SpringerLink
Log in

Hypofractionated radiotherapy after breast-conserving surgery: Clinical and dosimetric factors predictive of acute skin toxicity

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to evaluate acute skin toxicity in early breast cancer patients treated with hypofractionated radiotherapy (HFRT) after breast-conserving surgery and to identify factors predictive for grade ≥ 2 acute skin toxicity.

Materials and methods

A monocentric retrospective study was carried out using cases treated between December 2017 and November 2020. We analyzed data from 202 patients with early breast cancer treated with 3D hypofractionated RT (40.05 Gy in 15 fractions) to the whole breast with or without regional lymph nodes, followed by 13.35 Gy in 5 fractions to the tumor bed. Acute skin toxicity was monitored during RT according to CTCAE (common toxicity criteria for adverse events) scale. Univariate and multivariate analyses were performed to assess predictive factors of acute skin toxicity.

Results

Overall, there was no erythema in 9%, grade 1 erythema in 64.5%, grade 2 in 24%, and grade 3 in 2.5%. No grade 4 erythema was seen. Median delay between RT initiating and maximum skin reaction was 22 days (range 4–44 days). No patient interrupted treatment. In univariate analysis, the rate of acute skin toxicity grade 2--–3 (G2-3) was significantly higher for patients with larger tumor size (p = 0.02), body mass index > 27 (p = 0.04), and time between chemotherapy (CT) and RT less than 20 days (p = 0.01). Dosimetric risk factors for acute skin toxicity G2‑3 were breast volume > 800 cc (p = 0.000), boost volume > 18 cc (p = 0.002), V105% > 40 cc (p = 0.03), and Dmax > 56 Gy (p = 0.007). CT, trastuzumab, regional lymph node radiation, and age were not correlated with increased skin toxicity. In multivariate analysis, acute skin toxicity correlated with T stage (p = 0.032), breast volume > 800 cc (p = 0.012), boost volume > 18 cc (p = 0.04), and Dmax > 56 Gy (p = 0.035).

Conclusion

Our results confirm that whole breast with or without lymph nodes hypofractionated RT is safe and well tolerated. The factors strongly associated with a decreased risk of G2‑3 skin toxicity are T1, breast volume < 800 c, boost volume < 18 cc, and Dmax < 56 Gy. Long-term follow-up is needed to evaluate late toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale P, Taylor C, Correa C, Cutter D, Duane F et al (2014) 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 383(9935):2127–2135

    Article  Google Scholar 

  2. START Trialists’ Group, Bentzen SM, Agrawal RK, Aird EGA, Barrett JM, Barrett-Lee PJ 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(9618):1098–1107

    Article  Google Scholar 

  3. Whelan TJ, Kim D‑H, Sussman J (2008) Clinical experience using hypofractionated radiation schedules in breast cancer. Semin Radiat Oncol 18(4):257–264

    Article  Google Scholar 

  4. Shaitelman SF, Schlembach PJ, Arzu I, et al (2015) Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation: A randomized clinical trial. JAMA Oncol 1(7):931–941. https://doi.org/10.1001/jamaoncol.2015.2666

    Article  Google Scholar 

  5. Murray Brunt A, 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(10237):1613–1626. https://doi.org/10.1016/S0140-6736(20)30932-6

    Article  Google Scholar 

  6. CTEP Common terminology criteria for adverse events (CTCAE) | protocol development. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. Accessed 12.2021

  7. Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A et al (2015) ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol 114(1):3–10

    Article  Google Scholar 

  8. Sanz J, Rodríguez N, Foro P, et al (2017) Hypofractionated boost after whole breast irradiation in breast carcinoma: chronic toxicity results and cosmesis. Clin Transl Oncol 19(4):464–469. https://doi.org/10.1007/s12094-016-1548-3

    Article  CAS  Google Scholar 

  9. Tortorelli G, Di Murro L, Barbarino R, Cicchetti S, di Cristino D, Falco MD et al (2013) Standard or hypofractionated radiotherapy in the postoperative treatment of breast cancer: a retrospective analysis of acute skin toxicity and dose inhomogeneities. Bmc Cancer 13(1):230. https://doi.org/10.1186/1471-2407-13-230

    Article  Google Scholar 

  10. Brunt AM, Wheatley D, Yarnold J, Somaiah N, Kelly S, Harnett A 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(1):114–118

    Article  Google Scholar 

  11. Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP et al (2016) Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003860.pub4

    Article  Google Scholar 

  12. Nozaki M, Kagami Y, Shibata T, Nakamura K, Ito Y, Nishimura Y et al (2019) A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. Jpn J Clin Oncol 49(1):57–62. https://doi.org/10.1093/jjco/hyy160

    Article  Google Scholar 

  13. Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson 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(1):9–17

    Article  Google Scholar 

  14. Holloway CL, Panet-Raymond V, Olivotto I (2010) Hypofractionation should be the new ‘standard’ for radiation therapy after breast conserving surgery. Breast 19(3):163–167

