Hyperfractionated-Accelerated Reirradiation with Proton Therapy for Radiation-Associated Breast Angiosarcoma

Abstract

Purpose: Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity.

Materials and methods: Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60-75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0.

Results: The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1-4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her posttreatment PET/CT (positron emission tomography-computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved.

Conclusion: HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

Keywords: angiosarcoma; breast cancer; cancer outcomes; hyperfractionated radiation; second malignancies.

Figure 1.

Delineation of gross disease with radio-opaque wire during computed tomography simulation for patient 2 (A) and patient 5 (B). The skin must be closely examined for erythema and edema.

Figure 2.

(A) PBS proton-dose colorwash diagram of the first phase of HART, delivering 45 GyRBE. The clinical target volume is outlined in yellow. The yellow and blue arrows indicate the direction of the en face beams with gantry angles of 10° and 30°, respectively. (B) The same dose colorwash with green crosses and green circles indicating PBS spot placement from the medial beam. The spot weighting is proportional to the circle size. (C) The same dose colorwash with green crosses and green circles indicating PBS spot placement from the lateral beam. The spot weighting is proportional to the circle size. A smooth dose gradient was planned across the overlap region of the 2 beams; a distinct matchline is not required for PBS. Abbreviations: HART, hyperfractionated-accelerated reirradiation; PBS, pencil-beam scanning.

Figure 3.

Photographs of a patient with radiation-associated angiosarcoma of the left lower inner breast showing violaceous skin changes, erythema, and superficial edema in the (A) seated and (B) supine positions. (C) An axial image of the staging positron emission tomography/computed tomography study of the same patient demonstrating extensive skin thickening with moderate fluorodeoxyglucose tracer uptake of the medial left breast.

Figure 4.

Dose colorwash depicting the initial phase to 45 Gy for (A) a PBS treatment plan (mean heart dose, 0.9 GyRBE) and (B) an intensity-modulated radiation therapy treatment plan (mean heart dose, 12.7 Gy). The clinical target volume 1 is outlined in yellow. Abbreviation: PBS, pencil-beam scanning.

Figure 5.

(A) Clinical presentation at the start of radiation therapy. (B) Partial tumor response and associated radiation dermatitis present at the completion of radiation therapy. (C) Radiation dermatitis 13 days after radiation therapy. (D) Clinical appearance 11 months after radiation therapy with no evidence of progressive disease.