Hypofractionated Adjuvant Radiotherapy for Thymic Epithelial Tumors (THOR)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Thymic Carcinoma; Thymoma; Thymus Neoplasms; Thymic Epithelial Tumor
• Intervention / Treatment: Radiation: Hypofractionated Adjuvant Proton Therapy; Radiation: Hypofractionated Adjuvant Photon Radiation Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feng-Ming Hsu, M.D., Ph.D.; Phone Number: 67061 +886-23123456; Email: hsufengming@ntuh.gov.tw

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
    • Contact: Study Contact; Phone Number: 17450 +886-42205-2121; Email: 094872@tool.caaumed.org.tw
    • Principal Investigator: Chun-Ru Chien, M.D., Ph.D.
  • Taipei, Taiwan, 100229
    • National Taiwan University Hospital
    • Contact: Study Contact; Phone Number: 262643 +886-22312-3456; Email: dr.hsufm@gmail.com
    • Principal Investigator: Chao-Lin Tsai, M.D., Ph.D.
  • Taipei, Taiwan, 106037
    • National Taiwan University Cancer Center
    • Contact: Study Contact; Phone Number: 231600 +886-22322-0322; Email: A01450@ntucc.gov.tw
    • Principal Investigator: Feng-Ming Hsu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypofractionated Adjuvant Radiation Therapy; Participants receive hypofractionated adjuvant radiotherapy after radical thymothymectomy. Photon therapy or proton therapy is selected by shared decision-making between the participant and treating radiation oncologist.

Radiation: 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.; Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year local control rate	Local control is defined as absence of radiologically or pathologically confirmed tumor recurrence within the original tumor bed or adjacent mediastinal region.	5 years after start of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Time from start of radiotherapy to first documented disease progression, including local, regional, or distant progression, or death from any cause.	Up to 5 years after start of radiotherapy
Overall survival	Time from start of radiotherapy to death from any cause.	Up to 5 years after start of radiotherapy
Treatment-related adverse events	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.	From treatment start through 5 years of follow-up
Health-related quality of life	EORTC QLQ-C30 Taiwanese Mandarin version scores, transformed to a 0 to 100 scale according to EORTC guidelines.	Baseline and 1, 3, 6, 12, 18, and 24 months after radiotherapy
Cardiac and pulmonary function changes	Changes in pulmonary function tests, cardiac sonography, and electrocardiography from baseline to post-treatment follow-up time points.	Baseline through 5 years after radiotherapy
Patterns of failure after disease progression	Patterns of disease failure after progression, including local, regional, distant, pleural, or pericardial recurrence patterns as assessed by protocol-specified imaging and clinical review.	Up to 5 years after start of radiotherapy
Exploratory comparison of photon and proton therapy outcomes	Exploratory comparison of baseline characteristics, local control, survival, toxicity, quality of life, cardiopulmonary function, and dosimetric endpoints between patients treated with photon therapy and proton therapy.	Up to 5 years after start of radiotherapy

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: National Taiwan University
• Investigators: Study Chair: Feng-Ming Hsu, M.D., Ph.D., National Taiwan University Cancer Center and National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): April 30, 2035
• Study Completion (Estimated): April 30, 2035

Study Registration Dates

• First Submitted: July 5, 2026
• First Submitted That Met QC Criteria: July 5, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: clinical trial; adverse events; multicenter; health-related quality of life; hypofractionation; thymoma; thymic carcinoma; proton radiotherapy; thymic epithelial tumors; postoperative radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Thoracic Neoplasms; Lymphatic Diseases; Neoplasms, Complex and Mixed; Hemic and Lymphatic Diseases; Thymus Neoplasms; Thymoma; Thymic epithelial tumor
• Other Study ID Numbers: 202603115RINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No