Risk Factors for Fat Necrosis After Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer in a Phase 1 Clinical Trial

Purpose: This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI).

Methods and materials: Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size <3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up. Treatment data were extracted from the Multiplan Treatment Planning System (Cyberknife, Accuray). Univariate and stepwise logistic regression analyses were conducted to identify factors associated with palpable fat necrosis.

Results: With a median follow-up of 61 months (range: 4.3-99.5 months), 11 patients experienced palpable fat necrosis, 5 cases of which were painful. The median time to development of fat necrosis was 12.7 months (range, 3-42 months). On univariate analyses, higher V32.5-47.5 Gy (P < .05) and larger breast volume (P < .01) were predictive of any fat necrosis; higher V35-50 Gy (P < .05), receiving 2 treatments on consecutive days (P = .02), and higher Dmax (P = .01) were predictive of painful fat necrosis. On multivariate analyses, breast volume larger than 1063 cm³ remained a predictive factor for any fat necrosis; receiving 2 treatments on consecutive days and higher V45 Gy were predictive of painful fat necrosis. Breast laterality, planning target volume (PTV), race, body mass index, diabetic status, and tobacco or drug use were not significantly associated with fat necrosis on univariate analysis.

Conclusions: Early-stage breast cancer patients treated with breast conserving surgery and S-PBI in our study had a fat necrosis rate comparable to other accelerated partial breast irradiation modalities, but S-PBI is less invasive. To reduce risk of painful fat necrosis, we recommend not delivering fractions on consecutive days; limiting V42.5 < 50 cm³, V45 < 20 cm³, V47.5 < 1 cm³, Dmax ≤ 48 Gy and PTV < 100 cm³ when feasible; and counseling patients about the increased risk for fat necrosis when constraints are not met and for those with breast volume >1000 cm³.