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. 2023 Nov;27(25):1–176. doi: 10.3310/WWBF1044

One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT.

Adrian Murray Brunt, Joanne S Haviland, Duncan A Wheatley, Mark A Sydenham, David J Bloomfield, Charlie Chan, Suzy Cleator, Charlotte E Coles, Ellen Donovan, Helen Fleming, David Glynn, Andrew Goodman, Susan Griffin, Penelope Hopwood, Anna M Kirby, Cliona C Kirwan, Zohal Nabi, Jaymini Patel, Elinor Sawyer, Navita Somaiah, Isabel Syndikus, Karen Venables, John R Yarnold, Judith M Bliss; FAST-Forward Trial Management Group
PMCID: PMC11017153  PMID: 37991196

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.

Plain language summary

Patients diagnosed with early breast cancer are often recommended to have radiotherapy after surgery because research has shown that it lowers the risk of the cancer returning. However, it may cause some short- and long-term side effects. Previous clinical trials showed that the same, or even better, outcomes with a lower total dose of radiotherapy given in fewer, larger daily doses compared with older historical treatment schedules. The National Institute for Health and Care Research Health Technology Assessment Programme-funded FAST-Forward Trial aimed to see whether the number of doses could be reduced further without reducing the beneficial effects of radiotherapy. Between November 2011 and June 2014, 4096 patients agreed to take part in the FAST-Forward Main Trial testing three schedules of radiotherapy to the breast. Standard treatment given on 15 days over 3 weeks (Control Group) was compared with two different lower dose schedules where treatment was given on 5 days over 1 week (lower dose Test Groups). An additional 469 patients entered a sub-study where the gland area under the arm also received radiotherapy (Nodal Sub-Study). Main Trial 5-year results reported in April 2020 showed that the number of patients whose cancer had returned in the treated breast was low in all groups: around 2 in 100 (2.1%) for the Control Group, and 1.7% in the higher dose and 1.4% in the lower dose Test Groups. The majority of reported side effects assessed by patients and doctors up to 5 years after radiotherapy were mild for all treatment groups. Patients in the Control Group and in the lower dose Test Group experienced similar levels of side effects. More side effects were reported in the higher dose Test Group, although differences were small. Overall, the FAST-Forward findings suggest that the lower dose 1-week schedule gave similar results in terms of the cancer returning and side effects to the standard 3-week treatment and this schedule can now be used to help treat future patients.

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References

  1. Brunt AM, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet 2020;395:1613–26. https://doi.org/10.1016/s0140-6736(20)30932-6 doi: 10.1016/S0140-6736(20)30932-6. [DOI] [PMC free article] [PubMed]
  2. Brunt AM, Haviland JS, Kirby AM, Somaiah N, Wheatley DA, Bliss JM, Yarnold JR. Five-fraction radiotherapy for breast cancer: FAST-Forward to Implementation. Clin Oncol (R Coll Radiol) 2021;33:430–9. https://doi.org/10.1016/j.clon.2021.04.016 doi: 10.1016/j.clon.2021.04.016. [DOI] [PubMed]
  3. Brunt AM, Wheatley D, Yarnold J, Somaiah N, Kelly S, Harnett A, et al.; FAST-Forward Trial Management Group. Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial. Radiother Oncol 2016;120:114–8. https://doi.org/10.1016/j.radonc.2016.02.027 doi: 10.1016/j.radonc.2016.02.027. [DOI] [PMC free article] [PubMed]
  4. Brunt AM, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield D, et al.; NIHR National Institute for Health and Care Research Funding & Awards. Fast-Forward: A Randomised Clinical Trial Testing a 1-Week Course of Curative Whole Breast Radiotherapy against a Standard 3-Week Schedule in Terms of Local Cancer Control and Late Adverse Effects in Women with Early Breast Cancer (Award ID 09/01/47). URL: https://fundingawards.nihr.ac.uk/award/09/01/47 (accessed 8 September 2022).
  5. Cancer Research UK. Breast Cancer Statistics. 2022. URL: www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer#heading-Zero (accessed 27 May 2022).
