Overview

To evaluate the efficacy and safety of oral thalidomide for the prevention of radiation-induced dermatitis (RID) in breast-conserving surgery patients receiving intensity-modulated whole-breast radiotherapy. This is a single-center randomized controlled trial. Female breast cancer patients aged \>18 and \<70 years after breast-conserving surgery scheduled for whole-breast intensity-modulated radiotherapy will be enrolled. Subjects will be randomized at a 1:1 ratio to the intervention group (thalidomide 75 mg orally every bedtime plus standard skin care) or the control group (standard skin care alone). The observation window is defined as from the start of first radiotherapy to 42 days after completion of last radiotherapy. RID will be assessed weekly according to CTCAE v5.0, and the maximum grade within the observation window will be recorded for each subject. The primary endpoint is the incidence of grade ≥2 RID within the observation window. Secondary endpoints include incidence of grade ≥3 RID, time-to-first-onset of grade ≥2 RID, RID-related symptoms (burning, pruritus, pulling pain, tenderness), quality-of-life measured by EORTC QLQ-C30 / QLQ-BR23. Treatment-emergent adverse events will be documented using CTCAE v5.0, with special attention to thalidomide-related toxicities such as somnolence, peripheral sensory neuropathy and thromboembolism. A total of 68 participants are planned for enrolment.

Eligibility

Inclusion Criteria:

• Female patients with histopathologically confirmed breast cancer after breast-conserving surgery, no distant metastasis, scheduled for intensity-modulated radiotherapy (IMRT).
• Age greater than 18 years and less than 70 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Adequate laboratory examinations obtained within 14 days before enrolment (without prior blood transfusion): white blood cell (WBC) ≥3.0 × 10⁹/L, absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet (PLT) ≥100 × 10⁹/L, hemoglobin (Hb) ≥90 g/L; total bilirubin (TBIL) ≤2.0 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; blood urea nitrogen (BUN) and creatinine (Cr) ≤1.5 × ULN, or creatinine clearance ≥60 mL/min calculated by the Cockcroft-Gault formula.
• No prior history of breast or chest-wall radiotherapy.
• For women of child-bearing potential: negative serum or urine pregnancy test within 72 hours prior to enrolment; fully informed of the teratogenic risk of thalidomide and agree to use dual effective contraception throughout study-drug administration and for 4 weeks after drug discontinuation; subjects refusing contraception are excluded. Post-menopausal women (amenorrhea for ≥12 consecutive months) do not require pregnancy testing.
• Fully informed of the study content, voluntarily provide written informed consent, and are able to complete radiotherapy, study medication, scheduled assessments and follow-up visits.
• For patients who received prior adjuvant chemotherapy: at least a 2-week interval between completion of chemotherapy and commencement of radiotherapy.

Exclusion Criteria:

• History of other malignant tumours (except cured in situ carcinoma).
• Psychiatric disorders or severe cognitive impairment that prevent subjects from completing questionnaires and assessments.
• Pregnant or lactating women.
• Poorly controlled diabetes mellitus (HbA1c \> 7.5%); patients with well-controlled diabetes are eligible.
• Active autoimmune or rheumatic diseases (systemic lupus erythematosus, dermatomyositis, scleroderma, etc.); subjects with stable mild disease without systemic medication may be considered.
• Pre-existing or past history of peripheral neuropathy (numbness, tingling, paraesthesia); prior exposure to thalidomide, lenalidomide, pomalidomide; concomitant use of medications known to induce peripheral neurotoxicity.
• Past history of venous thromboembolism (VTE); hereditary thrombophilia; ongoing oestrogen-containing therapy.
• Severe cardiovascular and cerebrovascular diseases: myocardial infarction, unstable angina or stroke within the past 6 months; left ventricular ejection fraction (LVEF) \< 50%.
• Pre-existing active eczema, psoriasis, chronic dermatitis, unhealed wounds or extensive scarring within the radiation field.
• Contraindications to radiotherapy.
• Known hypersensitivity to thalidomide or excipients of the preparation.
• Planned use of any additional oral or topical agents or dressings for prevention or treatment of radiation-induced dermatitis during study participation.
• Other conditions judged by the investigator making the subject unsuitable for this clinical trial.