 Gy groups on amendment, with the primary endpoint of 5-year patient-reported arm/hand swelling., Limitations: A sequential hypofractionated or simultaneous integrated boost has not been studied., Participants: Ninety-seven UK centres recruited 4096 patients (1361:40 Gy, 1367:27 Gy, 1368:26 Gy) into the Main Trial from November 2011 to June 2014. The Nodal Sub-Study recruited an additional 469 patients from 50 UK centres. One hundred and ninety and 162 Main Trial patients were included in the acute toxicity sub-studies., Results: Acute toxicity sub-studies evaluable patients: (1) acute grade 3 Radiation Therapy Oncology Group toxicity reported in 40 Gy/15 fractions 6/44 (13.6%); 27 Gy/5 fractions 5/51 (9.8%); 26 Gy/5 fractions 3/52 (5.8%). (2) Grade 3 common toxicity criteria for adverse effects toxicity reported for one patient. At 71-month median follow-up in the Main Trial, 79 ipsilateral breast tumour relapse events (40 Gy: 31, 27 Gy: 27, 26 Gy: 21); hazard ratios (95% confidence interval) versus 40 Gy were 27 Gy: 0.86 (0.51 to 1.44), 26 Gy: 0.67 (0.38 to 1.16). With 2.1% (1.4 to 3.1) 5-year incidence ipsilateral breast tumour relapse after 40 Gy, estimated absolute differences versus 40 Gy (non-inferiority test) were -0.3% (-1.0-0.9) for 27 Gy ( p = 0.0022) and -0.7% (-1.3-0.3) for 26 Gy ( p = 0.00019). Five-year prevalence of any clinician-assessed moderate/marked breast normal tissue effects was 40 Gy: 98/986 (9.9%), 27 Gy: 155/1005 (15.4%), 26 Gy: 121/1020 (11.9%). Across all clinician assessments from 1 to 5 years, odds ratios versus 40 Gy were 1.55 (1.32 to 1.83; p < 0.0001) for 27 Gy and 1.12 (0.94-1.34; p = 0.20) for 26 Gy. Patient and photographic assessments showed higher normal tissue effects risk for 27 Gy versus 40 Gy but not for 26 Gy. Nodal Sub-Study reported no arm/hand swelling in 80% and 77% in 40 Gy and 26 Gy at baseline, and 73% and 76% at 24 months. The prevalence of moderate/marked arm/hand swelling at 24 months was 10% versus 7% for 40 Gy compared with 26 Gy., Interpretation: Five-year local tumour incidence and normal tissue effects prevalence show 26 Gy in 5 fractions in 1 week is a safe and effective alternative to 40 Gy in 15 fractions for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer., Future Work: Ten-year Main Trial follow-up is essential. Inclusion in hypofractionation meta-analysis ongoing. A future hypofractionated boost trial is strongly supported., Trial Registration: FAST-Forward was sponsored by The Institute of Cancer Research and was registered as ISRCTN19906132., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/01/47) and is published in full in Health Technology Assessment ; Vol. 27, No. 25. See the NIHR Funding and Awards website for further award information.
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- 2023
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41. Safety profile of cyclin-dependent kinase (CDK) 4/6 inhibitors with concurrent radiation therapy: A systematic review and meta-analysis.
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Becherini C, Visani L, Caini S, Bhattacharya IS, Kirby AM, Nader Marta G, Morgan G, Salvestrini V, Coles CE, Cortes J, Curigliano G, de Azambuja E, Harbeck N, Isacke CM, Kaidar-Person O, Marangoni E, Offersen B, Rugo HS, Morandi A, Lambertini M, Poortmans P, Livi L, and Meattini I
- Subjects
- Humans, Female, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase 4, Protein Kinase Inhibitors adverse effects, Cyclin-Dependent Kinase 6, Antineoplastic Combined Chemotherapy Protocols, Radiosurgery, Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy
- Abstract
The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the standard of care for hormone receptor-positive (HR + ) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, improving survival outcomes compared to endocrine therapy alone. Abemaciclib and ribociclib, in combination with endocrine therapy, have demonstrated significant benefits in invasive disease-free survival for high-risk HR+/HER2- early breast cancer patients. Each CDK4/6i-palbociclib, ribociclib, and abemaciclib-exhibits distinct toxicity profiles. Radiation therapy (RT) can be delivered with a palliative or ablative intent, particularly using stereotactic body radiation therapy for oligometastatic or oligoprogressive disease. However, pivotal randomized trials lack information on concomitant CDK4/6i and RT, and existing preclinical and clinical data on the potential combined toxicities are limited and conflicting. As part of a broader effort to establish international consensus recommendations for integrating RT and targeted agents in breast cancer treatment, we conducted a systematic review and meta-analysis to evaluate the safety profile of combining CDK4/6i with palliative and ablative RT in both metastatic and early breast cancer settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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42. Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-analysis.