  6. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al.; Early Breast Cancer Trialists’ Collaborative G. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 2011;378:1707–16. https://doi.org/10.1016/S0140-6736(11)61629-2 doi: 10.1016/S0140-6736(11)61629-2. [DOI] [PMC free article] [PubMed]
  7. Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, et al. A randomised controlled trial of postoperative radiotherapy following breast-conserving surgery in a minimum-risk older population. The PRIME trial. Health Technol Assess 2007;11:1–149, iii–iv. https://doi.org/10.3310/hta11310 doi: 10.3310/hta11310. [DOI] [PubMed]
  8. Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al.; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet 2016;387:229–38. https://doi.org/10.1016/s0140-6736(15)00471-7 doi: 10.1016/S0140-6736(15)00471-7. [DOI] [PubMed]
  9. Polgár C, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, et al.; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol 2017;18:259–68. https://doi.org/10.1016/s1470-2045(17)30011-6 doi: 10.1016/S1470-2045(17)30011-6. [DOI] [PubMed]
  10. Schäfer R, Strnad V, Polgár C, Uter W, Hildebrandt G, Ott OJ, et al.; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial. Lancet Oncol 2018;19:834–44. https://doi.org/10.1016/s1470-2045(18)30195-5 doi: 10.1016/S1470-2045(18)30195-5. [DOI] [PubMed]
  11. Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer 2015;51:451–63. https://doi.org/10.1016/j.ejca.2014.12.013 doi: 10.1016/j.ejca.2014.12.013. [DOI] [PubMed]
  12. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al.; IMPORT Trialists. 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. Lancet 2017;390:1048–60. https://doi.org/10.1016/S0140-6736(17)31145-5 doi: 10.1016/S0140-6736(17)31145-5. [DOI] [PMC free article] [PubMed]
  13. Bates TD. The 10-year results of a prospective trial of post-operative radiotherapy delivered in 3 fractions per week versus 2 fractions per week in breast carcinoma. Br J Radiol 1988;61:625–30. https://doi.org/10.1259/0007-1285-61-727-625 doi: 10.1259/0007-1285-61-727-625. [DOI] [PubMed]
  14. Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143–50. https://doi.org/10.1093/jnci/94.15.1143 doi: 10.1093/jnci/94.15.1143. [DOI] [PubMed]
  15. Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson J, et al. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol 2005;75:9–17. https://doi.org/10.1016/j.radonc.2005.01.005 doi: 10.1016/j.radonc.2005.01.005. [DOI] [PubMed]
  16. Owen JR, Ashton A, Bliss JM, Homewood J, Harper C, Hanson J, et al. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. Lancet Oncol 2006;7:467–71. https://doi.org/10.1016/S1470-2045(06)70699-4 doi: 10.1016/S1470-2045(06)70699-4. [DOI] [PubMed]
  17. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, et al.; START Trialists’ Group. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 2008;9:331–41. https://doi.org/10.1016/S1470-2045(08)70077-9 doi: 10.1016/S1470-2045(08)70077-9. [DOI] [PMC free article] [PubMed]
  18. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, et al. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 2008;371:1098–107. https://doi.org/10.1016/S0140-6736(08)60348-7 doi: 10.1016/S0140-6736(08)60348-7. [DOI] [PMC free article] [PubMed]
  19. James ML, Lehman M, Hider PN, Jeffery M, Francis DP, Hickey BE. Fraction size in radiation treatment for breast conservation in early breast cancer. Cochrane Database Syst Rev 2008;3:CD003860. https://doi.org/10.1002/14651858.CD003860.pub2 doi: 10.1002/14651858.CD003860.pub2. [DOI] [PubMed]
  20. Courdi A, Ortholan C, Hannoun-Levi JM, Ferrero JM, Largillier R, Balu-Maestro C, et al. Long-term results of hypofractionated radiotherapy and hormonal therapy without surgery for breast cancer in elderly patients. Radiother Oncol 2006;79:156–61. https://doi.org/10.1016/j.radonc.2006.04.005 doi: 10.1016/j.radonc.2006.04.005. [DOI] [PubMed]
  21. Kirova YM, Campana F, Savignoni A, Laki F, Muresan M, Dendale R, et al.; Institut Curie Breast Cancer Study Group. Breast-conserving treatment in the elderly: long-term results of adjuvant hypofractionated and normofractionated radiotherapy. Int J Radiat Oncol Biol Phys 2009;75:76–81. https://doi.org/10.1016/j.ijrobp.2008.11.005 doi: 10.1016/j.ijrobp.2008.11.005. [DOI] [PubMed]
  22. Brunt AM, Sydenham M, Bliss J, Coles C, Gothard L, Harnett A, et al. A 5-fraction regimen of adjuvant radiotherapy for women with early breast cancer: first analysis of the randomised UK FAST trial (ISRCTN62488883, CRUKE/04/015. EJC Suppl 2009;7(3):2. https://doi.org/10.1016/S1359-6349(09)72026-9
  23. Brunt AM, Haviland JS, Sydenham M, Agrawal RK, Algurafi H, Alhasso A, et al. Ten-year results of FAST: a randomized controlled trial of 5-fraction whole breast radiotherapy for early breast cancer. J Clin Oncol 2020;38:3261–72. https://doi.org/10.1200/JCO.19.02750 doi: 10.1200/JCO.19.02750. [DOI] [PMC free article] [PubMed]
  24. Huang J, Barbera L, Brouwers M, Browman G, Mackillop WJ. Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol 2003;21:555–63. doi: 10.1200/JCO.2003.04.171. [DOI] [PubMed]
  25. Hebert-Croteau N, Freeman CR, Latreille J, Brisson J. Delay in adjuvant radiation treatment and outcomes of breast cancer – a review. Breast Cancer Res Treat 2002;74:77–94. doi: 10.1023/a:1016089215070. [DOI] [PubMed]
  26. Martin S, Mannino M, Rostom A, Tait D, Donovan E, Eagle S, et al. Acute toxicity and 2-year adverse effects of 30 Gy in five fractions over 15 days to whole breast after local excision of early breast cancer. Clin Oncol (R Coll Radiol) 2008;20:502–5. https://doi.org/10.1016/j.clon.2008.04.020 doi: 10.1016/j.clon.2008.04.020. [DOI] [PubMed]
