Carbon-Ion Radiation Therapy as Nonsurgical Treatment for Early-Stage Breast Cancer: 5-Year Results From the Phase 2 Part of the First Prospective Clinical Trial.

To evaluate the long-term efficacy, safety, and cosmetic outcomes of carbon-ion radiation therapy (C-ion RT) as a nonsurgical treatment option for patients with early-stage breast cancer.

This single-center, prospective phase 1/2 trial enrolled women aged ≥60 years with stage I (cT1N0M0), estrogen receptor-positive, human epidermal growth factor receptor type 2-negative invasive ductal carcinoma, ≤2 cm in diameter. Patients received C-ion RT at a total dose of 60 Gy (relative biological effectiveness) in 4 fractions, followed by adjuvant aromatase inhibitors. The primary endpoint was 5-year local control. Secondary endpoints included complete response (CR) rate, adverse events (AEs), cosmetic outcomes, disease-free survival, and overall survival. Imaging was used for evaluating tumor response, and follow-up was conducted for a median of 73 months.

Twelve patients were treated in the phase 2 component of the trial. The CR rate was 100%, with a median time to CR of 12 months (range, 4-36 months). The 5-year local control and disease-free survival rates were both 92%, and the overall survival rate was 100%. One case of in-field recurrence occurred in a patient with a high Ki-67 index. Acute grade 1 dermatitis was observed in 6 patients. No grade ≥2 acute AEs were reported. Regarding late AEs, grade 1 rib fractures (n = 2) and grade 1 mastitis-related pain (n = 3) were managed conservatively. Magnetic resonance imaging revealed subclinical pectoral muscle inflammation in 7 cases. All patients except one (who underwent mastectomy due to recurrence) maintained excellent cosmetic outcomes.

C-ion RT demonstrated excellent long-term tumor control with minimal toxicity and favorable cosmetic outcomes in selected patients with early-stage breast cancer. These findings support its potential as a nonsurgical alternative for patients who are medically inoperable or decline surgery, warranting further investigation in larger, controlled trials.
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Authors

Okonogi Okonogi, Karasawa Karasawa, Murata Murata, Omatsu Omatsu, Murata Murata, Wakatsuki Wakatsuki, Ishikawa Ishikawa
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