Safety and Efficacy of IMPT or IMRT for Breast Cancer

Ruijin Hospital500 enrolled

Overview

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.

Eligible breast cancer patients will receive either preoperative, postoperative, or definitive radiotherapy based on the MDT's recommendation. Patients with indications for treatment will receive either the IMPT or IMRT technique. The specific technique will be chosen based on the benefits of IMPT, patient preference, and reimbursement policies after discussion between the doctor and the patient. The primary endpoint is the occurrence of any acute radiation-induced toxicities of grade ≥2. Patients will be monitored for at least five years to evaluate acute and late radiation-induced toxicities, loco-regional recurrence, overall survival, distant metastasis, and quality of life.

Study Type

OBSERVATIONAL

Enrollment

500

Conditions

Breast Cancer Proton Therapy Intensity Modulated Radiation Therapy

Interventions

Postoperative radiotherapyRADIATION

Radiotherapy 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 RadiotherapyRADIATION

Definitive RadiotherapyRADIATION

Radiotherapy 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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria * 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. * Women of child-bearing potential must agree to use adequate contraception starting 1 month before study treatment and throughout the duration of study participation. * Ability to understand and willingness to participate in the research and sign the informed consent form. Exclusion Criteria * 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.

Outcomes

Primary Outcomes

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.

Time frame: 6 months

Secondary Outcomes

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

Time frame: 5 years

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)

Time frame: 5 years

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.

Time frame: 5 years

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.

Time frame: 5 years

Overall Survival (OS)

The duration from the date of enrollment to the date of death from any cause or the last follow-up.

Time frame: 5 years

Pathologic Complete Response (pCR) Rate After Preoperative Radiotherapy

The percentage of patients who achieve ypT0/is and ypN0 (no invasive residual in the breast or lymph nodes) after preoperative radiotherapy.

Time frame: 8-12 weeks

Progression-Free Survival (PFS) After Definitive Radiotherapy

The duration from the initiation of definitive radiotherapy to the earliest occurrence of any of the following events: Disease Progression: As determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Death: From any cause. Last Follow-Up: If neither progression nor death occurs during the study period.

Time frame: 5 years

Objective Response Rate (ORR) After Definitive Radiotherapy

The percentage of patients who achieve a complete response (CR) or partial response (PR) to definitive radiotherapy, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time frame: 3 to 12 months

Disease Control Rate (DCR) After Definitive Radiotherapy

The percentage of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) to definitive radiotherapy, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time frame: 3 to 12 months

Safety and Efficacy of IMPT or IMRT for Breast Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts