Molecular Characterization of Testicular Mesothelioma and the Role of Asbestos as a Causative Factor.

CONTEXT.­: Mesothelioma of the tunica vaginalis testis (TVT) is an extremely rare form of mesothelioma. OBJECTIVE.­: To compare the clinical and molecular characteristics of mesothelioma of the TVT with those of mesothelioma at other more common sites, including the relationship with exposure to asbestos. DESIGN.­: We present clinical and pathological data for 9 cases of primary TVT mesothelioma. We performed whole-genome sequencing on 3 cases for the first time. RESULTS.­: The majority (7 of 9 cases) of TVT mesotheliomas were epithelioid, with the remaining 2 cases showing biphasic morphology. Morphology and immunohistochemical profiles were indistinguishable from mesothelioma elsewhere. Asbestos exposure was documented for 7 of the 9 cases, with no information for 2 cases. The 3 TVT mesothelioma cases that underwent whole-genome sequencing displayed a mutational profile similar to that of mesothelioma at other sites, including NF2 and TP53 mutations. CONCLUSIONS.­: The clinical and molecular profile of TVT mesothelioma is similar to that of mesothelioma elsewhere.

Study protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).

INTRODUCTION: This is a phase 1, open-label, single-centre, uncontrolled, dose-escalation study to evaluate the feasibility, tolerability and pharmacokinetic profiles of a single dose of liposomal curcumin, administered via an existing tunnelled indwelling pleural catheter (TIPC) directly to the tumour site in individuals with diagnoses of malignant pleural effusion. Primarily, we aim to determine a maximum tolerated dose of liposomal curcumin administered via this method. METHODS AND ANALYSIS: We will use a 3+3 expanded cohort for predefined dose-escalation levels or until a predefined number of dose-limiting toxicities are reached. Participants will be administered a single dose of liposomal curcumin (LipoCurc, SignPath Pharma) via their existing TIPC as a sequential enrolling case series with the following dose cohorts: 100, 200 and 300 mg/m2. Primary endpoints are determination of the maximum tolerated dose within the predetermined dose range, and determination of the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC. Secondary endpoints include determination of the safety and tolerability of intrapleural administration of liposomal curcumin, median overall survival, effects on quality of life and on feelings of breathlessness, and the pharmacokinetics and concentrations of curcumin from the plasma and the pleural fluid. Important inclusion criteria include age ≥18 years, an existing TIPC, a pleural biopsy or pleural fluid cytology-proven diagnosis of malignant pleural effusion and for whom no antitumour therapy of proven benefit is available or has been previously declined, eastern cooperative group performance status <2. ETHICS AND DISSEMINATION: The study protocol has been approved by the Southern Adelaide Local Health Network Human Research Ethics Committee (HREC) (approval number: HREC/20/SAC/11). Study results will be published in peer-reviewed journals, and presented at conferences, in field of medical oncology and respiratory medicine. TRIAL REGISTRATION NUMBER: ACTRN12620001216909. PROTOCOL VERSION NUMBER: V.1.0.