  27. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al.; Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087–106. https://doi.org/10.1016/S0140-6736(05)67887-7 doi: 10.1016/S0140-6736(05)67887-7. [DOI] [PubMed]
  28. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial. JAMA 2011;305:569–75. https://doi.org/10.1001/jama.2011.90 doi: 10.1001/jama.2011.90. [DOI] [PMC free article] [PubMed]
  29. Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al.; International Breast Cancer Study Group Trial 23-01 investigators. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 2013;14:297–305. https://doi.org/10.1016/s1470-2045(13)70035-4 doi: 10.1016/S1470-2045(13)70035-4. [DOI] [PMC free article] [PubMed]
  30. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 2014;15:1303–10. https://doi.org/10.1016/S1470-2045(14)70460-7 doi: 10.1016/S1470-2045(14)70460-7. [DOI] [PMC free article] [PubMed]
  31. Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, et al.; EORTC Radiation Oncology and Breast Cancer Groups. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 2015;373:317–27. https://doi.org/10.1056/NEJMoa1415369 doi: 10.1056/NEJMoa1415369. [DOI] [PubMed]
  32. Stoll BA, Andrews JT. Radiation-induced peripheral neuropathy. Br Med J 1966;1:834–7. https://doi.org/10.1136/bmj.1.5491.834 doi: 10.1136/bmj.1.5491.834. [DOI] [PMC free article] [PubMed]
  33. Barr LC, Kissin MW. Radiation-induced brachial plexus neuropathy following breast conservation and radical radiotherapy. Br J Surg 1987;74:855–6. https://doi.org/10.1002/bjs.1800740935 doi: 10.1002/bjs.1800740935. [DOI] [PubMed]
  34. Basso-Ricci S, della Costa C, Viganotti G, Ventafridda V, Zanolla R. Report on 42 cases of postirradiation lesions of the brachial plexus and their treatment. Tumori 1980;66:117–22. doi: 10.1177/030089168006600113. [DOI] [PubMed]
  35. Johansson S, Svensson H, Denekamp J. Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients. Int J Radiat Oncol Biol Phys 2000;48:745–50. https://doi.org/10.1016/s0360-3016(00)00674-x doi: 10.1016/s0360-3016(00)00674-x. [DOI] [PubMed]
  36. Powell S, Cooke J, Parsons C. Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules. Radiother Oncol 1990;18:213–20. https://doi.org/10.1016/0167-8140(90)90057-4 doi: 10.1016/0167-8140(90)90057-4. [DOI] [PubMed]
  37. Hoeller U, Bonacker M, Bajrovic A, Alberti W, Adam G. Radiation-induced plexopathy and fibrosis. Is magnetic resonance imaging the adequate diagnostic tool? Strahlenther Onkol 2004;180:650–4. https://doi.org/10.1007/s00066-004-1240-3 doi: 10.1007/s00066-004-1240-3. [DOI] [PubMed]
  38. Fairchild AM, Weir LM, Mates D, Olivotto IA. Locoregional radiation for high-risk breast cancer-results of short fractionation. Breast Cancer Res Treat 2000;64:Abstract 38.
  39. Livsey JE, Magee B, Stewart AL, Swindell R. Axillary recurrence following conservative surgery and radiotherapy in early breast cancer. Clin Oncol (R Coll Radiol) 2000;12:309–14. https://doi.org/10.1053/clon.2000.9181 doi: 10.1053/clon.2000.9181. [DOI] [PubMed]
  40. Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956–62. https://doi.org/10.1056/NEJM199710023371402 doi: 10.1056/NEJM199710023371402. [DOI] [PubMed]
  41. Olsen NK, Pfeiffer P, Johannsen L, Schroder H, Rose C. Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients. Int J Radiat Oncol Biol Phys 1993;26:43–9. https://doi.org/10.1016/0360-3016(93)90171-q doi: 10.1016/0360-3016(93)90171-q. [DOI] [PubMed]
  42. Delouche G, Bachelot F, Premont M, Kurtz JM. Conservation treatment of early breast cancer: long term results and complications. Int J Radiat Oncol Biol Phys 1987;13:29–34. https://doi.org/10.1016/0360-3016(87)90256-2 doi: 10.1016/0360-3016(87)90256-2. [DOI] [PubMed]
  43. Fowble BL, Solin LJ, Schultz DJ, Goodman RL. Ten year results of conservative surgery and irradiation for stage I and II breast cancer. Int J Radiat Oncol Biol Phys 1991;21:269–77. https://doi.org/10.1016/0360-3016(91)90771-u doi: 10.1016/0360-3016(91)90771-u. [DOI] [PubMed]
  44. Pierce SM, Recht A, Lingos TI, Abner A, Vicini F, Silver B, et al. Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys 1992;23:915–23. https://doi.org/10.1016/0360-3016(92)90895-o doi: 10.1016/0360-3016(92)90895-o. [DOI] [PubMed]
  45. Galecki J, Hicer-Grzenkowicz J, Grudzien-Kowalska M, Michalska T, Zalucki W. Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant irradiation of patients with breast cancer – a review. Acta Oncol 2006;45:280–4. https://doi.org/10.1080/02841860500371907 doi: 10.1080/02841860500371907. [DOI] [PubMed]
  46. Chen AM, Hall WH, Li BQ, Guiou M, Wright C, Mathai M, et al. Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer. Br J Radiol 2011;84:58–63. https://doi.org/10.1259/bjr/62332495 doi: 10.1259/bjr/62332495. [DOI] [PMC free article] [PubMed]
  47. The FAST Trialists Group, JM) mB. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol 2011;100:93–100. https://doi.org/10.1016/j.radonc.2011.06.026 doi: 10.1016/j.radonc.2011.06.026. [DOI] [PubMed]
  48. Weis J, Arraras JI, Conroy T, Efficace F, Fleissner C, Gorog A, et al. Development of an EORTC quality of life phase III module measuring cancer-related fatigue (EORTC QLQ-FA13). Psychooncology 2012;22(5):1002–7. https://doi.org/10.1002/pon.3092 doi: 10.1002/pon.3092. [DOI] [PubMed]
  49. Haviland JS, Ashton A, Broad B, Gothard L, Owen JR, Tait D, et al. Evaluation of a method for grading late photographic change in breast appearance after radiotherapy for early breast cancer. Clin Oncol (R Coll Radiol) 2008;20:497–501. https://doi.org/10.1016/j.clon.2008.03.017 doi: 10.1016/j.clon.2008.03.017. [DOI] [PubMed]
  50. National Institute for Health and Care Excellence (NICE). Early and locally advanced breast cancer: diagnosis and management (NICE Guideline 101). London: National Institute for Health and Care Excellence (NICE); 2018.
