Hypofractionated Adjuvant Radiotherapy for Thymic Epithelial Tumors

Официальное название

Thymic Epithelial Tumor Hypofractionated Adjuvant Radiotherapy (THOR): A Multi-center Single-Arm Prospective Clinical Trial

Обзор

This is a multi-center, open-label, single-arm, prospective interventional study evaluating hypofractionated adjuvant radiotherapy (HART) after radical thymothymectomy in patients with thymic epithelial tumors. The study estimates 5-year local control and prospectively characterizes acute and late treatment-related adverse events, quality of life, cardiopulmonary function, and patterns of failure. Photon therapy and proton therapy are both protocol-acceptable modalities and are selected by shared decision-making rather than randomization.

Подробное описание

Patients with pathologically confirmed thymic epithelial tumors, including thymoma and thymic carcinoma, who have undergone radical thymothymectomy and have an indication for postoperative radiotherapy will receive hypofractionated adjuvant radiotherapy. Base regimens are 40 Gy (RBE) in 15 fractions or 42.5 Gy (RBE) in 16 fractions. For patients with incomplete resection, close margins, residual disease, or other high-risk tumor-bed features, an optional tumor-bed boost may be delivered at investigator discretion, using 10 Gy (RBE) in 4 fractions or, for R2 macroscopic residual disease, 16 Gy (RBE) in 6 fractions. Treatment is delivered once per workday over approximately 3 to 4 weeks, with an additional 1 to 2 weeks if boost is delivered.

Photon therapy with IMRT or VMAT/RapidArc and proton therapy with pencil-beam scanning IMPT are both allowed. Mixed photon and proton treatment courses are not allowed. Target volumes include the mediastinal tumor bed, with pleural or pericardial tumor bed coverage when clinically indicated. Routine elective irradiation of uninvolved mediastinal lymph node stations is not allowed.

Participants are followed at baseline, during treatment, and after treatment at 1, 3, and 6 months, every 6 months through 2 years, and then annually until progression, death, or completion of protocol-specified follow-up. Assessments include clinical evaluation, adverse event assessment using CTCAE version 6.0, CT imaging assessed using RECIST 1.1, pulmonary function testing, cardiac sonography and electrocardiography, EORTC QLQ-C30, and protocol-specified dosimetric analyses.

The primary efficacy analysis uses a Bayesian beta-binomial model for the 5-year local control rate. The study requires 55 evaluable patients, with a total accrual goal of 69 patients to account for approximately 20 percent attrition. Safety monitoring includes semiannual interim reports, annual reports to the ethics committee, and stopping rules for excessive serious adverse events related to the intervention.

Вмешательства

• Лучевая терапия Hypofractionated Adjuvant Proton Therapy
  Base regimen of 40 Gy (RBE) in 15 fractions or 42.5 Gy (RBE) in 16 fractions. Optional tumor-bed boost of 10 Gy (RBE) in 4 fractions or 16 Gy (RBE) in 6 fractions for R2 macroscopic residual disease may be delivered at investigator discretion if normal tissue constraints are met. Radiation is delivered using Proton pencil-beam scanning IMPT.
• Лучевая терапия Hypofractionated Adjuvant Photon Radiation Therapy
  Base regimen of 40 Gy in 15 fractions or 42.5 Gy in 16 fractions. Optional tumor-bed boost of 10 Gy in 4 fractions or 16 Gy in 6 fractions for R2 macroscopic residual disease may be delivered at investigator discretion if normal tissue constraints are met. Treatment is delivered by Photon IMRT/VMAT/RapidArc techniques.

Первичные конечные точки

• 5-year local control rate [Срок оценки: 5 years after start of radiotherapy]

Вторичные конечные точки (7)

• Progression-free survival [Срок оценки: Up to 5 years after start of radiotherapy]
• Overall survival [Срок оценки: Up to 5 years after start of radiotherapy]
• Treatment-related adverse events [Срок оценки: From treatment start through 5 years of follow-up]
• Health-related quality of life [Срок оценки: Baseline and 1, 3, 6, 12, 18, and 24 months after radiotherapy]
• Cardiac function changes [Срок оценки: Baseline through 5 years after radiotherapy]
• Pulmonary function changes [Срок оценки: Baseline through 5 years after radiotherapy]
• Patterns of failure after disease progression [Срок оценки: Up to 5 years after start of radiotherapy]

Критерии участия

Критерии включения

• Thymic epithelial tumor, including thymoma or thymic carcinoma, confirmed by pathology.
• Received radical thymothymectomy.
• Masaoka-Koga stage I to III disease with an indication for postoperative radiotherapy.
• Age >= 18 years.
• Karnofsky performance status >= 70%.
• Life expectancy >= 1 year.
• Sufficient bone marrow reserve, renal function, and liver function within 90 days prior to registration, defined as: white blood cell count >= 2000/mm3; platelet count >= 50,000/mm3; hemoglobin >= 8 g/dL; serum creatinine <= 2.0 mg/dL or estimated glomerular filtration rate >= 30 mL/min; AST/ALT <= 2.5 times the upper limit of normal.
• Women of childbearing potential must have a negative qualitative serum or urine pregnancy test within 14 days prior to study entry.
• Able to comply with study procedures and follow-up schedules and willing to provide study-specific informed consent.

Критерии исключения

• Prior radiotherapy to the thorax.
• Severe active comorbidities that, in the judgment of the investigator, make the patient inappropriate for study entry, interfere with safety or adverse event assessment, or limit compliance with study requirements, including: uncontrolled active infection requiring intravenous antibiotics at registration; transmural myocardial infarction <= 6 months prior to registration; unstable angina or congestive heart failure requiring hospitalization <= 6 months prior to registration; life-threatening uncontrolled clinically significant cardiac arrhythmias; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at registration; uncontrolled psychiatric disorder.
• Planned receipt of another investigational treatment during radiotherapy.
• Planned concurrent chemotherapy during radiotherapy. Prior induction or neoadjuvant chemotherapy, or planned sequential adjuvant chemotherapy after adjuvant radiotherapy, is allowed.
• Pregnant or breastfeeding women.
• Women of childbearing potential and sexually active male participants who are unwilling or unable to use medically acceptable contraception during radiotherapy and for 3 weeks after completing treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 3 центра

• China Medical University Hospital — Taichung
• National Taiwan University Hospital — Taipei
• National Taiwan University Cancer Center — Taipei

Идентификаторы

NCT: NCT07693855 · 202603115RINE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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