Skip to main content

Ultra-Short Fraction Schedules as Part of De-intensification Strategies for Early-Stage Breast Cancer

Annals of Surgical Oncology volume 28, pages 5005–5014 (2021)Cite this article

Abstract

Adjuvant radiation therapy (RT) following breast-conserving surgery (BCS) represents a standard approach for most patients treated with breast-conserving therapy (BCT) for early-stage breast cancer. The first-generation of adjuvant RT schedules delivered daily treatment to the whole breast over 5–7 weeks. Although efficacious, this presented patients with a protracted course of treatment, reducing compliance and quality of life. While hypofractionated whole-breast irradiation (WBI) has become the standard, and part of the second-generation of RT regimens, it still requires 3–4 weeks. Concurrently, partial-breast irradiation (PBI) has also been explored as a technique to complete RT in a much shorter time period (1–3 weeks). There are now seven trials confirming the efficacy of this shorter treatment approach compared with standard WBI. In an effort to further reduce treatment duration, ultra-short WBI and PBI regimens have recently emerged as the third-generation of breast radiation schedules, allowing for the completion of treatment in 5 days or less. With respect to WBI, recent data from the FAST-Forward trial (which evaluated five fractions of WBI delivered in 1 week) demonstrated no difference in clinical outcomes at 5 years, with limited difference in toxicity, compared with hypofractionated 3-week WBI. Regarding PBI, published data on five-fraction regimens delivered in 2 weeks have also demonstrated comparable outcomes at 10 years, with reduced toxicities with long-term follow-up. This report will review additional ongoing studies evaluating even shorter courses of adjuvant RT treatment (one to five fractions), including single-fraction PBI or WBI.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Smith BD, Bellon JR, Blitzblau R, 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.

    PubMed  Article  Google Scholar 

  2. Early Breast Cancer Trialists’ Collaborative Group (EBCTG). 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.

    Article  CAS  Google Scholar 

  3. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513–20.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  4. Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of earl breast cancer: 10-year follow-up results of two randomized controlled trials. Lancet Oncol. 2013;14:1086–94.

    PubMed  Article  Google Scholar 

  5. Brunt AM, Haviland J, Sydenham M, et al. FAST Phase III RCT of radiotherapy hypofractionation for treatment of early breast cancer: 10-year results (CRUKE/04/015). Int J Radiat Oncol Biol Phys. 2018;102:LBA2.

    Article  Google Scholar 

  6. Brunt AM, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicenter, non-inferiority, randomised, phase 3 trial. Lancet. 2020;395:1613–26.

    Article  Google Scholar 

  7. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–41.

    PubMed  Article  Google Scholar 

  8. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347:1227–32.

    PubMed  Article  Google Scholar 

  9. Van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst. 2000;92:1143–50.

    PubMed  Article  Google Scholar 

  10. Correa C, Hariss EE, Leonardi MC, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol. 2017;17:73–9.

    Article  Google Scholar 

  11. Shah C, Vicini F, Shaitelman SF, et al. The American Brachytherapy Society consensus statement for accelerated partial breast irradiation. Brachytherapy. 2018;17:154–70.

    PubMed  Article  Google Scholar 

  12. Fentiman IS, Poole C, Tong D, et al. Inadequacy of iridium implant as sole radiation treatment for operable breast cancer. Eur J Cancer. 1996;32A:608–11.

    CAS  PubMed  Article  Google Scholar 

  13. Polgar C, Fodor J, Major T, et al. Breast-conserving therapy with partial or whole breast irradiation: 10-year results of the Budapest randomized trial. Radiother Oncol. 2013;108:197–202.

    PubMed  Article  Google Scholar 

  14. Shah C, Antonucci JV, Wilkinson JB, et al. Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: results of a matched-pair analysis. Radiother Oncol. 2011;100:210–4.

    PubMed  Article  Google Scholar 

  15. Kamrava M, Kuske RR, Anderson B, et al. Outcomes of breast cancer patients treated with accelerated partial breast irradiation via multicatheter interstitial brachytherapy: the pooled interstitial sites (PROMIS) experience. Ann Surg Oncol. 2015;22:s404–11.