    Article  Google Scholar 

  15. Dorn PL, Corbin KS, Al-Hallaq H, Hasan Y, Chmura SJ (2012) Feasibility and acute toxicity of Hypofractionated radiation in large-breasted patients. Int J Radiat Oncol Biol Phys 83(1):79–83

    Article  Google Scholar 

  16. Ciammella P, Podgornii A, Galeandro M, Micera R, Ramundo D, Palmieri T et al (2014) Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors. Radiat Oncol 9(1):97. https://doi.org/10.1186/1748-717X-9-97

    Article  Google Scholar 

  17. Harsolia A, Kestin L, Grills I, Wallace M, Jolly S, Jones C et al (2007) Intensity-modulated radiotherapy results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. Int J Radiat Oncol Biol Phys 68(5):1375–1380

    Article  Google Scholar 

  18. Hijal T, Al Hamad AA, Niazi T, Sultanem K, Bahoric B, Vuong T et al (2010) Hypofractionated radiotherapy and adjuvant chemotherapy do not increase radiation-induced dermatitis in breast cancer patients. Curr Oncol 17(5):22–27

    Article  CAS  Google Scholar 

  19. Kouloulias V, Zygogianni A, Kypraiou E, Georgakopoulos J, Thrapsanioti Z, Beli I et al (2014) Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer. WJCC 2(11):705–710

    Article  Google Scholar 

  20. Zygogianni A, Kouloulias V, Antypas C, Armpilia C, Kyrgias G, Kouvaris J (2014) The impact of intermediate time between chemotherapy and hypofractionated radiotherapy to the radiation induced skin toxicity for breast adjuvant treatment. Breast J 20(1):74–78. https://doi.org/10.1111/tbj.12206

    Article  CAS  Google Scholar 

  21. De Langhe S, Mulliez T, Veldeman L, Remouchamps V, van Greveling A, Gilsoul M et al (2014) Factors modifying the risk for develo** acute skin toxicity after whole-breast intensity modulated radiotherapy. Bmc Cancer 14(1):711. https://doi.org/10.1186/1471-2407-14-711

    Article  CAS  Google Scholar 

  22. Azria D, Belkacemi Y, Romieu G, Gourgou S, Gutowski M, Zaman K et al (2010) Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial. Lancet Oncol 11(3):258–265

    Article  CAS  Google Scholar 

  23. Keenan LG, Lavan N, Dunne M, McArdle O (2019) Modifiable risk factors for acute skin toxicity in adjuvant breast radiotherapy: dosimetric analysis and review of the literature. Med Dosim 44(1):51–55

    Article  Google Scholar 

  24. Taher AN, El-Baradie MM, Essa H, Zaki O, Ezzat S (2004) Hypofractionation versus conventional fractionation radiotherapy after conservative treatment of breast cancer: early skin reactions and cosmetic results. J Egypt Natl Canc Inst 16(3):178–187

    Google Scholar 

  25. De Santis MC, Bonfantini F, Di Salvo F, Dispinzieri M, Mantero E, Soncini F et al (2016) Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy. Breast 29:90–95

    Article  Google Scholar 

Download references

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Tunis El Manar, 1007, Tunis, Tunisia

    Raouia Ben Amor, Meriem Bohli, Zeineb Naimi, Dorra Aissaoui, Nesrine Mejri & Lotfi Kochbati

  2. Department of Radiation Oncology, Abderrahmen Mami Hospital, 2080, Ariana, Tunisia

    Raouia Ben Amor, Meriem Bohli, Zeineb Naimi, Dorra Aissaoui, Jamel Yahyaoui, Awatef Hamdoun & Lotfi Kochbati

  3. Department of Medical Oncology, Abderrahmen Mami Hospital, 2080, Ariana, Tunisia

    Nesrine Mejri

Authors
  1. Raouia Ben Amor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meriem Bohli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zeineb Naimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dorra Aissaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nesrine Mejri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jamel Yahyaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Awatef Hamdoun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lotfi Kochbati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raouia Ben Amor.

Ethics declarations

Conflict of interest

R. Ben Amor, M. Bohli, Z. Naimi, D. Aissaoui, N. Mejri, J. Yahyaoui, A. Hamdoun, and L. Kochbati certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript.

Ethical standards

The study has been approved by the institution’s ethics committee. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Patients signed informed consent regarding publishing their data.

Additional information

Data Availability

Research data are stored in an institutional repository and will be shared upon request to the corresponding author.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ben Amor, R., Bohli, M., Naimi, Z. et al. Hypofractionated radiotherapy after breast-conserving surgery: Clinical and dosimetric factors predictive of acute skin toxicity. Strahlenther Onkol 199, 48–54 (2023). https://doi.org/10.1007/s00066-022-01985-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-022-01985-4

Keywords

Search

Navigation