Thymic Carcinoma, Thymic Epithelial Tumor, Thymoma, Thymus Neoplasms
Conditions
Keywords
adverse events, thymoma, thymic carcinoma, clinical trial, thymic epithelial tumors, multicenter, health-related quality of life, postoperative radiotherapy, hypofractionation, proton radiotherapy
Brief summary
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.
Detailed description
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.
Interventions
RADIATIONHypofractionated 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.
RADIATIONHypofractionated 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.
Sponsors
National Taiwan University Hospital
National Taiwan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm study of hypofractionated adjuvant radiotherapy after radical thymothymectomy; photon or proton modality is selected by shared decision-making and is not randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Thymic epithelial tumor, including thymoma or thymic carcinoma, confirmed by pathology. 2. Received radical thymothymectomy. 3. Masaoka-Koga stage I to III disease with an indication for postoperative radiotherapy. 4. Age \>= 18 years. 5. Karnofsky performance status \>= 70%. 6. Life expectancy \>= 1 year. 7. 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. 8. Women of childbearing potential must have a negative qualitative serum or urine pregnancy test within 14 days prior to study entry. 9. Able to comply with study procedures and follow-up schedules and willing to provide study-specific informed consent.
Exclusion criteria
1. Prior radiotherapy to the thorax. 2. 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. 3. Planned receipt of another investigational treatment during radiotherapy. 4. Planned concurrent chemotherapy during radiotherapy. Prior induction or neoadjuvant chemotherapy, or planned sequential adjuvant chemotherapy after adjuvant radiotherapy, is allowed. 5. Pregnant or breastfeeding women. 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 5-year local control rate | 5 years after start of radiotherapy | Local control is defined as absence of radiologically or pathologically confirmed tumor recurrence within the original tumor bed or adjacent mediastinal region. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | Up to 5 years after start of radiotherapy | Time from start of radiotherapy to first documented disease progression, including local, regional, or distant progression, or death from any cause. |
| Overall survival | Up to 5 years after start of radiotherapy | Time from start of radiotherapy to death from any cause. |
| Treatment-related adverse events | From treatment start through 5 years of follow-up | Acute and late treatment-related adverse events graded using CTCAE version 6.0, including grade 2 or higher and grade 3 or higher events, with attention to radiation pneumonitis, esophagitis, and cardiac events. |
| Health-related quality of life | Baseline and 1, 3, 6, 12, 18, and 24 months after radiotherapy | EORTC QLQ-C30 Taiwanese Mandarin version scores, transformed to a 0 to 100 scale according to EORTC guidelines. |
| Cardiac function changes | Baseline through 5 years after radiotherapy | Changes in cardiac sonography (left ventricular ejection fraction \[%\]) from baseline to post-treatment follow-up time points. |
| Pulmonary function changes | Baseline through 5 years after radiotherapy | Changes in pulmonary function tests (including FEV1/FVC ratio \[%\] and DLCO \[%\]) from baseline to post-treatment follow-up time points. |
| Patterns of failure after disease progression | Up to 5 years after start of radiotherapy | Patterns of disease failure after progression, including local, regional, distant, pleural, or pericardial recurrence patterns as assessed by protocol-specified imaging and clinical review. |
Countries
Taiwan
Contacts
CONTACTFeng-Ming Hsu, M.D., Ph.D.
STUDY_CHAIRFeng-Ming Hsu, M.D., Ph.D.
National Taiwan University Cancer Center and National Taiwan University Hospital
Outcome results
None listed