    PubMed  Article  Google Scholar 

  16. Strnad V, Ott OJ, Hildebrandt G, et al. 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.

    PubMed  Article  Google Scholar 

  17. Polgar C, Ott OJ, Hildebrandt G, et al. 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.

    PubMed  Article  Google Scholar 

  18. Vicini FA, Cecchini RS, White JR, et al. 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. 2019;394:2155–64.

    PubMed  PubMed Central  Article  Google Scholar 

  19. Shah C, Badiyan S, Ben Wilkinson J, et al. Treatment efficacy with accelerated partial breast irradiation (APBI): final analysis of the American Society of Breast Surgeons MammoSite breast brachytherapy trial. Ann Surg Oncol. 2010;20:3279–85.

    Article  Google Scholar 

  20. Shah C, Khwaja S, Badiyan S, et al. Brachytherapy-based partial breast irradiation is associated with low rates of complications and excellent cosmesis. Brachytherapy. 2013;12:278–84.

    PubMed  Article  Google Scholar 

  21. Wilkinson JB, Chen PY, Wallace MF, et al. Six-year results from a Phase I/II trial for hypofractionated accelerated partial breast irradiation using a 2-day dose schedule. Am J Clin Oncol. 2018;41:986–91.

    PubMed  Article  Google Scholar 

  22. Khan AJ, Vicini FA, Brown S, et al. Dosimetric feasibility and acute toxicity in a prospective trial of ultrashort-course accelerated partial breast irradiation (APBI) using a multi-lumen balloon brachytherapy device. Ann Surg Oncol. 2013;20:1295–301.

    CAS  PubMed  Article  Google Scholar 

  23. Khan AJ, Chen PY, Yashar C, et al. Three-fraction accelerated partial breast irradiation (APBI) delivered with brachytherapy applicators is feasible and safe: first results from the TRIUMPH-T trial. Int J Radiat Oncol Biol Phys. 2019;104:67–74.

    PubMed  PubMed Central  Article  Google Scholar 

  24. Hepel JT, Yashar C, Leonard KL, et al. Five fraction accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy: feasibility and acute toxicity. Brachytherapy. 2018;17:825–30.

    PubMed  Article  Google Scholar 

  25. Showalter SL, Petroni G, Trifletti DM, et al. A novel form of breast intraoperative radiation therapy with CT-guided high-dose rate brachytherapy: results of a prospective Phase I clinical trial. Int J Radiat Oncol Biol Phys. 2016;96:46–54.

    PubMed  Article  Google Scholar 

  26. Hannoun-Levi JM, Kee DLC, Gal J, et al. Accelerated partial breast irradiation in the elderly: 5-year results of the single fraction elderly breast irradiation (SiFEBI) Phase I/II trial. Brachytherapy. 2020;19:90–6.

    PubMed  Article  Google Scholar 

  27. Kinj R, Chand ME, Gal J, et al. Five-year oncological outcome after a single fraction of accelerated partial breast irradiation in the elderly. Radiat Oncol. 2019;14:234.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. Pignol JP, Caudrelier JM, Crook J, et al. Report on the clinical outcomes of permanent breast seed implant for early-stage breast cancers. Int J Radiat Oncol Biol Phys. 2015;93:614–21.

    PubMed  Article  Google Scholar 

  29. Livi L, Meattini I, Marrazzo L, 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.

    PubMed  Article  Google Scholar 

  30. Meattini I, Saieva C, Lucidi S, et al. Accelerated partial breast or whole breast irradiation after breast conservation surgery for patients with early breast cancer: 10-year follow up results of the APBI IMRT Florence randomized phase 3 trial. Cancer Res. 2020;80:GS4-06.

    Google Scholar 

  31. Grendarova P, Roumeliotis M, Quirk S, et al. One-year cosmesis and fibrosis from ACCEL: accelerated partial breast irradiation (APBI) using 27 Gy in 5 fractions. Pract Radiat Oncol. 2019;9(5):e457–64.

    PubMed  Article  Google Scholar 

  32. Kennedy WR, Thomas MA, Stanley JA, et al. Single-institution Phase ½ prospective clinical trial of single-fraction, high-gradient adjuvant partial-breast irradiation for hormone sensitive Stage -I breast cancer. Int J Radiat Oncol Biol Phys. 2020;107:344–52.