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Salvestrini V, Kim K, Caini S, Alkner S, Ekholm M, Skyttä T, Becherini C, Coles CE, Kaidar-Person O, Offersen B, de Azambuja E, Visani L, Cortes J, Harbeck N, Rugo HS, Isacke CM, Marangoni E, Morandi A, Lambertini M, Poortmans P, Livi L, and Meattini I
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- Humans, Female, Ado-Trastuzumab Emtansine adverse effects, Trastuzumab adverse effects, Receptor, ErbB-2 analysis, Receptor, ErbB-2 therapeutic use, Antibodies, Monoclonal, Humanized, Treatment Outcome, Maytansine adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology
- Abstract
Background and Purpose: In recent years, the treatment landscape for breast cancer has undergone significant advancements, with the introduction of several new anticancer agents. One such agent is trastuzumab emtansine (T-DM1), an antibody drug conjugate that has shown improved outcomes in both early and advanced breast cancer. However, there is currently a lack of comprehensive evidence regarding the safety profile of combining T-DM1 with radiation therapy (RT). In this study, we aim to provide a summary of the available data on the safety of combining RT with T-DM1 in both early and metastatic breast cancer settings., Materials and Methods: This systematic review and meta-analysis project is part of the consensus recommendations by the European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee on integrating RT with targeted treatments for breast cancer. A thorough literature search was conducted using the PUBMED/MedLine, Embase, and Cochrane databases to identify original studies focusing on the safety profile of combining T-DM1 with RT., Results: After applying eligibility criteria, nine articles were included in the meta-analysis. Pooled data from these studies revealed a high incidence of grade 3 + radionecrosis (17%), while the rates of grade 3 + radiation-related pneumonitis (<1%) and skin toxicity (1%) were found to be very low., Conclusion: Although there is some concern regarding a slight increase in pneumonitis when combining T-DM1 with postoperative RT, the safety profile of this combination was deemed acceptable for locoregional treatment in non-metastatic breast cancer. However, caution is advised when irradiating intracranial sites concurrently with T-DM1. There is a pressing need for international consensus guidelines regarding the safety considerations of combining T-DM1 and RT for breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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43. Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.
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Oladeru OT, Dunn SA, Li J, Coles CE, Yamauchi C, Chang JS, Cheng SH, Kaidar-Person O, Meattini I, Ramiah D, Kirby A, Hijal T, Marta GN, Poortmans P, Isern-Verdum J, Zissiadis Y, Offersen BV, Refaat T, Elsayad K, Hijazi H, Dengina N, Belkacemi Y, Luo FD, Lu S, Griffin C, Collins M, Ryan P, Larios D, Warren LE, Punglia RS, Wong JS, Spiegel DY, Jagsi R, Taghian A, Bellon JR, and Ho AY
- Subjects
- Humans, United States, Female, Pandemics, Reactive Oxygen Species, Surveys and Questionnaires, COVID-19 epidemiology, Carcinoma, Intraductal, Noninfiltrating, Radiation Oncology, Breast Neoplasms radiotherapy
- Abstract
Purpose: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries., Materials and Methods: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests., Results: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC., Conclusion: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.
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- 2023
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44. The role of irradiation in the management of the axilla in early breast cancer patients.
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Elumalai T, Jain U, Coles CE, and Benson JR
- Abstract
The need for axillary radiotherapy in patients with invasive breast cancer (IBC) has been a topic of great debate in the last decade. Management of the axilla has evolved significantly over the past four decades with a trend towards de-escalation of surgical interventions and the aim of reducing morbidity and enhancing QOL without compromising long-term oncology outcomes. This review article will address the role of axillary irradiation with a focus on the omission of completion axillary lymph node dissection in selected patients with sentinel lymph node (SLN) positive early breast cancer (EBC) with reference to current guidelines based on evidence to date., Competing Interests: CC is funded by the National Institute of Health and Social Care Research NIHR and supported by the NIHR Cambridge Biomedical Research Centre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elumalai, Jain, Coles and Benson.)
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- 2023
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45. Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial.
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Coles CE, Haviland JS, Kirby AM, Griffin CL, Sydenham MA, Titley JC, Bhattacharya I, Brunt AM, Chan HYC, Donovan EM, Eaton DJ, Emson M, Hopwood P, Jefford ML, Lightowlers SV, Sawyer EJ, Syndikus I, Tsang YM, Twyman NI, Yarnold JR, and Bliss JM
- Subjects
- Humans, Female, Neoplasm Staging, Neoplasm Recurrence, Local epidemiology, Breast pathology, Mastectomy, Segmental, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Breast Neoplasms pathology, Breast Diseases pathology
- Abstract
Background: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity., Methods: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants., Findings: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm
3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group)., Interpretation: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits., Funding: Cancer Research UK., Competing Interests: Declaration of interests JMB, EMD, ME, CLG, JSH, PH, MAS, JCT, and YT report grants from Cancer Research UK during the conduct of the study. SVL reports PhD funding from Cancer Research UK. JMB reports grants and non-financial support from AstraZeneca, Clovis Oncology, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis (previously GlaxoSmithKline), Pfizer, Puma Biotechnology, and Roche outside the submitted work. CEC reports grants from National Institute for Health Research Efficacy and Mechanism Evaluation, RADNET, the Lancet Breast Cancer Commission, and Addenbrooke's Charitable Trust outside the submitted work. CEC also reports membership of five external independent monitoring committees and is Chair of the Lancet Breast Cancer Commission. AMK is President of the European Society of Radiation Oncology. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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46. Should patients requiring radiotherapy for breast cancer be treated with proton beam therapy?