  51. Brunt AM, Haviland J, Sydenham M, Al-hasso A, Bloomfield D, Chan C, et al. OC-0595: FAST-Forward phase 3 RCT of 1-week hypofractionated breast radiotherapy:3-year normal tissue effects. Radiother Oncol 2018;127:S311–2. https://doi.org/10.1016/S0167-8140(18)30905-8
  52. Horiot JC, van der Schueren E, Johansson KA, Bernier J, Bartelink H. The programme of quality assurance of the EORTC radiotherapy group. A historical overview. Radiother Oncol 1993;29:81–4. doi: 10.1016/0167-8140(93)90229-2. [DOI] [PubMed]
  53. Bolla M, Bartelink H, Garavaglia G, Gonzalez D, Horiot JC, Johansson KA, et al. EORTC guidelines for writing protocols for clinical trials of radiotherapy. Radiother Oncol 1995;36:1–8. https://doi.org/10.1016/0167-8140(95)01573-y doi: 10.1016/0167-8140(95)01573-y. [DOI] [PubMed]
  54. Bleehen NM (Chair). Quality Assurance in Radiotherapy; Report of a Working Party. Standing Medical Advisory Committee (SMAC); 1991. URL: https://depositedpapers.parliament.uk/depositedpaper/2212040/details
  55. Aird EG, Williams C, Mott GT, Dische S, Saunders MI. Quality assurance in the CHART clinical trial. Radiother Oncol 1995;36:235–44. https://doi.org/10.1016/0167-8140(95)01598-b doi: 10.1016/0167-8140(95)01598-b. [DOI] [PubMed]
  56. Venables K, Winfield E, Deighton A, Aird E, Hoskin P; START Trial management group. The START trial-measurements in semi-anatomical breast and chest wall phantoms. Phys Med Biol 2001;46:1937–48. doi: 10.1088/0031-9155/46/7/314. [DOI] [PubMed]
  57. IPEM. 81 Physics Aspects of Quality Control in Radiotherapy. IPEM Report. York: IPEM 1999.
  58. Zotova R, Conibear J, Tsang Y. PD-0317: Field-based and volume-based PTV as plan evaluation structures in the UK FAST-Forward breast trial. Radiother Oncol 2013;106:S122. https://doi.org/10.1016/S0167-8140(15)32623-2
  59. Zotova R, Tsang Y.M., Miles E., Yarnold J.R. Interim Analysis of treatment plans in the FAST – Forward hypofractionation breast radiotherapy trial. Paper presented at: UK Radiation Oncology 13, Nottingham, UK.
  60. Zotova R, Yarnold J, Wheatley D, Griffin C, Murray B. PD-0430: Results from the radiotherapy quality assurance programme for the FAST-Forward breast trial. Radiother Oncol 2015;115:S209–10. https://doi.org/10.1016/S0167-8140(15)40426-8
  61. Megias D, Sydenham M, Wheatley D, Maclennan M, Spezi E, Brunt AM. OC-0265: Evaluating variability of contouring using ESTRO guidelines for elective breast cancer radiotherapy. Radiother Oncol 2017;123:S136–7. https://doi.org/10.1016/S0167-8140(17)30708-9
  62. Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A, et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol 2015;114:3–10. https://doi.org/10.1016/j.radonc.2014.11.030 doi: 10.1016/j.radonc.2014.11.030. [DOI] [PubMed]
  63. Miles E, Venables K. Radiotherapy quality assurance: facilitation of radiotherapy research and implementation of technology. Clin Oncol (R Coll Radiol) 2012;24:710–2. https://doi.org/10.1016/j.clon.2012.06.006 doi: 10.1016/j.clon.2012.06.006. [DOI] [PubMed]
  64. Van Gestel D, Dragan T, Gregoire V, Evans M, Budach V. Radiotherapy Quality Assurance for Head and Neck Squamous Cell Carcinoma. Front Oncol 2020;10:282. https://doi.org/10.3389/fonc.2020.00282 doi: 10.3389/fonc.2020.00282. [DOI] [PMC free article] [PubMed]
  65. Turesson I, Notter G, Wickstrom I, Johansson KA, Eklund S. The influence of irradiation time per treatment session on acute and late skin reactions: a study on human skin. Radiother Oncol 1984;2:235–45. https://doi.org/10.1016/s0167-8140(84)80064-x doi: 10.1016/s0167-8140(84)80064-x. [DOI] [PubMed]
  66. Turesson I, Thames HD. Repair capacity and kinetics of human skin during fractionated radiotherapy: erythema, desquamation, and telangiectasia after 3 and 5 year’s follow-up. Radiother Oncol 1989;15:169–88. https://doi.org/10.1016/0167-8140(89)90131-x doi: 10.1016/0167-8140(89)90131-x. [DOI] [PubMed]
  67. Nyman J, Turesson I. Does the interval between fractions matter in the range of 4–8 h in radiotherapy? A study of acute and late human skin reactions. Radiother Oncol 1995;34:171–8. https://doi.org/10.1016/0167-8140(95)01525-l doi: 10.1016/0167-8140(95)01525-l. [DOI] [PubMed]
  68. National Institute of Health and Care Excellence. Guide to the Methods of Technology Appraisal 2013. Process and Methods [PMG9]. 2013. [PubMed]
