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. 2018 Oct 3:10:143-151.
doi: 10.2147/BCTT.S167914. eCollection 2018.

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

Cinzia Digesù  1 , Francesco Deodato  1 , Gabriella Macchia  1 , Savino Cilla  2 , Martina Pieri  3 , Alice Zamagni  4 , Andrea Farioli  5 , Milly Buwenge  4 , Gabriella Ferrandina  6 , Alessio G Morganti  4
Affiliations

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

Cinzia Digesù et al. Breast Cancer (Dove Med Press). .

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.

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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.
See this image and copyright information in PMC

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