Advertisement

Breast Cancer Research and Treatment

, Volume 162, Issue 3, pp 409–417 | Cite as

Hypofractionated whole breast radiotherapy in breast conservation for early-stage breast cancer: a systematic review and meta-analysis of randomized trials

  • Luca F. ValleEmail author
  • Surbhi Agarwal
  • Kathleen E. Bickel
  • Haley A. Herchek
  • David C. Nalepinski
  • Nirav S. Kapadia
Review

Abstract

Purpose

Breast conservation therapy (BCT) for early-stage breast cancer involves lumpectomy followed by whole breast radiotherapy, which can involve either standard fractionation (SRT) or accelerated fractionation (ART). This systematic review and meta-analysis was performed to determine whether any benefit exists for ART or SRT.

Materials and methods

We searched MEDLINE (1966–2014), all seven databases of the Cochrane Library (1968–2014), EMBASE (1974–2014), clinicaltrials.gov, ISRCTN, WHO ICTRP, and meeting abstracts in the Web of Science Core Collection (1900–2014). RCTs comparing SRT to ART among women undergoing BCT with stage T1–T2 and/or N1 breast cancer or carcinoma in situ were included. Follow-up was 30 days for acute toxicity, or three years for disease control and late toxicity.

Results

13 trials with 8189 participants were included. No differences were observed in local failure (n = 7 trials; RR 0.97; 95% CI 0.78–1.19, I 2 = 0%), locoregional failure, (n = 8 trials; RR 0.86; 95% CI 0.63–1.16, I 2 = 0%), or survival (n = 4 trials; RR 1.00; 95% CI 0.85–1.17, I 2 = 0%). ART was associated with significantly less acute toxicity (n = 5 trials; RR 0.36; 95% CI 0.21–0.62, I 2 = 20%), but no difference in late cosmesis (RR 0.95; 95% CI 0.81–1.12, I 2 = 54%).

Conclusions

ART use does not reduce disease control or worsen long-term cosmetic outcome, and may decrease the risk of acute radiation toxicity as compared to SRT.