    PubMed  Article  Google Scholar 

  33. Rahimi A, Thomas K, Spangler A, et al. Preliminary results of a Phase I dose escalation trial for early-stage breast cancer using 5-fraction stereotactic body radiation therapy for partial-breast irradiation. Int J Radiat Oncol Biol Phys. 2017;98:196–205.

    PubMed  Article  Google Scholar 

  34. Yu CX, Shao X, Zhang J, et al. GammaPod—a new device dedicated for stereotactic radiotherapy of breast cancer. Med Phys. 2013;40(5):051703.

    PubMed  PubMed Central  Article  Google Scholar 

  35. Lozza L, Fariselli L, Sandri M, et al. Partial breast irradiation with CyberKnife after breast conserving surgery: a pilot study in early breast cancer. Radiat Oncol. 2018;13:49.

    PubMed  PubMed Central  Article  Google Scholar 

  36. Horton JK, Blitzblau RC, Yoo S, et al. Preoperative single-fraction partial breast radiation therapy. A novel Phase 1, dose-escalation protocol with radiation response biomarkers. Int J Radiat Oncol Biol Phys. 2015;92:846–55.

    PubMed  PubMed Central  Article  Google Scholar 

  37. Charaghvandi RK, van Asselen B, Philippens ME, et al. Treatment constraints for a single dose external beam preoperative partial breast irradiation in early-stage breast cancer. BMC Cancer. 2017;17:181.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Khan AJ, Arthur DW, Vicini FA. On the road to intraoperative: more ‘proceed with caution’ sign. Oncology. 2013;27:113–4.

    PubMed  Google Scholar 

  39. Shah C, Wobb J, Khan A. Intraoperative radiation therapy in breast cancer: still not ready for prime time. Ann Surg Oncol. 2016;23:1796–8.

    PubMed  Article  Google Scholar 

  40. Vaidya JS, Bulsara M, Baum M, et al. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT: a randomised clinical trial. BMJ. 2020;370:m2836.

    PubMed  PubMed Central  Article  Google Scholar 

  41. Vaidya JS, Bulsara M, Saunders C, et al. Effect of delayed targeted intraoperative radiotherapy versus whole-breast radiotherapy on local control recurrence and survival: long-term results from the TARGIT: a randomized clinical trial in early breast cancer. JAMA Oncol 2020;6:e200249.

    PubMed  PubMed Central  Article  Google Scholar 

  42. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14:1269–77.

    PubMed  Article  Google Scholar 

  43. Kirby AM, MacKenzie M, Coles C, Poortmans P, Yarnold J. Re: long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT—a randomised clinical trial. BMJ. 2020;370:m2836.

    Google Scholar 

  44. Bentzen SM, Haviland JS. No apparent effect of 50 kv intra-operative radiation therapy in loco-regional control after lumpectomy for early breast cancer. BMJ. Epub 28 Aug 2020.

  45. Ganz, PA, Cecchini RS, White JR, et al. Patient-reported outcomes (PROs) in NRG oncology/NSABP B-39/RTOG 0413: a randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) in stage 0, I, or II breast cancer. J Clin Oncol. 2019;37:508.

    Article  Google Scholar 

  46. White JR, Winter K, Cecchini RS, et al. Cosmetic outcome from post-lumpectomy whole breast irradiation (WBI) versus partial breast irradiation (PBI) on the NRG Oncology/NSABP B39-RTOG0413 Phase III Clinical Trial. Int J Radiat Oncol Biol Phys. 2019;105:S5.

    Google Scholar 

  47. Meattini I, Saieva C, Miccinesi G, et al. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: health-related quality of life final analysis from the Florence Phase 3 trial. Eur J Cancer. 2017;76:17–26.

    PubMed  Article  Google Scholar 

  48. Dvoark T, Coltey D, Waters J, et al. Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients; Cancer Res. 2018;78:sPD7-04.

    Google Scholar 

  49. Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 2010–2020. J Natl Cancer Inst. 2011;103:117–28.

    PubMed  PubMed Central  Article  Google Scholar 

  50. Shah C, Lanni TB, Saini H, et al. Cost-efficacy of accelerated partial-breast irradiation compared with whole breast irradiation. Breast Cancer Res Treat. 2013;138:127–35.

