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Open Access 01-04-2021 | Breast Cancer | Review Article

Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward

Authors: David Krug, René Baumann, Stephanie E. Combs, Marciana Nona Duma, Jürgen Dunst, Petra Feyer, Rainer Fietkau, Wulf Haase, Wolfgang Harms, Thomas Hehr, Marc D. Piroth, Felix Sedlmayer, Rainer Souchon, Vratislav Strnad, Wilfried Budach, Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

Published in: Strahlentherapie und Onkologie | Issue 4/2021

Abstract

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40–42.5 Gy over 15–16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

Ditsch N, Untch M, Thill M et al (2019) AGO recommendations for the diagnosis and treatment of patients with early breast cancer: update 2019. Breast Care 14:224–245. https://doi.org/10.1159/000501000CrossRefPubMedPubMedCentral

Smith BD, Bellon JR, Blitzblau R et al (2018) Radiation therapy for the whole breast: executive summary of an American society for radiation oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol 8:145–152. https://doi.org/10.1016/j.prro.2018.01.012CrossRefPubMed

Wöckel A, Festl J, Stüber T et al (2018) Interdisciplinary screening, diagnosis, therapy and follow-up of breast cancer. Guideline of the DGGG and the DKG (S3-level, AWMF registry number 032/045OL, December 2017)—part 2 with recommendations for the therapy of primary, recurrent and advanced breast cancer. Geburtshilfe Frauenheilkd 78:1056–1088. https://doi.org/10.1055/a-0646-4630CrossRefPubMedPubMedCentral

Shaitelman SF, Schlembach PJ, Arzu I et al (2015) Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation. JAMA Oncol 1:931–941. https://doi.org/10.1001/jamaoncol.2015.2666CrossRefPubMedPubMedCentral

Shaitelman SF, Lei X, Thompson A et al (2018) Three-year outcomes with hypofractionated versus conventionally fractionated whole-breast irradiation: results of a randomized, noninferiority clinical trial. J Clin Oncol. https://doi.org/10.1200/JCO.18.00317CrossRefPubMedPubMedCentral

START Trialists’ Group, Bentzen SM, Agrawal RK et al (2008) The UK standardisation of breast radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 9:331–341. https://doi.org/10.1016/S1470-2045(08)70077-9CrossRef

START Trialists’ Group, Agrawal RK, Aird EGA et al (2008) The UK standardisation of breast radiotherapy (START) trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 371:1098–1107. https://doi.org/10.1016/S0140-6736(08)60348-7CrossRef

Haviland JS, Owen JR, Dewar JA et al (2013) 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 14:1086–1094. https://doi.org/10.1016/S1470-2045(13)70386-3CrossRefPubMed

Whelan T, MacKenzie R, Julian J et al (2002) Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143–1150CrossRef

10.

Whelan TJ, Pignol J‑P, Levine MN et al (2010) Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 362:513–520. https://doi.org/10.1056/NEJMoa0906260CrossRefPubMed

11.

Offersen BV, Alsner J, Nielsen HM, Jakobsen EH, Nielsen MH, Krause M et al (2020) 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 38(31):3615–3625CrossRef

12.

Wang S‑L, Fang H, Hu C, Song Y‑W, Wang W‑H, Jin J et al (2020) Hypofractionated versus conventional fractionated radiotherapy after breast-conserving surgery in the modern treatment era: a multicenter, randomized controlled trial from China. J Clin Oncol 38(31):3604–3614CrossRef

13.

Wang S‑L, Fang H, Song Y‑W et al (2019) Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol 20:352–360. https://doi.org/10.1016/S1470-2045(18)30813-1CrossRefPubMed

14.

Khan AJ, Poppe MM, Goyal S et al (2017) Hypofractionated postmastectomy radiation therapy is safe and effective: first results from a prospective phase II trial. J Clin Oncol 35:2037–2043. https://doi.org/10.1200/JCO.2016.70.7158CrossRefPubMedPubMedCentral

15.

Poppe MM, Yehia ZA, Baker C et al (2020) 5‑year update of a multi-institution, prospective phase 2 hypofractionated postmastectomy radiation therapy trial. Int J Radiat Oncol Biol Phys 107:694–700. https://doi.org/10.1016/j.ijrobp.2020.03.020CrossRefPubMed

16.

Recht A, McArthur H, Solin LJ et al (2019) Contemporary guidelines in whole-breast irradiation: an alternative perspective. Int J Radiat Oncol Biol Phys 104:567–573. https://doi.org/10.1016/j.ijrobp.2018.10.014CrossRefPubMed

17.

Nitsche M, Dunst J, Carl UM, Hermann RM (2015) Emerging role of hypofractionated radiotherapy with simultaneous integrated boost in modern radiotherapy of breast cancer. Breast Care 10:320–324. https://doi.org/10.1159/000436951CrossRefPubMedPubMedCentral

18.

Sedlmayer F, Reitsamer R, Wenz F et al (2017) Intraoperative radiotherapy (IORT) as boost in breast cancer. Radiat Oncol. https://doi.org/10.1186/s13014-016-0749-9CrossRefPubMedPubMedCentral

19.

Fastner G, Reitsamer R, Urbański B et al (2020) Toxicity and cosmetic outcome after hypofractionated whole breast irradiation and boost-IOERT in early stage breast cancer (HIOB): first results of a prospective multicenter trial (NCT01343459). Radiother Oncol 146:136–142. https://doi.org/10.1016/j.radonc.2020.02.001CrossRefPubMed

20.

Burgos-Burgos J, Vega V, Macias-Verde D et al (2020) Hypofractionated whole breast irradiation after IORT treatment: evaluation of acute toxicity and cosmesis. Clin Transl Oncol. https://doi.org/10.1007/s12094-020-02400-zCrossRefPubMed

21.