Keywords

Adjuvant radiation Breast conservation therapy Whole breast radiation Hypofractionation Hypofractionated radiotherapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30. doi: 10.3322/caac.21332 CrossRefPubMedGoogle Scholar
  2. 2.
    Kohler BA, Sherman RL, Howlader N et al (2015) Annual report to the nation on the status of cancer, 1975–2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst 107:djv048. doi: 10.1093/jnci/djv048 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Early Breast Cancer Trialists’ Collaborative Group, Darby S, McGale P et al (2011) 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 378:1707–1716CrossRefGoogle Scholar
  4. 4.
    Baillet F, Housset M, Maylin C et al (1990) The use of a specific hypofractionated radiation therapy regimen versus classical fractionation in the treatment of breast cancer: a randomized study of 230 patients. Int J Radiat Oncol Biol Phys 19:1131–1133CrossRefPubMedGoogle Scholar
  5. 5.
    Whelan TJ, Pignol J, Levine MN et al (2010) Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 362:513–520CrossRefPubMedGoogle Scholar
  6. 6.
    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 312:2542–2550CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaborationprisma: explanation and elaboration. PLoS Med 151:65Google Scholar
  8. 8.
    Higgins JP, Altman DG, Gotzsche PC et al (2011) The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. doi: 10.1136/bmj.d5928 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Nordic Cochrane Centre The Cochrane Collaboration (2014) Review manager (RevMan)[computer program] Version 53. The Nordic Cochrane Centre, The Cochrane Collaboration, CopenhagenGoogle Scholar
  10. 10.
    Van Parijs H, Miedema G, Vinh-Hung V et al (2012) Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial. Radiat Oncol 7:80CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Li S, Wang S, Song Y et al (2014) Interim analysis of 354 breast cancer patients randomly treated with hyperfractionated or conventional fractionated radiation therapy after breast-conserving surgery. Int J Radiat Oncol Biol Phys 90:S256CrossRefGoogle Scholar
  12. 12.
    Medicine ABoI (2003) Choosing wisely: five things physicians and patients should questionGoogle Scholar
  13. 13.
    Anonymous (2013) Accelerated radiotherapy after breast-conserving surgery for early stage breast cancer. 27:1–6Google Scholar
  14. 14.
    Hickey BE, James ML, Lehman M et al (2016) Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Libr 7:CD003860Google Scholar
  15. 15.
    Zhou Z, Mei X, Chen X et al (2015) Systematic review and meta-analysis comparing hypofractionated with conventional fraction radiotherapy in treatment of early breast cancer. Surg Oncol 24:200–211CrossRefPubMedGoogle Scholar
  16. 16.
    Smith BD, Bentzen SM, Correa CR et al (2011) Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Int J Radiat Oncol Biol Phys 81:59–68CrossRefPubMedGoogle Scholar
  17. 17.
    Whelan T, Pignol J, Julian J et al (2008) Long-term results of a randomized trial of accelerated hypofractionated whole breast irradiation following breast conserving surgery in women with node-negative breast cancer. Int J Radiat Oncol Biol Phys 72:S28CrossRefGoogle Scholar
  18. 18.
    Spooner D, Stocken DD, Jordan S et al (2012) A randomised controlled trial to evaluate both the role and the optimal fractionation of radiotherapy in the conservative management of early breast cancer. Clin Oncol 24:697–706CrossRefGoogle Scholar
  19. 19.
    Jagsi R, Griffith KA, Boike TP et al (2015) Differences in the acute toxic effects of breast radiotherapy by fractionation schedule: comparative analysis of physician-assessed and patient-reported outcomes in a large multicenter cohort. JAMA Oncol 1:918–930CrossRefPubMedGoogle Scholar
  20. 20.
    Hall EJ, Giaccia AJ (2006) Radiobiology for the radiologist. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  21. 21.
    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 14:1086–1094CrossRefPubMedGoogle Scholar
  22. 22.
    DeSantis C, Ma J, Bryan L et al (2014) Breast cancer statistics. CA 64:52–62PubMedGoogle Scholar
  23. 23.
    Smith BD, Haffty BG, Wilson LD et al (2010) The future of radiation oncology in the United States from 2010 to 2020: will supply keep pace with demand? J Clin Oncol 28:5160–5165. doi: 10.1200/JCO.2010.31.2520 CrossRefPubMedGoogle Scholar
  24. 24.
    Schroen AT, Brenin DR, Kelly MD et al (2005) Impact of patient distance to radiation therapy on mastectomy use in early-stage breast cancer patients. J Clin Oncol 23:7074–7080. doi: 10.1200/JCO.2005.06.032 CrossRefPubMedGoogle Scholar
  25. 25.
    Barsoum M, El Mongi M, Khalil E, Eisa H, Hamed I, Attia G (2010) Prospective randomized trial comparing postoperative adjuvant concurrent versus sequential hormonal and different radiation fractionation schedule in breast cancer patients. J Clin Oncol 28(15_suppl):544CrossRefGoogle Scholar