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Kirby AM, Holt F, Taylor CW, Haviland JS, MacKenzie M, and Coles CE
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- Humans, Female, Radiotherapy Dosage, Proton Therapy, Breast Neoplasms radiotherapy, Breast Neoplasms etiology, Radiotherapy, Intensity-Modulated adverse effects
- Abstract
Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests can be found here: https://www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf.
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- 2023
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47. Equity, Diversity, and Inclusion in Radiation Oncology: A Bibliometric Analysis and Critical Review.
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Franco P, De Felice F, Kaidar-Person O, Gabrys D, Marta GN, Banini M, Livi L, Jagsi R, Coles CE, Poortmans P, and Meattini I
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- Humans, Diversity, Equity, Inclusion, Medical Oncology, Bibliometrics, Radiation Oncology
- Abstract
The promotion of equity, diversity, and inclusion (EDI) is being increasingly pursued in health care, both in general and within radiation oncology. Because bibliometrics is a powerful tool to reveal the scientific literature on a specific topic during a certain timespan, a systematic bibliometric analysis of the documents published on EDI in radiation oncology was performed, aiming at exploring common patterns in research and emerging trends, tracking collaborations and networks, and anticipating future directions in clinical research. Standard descriptive statistics and bibliometric techniques were used in the analysis. A collaboration network and thematic map were generated from the data. Four domains were represented: (1) motor themes, including themes well developed and important for the structuring of the research field; (2) niche themes, representing the isolated topics that do not share important external links with other themes; (3) emerging themes, referring to still weakly developed topics; and (4) basic themes, including the essential topics. EDI in the profession of radiation oncology is essential to ensure that the workforce delivering radiation oncology care both draws from the full talent pool of human capital and delivers the highest quality science and clinical care to all patients. The burgeoning literature on EDI in radiation oncology suggests that a large and growing cohort of scholars within radiation oncology are dedicated to addressing these important challenges., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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48. Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study.
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Dave RV, Elsberger B, Taxiarchi VP, Gandhi A, Kirwan CC, Kim B, Camacho EM, Coles CE, Copson E, Courtney A, Horgan K, Fairbrother P, Holcombe C, Kirkham JJ, Leff DR, McIntosh SA, O'Connell R, Pardo R, Potter S, Rattay T, Sharma N, Vidya R, and Cutress RI
- Subjects
- Humans, Female, Pandemics, Ki-67 Antigen metabolism, Cohort Studies, Prognosis, Neoadjuvant Therapy, Breast Neoplasms drug therapy, Breast Neoplasms surgery, COVID-19
- Abstract
Purpose: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources., Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb-July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis., Results: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32-81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7-8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months' treatment duration; median of 4 mm [IQR - 20, 4]. In a small subset of patients (n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month's duration of BrET., Discussion: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials., (© 2023. The Author(s).)
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- 2023
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49. Use of tumour bed boost radiotherapy in volume replacement oncoplastic breast surgery: A systematic review.
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Garreffa E, Meattini I, Coles CE, and Agrawal A
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- Humans, Female, Mastectomy, Segmental, Radiotherapy, Adjuvant, Breast pathology, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Breast Neoplasms pathology
- Abstract
Tumour bed boost radiotherapy (RT) following breast conserving surgery reduces local recurrence in high-risk disease. There is recent debate over challenges to accurately localise tumour bed for RT boost delivery following volume replacement oncoplastic breast surgery (VR-OBS). This review evaluates the reporting of RT boost following VR-OBS in the literature published between January 2010 and December 2021. This review was in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Nine studies met the inclusion criteria (n = 670 patients), and RT boost was used in eight studies. Boost was administered in total to 384 patients (62.5% of irradiated patients). Only two studies reported boost planned target volumes and only one compared these against surgical specimen volumes. RT boost was not reported in most published studies on VR-OBS. Future prospective research are strongly needed to evaluate long-term outcomes of VR-OBS following RT boost, especially on breast cosmesis and patients' satisfaction., Competing Interests: Declaration of Competing Interest None of the authors or collaborators declared any conflict of interest related to this project., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)
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- 2023
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50. Proton Beam Therapy in Breast Cancer Patients: The UK PARABLE Trial is Recruiting.
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Kirby AM, Haviland JS, Mackenzie M, Fleming H, Anandadas C, Wickers S, Miles E, Iles N, Bliss JM, and Coles CE
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- Humans, Female, Radiotherapy Dosage, United Kingdom epidemiology, Breast Neoplasms radiotherapy, Proton Therapy
- Published
- 2023
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