  69. Curtis L, Burns A. Unit Costs of Health and Social Care 2019. Canterbury: University of Kent; 2019.
  70. Alarid-Escudero F, Krijkamp EM, Enns EA, Hunink M, Pechlivanoglou P, Jalal H. Cohort state-transition models in R: From conceptualization to implementation. 2020. https://doi.org/10.48550/arXiv.2001.07824
  71. Team RC. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.
  72. England N. 2018/2019 National Cost Collection data. London: NHS England and NHS Improvement; 2020.
  73. Bartlett FR, Colgan RM, Carr K, Donovan EM, McNair HA, Locke I, et al. The UK HeartSpare Study: randomised evaluation of voluntary deep-inspiratory breath-hold in women undergoing breast radiotherapy. Radiother Oncol 2013;108:242–7. https://doi.org/10.1016/j.radonc.2013.04.021 doi: 10.1016/j.radonc.2013.04.021. [DOI] [PubMed]
  74. Bartlett FR, Donovan EM, McNair HA, Corsini LA, Colgan RM, Evans PM, et al. The UK HeartSpare Study (Stage II): Multicentre Evaluation of a Voluntary Breath-hold Technique in Patients Receiving Breast Radiotherapy. Clin Oncol (R Coll Radiol) 2017;29:e51–6. https://doi.org/10.1016/j.clon.2016.11.005 doi: 10.1016/j.clon.2016.11.005. [DOI] [PubMed]
  75. StataCorp. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC; 2019.
  76. Latimer N. NICE DSU Technical Support Document 14: Survival Analysis for Economic Evaluations Alongside Clinical Trials-Extrapolation with Patient-level Data. University of Sheffield, UK: School of Health and Related Research; 2011. [PubMed]
  77. Royal College of Radiologists (RCR). Postoperative Radiotherapy for Breast Cancer: UK Consensus Statements. London: The Royal College of Radiologists; 2016. doi: 10.1016/j.clon.2017.06.011. [DOI] [PubMed]
  78. Office for National Statistics (ONS). National Life Tables: UK; 2019.
  79. Deluche E, Antoine A, Bachelot T, Lardy-Cleaud A, Dieras V, Brain E, et al. Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008–2016. Eur J Cancer 2020;129:60–70. https://doi.org/10.1016/j.ejca.2020.01.016 doi: 10.1016/j.ejca.2020.01.016. [DOI] [PubMed]
  80. de Bock GH, Putter H, Bonnema J, van der Hage JA, Bartelink H, van de Velde CJ. The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model. Breast Cancer Res Treat 2009;117:401–8. https://doi.org/10.1007/s10549-008-0300-2 doi: 10.1007/s10549-008-0300-2. [DOI] [PubMed]
  81. Faria R, Gomes M, Epstein D, White IR. A guide to handling missing data in cost-effectiveness analysis conducted within randomised controlled trials. PharmacoEcon 2014;32:1157–70. https://doi.org/10.1007/s40273-014-0193-3 doi: 10.1007/s40273-014-0193-3. [DOI] [PMC free article] [PubMed]
  82. England N. 2012/2013 National Cost Collection Data. London: NHS England and NHS Improvement; 2014.
  83. Picot J, Copley V, Colquitt JL, Kalita N, Hartwell D, Bryant J. The INTRABEAM® Photon Radiotherapy System for the adjuvant treatment of early breast cancer: a systematic review and economic evaluation. Health Technol Assess 2015;19(69):1–190. https://doi.org/10.3310/hta19690 doi: 10.3310/hta19690. [DOI] [PMC free article] [PubMed]
  84. NHS Digital. National Mastectomy and Breast Reconstruction Audit, Fourth Annual Report; 2011.
  85. Thomas RJ, Williams M, Marshall C, Glen J, Callam M. The total hospital and community UK costs of managing patients with relapsed breast cancer. Br J Cancer 2009;100:598–600. https://doi.org/10.1038/sj.bjc.6604911 doi: 10.1038/sj.bjc.6604911. [DOI] [PMC free article] [PubMed]
  86. Perry-Duxbury M, Asaria M, Lomas J, van Baal P. Cured today, ill tomorrow: A method for including future unrelated medical costs in economic evaluation in England and Wales. Value Health 2020;23:1027–33. https://doi.org/10.1016/j.jval.2020.05.006 doi: 10.1016/j.jval.2020.05.006. [DOI] [PubMed]
  87. van Hout B, Janssen MF, Feng YS, Kohlmann T, Busschbach J, Golicki D, et al. Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets. Value Health 2012;15:708–15. https://doi.org/10.1016/j.jval.2012.02.008 doi: 10.1016/j.jval.2012.02.008. [DOI] [PubMed]
  88. Campbell HE, Epstein D, Bloomfield D, Griffin S, Manca A, Yarnold J, et al. The cost-effectiveness of adjuvant chemotherapy for early breast cancer: A comparison of no chemotherapy and first, second, and third generation regimens for patients with differing prognoses. Eur J Cancer 2011;47:2517–30. https://doi.org/10.1016/j.ejca.2011.06.019 doi: 10.1016/j.ejca.2011.06.019. [DOI] [PubMed]
  89. Ara R, Brazier JE. Populating an economic model with health state utility values: moving toward better practice. Value Health 2010;13:509–18. https://doi.org/10.1111/j.1524-4733.2010.00700.x doi: 10.1111/j.1524-4733.2010.00700.x. [DOI] [PubMed]
  90. NHS Quality Improvement Scotland. Best Practice Statement: Skincare of Patients Receiving Radiotherapy; 2010.
  91. Claxton K, Martin S, Soares M, Rice N, Spackman E, Hinde S, et al. Methods for the estimation of the National Institute for Health and Care Excellence cost-effectiveness threshold. Health Technol Assess 2015;19:1–503, v. https://doi.org/10.3310/hta19140 doi: 10.3310/hta19140. [DOI] [PMC free article] [PubMed]
  92. Lomas J, Martin S, Claxton K. Estimating the marginal productivity of the English National Health Service from 2003 to 2012. Value Health 2019;22:995–1002. https://doi.org/10.1016/j.jval.2019.04.1926 doi: 10.1016/j.jval.2019.04.1926. [DOI] [PubMed]
  93. Buyukkaramikli NC, Rutten-van Molken M, Severens JL, Al M TECH-VER: A verification checklist to reduce errors in models and improve their credibility. PharmacoEcon 2019;37:1391–408. https://doi.org/10.1007/s40273-019-00844-y doi: 10.1007/s40273-019-00844-y. [DOI] [PMC free article] [PubMed]
  94. Karnon J, Kerr GR, Jack W, Papo NL, Cameron DA. Health care costs for the treatment of breast cancer recurrent events: estimates from a UK-based patient-level analysis. Br J Cancer 2007;97:479–85. https://doi.org/10.1038/sj.bjc.6603887 doi: 10.1038/sj.bjc.6603887. [DOI] [PMC free article] [PubMed]
  95. Rautalin M, Färkkilä N, Sintonen H, Saarto T, Taari K, Jahkola T, et al. Health-related quality of life in different states of breast cancer – comparing different instruments. Acta Oncol 2018;57:622–8. https://doi.org/10.1080/0284186X.2017.1400683 doi: 10.1080/0284186X.2017.1400683. [DOI] [PubMed]
  96. Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, et al. The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study. Lancet Oncol 2021;22:309–20. https://doi.org/10.1016/S1470-2045(20)30743-9 doi: 10.1016/S1470-2045(20)30743-9. [DOI] [PMC free article] [PubMed]
  97. Williams C, Lewsey JD, Briggs AH, Mackay DF. Cost-effectiveness analysis in R using a multi-state modeling survival analysis framework: A tutorial. Med Decis Making 2017;37:340–52. https://doi.org/10.1177/0272989x16651869 doi: 10.1177/0272989X16651869. [DOI] [PMC free article] [PubMed]
  98. Crowther MJ, Lambert PC. Parametric multistate survival models: Flexible modelling allowing transition-specific distributions with application to estimating clinically useful measures of effect differences. Stat Med 2017;36:4719–42. https://doi.org/10.1002/sim.7448 doi: 10.1002/sim.7448. [DOI] [PubMed]
  99. Moeschberger ML, Klein JP. Statistical methods for dependent competing risks. Lifetime Data Anal 1995;1:195–204. https://doi.org/10.1007/BF00985770 doi: 10.1007/BF00985770. [DOI] [PubMed]
  100. Gelman R, Gelber R, Henderson IC, Coleman CN, Harris JR. Improved methodology for analyzing local and distant recurrence. J Clin Oncol 1990;8:548–55. https://doi.org/10.1200/JCO.1990.8.3.548 doi: 10.1200/JCO.1990.8.3.548. [DOI] [PubMed]
  101. Deshmukh AA, Shirvani SM, Lal L, Swint JM, Cantor SB, Smith BD, et al. Cost-effectiveness analysis comparing conventional, hypofractionated, and intraoperative radiotherapy for early-stage breast cancer. J Natl Cancer Inst 2017;109:djx068-90. https://doi.org/10.1093/jnci/djx068 doi: 10.1093/jnci/djx068. [DOI] [PubMed]
  102. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, et al. Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol 2018;8:145–52. https://doi.org/10.1016/j.prro.2018.01.012 doi: 10.1016/j.prro.2018.01.012. [DOI] [PubMed]
  103. Bloomfield D, Sydenham M, Haviland J, Morden J, Bliss J, Yarnold J, et al. A 5-fraction Regimen of Adjuvant Radiotherapy for Women with Early breast Cancer: first results of the randomised UK FAST trial (ISRCTN62488883, CRUK/04/015). NCRI National Cancer Conference; Liverpool, abstract no. 110, p. #A41.
