Hyperthermic Intrathoracic Chemotherapy (HITHOC) for Pleural Disseminated Thymoma: A Systematic Literature Review.

Background: Optimal treatment for thymoma with pleural dissemination (TPD) remains unclear. Extended radical resection is the cornerstone for local treatment but the need for pleuro-pneumonectomy is debatable. Cytoreductive surgery with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) provides an alternative strategy to reduce tumor load and prevent pleural recurrence.

Objective: The aim of this review was to provide an overview of current literature regarding HITHOC for TPD.

Methods: A systematic literature review (PRISMA) was performed in the EMBASE, MEDLINE, Cochrane and Web of Science databases, resulting in 154 papers selected for screening (PROSPERO: CRD42020208242). Title, abstract, and full-text screening resulted in 13 papers subjected to structured data extraction and methodological quality assessment. One additional case from our department was included. Inclusion criteria were original research reporting on patients diagnosed with TPD; oncological outcome reporting; intraoperative HITHOC; and papers written in English, Dutch or German. Methodological quality was assessed using the Risk-of-Bias (RoB)-2 Tool and the Newcastle-Ottawa scale.

Results: HITHOC for TPD was reported in 171 cases. HITHOC-related mortality was absent and morbidity was reported in three cases. Intrathoracic perfusion of a platinum-derivative, often combined with other chemotherapeutic drugs at >40°C for 60 min or longer was always used. Post-HITHOC recurrence was reported in 37/120 cases (31%). In patients with a minimal 1-year follow-up, average time to recurrence was 68.5 months.

Conclusion: Combining cytoreductive surgery and HITHOC is feasible and safe for TPD. The strong heterogeneity in the literature impedes proper outcome analysis. More research is needed to better understand the additional benefit of HITHOC in the TPD setting.