Omission of Adjuvant Radiotherapy in Low- and Intermediate-Risk Ductal Carcinoma In Situ After Breast-Conserving Surgery

Phase 3RecruitingNCT07762885

Fudan University636 enrolled

Overview

This is a prospective, multicenter, randomized, open-label, phase III non-inferiority trial designed to evaluate whether omission of postoperative radiotherapy is clinically acceptable in patients with low- and intermediate-risk ductal carcinoma in situ (DCIS) following breast-conserving surgery. Eligible patients include women aged ≥40 years with ER-positive, low- or intermediate-grade DCIS, tumor size ≤2.5 cm, negative surgical margins ≥3 mm, absence of comedo necrosis, and screen-detected unifocal disease. Patients will be randomized to postoperative observation alone or adjuvant radiotherapy. The primary endpoint is 5-year ipsilateral breast tumor recurrence (IBTR).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

636

Conditions

Ductal Carcinoma In Situ, DCIS

Interventions

One of the following protocol-approved radiotherapy regimens may be delivered: * Partial breast irradiation (PBI): 26 Gy in 5 fractions； * Partial breast irradiation (PBI): 40.05 Gy in 15 fractions. * Whole breast ultrahypofractionated radiotherapy: 26 Gy in 5 fractions； * Moderate hypofractionated whole breast radiotherapy: 40.05 Gy in 15 fractions. Radiotherapy should start within 3 months after surgery.

Eligibility

Sex: FEMALEMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female patients aged ≥40 years； 2. Histologically confirmed low- or intermediate-grade ductal carcinoma in situ (DCIS) without invasive carcinoma, including incidental DCIS identified within benign breast lesions； 3. Tumor size ≤2.5 cm on final pathology； 4. Negative surgical margins ≥3 mm, including margins obtained after re-excision； 5. Estrogen receptor-positive disease (ER ≥10%) with planned endocrine therapy using tamoxifen； 6. Unifocal lesion； 7. Absence of comedo necrosis； 8. Screen-detected disease without bloody nipple discharge or palpable mass； 9. Clinically node-negative disease； 10. Patients randomized to the radiotherapy arm must initiate radiotherapy within 3 months after surgery； 11. Central pathology review by the participating institution required； 12. Ability to understand and willingness to sign written informed consent. Exclusion Criteria: 1. Known BRCA1 or BRCA2 germline mutation carriers (genetic testing not mandatory)； 2. Contraindications to radiotherapy, including active connective tissue disease； 3. Active infection requiring systemic treatment； 4. Bilateral breast cancer or prior contralateral breast cancer； 5. Severe uncontrolled comorbidities, including significant cardiac, pulmonary, hepatic, renal, hematologic, or psychiatric disorders； 6. History of other malignancies, including thyroid cancer, except adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ； 7. Prior thoracic radiotherapy； 8. Pregnant or breastfeeding patients； 9. Estimated life expectancy ≤5 years； 10. Poor compliance or inability to adhere to study follow-up requirements.

Outcomes

Primary Outcomes

Ipsilateral Breast Tumor Recurrence (IBTR)

Defined as recurrence of invasive carcinoma or DCIS in the ipsilateral breast.

Time frame: 5 years

Secondary Outcomes

Local-Regional Recurrence (LRR)

Defined as recurrence in the ipsilateral breast, chest wall, supraclavicular region, axilla, or internal mammary region.

Time frame: 5 years

Breast Cancer-Specific Survival (BCSS)

Defined as time from randomization to death due to breast cancer.

Time frame: 5 years

Overall Survival (OS)

Defined as time from randomization to death from any cause.

Time frame: 5 years

Distant Metastasis-Free Survival (DMFS)

Defined as recurrence outside local-regional sites.

Time frame: 5 years

Contralateral Breast Cancer Events

Defined as participants diagnosed with a new primary breast cancer in the contralateral breast. Diagnosis will be confirmed by pathological examination.

Time frame: 5 years

Mastectomy-Free Survival

Defined as participants who are alive and have not undergone mastectomy of the treated breast after initiation of study treatment.

Time frame: 5 years

Second primary malignancies

Defined as participants diagnosed with a new primary malignancy, excluding recurrence or metastasis of the index breast cancer.

Time frame: 5 years

Acute and Late Toxicities

Including radiation dermatitis, radiation pneumonitis, pulmonary fibrosis, cardiovascular events, upper extremity lymphedema, shoulder dysfunction, brachial plexopathy, and hypothyroidism. Toxicity assessment is based on CTCAE 4.0 and RTOG classification.

Time frame: 5 years

Quality-of-Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

Global health quality of life is assessed using the EORTC QLQ-C30. Scores are transformed to a 0-100 scale, with higher scores indicating better global health status and quality of life. Change from baseline will be evaluated during follow-up.

Time frame: 5 years

Quality-of-Life Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module 23 (EORTC QLQ-BR23)

Breast cancer-specific symptom burden is assessed using the EORTC QLQ-BR23. Scores are transformed to a 0-100 scale. Change from baseline will be evaluated during follow-up.

Time frame: 5 years

Omission of Adjuvant Radiotherapy in Low- and Intermediate-Risk Ductal Carcinoma In Situ After Breast-Conserving Surgery

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts