Surgical Cytoreduction and HITOC for Thymic Malignancies with Pleural Dissemination

Abstract

Background Objective of this study was to assess postoperative morbidity and mortality as well as recurrence-free and overall survival in patients with thymic malignancies and pleural dissemination undergoing surgical cytoreduction and hyperthermic intrathoracic chemotherapy (HITOC). Methods Retrospective study between September 2008 and December 2017 with follow-up analysis in May 2018. Results A total of 29 patients (male: n = 17) with thymic malignancies and pleural spread (primary stage IVa: n = 11; pleural recurrence: n = 18) were included. Surgical cytoreduction was performed via pleurectomy/decortication (P/D; n = 11), extended P/D (n = 15), and extrapleural pneumonectomy (EPP; n = 3). These procedures resulted in 25 (86%) patients with macroscopically complete (R0/R1) resection. Intraoperative HITOC was performed for 60 minutes at 42°C either with cisplatin (100 mg/m2 body surface area [BSA] n = 8; 150 mg/m2 BSA n = 6; 175 mg/m2 BSA n = 1) or with a combination of cisplatin (175 mg/m2 BSA)/doxorubicin (65 mg; n = 14). Postoperative complications occurred in nine patients (31%). Cytoprotective therapy resulted in lower postoperative creatinine levels (p = 0.036), and there was no need for temporary dialysis in these patients. The 90-day mortality rate was 3.4%, as one patient developed multiple organ failure. While recurrence-free 5-year survival was 54%, an overall 5-year survival rate of 80.1% was observed. Survival depended on histological subtype (p = 0.01). Conclusion Surgical cytoreduction with HITOC is feasible in selected patients and offers encouraging survival rates. The application of cytoprotective agents appears to be effective for the prevention of postoperative renal insufficiency.

Hyperthermic intrathoracic chemotherapy (HITHOC): narrative review of the current literature, recommendations and future studies

“…The cohorts range from case series with four patients to a maximum of 104 patients (20,24). The survival (30,31,37). With treatment concepts including only surgery and radiochemotherapy reported 5-year survival rates are between 53% and 88% (38,39).…”

“…With treatment concepts including only surgery and radiochemotherapy reported 5-year survival rates are between 53% and 88% (38,39). When combined with HITHOC, 5-year survival rates of 80-92% were demonstrated (26,28,30,37). Survival in these studies has depended especially on tumor histology since thymic carcinoma showed a considerably worse survival and therefore should be treated and reported as a separate entity (30,37).…”

“…When combined with HITHOC, 5-year survival rates of 80-92% were demonstrated (26,28,30,37). Survival in these studies has depended especially on tumor histology since thymic carcinoma showed a considerably worse survival and therefore should be treated and reported as a separate entity (30,37). The indolent nature of histological subtypes A, AB and B1-3, in turn, makes it certainly difficult to verify an advantage in survival by the application of HITHOC.…”

“…Since approximately 10 years surgical cytoreduction in combination with HITHOC is performed more routinely in several departments for thoracic surgery in Germany, especially in University Hospitals. First experiences have been presented as retrospective studies in meetings and publications (17,25,30,32,43). Based on research data and clinical experiences, the next step was to generate the first expert recommendation in order to develop elementary recommendations for a standardized HITHOC protocol (44).…”

Protocol of a retrospective, multicentre observational study on hyperthermic intrathoracic chemotherapy in Germany

“…2 With the application of the HITOC after macroscopic complete pleural tumour resection, it is expected to obtain better local tumour control, and thereby improve progression-free as well as overall survival. [2][3][4] The few existing case series or single-centre retrospective studies in patients with MPM and thymic tumours have shown some encouraging results in this regard. 2 5-9 However, a prospective study showing an advantage in survival does not yet exist.…”