Observed and Predicted Toxicity in Daily Cone-Beam CT-Based Online Adaptive Stereotactic Partial Breast Irradiation with Decreased PTV Margins

Abstract

Accelerated partial breast irradiation (APBI) delivers smaller radiation volumes over less time compared to whole breast irradiation (WBI), but the organ-at-risk (OAR) sparing allowed by its large (up to 1 cm) planning target volume (PTV) can be improved. PTV can be decreased with daily online adaptive planning, which we hypothesized yields low rates of adverse events observed and predicted by normal tissue complication probability (NTCP) models. Intensity-modulated (IMRT) cone-beam CT (CBCT)-based daily online adaptive stereotactic PBI (A-SPBI) plans with 3-mm PTV from 8 patients were recreated with 1-cm PTV per the Florence APBI IMRT trial planning guideline. Dose statistics with evidence for association with toxicity were compared. Documented toxicities were collected for patients treated with A-SPBI with a minimum follow-up of 3.5 months and Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 grade was assigned. Using α/β = 3 for breast and lung, dose statistics were converted to equivalent doses in 2-Gy fractions (EQD2) for use in NTCP models and for comparison using paired t tests, with differences considered significant if p≤0.05. The table details EQD2 dose statistics for breast, lung, and cosmetic toxicity for A-SPBI plans with 3-mm PTV and their 1-cm PTV re-plans in 8 patients. PTV volume, mean lung dose (MLD), and lung V5, V20, and V30 were significantly lower in 1-cm plans. Acute, subacute (3-6 months), and late toxicities were collected for 30 patients followed for a median of 8 months (range 4-13 months). Radiation dermatitis was the most common acute toxicity (n = 16, 53%), followed by hyperpigmentation (n = 12, 40%), fibrosis (n = 9, 30%), and fatigue (n = 9, 30%). One grade 3 radiation dermatitis was the only grade ≥3 toxicity. Six patients (20%) acutely developed breast or axillary edema: 4 (13.3%) resolved, and 2 (6.7%) developed acutely and persist at last follow-up, >6 months after RT. No patient had a lung V20, V30, or MLD meeting thresholds for radiation-induced lung injury, radiation pneumonitis, or symptomatic or imaging-based pneumonitis models, respectively. The breast V55 model predicted a median risk of unfavorable cosmesis of 33% (range 26-44%) for A-SBPI plans and 35% (range 28-51) for 1-cm PTV plans (p = 0.28). Observed acute toxicities are tolerable and rarely persist in patients treated with A-SPBI with 3-mm PTV margins with daily CBCT-based online adaptation. NTCP modeling predicts similar cosmetic outcome to 1-cm margins. The significant reduction in ipsilateral lung dose with a 3-mm PTV in our first 8 patients especially supports daily adaptation in low-risk breast cancer patients with smoking history and/or lung comorbidity.