The appropriate therapy and prognosis of patients with thymic malignancies is decisively influenced by the local extent and dissemination of the tumor. For this reason, a staging system that reflects these factors is essential. Mainly the Masaoka-Koga classification, which was introduced in 1994, has been applied for this purpose. The rarity of thymic malignancies makes it difficult not only to establish internationally standardized diagnostics and treatment, but also to progress staging. Besides, efforts were made to adapt the classification into a tumor-node-metastasis-based (TNM) system for standardization with the staging of other tumor entities. The 2017 published 8th edition of the TNM Classification of Malignant Tumors introduced several adjustments based on a proposal of the International Association for the Study of Lung Cancer (IASLC) and the International Thymic Malignancy Interest Group (ITMIG). Compared to the Masaoka-Koga classification, surgically good resectable tumor involvements like pericardium, mediastinal fat or mediastinal pleura have been shifted to lower stages. Thus, even more than in Masaoka-Koga classification, tumors are basically divided into completely resectable and thus surgically treatable tumors (stage I, II, IIIA) and advanced stages (stage IIIB, IVA and IVB) that require multimodal therapy.

Background and Objectives: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern.Methods: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018.Results: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m 2 BSA n = 36; 175 mg/m 2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m 2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%).Conclusions: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies. K E Y W O R D S cytoprotection, hyperthermic intrathoracic chemotherapy, hyperthermic intrathoracic chemotherapy, nephroprotection, renal insufficiency

IntroductionObjective of the ‘German hyperthermic intrathoracic chemotherapy (HITOC) study’ is to evaluate the HITOC as additional treatment after surgical cytoreduction for malignant pleural tumours. Even though HITOC is applied with increasing frequency, there is no standardised therapy protocol concerning the technique of HITOC, the selection as well as dosage of chemotherapeutic agents and perioperative management in order to provide a safe and comparable, standardised treatment regime.Methods and analysisThis trial is a retrospective, multicentre observational study, which is funded by the German Research Foundation. Approximately 300 patients will be included. Four departments of thoracic surgery, which are performing the most HITOC procedures in Germany, are contributing to this study: Center for Thoracic Surgery at the University Hospital Regensburg, Thoracic Clinic Heidelberg of the University of Heidelberg, Center for Thoracic Surgery of the Hospital University of Munich and the Department of Thoracic Surgery at the University Hospital Freiburg. All patients who underwent surgical cytoreduction and subsequent HITOC at one of the four centres between starting the HITOC programme in 2008 and December 2019 will be included. Information on the performed HITOC will be obtained, focusing on the technique as well as the applied perfusion solution including the chemotherapeutic agent. Furthermore, parameters of the patient’s postoperative recovery will be analysed to determine 30-day morbidity and mortality.Ethics and disseminationThe approvals by the local ethics committee of the respective clinic and the three participating clinics have been obtained. The results will be presented in conferences and published in a peer-reviewed journal.Trial registration numberGerman Clinical Trials Registry (DRKS00015012; Pre-results).

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.

Although the method of hyperthermic intrathoracic chemotherapy (HITHOC) after cytoreductive surgery is known for more than 20 years now, the interest of the scientific community has been growing especially in recent years with annually increasing numbers of publications. The feasibility and safety of HITHOC has already been demonstrated. The primary objective now is to reach a consent about the optimal implementation and standardization of the procedure. In the international clinical practice of HITHOC the parameters of temperature, duration, type and number of chemotherapeutic agents vary, making a comparison of the short-and long-term results difficult. For about ten years, the combination of surgical cytoreduction and HITHOC has been performed more routinely in several departments of thoracic surgery in Germany, especially in university hospitals. Recently, a group of experts for thoracic surgery of five departments of thoracic surgery elaborated recommendations for the HITHOC procedure in Germany.These recommendations represent a standardized and consistent implementation of HITHOC. Through this, postoperative complications associated to HITHOC should be reduced and a better comparison of the results should be enabled. This article is intended to give a brief overview of the literature, current recommendations in the implementation of HITHOC and also aims to show future perspectives of this procedure.

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients (n = 350) with malignant pleural mesothelioma (n = 261; 75%) and thymic tumours with pleural spread (n = 58; 17%) or pleural metastases (n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone (n = 212; 61%) or cisplatin plus doxorubicin (n = 138; 39%). Low-dose cisplatin (≤125 mg/m2 BSA) was given in 67% of patients (n = 234), and high-dose cisplatin (>125 mg/m2 BSA) was given in 33% of patients (n = 116). Postoperative renal insufficiency appeared in 12% of the patients (n = 41), and 1.4% (n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% (n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin (p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range.

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A complete resection of thymic tumors is known to be the most important prognostic factor, but it is often difficult to perform, especially in advanced stages. In this study, 73 patients with advanced thymic tumors of UICC stages III and IV who underwent radical resection were examined retrospectively. The primary endpoint was defined as the postoperative resection status. Secondary endpoints included postoperative morbidity, mortality, recurrence/progression-free, and overall survival. In total, 31.5% of patients were assigned to stage IIIa, 9.6% to stage IIIb, 47.9% to stage IVa, and 11% to stage IVb. In stages III a R0 resection was achieved in 53.3% of patients. In stages IV a R0/R1 resection was documented in 76.7% of patients. Surgical revision was necessary in 17.8% of patients. In-hospital mortality was 2.7%. Median recurrence/progression-free interval was 43 months (p = 0.19) with an overall survival of 79 months. The 5-year survival rate was 61.3%, respectively. Median survival after R2 resection was 25 months, significantly shorter than after R0 or R1 resection (115 months; p = 0.004). Advanced thymic tumors can be resected with an acceptable risk of complications and low mortality. In stage III as well as in stage IV the promising survival rates are dependent on the resection-status.