Comparative Toxicity of Postoperative Proton Versus Photon Intensity-Modulated Radiotherapy(IMRT) in Breast Cancer: A Multicenter, Prospective, Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- Composite Toxicity Event
研究概览
简要总结
This study aims to compare the differences in acute and long-term toxicities between intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT/VMAT) in postoperative breast cancer patients, with a focus on evaluating their impact on critical organs, including the heart, lungs, skin, esophagus, thyroid, and lymphatic tissues. Eligible patients will be followed for at least one year to assess the incidence and severity of both acute and late toxicities, as well as differences in patient-reported outcomes (PROs), cosmetic outcomes following breast-conserving surgery, and overall quality of life.
详细描述
Eligible breast cancer patients will receive either 4005 cGy (RBE) in 15 fractions once daily or 4256 cGy (RBE) in 16 fractions once daily, five times per week. The radiation dose will be delivered to the ipsilateral chest wall or whole breast, with or without regional nodal irradiation, including the ipsilateral supraclavicular, infraclavicular, and high-risk axillary lymph node regions, and optionally the internal mammary lymph node regions. The decision to administer a tumor bed boost will be made by the treating physician. The boost may be delivered either sequentially (10-12.5 Gy (RBE) in 4-5 fractions) or concurrently (48-49.5 Gy (RBE) in 15-16 fractions). The treating physician will evaluate clinical indications to determine the necessity of regional nodal irradiation and whether the internal mammary nodes should be included in the regional nodal clinical target volume (CTV). All patients will undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT).
The primary endpoint is a composite of toxicity events, including grade ≥2 ipsilateral arm lymphedema within one year post-radiotherapy, grade ≥2 lymphopenia within three months post-treatment, or grade ≥1 cardiac toxicity within one year post-treatment. Patients will be followed for at least one year to assess acute and late toxicities, cosmetic outcomes (patient-reported) in those undergoing breast-conserving surgery, and quality of life.
Due to the greater difficulty in enrolling patients for IMPT compared to IMRT, the study employs an unbalanced 2:1 allocation ratio (IMRT : IMPT = 2:1). Based on an alpha level of 0.05, 80% power, a 2:1 allocation ratio, an assumed 11% difference in toxicity rates between conventional radiotherapy and IMPT during and within one year post-treatment, and a 6.4% anticipated loss-to-follow-up rate, the estimated total sample size is 750 patients (500 in the IMRT/VMAT group and 250 in the IMPT group).
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients aged ≥18 years.
- •Pathological diagnosis of invasive breast cancer or ductal carcinoma in situ.
- •Undergone breast-conserving surgery or total mastectomy, with or without stage I breast reconstruction.
- •For invasive carcinoma, sentinel lymph node biopsy, axillary lymph node sampling, or axillary lymph node dissection was performed.
- •Required postoperative adjuvant radiotherapy.
- •Karnofsky Performance Status (KPS) score ≥
- •The estimated life expectancy of greater than 5 years .
- •Planned to receive photon intensity-modulated radiotherapy (IMRT) or proton IMRT, with written informed consent obtained.
排除标准
- •Prior history of chest radiotherapy.
- •Severe cardiopulmonary dysfunction or other conditions that contraindicate radiotherapy.
- •Pregnancy or breastfeeding.
- •Concurrent active malignancies.
研究组 & 干预措施
Intensity-modulated photon radiotherapy (IMRT/VMAT)
Participants will receive photon intensity-modulated radiation therapy (IMRT) targeting the whole breast or chest wall, with or without regional lymph node irradiation (including the ipsilateral supraclavicular, infraclavicular, and high-risk axillary lymph node regions, and optionally the internal mammary lymph node regions).
干预措施: Intensity-modulated photon radiotherapy (IMRT/VMAT) (Radiation)
Intensity-modulated proton therapy (IMPT)
Participants will receive photon Intensity-modulated proton therapy (IMPT) targeting the whole breast or chest wall, with or without regional lymph node irradiation (including the ipsilateral supraclavicular, infraclavicular, and high-risk axillary lymph node regions, and optionally the internal mammary lymph node regions).
干预措施: Intensity-modulated proton therapy (IMPT) (Radiation)
结局指标
主要结局
Composite Toxicity Event
时间窗: 1 year
Definition: The composite toxicity endpoint is a binary outcome (yes/no), defined as the occurrence of at least one of the following events from the start of radiotherapy up to 1 year post-treatment: Event A (Lymphedema): Development of ≥ Grade 2 upper limb lymphedema;Event B (Lymphopenia): Development of ≥ Grade 2 lymphopenia within 3 months after completion of treatment;Event C (Cardiotoxicity): Development of ≥ Grade 1 cardiotoxicity within 1 year post-treatment. All assessed according to CTCAE v5.0.This primary outcome measure will report the proportion (%) of subjects who experience at least one composite toxicity event.
次要结局
- Acute Radiation-Induced Cardiac Toxicity (RTOG/EORTC)(3 months)
- Acute Radiation-Induced Non-Cardiac Toxicity (CTCAE v5.0)(3 months)
- Chronic Radiation-Induced Skin and Cardiac Toxicity (RTOG/EORTC)(1 year)
- Chronic Radiation-Induced Toxicity - Multi-System (CTCAE v5.0)(1 year)
- Late Radiation-Induced Breast Toxicity (LENT-SOMA)(1 year)
- Breast Cosmetic Outcome(1 year)
- Patient-Reported Outcomes (PROs)(3, 6, 12, 18, 24, 36,48, 60 months)
- Health-Related Quality of Life (HRQoL)(3, 6, 12, 24, 60 months)
- Dose-volume parameters of the Planning treatment volume (PTV)(Upon completion of radiotherapy treatment planning, prior to the first fraction of treatment.)
- Dose-volume parameters of the organs at risk (OARs)(From CT simulation through completion of all treatment fractions (approximately 4 weeks per patient))
研究者
Lu Cao
Associated professor of Department of Radiation Oncology
Ruijin Hospital