Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma *

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From: Chest(Vol. 121, Issue 2)
Publisher: Elsevier B.V.
Document Type: Article
Length: 5,415 words

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Study objectives: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the feasibility and safety of this multimodality treatment in the thoracic cavity.

Design: Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded.

Setting: The Netherlands Cancer Institute.

Patients: Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated.

Interventions: Cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were performed. The mesothelioma patients received adjuvant radiotherapy on the thoracotomy wound and drainage tracts.

Measurements and results: Morbidity and mortality rates were 47% and 0%, respectively. Reoperation was necessary in four cases. Severe chemotherapy-related complications were not observed. A solitary mediastinal and a contralateral pleural thymoma recurrence were successfully treated by radiotherapy and a contralateral HITHOC procedure. All thymoma patients were alive and free of disease after a mean follow-up period of 18 months. After a mean follow-up period of 7.4 months, nine mesothelioma patients are alive. Two mesothelioma patients died of contralateral pleural and peritoneal recurrent disease, while one patient is alive with locoregional recurrence.

Conclusions: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is feasible in patients with pleural thymoma metastases and early-stage MPM, and is associated with acceptable morbidity rates. Early data on locoregional disease control are encouraging, and a phase II study will be conducted.

Key words: cytoreductive; hyperthermia; intrapleural chemotherapy; intrathoracic chemotherapy; malignant mesothelioma; pleural malignancy; surgery; thymoma; thymic carcinoma

Abbreviations: HITHOC = hyperthermic intrathoracic perfusion chemotherapy; MMC = mytomycin-C; MPM = malignant pleural mesothelioma


Intracavitary chemotherapy is based on the dose-response relation of cytostatic drugs, meaning that increased concentrations of cytostatic agents lead to increased tumor cell kill. Infusion of the drug into the cavity will lead to increased exposure of tumor cells adjacent to its surface, while systemic concentrations will remain below toxic levels due to the limited absorption of the drug from the cavity, resulting in limited systemic side effects. (1) Prerequisites for effective intracavitary chemotherapy are the absence of tumor outside the cavity and the surgical removal of all macroscopic tumor, as the penetration of most drugs is limited to a few millimeters. (2,3) To improve the efficacy of chemotherapy, it can be combined with regional hyperthermia. (4) Based on these principles, intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery has been used in the treatment of primary and secondary peritoneal malignancies. (5-11) Results of this treatment in patients with peritoneal mesothelioma were promising. (9-11) The experience with this treatment modality in the thoracic cavity is still limited. (12-16)

Recurrence of thymoma is frequently confined to the pleural cavities opened during the primary surgery, presumably as a result of peroperative seeding. In the stage of pleural dissemination, no curative therapy is known. (17) In several phase II studies, systemic chemotherapy has been reported to be of temporary success....

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Gale Document Number: GALE|A83759061