  104. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010;362:513–20. https://doi.org/10.1056/NEJMoa0906260 doi: 10.1056/NEJMoa0906260. [DOI] [PubMed]
  105. Wang SL, Fang H, Song YW, Wang WH, Hu C, Liu YP, et al. Hypofractionated versus conventional fractionated post-mastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 2019;20:352–60. https://doi.org/10.1016/s1470-2045(18)30813-1 doi: 10.1016/S1470-2045(18)30813-1. [DOI] [PubMed]
  106. Smith BD, Bentzen SM, Correa CR, Hahn CA, Hardenbergh PH, Ibbott GS, et al. Fractionation for whole breast irradiation: An American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline. Int J Radiat Oncol Biol Phys 2011;81:59–68. https://doi.org/10.1016/j.ijrobp.2010.04.042 doi: 10.1016/j.ijrobp.2010.04.042. [DOI] [PubMed]
  107. Haviland JS, Yarnold JR, Bentzen SM. Hypofractionated radiotherapy for breast cancer. N Engl J Med 2010;362:1843. doi: 10.1056/NEJMc1002798. [DOI] [PubMed]
  108. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 2013;14:1086–94. https://doi.org/10.1016/S1470-2045(13)70386-3 doi: 10.1016/S1470-2045(13)70386-3. [DOI] [PubMed]
  109. Offersen BV, Alsner J, Nielsen HM, Jakobsen EH, Nielsen MH, Krause M, et al. Hypofractionated versus standard fractionated radiotherapy in patients with early breast cancer or ductal carcinoma in situ in a randomized phase III trial: The DBCG HYPO Trial. J Clin Oncol 2020;38:3615–25. https://doi.org/10.1200/jco.20.01363 doi: 10.1200/JCO.20.01363. [DOI] [PubMed]
  110. Shaitelman SF, Lei X, Thompson A, Schlembach P, Bloom ES, Arzu IY, et al. Three-year outcomes with hypofractionated versus conventionally fractionated whole-breast irradiation: Results of a randomized, noninferiority clinical trial. J Clin Oncol 2018;36:3495–503. https://doi.org/10.1200/jco.18.00317 doi: 10.1200/JCO.18.00317. [DOI] [PMC free article] [PubMed]
  111. Tsang YM, Venables K, Sydenham M, on behalf of the FAST Working Party. Interim Quality Assurance (QA) Analysis of Treatment Plans in the ‘Faster Radiotherpay for Breast Cancer patients’ (FAST) Trial. NCRI National Cancer Conference; Birmingham, abstract no. 113.
  112. Withers HR. Biologic basis of radiation therapy. In: Perez CA, Brady, LW, editors. Principles and Practice of Radiation Oncology. 2nd edn. Philadelphia: J.B. Lippincott; 1992:64–96.
  113. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013;368:987–98. https://doi.org/10.1056/NEJMoa1209825 doi: 10.1056/NEJMoa1209825. [DOI] [PubMed]
  114. Brand DH, Yarnold JR. The linear–quadratic model and implications for fractionation. Clin Oncol – UK 2019;31:673–7. https://doi.org/10.1016/j.clon.2019.06.007 doi: 10.1016/j.clon.2019.06.007. [DOI] [PubMed]
  115. Withers HR, Taylor JMG, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 1988;27:131–46. https://doi.org/10.3109/02841868809090333 doi: 10.3109/02841868809090333. [DOI] [PubMed]
  116. Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6&7 randomised controlled trial. Lancet 2003;362:933–40. https://doi.org/10.1016/S0140-6736(03)14361-9 doi: 10.1016/s0140-6736(03)14361-9. [DOI] [PubMed]
  117. Haviland JS, Bentzen SM, Bliss JM, Yarnold JR; START Trial Management Group. Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: An analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation. Radiother Oncol 2016;121:420–3. https://doi.org/10.1016/j.radonc.2016.08.027 doi: 10.1016/j.radonc.2016.08.027. [DOI] [PubMed]
  118. National Institute of Health and Care Excellence. COVID-19 Rapid Guideline: Delivery of Systemic Anticancer Treatments. NICE Guideline [NG161]; 2020. [PubMed]
