Effect of HITHOC After Pleurectomy Decortication for Treatment of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Median survival from diagnosis is less than 12 months (1). The widespread use of asbestos in past decades together with the long latency of MPM are responsible for the still increasing incidence of MPM (2), affecting 7-40 people per million inhabitants depending on the geographic region (3). The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). Multimodality treatment for MPM is a topic that has been attracting a lot of attention from researchers, as therapeutic modalities such as surgery, chemotherapy, or radiotherapy have not proven to be effective as single-modality treatments (4). surgery alone is not able to achieve microscopic complete (R0) resection. Therefore, combined treatment modalities have been established in many centres during the last years to achieve a better local tumor control with increasing overall survival (5). In this regard, hyperthermic intrathoracic or intrapleural chemotherapy has been used as one of the multimodality therapies. Intrapleural injection of cytotoxic drugs with hyperthermic perfusion has been proved to enhance cytotoxic effect on tumor cells with limited systemic side effect (6). While cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) has become a standard therapy for intraperitoneal original carcinoma or carcinomatosis peritonei such as pseudomyxoma and colorectal cancer induced ascites (7), limited studies have been reported on the application of hyperthermic intrathoracic chemotherapy (HITHOC) in combination with cytoreductive surgery for the treatment of the malignant pleural mesothelioma (8). 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 (9).

In this study, we aim to compare results of HITHOC after P/D versus P/D alone in managing patients with localised MPM and our main outcomes are disease free survival, overall survival and possible perioperative complications.

Malignant pleural mesothelioma (MPM) is a fatal malignancy with limited options of therapies including surgery, radiotherapy and chemotherapy (10). extensive tumor extraction can be achieved with either extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D. However, significant proportion of patients have relapse of the disease following EPP or P/D and they usually die within a few months (11). Thus, surgery-based multimodality therapies have been clinically explored in the past decades. Intraoperative intrapleural injection of cytotoxic drugs, such as cisplatin, doxorubicin, gemcitabine, or epirubicin, with hyperthermic perfusion at the time of surgery, i.e, hyperthermic intrathoracic chemotherapy (HITHOC), is a widely used method of multimodality treatment for MPM to optimize local disease control (12). The most popular cytotoxic drugs used for HITHOC were cisplatin followed by doxorubicin and mitomycin C, and 41-43 ◦C was most commonly used in HITHOC. The standard time for infusion was 60-90 min across the studies. Intrathoracic instillation of chemotherapeutic agents allows for a much higher concentration of the drug in the pleural cavity potentially improving the cytotoxic effect to the tumor cells and minimizing systemic adverse effects (13).

Eligibility Criteria:
Inclusion Criteria:

* patients presented with localised MPM are the main target and histopathological diagnosis of MPM is made via video-assisted thoracoscopic surgery or open multiple pleural biopsies.

Exclusion Criteria:

* patients with stage III or IV MPM in which cytoreductive surgery has no role.
* Patients underwent extrapleural pneumonectomy (EPP) as a cytoreductive surgery , because we are focusing on P/D only either conventional P/D or extended P/D