Abstract PS15-05: Hypofractionated volumetric modulated arc therapy for breast cancer: A propensity-score-weighted comparison of radiation-related toxicity according to fractionation and modality
Authors: Kim Nalee , Chang Jee Suk , Keum Ki Chang , Suh Chang-Ok , Shin Hyejung , Kim Yong Bae 
Published: February 2021

Abstract
Background: Recent trials support a shorter, hypofractionated regimen (HF-RT) for breast cancer. Based on START-B trial, 3-week schedules of hypofractionated-RT (HF, 40 Gy/15 fractions) has been adopted as the one of standard of cares. We studied the clinical benefit of combining volumetric modulated arc therapy (VMAT) and HF-RT in the incidence of radiation-related toxicities.Methods: We retrospectively reviewed 4209 patients treated with three-dimensional conventional fractionation (CF-3D, mostly 50·4 Gy/28 fractions) and 1540 patients treated with HF-RT (768 received HF-3D and 772 received HF-VMAT, mostly 40 Gy/15 fractions) between 2005 and 2017 at a tertiary academic center. A total of 2229 patients (38.8%) received regional node irradiation (RNI): 1642 (39.0%), 167 (21.7%), and 420 (54.4%) patients received RNI in the CF-3D, HF-3D, and HF-VMAT, respectively. VMAT was used to HF patients either to minimize cardiac dose in regional RT for unfavorable/challenging cardio-thoracic anatomy (n = 420) or to shorten the treatment time by using 3.2 Gy of simultaneous integrated boost (SIB) in 15 fractions for breast conservation (n = 352). Physician-reported events during/within 3 months after RT were defined as acute/subacute toxicity. Late toxicities included radiation pneumonitis, lymphedema, hypothyroidism, and cardiotoxicity. Propensity scores were calculated via logistic regression then inverse probability of treatment weighting analysis was performed for pairwise comparison.Result: The rate of grade 2+ acute/subacute toxicities were the highest in patients treated with CF-3D (15.0%, 2.6%, and 1.6% in patients treated with CF-3D, HF-3D, and HF-VMAT, respectively; p &lt; 0.001). HF-VMAT significantly reduced grade 2+ acute/subacute toxicities compared to CF-3D (odds ratio [OR] 0.11, p &lt; 0.001) and HF-3D (OR 0.45, p = 0.010). The 3-year cumulative rate of late toxicities was 18·0% (20·1%, 10·9%, and 13·4% in patients treated with CF-3D, HF-3D, and HF-VMAT, respectively; p &lt; 0·001). The sensitivity analysis showed that the benefit of HF-VMAT was greater in the regional RT group. The local recurrence rate did not differ among the groups (p &gt; 0·05).Conclusion: HF was associated with decreased toxicities than CF in this real-world inverse probability of treatment weighting analysis cohort. HF-VMAT further decreased acute and late toxicity than HF-3D or CF-3D, especially in women underwent RNI, although prospective long-term follow-up is needed. The shortening of overall treatment time by SIB-VMAT in HF may be of value.
Table. Pairwise comparisons of outcomes by treatment group after propensity score weightingOutcomeCF-3D vs. HF-3D (reference: CF-3D)CF-3D vs. HF-VMAT (reference: CF-3D)HF-3D vs. HF-VMAT (reference: HF-3D)OR (95% CI)POR (95% CI)POR (95% CI)PAcute or subacute toxicity with any grade ≥20.20 (0.15-0.27)&lt;.00010.11 (0.08-0.17)&lt;.00010.45 (0.24- 0.83)0.0101HR (95% CI)PHR (95% CI)PHR (95% CI)PLate toxicity0.79 (0.69-0.90)0.00060.58 (0.50-0.68)&lt;.00010.79 (0.60-1.03)0.0838Radiation pneumonitis1.54 (1.16-2.04)0.00290.27 (0.15-0.48)&lt;.00010.14 (0.06-0.29)&lt;.0001Lymphedema0.96 (0.81-1.14)0.65400.85 (0.71-1.03)0.09470.98 (0.71-1.35)0.9279Hypothyroidism0.25 (0.15-0.42)&lt;.00010.16 (0.08-0.32)&lt;.00011.67 (0.40-6.67)0.4886Cardiotoxicity0.56 (0.38-0.83)0.00390.38 (0.23-0.66)0.00050.76 (0.32-1.79)0.5369Locoregional recurrence0.93 (1.28-1.79)0.13091.15 (0.79-1.67)0.47000.74 (0.39-1.41)0.3543Abbreviations: CF, Conventional fractionation; 3D, three-dimensional conformal radiation therapy; HF, Hypofractionation; VMAT, Volumetric-modulated arc therapy; OR, odds ratio; HR, hazard ratio; CI, confidence interval.
Citation Format: Nalee Kim, Jee Suk Chang, Ki Chang Keum, Chang-Ok Suh, Hyejung Shin, Yong Bae Kim. Hypofractionated volumetric modulated arc therapy for breast cancer: A propensity-score-weighted comparison of radiation-related toxicity according to fractionation and modality [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-05.