  119. Royal College of Radiologists (RCR). Radiotherapy Consent Form for Breast Cancer; 2021.
  120. Lewis P, Brunt AM, Coles C, Griffin S, Locke I, Roques T; Breast Radiotherapy Consensus Working Group. Moving forward fast with FAST-Forward. Clin Oncol (R Coll Radiol) 2021;33:427–9. https://doi.org/10.1016/j.clon.2021.04.007 doi: 10.1016/j.clon.2021.04.007. [DOI] [PubMed]
  121. Meattini I, Becherini C, Boersma L, Kaidar-Person O, Marta GN, Montero A, et al. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol 2022;23:e21–31. https://doi.org/10.1016/s1470-2045(21)00539-8 doi: 10.1016/S1470-2045(21)00539-8. [DOI] [PubMed]
  122. Thomssen C, Balic M, Harbeck N, Gnant MS. Gallen/Vienna 2021: A brief summary of the consensus discussion on customizing therapies for women with early breast cancer. Breast Care 2021;16:135–43. https://doi.org/10.1159/000516114 doi: 10.1159/000516114. [DOI] [PMC free article] [PubMed]
  123. Salerno KE. NCCN Guidelines Update: Evolving radiation therapy recommendations for breast cancer. J Natl Compr Canc Netw 2017;15:682–4. https://doi.org/10.6004/jnccn.2017.0072 doi: 10.6004/jnccn.2017.0072. [DOI] [PubMed]
  124. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424. https://doi.org/10.3322/caac.21492 doi: 10.3322/caac.21492. [DOI] [PubMed]
  125. Anderson BO, Ilbawi AM, Fidarova E, Weiderpass E, Stevens L, Abdel-Wahab M, Mikkelsen B. The Global Breast Cancer Initiative: a strategic collaboration to strengthen health care for non-communicable diseases. Lancet Oncol 2021;22:578–81. https://doi.org/10.1016/s1470-2045(21)00071-1 doi: 10.1016/S1470-2045(21)00071-1. [DOI] [PubMed]
  126. Early Breast Cancer Trialists Collaborative Group. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet 2011;378:1707–16. https://doi.org/10.1016/S0140-6736(11)61629-2 doi: 10.1016/S0140-6736(11)61629-2. [DOI] [PMC free article] [PubMed]
  127. Early Breast Cancer Trialists Collaborative Group. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014;383:2127–35. https://doi.org/10.1016/S0140-6736(14)60488-8 doi: 10.1016/S0140-6736(14)60488-8. [DOI] [PMC free article] [PubMed]
  128. Abdel-Wahab M, Gondhowiardjo SS, Rosa AA, Lievens Y, El-Haj N, Rubio JAP, et al. Global Radiotherapy: Current Status and Future Directions – White Paper. JCO Glob Oncol 2021;7:827–42. https://doi.org/10.1200/go.21.00029 doi: 10.1200/GO.21.00029. [DOI] [PMC free article] [PubMed]
  129. Rodin D, Tawk B, Mohamad O, Grover S, Moraes FY, Yap ML, et al. Hypofractionated radiotherapy in the real-world setting: An international ESTRO-GIRO survey. Radiother Oncol 2021;157:32–9. https://doi.org/10.1016/j.radonc.2021.01.003 doi: 10.1016/j.radonc.2021.01.003. [DOI] [PMC free article] [PubMed]
  130. Foerster M, McCormack V, Anderson BO, Boucheron P, Zietsman A, Cubasch H, et al. Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study. Lancet Oncol 2022;23(6):729–38. https://doi.org/10.1016/S1470-2045(22)00198-X doi: 10.1016/S1470-2045(22)00198-X. [DOI] [PMC free article] [PubMed]
  131. Poortmans PM, Weltens C, Fortpied C, Kirkove C, Peignaux-Casasnovas K, Budach V, et al.; European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups. Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial. Lancet Oncol 2020;21:1602–10. https://doi.org/10.1016/s1470-2045(20)30472-1 doi: 10.1016/S1470-2045(20)30472-1. [DOI] [PubMed]
  132. Vrieling C, van Werkhoven E, Maingon P, Poortmans P, Weltens C, Fourquet A, et al.; European Organisation for Research and Treatment of Cancer, Radiation Oncology and Breast Cancer Groups. Prognostic factors for local control in breast cancer after long-term follow-up in the EORTC Boost vs No Boost Trial: A randomized clinical trial. JAMA Oncology 2017;3:42–8. https://doi.org/10.1001/jamaoncol.2016.3031 doi: 10.1001/jamaoncol.2016.3031. [DOI] [PubMed]
  133. Levy A, Rivera S. 1-week hypofractionated adjuvant whole-breast radiotherapy: towards a new standard? Lancet 2020;395:1588–9. https://doi.org/10.1016/S0140-6736(20)30978-8 doi: 10.1016/S0140-6736(20)30978-8. [DOI] [PMC free article] [PubMed]
  134. Boersma LJ, Murrer LHP. Three large trials on radiotherapy for early breast cancer: What did we learn? Radiother Oncol 2021;156:239–43. https://doi.org/10.1016/j.radonc.2020.12.018 doi: 10.1016/j.radonc.2020.12.018. [DOI] [PubMed]
  135. Breast Cancer Now. Facts and Statistics 2021; 2021.
  136. James Lind Alliance. Priorities for Living With and Beyond Cancer; 2018.
  137. Bhattacharya IS, Haviland JS, Hopwood P, Coles CE, Yarnold JR, Bliss JM, Kirby AM; IMPORT Trialists. Can patient-reported outcomes be used instead of clinician-reported outcomes and photographs as primary endpoints of late normal tissue effects in breast radiotherapy trials? Results from the IMPORT LOW trial. Radiother Oncol 2019;134:220–30. doi: 10.1016/j.radonc.2019.01.036. [DOI] [PMC free article] [PubMed]
  138. Mills J, Haviland JS, Moynihan C, Bliss JM, Hopwood P. Women’s free-text comments on their quality of life: An exploratory analysis from the UK Standardisation of Breast Radiotherapy (START) Trials for early breast cancer. Clin Oncol (R Coll Radiol) 2018;30:433–41. https://doi.org/10.1016/j.clon.2018.03.007 doi: 10.1016/j.clon.2018.03.007. [DOI] [PMC free article] [PubMed]
  139. Curtis L. Unit Costs of Health and Social Care. Canterbury: University of Kent; 2010.
  140. Curtis L, Burns A. Unit Costs of Health and Social Care. Canterbury: University of Kent; 2018.
  141. Macmillan Cancer Support. The cost of Macmillan’s services fact sheet. 2019.

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