The purpose of this trial is to compare the toxicities and efficacy of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) for breast cancer patients indicated for radiotherapy including preoperative radiotherapy, postoperative radiotherapy, or definitive radiotherapy. IMPT or IMRT will be administered to the whole breast, chest wall, and/or regional lymph nodes. A boost dose will be delivered in patients with high-risk area, at the discretion of the radiation oncologist. Eligible breast cancer patients will be followed for at least 5 years to assess acute and late radiation induced toxicities, loco-regional recurrence, overall survival, distant metastasis, and quality of life.
Aged ≥18 years old
Karnofsky Performance Status (KPS) score ≥70
Histologically confirmed breast cancer with indications for preoperative radiotherapy, postoperative radiotherapy, or definitive radiotherapy as determined by the treating physician.
ER (estrogen-receptor), PR (progesterone-receptor), HER2 (human epidermal growth factor receptor 2), and Ki67 testing must be performed on the primary breast tumor.
Pregnant or lactating women.
Severe non-neoplastic medical comorbidities that may interfere with treatment or study participation.
Active collagen vascular disease or other autoimmune disorders that could significantly increase the risk of radiation toxicity.
Patients with contraindications to undergoing IMPT or IMRT, such as severe claustrophobia that cannot be managed or inability to remain immobilized during treatment.
Breast cancer patients aged ≥18 years with histologically confirmed disease and indications for preoperative radiotherapy, postoperative radiotherapy, or definitive radiotherapy, as determined by the treating physician, who are willing to receive radiotherapy using IMPT or IMRT.
Cohort
Prospective
Postoperative radiotherapy
RadiationRadiotherapy was administered using IMPT or IMRT. The target volume includes the ipsilateral whole breast, chest wall, and/or regional lymph nodes. A hypofractionated regimen of 40-42.5 Gy (RBE) in 15-16 fractions is preferred. A conventional fractionated regimen of 45-50.4 Gy (RBE) at 1.8-2 Gy per fraction in 25-28 fractions or an ultra-hypofractionated regimen of 26 Gy (RBE) in 5 fractions is also allowed. A tumor bed boost will be provided to patients with high-risk factors following breast-conserving surgery, at the discretion of the radiation oncologist. The tumor bed boost regimen may consist of a sequential boost of 10-16 Gy (RBE) in 5-8 fractions, or 10-13.35 Gy (RBE) in 4-5 fractions or 10.4 Gy (RBE) in 2 fractions, or a simultaneous integrated boost of 48-49.5 Gy (RBE) in 15-16 fractions.
Preoperative Radiotherapy
RadiationRadiotherapy was administered using IMPT or IMRT. The target volume includes the ipsilateral whole breast, chest wall, and/or regional lymph nodes. A hypofractionated regimen of 40-42.5 Gy (RBE) in 15-16 fractions is preferred. A conventional fractionated regimen of 45-50.4 Gy (RBE) at 1.8-2 Gy per fraction in 25-28 fractions or an ultra-hypofractionated regimen of 26 Gy (RBE) in 5 fractions is also allowed.
Definitive Radiotherapy
RadiationRadiotherapy was delivered using IMPT or IMRT. The target volume encompassed the ipsilateral whole breast and regional lymph nodes. A hypofractionated regimen of 40-42.5 Gy (RBE) in 15-16 fractions was preferred. Alternatively, a conventional fractionated regimen of 45-50.4 Gy (RBE) at 1.8-2 Gy per fraction in 25-28 fractions or an ultra-hypofractionated regimen of 26 Gy (RBE) in 5 fractions was permitted. Dose escalation was applied in high-risk areas, resulting in a total prescribed dose exceeding 66 Gy (RBE) when calculated as equivalent doses in 2-Gy fractions (EQD2), with an α/β ratio of 4.
Complication Rate of ≥Grade 2 Acute Radiation-Induced Toxicity
Acute radiation-induced toxicities will be assessed and recorded from the start of radiotherapy to six months after its completion. Evaluations will occur weekly during treatment, and at 2 weeks, 4 weeks, 3 months, and 6 months post-treatment. The assessment will utilize the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema and the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Complication Rate of ≥Grade 2 Late Radiation-induced Toxicity
From six months after the completion of radiotherapy to five years post-treatment, any late radiation-induced toxicity will be assessed and recorded every six months during the first two years, and annually thereafter. Assessments will utilize the Radiation Therapy Oncology Group (RTOG) /European Organization for Research on Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring Schema and CTCAE 5.0
Locoregional recurrence
Any first recurrence confirmed by histology or cytology within the ipsilateral breast or chest wall and/or regional nodes area (including supraclavicular, infraclavicular, axillary, or internal mammary lymph nodes)
Distant Metastasis-Free Survival (DMFS)
The duration from the date of enrollment to the occurrence of any breast tumor recurrence at distant sites, death from any cause, or the last follow-up.
Invasive Recurrence-Free Survival (iRFS)
The duration from the date of enrollment to the occurrence of the first invasive breast tumor recurrence, death from any cause, or the last follow-up.
Quality of Life using self-administered questionnaire EORTC QLQ-C30
The time from the date of enrollment to 5 years after completion of radiotherapy, Quality of life will be assessed before radiotherapy, every 6 months during the first 2 years and annually thereafter using self-administered questionnaire EORTC QLQ-C30
Number of Participants with Excellent or Good Cosmetic Outcomes Following Breast-Conserving Surgery
The duration from the date of enrollment to five years after the completion of radiotherapy will be assessed for cosmetic outcomes. Evaluations will occur before radiotherapy, every 6 months during the first two years, and annually thereafter. Cosmetic outcomes will be assessed using the Allegheny General Modification of the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scoring scale, which classifies patients into the following four categories: Excellent: Minimal or no difference in size or shape of the treated breast compared to the untreated breast. Good: Slight difference in size or shape of the treated breast. Fair: Obvious difference in size or shape of the treated breast. Poor: Marked change in size or shape of the treated breast.
Patient-Reported Outcomes (PRO) survey
PRO are measures that capture patients' perceptions of their health status, symptoms, and quality of life directly from the patients, without interpretation by healthcare providers. In this study, PROs will be assessed at baseline before the initiation of radiotherapy, then every 6 months during the first 2 years, and annually thereafter.
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Ruijin Hospital
Lead sponsor
Shandong Cancer Hospital and Institute
Collaborator
Sichuan Cancer Hospital and Research Institute
Collaborator
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Collaborator
Tongji Hospital
Collaborator