  26. 26.
    Fragandrea I, Kouloulias V, Sotiropoulou A, Gouliamos A, Kouvaris I (2012) 395 radiation induced skin toxicity following hypofractionated radiotherapy treatment in early breast cancer: single institution experience. Eur J Cancer 48:S158CrossRefGoogle Scholar
  27. 27.
    Fragkandrea-Nixon I (2013) Radiation-induced lung and heart toxicity in patients with early-stage breast cancer treated with hypofractionated radiotherapy following breast-conservative surgery. J Clin Oncol 31(26_suppl):73CrossRefGoogle Scholar
  28. 28.
    Fragkandrea-Nixon I, Kouloulias V, Mpaziotis N et al (2011) Preliminary results on the impact of hypofractionated radiotherapy in cardiac toxicity (cardiac function) in early staged left sided breast cancer patients: a prospective randomized phase ii study. Radiother Oncol 98:S41CrossRefGoogle Scholar
  29. 29.
    Fragkandrea I, Kouloulias V, Mavridis P et al (2013) Radiation induced pneumonitis following whole breast radiotherapy treatment in early breast cancer patients treated with breast conserving surgery: a single institution study. Hippokratia 17(3):233–238PubMedPubMedCentralGoogle Scholar
  30. 30.
    Fragandrea I, Zetos A, Georgolopoulou P et al (2009) 5127 hypofractionation versus conventional fractionation radiotherapy (RT) after breast conservative treatment of breast cancer: radiation induced pneumonitis. Eur J Cancer Suppl 7(2):297–298CrossRefGoogle Scholar
  31. 31.
    Haislund B, Bang T, Ellegaard MB, Offersen B (2012) Po-0954 acute morbidity in patients with early breast cancer in adjuvant radiotherapy in the dbcg hypo and dbcg pbi protocols. Radiother Oncol 103(Supplement 1):S375–S376. doi: 10.1016/S0167-8140(12)71287-2 CrossRefGoogle Scholar
  32. 32.
    Bentzen SM, Agrawal RK, Aird EG 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 9:331–341CrossRefPubMedGoogle Scholar
  33. 33.
    Hopwood P, Haviland JS, Sumo G, Mills J, Bliss JM, Yarnold JR (2010) Comparison of patient-reported breast, arm, and shoulder symptoms and body image after radiotherapy for early breast cancer: 5-year follow-up in the randomised standardisation of breast radiotherapy (START) trials. Lancet Oncol 11(3):231–240. doi: 10.1016/S1470-2045(09)70382-1 CrossRefPubMedGoogle Scholar
  34. 34.
    Bentzen SM, Agrawal RK, Aird EG 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 371:1098–1107CrossRefPubMedGoogle Scholar
  35. 35.
    Karmacharya R, Shah A, Jha A, Shrestha S, Pandit S (2012) A comparative study of acute toxicity between conventional and hypofractionated adjuvant radiotherapy in breast cancer. J Cancer Res Ther 8:S145CrossRefGoogle Scholar
  36. 36.
    Patni N, Jain M, Patni S, Bapna A (2012) A comparison of acute and chronic toxicity profile between conventional and hypofractionated whole breast irradiation in patients undergoing breast conserving surgery. Int J Radiat Oncol Biol Phys 84(3):S232CrossRefGoogle Scholar
  37. 37.
    Saha S, Dastidar AG, Gangopadhyay A, Ghorai S (2009) Evaluation of hypofractionated adjuvant radiotherapy for early breast cancer: a prospective randomized study. Int J Radiat Oncol Biol Phys 75(3):S76CrossRefGoogle Scholar
  38. 38.
    Whelan T, MacKenzie R, Levine M, ShelleyW JJ, Grimard L (2000) A randomized trial comparing two fractionation schedules for breast irradiation postlumpectomy in node-negative breast cancer. J Natl Cancer Inst 19:2aGoogle Scholar
  39. 39.
    Brunt A, Sydenham M, Bliss J et al (2009) 7LBA 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). Eur J Cancer Suppl 7(3):2CrossRefGoogle Scholar
  40. 40.
    Yarnold J, Owen R, Ashton A et al (2001) Fractionation sensitivity of change in breast appearance after radiotherapy for early breast cancer: Results of a phase III randomised trial. Breast Cancer Res Treat 69(3):230Google Scholar
  41. 41.
    Agrawal RK, Alhasso A, Barrett-Lee PJ et al (2011) First results of the randomised UK FAST trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol 100:93–100CrossRefPubMedGoogle Scholar
  42. 42.
    Yarnold J, Owen J, Bliss J et al (1993) Randomised comparison of a 13 fraction schedule with a conventional 25 fraction schedule of radiotherapy after local excision of early breast cancer: preliminary analysis. Breast 2(3):201CrossRefGoogle Scholar
  43. 43.
    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(6):467–471CrossRefPubMedGoogle Scholar
  44. 44.
    Owen J, Haviland J, Agrawal R et al (2007) 2026 ORAL results of the UK standardisation of breast radiotherapy (START) trials testing hypofractionation for early breast cancer–on behalf of the START trials centres. Eur J Cancer Suppl 5(4):191–192CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.The Geisel School of Medicine at DartmouthHanoverUSA
  2. 2.The Dartmouth Institute for Health Policy and Clinical PracticeLebanonUSA
  3. 3.Duke Cancer InstituteDurhamUSA
  4. 4.Norris Cotton Cancer Center at Dartmouth Hitchcock Medical CenterLebanonUSA

Personalised recommendations