Cytoreductive Pleurectomy and Intrathoracic Chemohyperthermia for Pleural Relapse of Thymomas.

Several surgical procedures, from debulking to extrapleural pneumonectomy, may be applied for stage IVa Masaoka thymomas, but their efficiency is still controversial. Case studies have favored R0 resection as the cornerstone of multimodal therapy for locoregional metastatic extension. This report describes a standardized procedure combining a cytoreductive surgical procedure and intrathoracic chemohyperthermia on a 46-year-old patient presenting with B2 thymoma and synchronous unilateral pleural metastasis.

[Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread]. / Radikale Pleurektomie und hypertherme intrathorakale Chemotherapie zur Behandlung pleural metastasierter Thymome.

INTRODUCTION: Patients with pleural thymoma spread (Masaoka stage IV a) should be treated within a multimodal treatment regime. However, the extent of local surgical resection to achieve optimal tumour control remains controversial. PATIENTS AND METHODS: Prospective analysis between September 2008 and April 2013 of all patients with a Masaoka stage IV a thymoma, who underwent radical pleurectomy/decortication (P/D) followed by hyperthermic intrathoracic chemotherapy (HITHOC). RESULTS: A total of 11 patients (male n = 7; mean age 46.5 ± 11.4 years) with a primary stage IV a thymoma (n = 3) or thymoma with pleural relapse (n = 8) were included after successful transsternal thymoma resection. WHO histological classification was: B1 n = 1, B2 n = 6, B3 n = 3 and C n = 1. A radical P/D (5/11; 45 %) was extended with resection of the pericardium and diaphragm in 6/11 (55 %) patients. After surgical resection (91 % complete macroscopic R0/R1-resection) the HITHOC with cisplatin (100 mg/m2 body surface area (BSA) n = 7; 150 mg/m2 BSA n = 4) was performed for one hour at 42 °C. Operative revision was necessary in two patients (chylo- and hematothorax) with one patient also requiring temporary renal replacement therapy due acute renal failure (cisplatin 150 mg/m2 BSA). 30-day mortality was 0 %. Local recurrence (pulmonary n = 1, paravertebral n = 2) was documented in 3/10 (30 %) patients after R0/R1 resection. After a mean follow-up of 23 months the overall median survival was 27 months and 82 % (9/11) patients are still alive at the end of the study period. CONCLUSIONS: Masaoka stage IV a thymoma could be safely treated with lung-sparing radical P/D and HITHOC with cisplatin in a multimodality treatment regime. Early results with respect to recurrence and survival are encouraging, but further studies are warranted and we have to await long-term results.

[Intraoperative chemotherapy after radical pleurectomy or extrapleural pneumonectomy]. / Intraoperative Chemotherapie nach radikaler Pleurektomie oder extrapleuraler Pneumonektomie.

Trimodality treatment including induction and/or adjuvant chemotherapy, surgical resection and in some cases radiotherapy offers a curative intention in selected patients with pleural malignancies (malignant pleural mesothelioma, thymoma with pleural spread). Nevertheless, locoregional tumor recurrence mainly limits the outcome and the quality of life. A few years ago an additional intraoperative chemotherapy perfusion was developed in order to improve local tumor control and prognosis after surgical resection in a multimodality treatment setting. Cytoreductive surgery with the purpose of a macroscopic complete resection could be achieved by radical pleurectomy or extrapleural pneumonectomy. The concept, techniques and perioperative management of this additional treatment option are presented along with a detailed review of the recent literature.

Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.

BACKGROUND: Assessing the pharmacokinetics of intrapleurally administered cisplatin during hyperthermic intrathoracic chemotherapy perfusion (HITHOC) following pleurectomy/decortication in patients with malignant pleural mesothelioma or advanced thymoma with pleural spread. METHODS: Pharmacokinetic analysis (ICP-MS) of intrapleural cisplatin with a dosage of 100 mg/m(2) (n = 5) or 150 mg/m(2) (n = 5) at 42°C perfusate temperature. Simultaneous pleural perfusion fluid and serum samples were collected at the beginning and every 15 min. Serum samples were collected at the end of the operation, 6, 12, and 24 hr postoperative. RESULTS: Mean cisplatin levels in the perfusate slightly decreased during the HITHOC. The mean area under the curve ratios (AUC perfusate :AUC serum ) of cisplatin were nearly similar. The mean AUCs of cisplatin in the perfusate were approximately 58 and 55 times greater than detected in the serum. The mean peak of cisplatin in the serum was reached after 1 hr of HITHOC. The AUC of cisplatin in the serum did not significantly differ (P = 0.18) between both groups up to 24 hr after perfusion. CONCLUSIONS: HITHOC with cisplatin provides a pharmacological advantage of high local intrapleural cisplatin concentrations. Elevation of the cisplatin dosage to 150 mg/m(2) did not lead to a significant increase of the systemic cisplatin concentration.

Induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic pleural irrigation in patients with stage IVA thymoma.

The optimal treatment for Masaoka stage IVA thymoma remains controversial. Whilst extrapleural pneumonectomy (EPP) has been proposed, we sought to examine the results of our institutional preference for induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic pleural irrigation. We undertook a retrospective study of patients undergoing surgery for Masaoka stage IVA thymoma following induction chemotherapy over a three-year period at our institution. Between February 2007 and February 2010, 42 patients underwent surgery for thymoma. Six patients underwent surgery with intent to perform cytoreductive surgery and intraoperative hyperthermic pleural irrigation. Complete cytoreductive surgery was not feasible in one patient and thymectomy only was performed. One patient had re-operation for recurrent disease 24 months after the first operation and there were therefore seven procedures undertaken in six patients during the study period. There were no in-hospital deaths. Median follow-up was 18.8 months (range 1.5-31.9 months). One patient died 14 months postoperatively from an acute cardiovascular event. The four remaining patients are alive and well with no evidence of disease recurrence. Multimodality therapy consisting of induction chemotherapy and cytoreductive surgery is a safe, feasible treatment for stage IVA thymoma. Our experience suggest that full pleurectomy is an alternative to EPP.

Long lasting response to the multikinase inhibitor bay 43-9006 (Sorafenib) in a heavily pretreated metastatic thymic carcinoma.

Metastatic thymic carcinoma is an aggressive neoplasm for which multimodal therapies are often ineffective. We describe here a heavily pretreated patient with advanced thymic carcinoma responsive to multikinases inhibitor BAY 43-9006 (Sorafenib). Of note, a hitherto unreported c-kit missense mutation on exon 17 (D820E) identified in tumor cells seems to explain the clinical response and highlight the key role of molecular analysis in predicting efficacy of targeted therapies even in thymic neoplasms.

Intrapleural perfusion hyperthermo-chemotherapy under video-assisted thoracoscopic surgery for malignant pleural dissemination: a case report.

We report the case of a 45-year-old man treated with intrathoracic hyperthermo-chemotherapy (IPHC) under video-assisted thoracoscopic surgery (VATS) for malignant pleural dissemination originating from invasive thymoma. The clinical course of invasive thymoma with malignant pleural dissemination is characterized by early and frequent metastasis and poor survival. In this case, we performed IPHC under VATS with good results. IPHC under VATS is considered a less invasive and more effective approach for malignant pleural dissemination.

Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread.

BACKGROUND: Thymoma and thymic carcinoma with pleural spread have a high rate of locoregional recurrence and poor prognosis. Maximal debulking coupled with aggressive local treatment could offer a chance for cure. This study evaluates the early and midterm results of operation and hyperthermic pleural perfusion with cisplatinum for thymic malignancies. METHODS: Fifteen patients (11 men), 20 to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst) underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All had pleural spread proven before or intraoperatively. Six of the thymoma cases were recurrent. Current operation included resection without pleurectomy (9 patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1 patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural temperature reached 40.3 degrees C to 43 degrees C. The total dose of cisplatinum was 150 mg or more in 14 patients. RESULTS: Complete resection (R0) was achieved in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative mortality, no hemodynamic or respiratory disturbances during perfusion, and no hematologic, neurologic, or renal complications. Complications consisted of significant bleeding (2 patients), fever (2), and air leak (1 patient). Two patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with no evidence of disease at 54 months. Two patients with thymoma died after 7 and 36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive without local recurrence more than 60 months after operation and hyperthermic pleural perfusion. CONCLUSIONS: Operation and thermochemotherpy is feasible and safe in patients with thymic tumors. This method seems to offer excellent local control for patients with stage IV-a thymic malignancies. Midterm results suggest that operation plus hyperthermic pleural perfusion may lengthen survival in stage IV-a thymoma.