Clinical Trials of Curative Partial Breast Irradiation for Early-Stage Breast Cancer Using Carbon Ion Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Our institute conducted clinical trials of curative partial breast irradiation using carbon ion radiotherapy (CIRT) to patients with stage 0 and I breast cancer since 2013. The purpose of this report is to evaluate treatment outcomes up to now. <h3>Materials/Methods</h3> To date, we have conducted three clinical trials and one advanced medical treatment (NIRS9404: AMT). The first study (UMIN000010848: known as Breast I) was 4 fractions partial breast CIRT for stage I luminal patients aged 60 years or older. The AMT protocol was provided in parallel with Breast I in same manner for stage I breast cancer patients who was difficult to register due to minor variant or reject to participate in Breast I. In principle, these patients received maintenance hormone therapy. The next clinical trial (UMIN000029478: known as Breast II) enrolled patients aged 20 years and older without 2 mm or more metastasis in sentinel lymph node for all types of Tis-1N0M0, tumor size 2 cm or less. In this study, 4 fractions CIRT partial breast irradiations were combined with standard systemic therapy and x-ray whole-breast irradiation. And the latest clinical trial (UMIN000046859: known as Breast III) is a single dose of CIRT for luminal Tis-1N0M0 patients aged 50 years and older. All Breast III patients received maintenance hormone therapy. In all trials, Phase I was a dose-escalation study and Phase II was treated with the recommended dose determined in Phase I. <h3>Results</h3> By December 2021, 56 cases have been enrolled. A total of 19 were enrolled In Breast I, 7 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE), and total of 14 were enrolled in AMT. A total of 17 were enrolled In Breast II, 5 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE). A total of 6 were enrolled in Breast III, 3 in Phase I, 3 in Phase II with a recommended dose of 50.0 Gy (RBE). As acute adverse effects, acute radiation dermatitis (grade 2 in 1, Grade1 in 37), mastitis (grade 1 in 6) and myositis (grade 1 in 7) were observed. As late adverse effects, grade 3 pneumonia of unknown causality were observed in 1 case. The cosmetic results of breast were excellent in all cases. Tumor disappearance after CIRT took 3 to 24 months. Local recurrence with axillary lymph node metastasis was observed in one high-risk AMT patient who refused any systemic therapy, but no other recurrences or metastases have been observed. <h3>Conclusion</h3> CIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.