Hyperthermic Intrathoracic Chemotherapy for the treatment of pleural metastases from thymic tumors: survival outcomes and prognostic factors

Background: Thymoma and thymic carcinoma (TC) are thymic epithelial tumors (TETs), which are the most frequent malignancies of the anterior mediastinum, but rare amongst all cancers. They frequently metastasize in the pleura and pericardium which presents a major therapeutic challenge due to a high recurrence rate. There is a lack of standardization in the treatment of pleural metastases. Surgery is the cornerstone of therapy, presenting the best strategy for overall survival, but it alone may not provide the best local disease control. Hyperthermic intrathoracic chemotherapy (HITOC) could provide a promising addition to surgery, to better eradicate microscopic residual disease, while simultaneously avoiding the systemic toxicity of traditional chemotherapy. Aim of the research: This study aims to determine the overall survival (OS) and recurrence free survival (RFS) of patients treated with HITOC in addition to cytoreductive surgery for pleural metastases of thymoma or TC, and prognostic factors influencing survival and recurrence after the intervention. Patients and methods: We retrospectively analyzed medical records and created a database for all the patients having undergone cytoreductive surgery followed by HITOC for pleural metastases of thymoma or TC in our institution. A total of 32 patients fit the inclusion criteria. The interventions were carried out between 2012 to 2025. Patients were classified according to the TNM stage and WHO histological subtype. Survival functions for OS and RFS were estimated using the Kaplan–Meier method and baseline variables were analyzed as potential risk factors for death or recurrence by univariable Cox regression. Significant risk factors identified in the univariable analysis were used to stratify patients for OS and RFS analyses, and survival curves were compared using the log-rank test. Complications were assessed according to the Clavien-Dindo system. Results: OS at 1 year was 92%, at 2 years 87% and at 5 years 76%. Median OS was 108 months. RFS at 1 year was 72%, at 2 years 61% and at 5 years 26%. Median RFS was 28 months. In univariate analysis, histological type of TC was found to be a statistically significant prognostic factor associated with an increased risk of death (p=0.017). OS at 1 year was 96% for thymoma and 50% for TC. At 2 years the OS was 90% for thymoma and 50% for TC. At 5 years OS was 84% for thymoma but there weren’t any TC patients alive after 5 years. Longer disease-free interval (DFI) between the treatment of primary tumor and diagnosis of recurrence was found to be a statistically significant prognostic factor associated with a lower risk of relapse (p=0.015) in univariate analysis. Patients with DFI ≤ 3 years had RFS of 62% at 1 year, 44% at 2 years and 8.9% at 5 years and they had median RFS of 24 months. Patients with DFI > 3 years had RFS of 88% at 1 year, 88% at 2 years and 55% at 5 years. Median RFS was not reached in this group. Relapse after HITOC occurred in 43.8% of cases. Conclusion: We found concerning prognostic factors for survival and recurrence in thymoma and TC patients undergoing surgical resection and HITOC for pleural metastases. Our analysis revealed TC to be a significant prognostic factor associated with shorter survival. Additionally, DFI > 3 years between primary intervention and diagnosis of recurrence was found to be a significant protective prognostic factor against recurrence. Our results on OS and RFS after HITOC are comparable to other literature but we did not find an increase in OS or RFS in patients treated with HITOC compared to other studies. However, comparative cohort studies or case control trials with larger sample sizes are necessary to better understand the efficacy of HITOC. Nevertheless, HITOC is a safe and feasible addition to surgery with potential benefits in local disease control worth exploring.