Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients

Cinzia Digesù, Francesco Deodato, Gabriella Macchia, Savino Cilla, Martina Pieri, Alice Zamagni, Andrea Farioli, Milly Buwenge, Gabriella Ferrandina, Alessio G Morganti, Cinzia Digesù, Francesco Deodato, Gabriella Macchia, Savino Cilla, Martina Pieri, Alice Zamagni, Andrea Farioli, Milly Buwenge, Gabriella Ferrandina, Alessio G Morganti

Abstract

Aim: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma.

Methods: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224.

Results: Median follow-up was 52 months (range: 3-115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38-3.34 and HR: 1.12, 95% CI: 1.07-1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08-1.20 and HR: 1.14, 95% CI: 1.01-1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61-3.41 and HR: 3.07, 95% CI: 1.11-8.53, respectively) compared to CG.

Conclusion: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1-G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

Keywords: breast cancer; hypofractionation; radiotherapy; retrospective study.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Example of the used IMRT technique (forward-planned). Notes: The two tangential beams were divided into two different segments: one segment (A) was designed to include the WB without filters (6 MV photons) and a second segment (B) was directed to the area of under dosage to compensate for dose loss (15 MV photons). Abbreviations: IMRT, intensity-modulated radiotherapy; WB, whole breast.
Figure 2
Figure 2
Actuarial grade 1 late subcutaneous toxicity-free survival vs treatment technique. Notes: The y axis indicates survival probability; the red colour shows the control group curve; the blue colour shows the MARA-1 curve.
Figure 3
Figure 3
Actuarial grade 2 late subcutaneous toxicity-free survival vs treatment technique. Notes: The y axis indicates survival probability; the red colour shows the control group curve; the blue colour shows the MARA-1 curve.

References

    1. Poortmans P. Evidence-based radiation oncology. Breast cancer. Radio-ther Oncol. 2007;84:84–101.
    1. Clarke M, Collins R, Darby S, et al. 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 randomized trials. Lancet. 2005;366:2087–2106.
    1. Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995;333(22):1456–1461.
    1. Xs Q, White J, Xa L. Is alpha/beta for breast cancer really low? Radiother Oncol. 2011;100:282–288.
    1. Evans PM, Donovan EM, Partridge M, et al. The delivery of intensity modulated radiotherapy to the breast using multiple static fields. Radiother Oncol. 2000;57(1):79–89.
    1. Fletcher GH. Hypofractionation: lessons from complications. Radiother Oncol. 1991;20(1):10–15.
    1. Owen JR, Ashton A, Bliss JM, 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(6):467–471.
    1. Haviland JS, Owen JR, Dewar JA, 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;14:1086–1094.
    1. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–520.
    1. Smith BD, Bentzen SM, Correa CR, 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(1):59–68.
    1. Jagsi R, Griffith KA, Boike TP, et al. 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, published online. 2015
    1. Morganti AG, Cilla S, Valentini V, et al. Phase I-II studies on accelerated IMRT in breast carcinoma: technical comparison and acute toxicity in 332 patients. Radiother Oncol. 2009;90(1):86–92.
    1. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) Int J Radiat Oncol Biol Phys. 1995;31(5):1341–1346.
    1. Yarnold J, Ashton A, Bliss 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(1):9–17.
    1. Buwenge M, Cammelli S, Ammendolia I, et al. Intensity modulated radiation therapy for breast cancer: current perspectives. Breast Cancer. 2017;9:121–126.
    1. Morganti AG, Cilla S, de Gaetano A, et al. Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When? J Appl Clin Med Phys. 2011;12(2):3451–222.
    1. Harsolia A, Kestin L, Grills I, et al. Intensity-modulated radiotherapy results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. Int J Radiat Oncol Biol Phys. 2007;68(5):1375–1380.
    1. Mcdonald MW, Godette KD, Butker EK, Davis LW, Johnstone PA. Long-term outcomes of IMRT for breast cancer: a single-institution cohort analysis. Int J Radiat Oncol Biol Phys. 2008;72(4):1031–1040.
    1. Pignol JP, Truong P, Rakovitch E, Sattler MG, Whelan TJ, Olivotto IA. Ten years results of the Canadian breast intensity modulated radiation therapy (IMRT) randomized controlled trial. Radiother Oncol. 2016;121(3):414–419.
    1. Yarnold J. Radiation therapy in treating women who have undergone breast conservation surgery and systemic therapy for early breast cancer. [Accessed February 26, 2018]. Available from: . NLM identifier NCT00818051.
    1. Vicini F. Higher per daily treatment-dose radiation therapy or standard per daily treatment radiation therapy in treating patients with early-stage breast cancer that was removed by surgery. [Accessed February 26, 2018]. Available from: . NLM identifier NCT01349322.

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