Livi L, Meattini I, Marrazzo L et al (2015) 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 51:451–463. https://doi.org/10.1016/j.ejca.2014.12.013CrossRefPubMed

22.

Meattini I, Marrazzo L, Saieva C et al (2020) Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-florence trial. J Clin Oncol. https://doi.org/10.1200/JCO.20.00650CrossRefPubMed

23.

Vicini FA, Cecchini RS, White JR et al (2019) Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet 394:2155–2164. https://doi.org/10.1016/S0140-6736(19)32514-0CrossRefPubMedPubMedCentral

24.

Whelan TJ, Julian JA, Berrang TS et al (2019) External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet 394:2165–2172. https://doi.org/10.1016/S0140-6736(19)32515-2CrossRefPubMed

25.

Olivotto IA, Whelan TJ, Parpia S et al (2013) Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 31:4038–4045. https://doi.org/10.1200/JCO.2013.50.5511CrossRefPubMed

26.

Brunt AM, Haviland JS, Wheatley DA et al (2020) 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 395:1613–1626. https://doi.org/10.1016/S0140-6736(20)30932-6CrossRefPubMedPubMedCentral

27.

Brunt AM, Haviland JS, Sydenham M et al (2020) Ten-year results of FAST: a randomized controlled trial of 5‑fraction whole-breast radiotherapy for early breast cancer. J Clin Oncol. https://doi.org/10.1200/JCO.19.02750CrossRefPubMed

28.

FAST Trialists group (2011) First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol 100:93–100. https://doi.org/10.1016/j.radonc.2011.06.026CrossRef

29.

Brunt AM, Wheatley D, Yarnold J et al (2016) 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 120:114–118. https://doi.org/10.1016/j.radonc.2016.02.027CrossRefPubMedPubMedCentral

30.

Whelan T, Levine M, Sussman J (2020) Hypofractionated breast irradiation: what’s next? J Clin Oncol. https://doi.org/10.1200/JCO.20.01243CrossRefPubMed

31.

Krug D (2020) Adjuvant radiotherapy for breast cancer: more than meets the eye. Breast Care 15:109–111. https://doi.org/10.1159/000506797CrossRefPubMed

32.

Matuschek C, Bölke E, Haussmann J et al (2017) The benefit of adjuvant radiotherapy after breast conserving surgery in older patients with low risk breast cancer—a meta-analysis of randomized trials. Radiat Oncol 12:60–68. https://doi.org/10.1186/s13014-017-0796-xCrossRefPubMedPubMedCentral

33.

Forster T, Köhler CVK, Debus J, Hörner-Rieber J (2020) Accelerated partial breast irradiation: a new standard of care? Breast Care 15:136–147. https://doi.org/10.1159/000506254CrossRefPubMed

34.

Coles CE, Griffin CL, Kirby AM et al (2017) 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 390:1048–1060. https://doi.org/10.1016/S0140-6736(17)31145-5CrossRefPubMedPubMedCentral

35.

Correa C, Harris EE, Leonardi MC et al (2017) Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol 7(2):73–79. https://doi.org/10.1016/j.prro.2016.09.007CrossRefPubMed

36.

Strnad V, Krug D, Sedlmayer F et al (2020) DEGRO practical guideline for partial-breast irradiation. Strahlenther Onkol 387:229. https://doi.org/10.1007/s00066-020-01613-zCrossRef

37.

Hickey BE, James ML, Lehman M et al (2016) Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database Syst Rev 7:CD3860. https://doi.org/10.1002/14651858.CD003860.pub4CrossRefPubMed

38.

Bekelman JE, Sylwestrzak G, Barron J et al (2014) Uptake and costs of hypofractionated vs conventional whole breast irradiation after breast conserving surgery in the United States, 2008–2013. JAMA 312:2542–2549. https://doi.org/10.1001/jama.2014.16616CrossRefPubMedPubMedCentral

39.

Deshmukh AA, Shirvani SM, Lal L et al (2017) Cost-effectiveness analysis comparing conventional, hypofractionated, and intraoperative radiotherapy for early-stage breast cancer. J Natl Cancer Inst 109:1–9. https://doi.org/10.1093/jnci/djx068CrossRef

40.

Owen JR, Ashton A, Bliss JM et al (2006) 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 7:467–471. https://doi.org/10.1016/S1470-2045(06)70699-4CrossRefPubMed

41.

Yarnold J, Ashton A, Bliss J et al (2005) 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 75:9–17. https://doi.org/10.1016/j.radonc.2005.01.005CrossRefPubMed

42.

Braunstein LZ, Gillespie EF, Hong L et al (2020) Breast radiotherapy under COVID-19 pandemic resource constraints—approaches to defer or shorten treatment from a comprehensive cancer center in the United States. Adv Radiat Oncol. https://doi.org/10.1016/j.adro.2020.03.013CrossRefPubMedPubMedCentral

43.

Combs SE, Belka C, Niyazi M et al (2020) First statement on preparation for the COVID-19 pandemic in large German speaking university-based radiation oncology departments. Radiat Oncol 15:1–12. https://doi.org/10.1186/s13014-020-01527-1CrossRef

Title: Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward
Authors: David Krug
René Baumann
Stephanie E. Combs
Marciana Nona Duma
Jürgen Dunst
Petra Feyer
Rainer Fietkau
Wulf Haase
Wolfgang Harms
Thomas Hehr
Marc D. Piroth
Felix Sedlmayer
Rainer Souchon
Vratislav Strnad
Wilfried Budach
Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Care
Breast Cancer
Radiotherapy
Published in: Strahlentherapie und Onkologie / Issue 4/2021
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-020-01744-3

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Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward

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