    PubMed  Article  Google Scholar 

  51. Smith BD, Pan IW, Shih YC, et al. Adoption of intensity-modulated radiation therapy for breast cancer in the United States. J Natl Cancer Inst. 2011;103:798–809.

    PubMed  Article  Google Scholar 

  52. Shah C, Ward MC, Tendulkar RD, et al. Cost and cost-effectiveness of image guided partial breast irradiation in comparison to hypofractionated whole breast irradiation. Int J Radiat Oncol Biol Phys. 2019;103:397–402.

    PubMed  Article  Google Scholar 

  53. Ward MC, Vicini F, Al-Hilli Z, et al. Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older. Breast Cancer Res Treat. 2020;182:355–65.

    CAS  PubMed  Article  Google Scholar 

  54. Centers for Medicare and Medicaid Services. Radiation Oncology Model. https://innovation.cms.gov/innovation-models/radiation-oncology-model. Accessed 31 May 2020.

  55. Grobmyer SR, Lightsey JL, Bryant CM, et al. Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program. J Am Coll Surg. 2013;216:617–23.

    PubMed  Article  Google Scholar 

  56. Alvarado MD, Mohan AJ, Esserman LJ, et al. Cost-effectiveness of intraoperative radiation therapy for early-stage breast cancer. Ann Surg Oncol. 2013;20: 2873–80.

    PubMed  Article  Google Scholar 

  57. Shah C, Badiyan S, Khwaja S, et al. Evaluating radiotherapy options in breast cancer: does intraoperative radiotherapy represent the most cost-efficacious option? Clin Breast Cancer. 2014;14:141–6.

    PubMed  Article  Google Scholar 

  58. Buszek SM, Liny HY, Bedrosian I, et al. Lumpectomy plus hormone or radiation thearpy alone for women aged 70 years or older with hormone receptor-positive early stage breast cancer in the modern era: an analysis of the National Cancer Database. Int J Radiat Oncol Biol Phys. 2019;105:795–802.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. Ward MC, Vicini F, Chadha M, et al. Radiation therapy without hormone therapy for women age 70 or above with low-risk early breast cancer: a microsimulation. Int J Radiat Oncol Biol Phys. 2019;105:296–306.

    PubMed  Article  Google Scholar 

  60. Ward MC, Vicini F, Al-Hilli Z, et al. Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older. Breast Cancer Res Treat. 2020;182(2):355–65.

    CAS  PubMed  Article  Google Scholar 

  61. Khan AJ, Rafique R, Zafar W, et al. Nation-scale adoption of shorter breast radiation therapy schedules can increase survival in resource constrained economies: results from a Markov chain analysis. Int J Radiat Oncol Biol Phys. 2017;97:287–95.

    PubMed  Article  Google Scholar 

Download references

Funding

None.

Author information

Affiliations

  1. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Chirag Shah MD

  2. Cancer HealthCare Associates, Miami, FL, USA

    Martin Keisch MD

  3. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Atif Khan MD

  4. Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA

    Douglas Arthur MD

  5. Lifespan Cancer Institute, Alpert Medical School of Brown University, Providence, RI, USA

    David Wazer MD

  6. Michigan Healthcare Professionals, GenesisCare, Farmington Hills, MI, USA

    Frank Vicini MD, FACR

Authors
  1. Chirag Shah MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Keisch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atif Khan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Douglas Arthur MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Wazer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Frank Vicini MD, FACR
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Vicini MD, FACR.

Ethics declarations

Disclosures

Chirag Shah is a consultant for Impedimed and PreludeDX, and has received grants from Varian Medical Systems, VisionRT, and PreludeDX. Frank Vicini is Chief Medical Officer at Impedimed; Martin Keisch is a consultant for Hologic; and David Wazer is a member of the Medical Advisory Board of Advanced Radiation Therapy, Inc. Atif Khan and Douglas Arthur have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shah, C., Keisch, M., Khan, A. et al. Ultra-Short Fraction Schedules as Part of De-intensification Strategies for Early-Stage Breast Cancer. Ann Surg Oncol 28, 5005–5014 (2021). https://doi.org/10.1245/s10434-020-09526-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-09526-y