Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Patients with Pleural Metastases from Thymic Malignancies

Abstract

Pleural metastases are common sites for recurrence and progression in patients with thymic malignancies. The management of pleural metastases typically involves surgical resection with or without neoadjuvant or adjuvant systemic therapy. After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is standardly used in the management of locally-advanced thymic malignancies, the role of RT in patients with pleural metastases in unclear. Intensity-modulated pleural radiation therapy (IMPRINT) is a RT technique currently being used to treat malignant pleural mesothelioma (MPM) patients with 2 intact lungs at centers that specialize in MPM treatment. This IMPRINT technique can potentially be extrapolated to thymic patients with pleural metastases. Because the risk of toxicity is of greater concern for thymic patients given their overall relatively favorable prognosis, the rate of toxicity, particularly radiation pneumonitis, needs to be established in the thymic patient population. This is a single-arm, single institution Phase II study of hemithoracic IMPRINT for patients with pleural metastases from thymic malignancies. The primary endpoint of this study is grade 3 or higher radiation pneumonitis within 4 months of completing RT. Secondary endpoints include any toxicity, progression-free survival, patterns of failure and overall survival. Patients must have a pathologically confirmed diagnosis of a thymic malignancy with radiologic or pathologic evidence of pleural metastases. Thymoma or thymic carcinoma are allowed. Patients may have de novo stage IVA disease or recurrent disease in the pleura. There must be no evidence of extrathoracic metastatic disease or contralateral pleural/pericardial disease. Surgical resection of the pleural nodules (ex: pleurectomy/decortication, debulking/metastasectomy) are allowed. Extrapleural pneumonectomy is not allowed. Patients are excluded if they have undergone prior thoracic radiation therapy preventing hemithoracic pleural IMRT, whereas prior thymic bed radiation and/or prior pleural SBRT are allowed. RT will be administered to the ipsilateral pleura to 50.4 Gy in 28 fractions. An optional dose-painting boost to gross disease up to 60 Gy while respecting normal tissue constraints is allowed. Patients can be treated with photon or proton therapy. Simulation, contouring and RT planning guidelines have been developed. Patients will be followed per protocol at regular intervals for at least 12 months following RT. The expected accrual is 36 patients over 4 years. Further information can be found on clinicaltrials.gov (NCT05354570). To be determined. To be determined.