A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer.

Circulating tumour cells (CTCs) from liquid biopsies are under current investigation in several cancers, including epithelial ovarian cancer (EOC) but face significant drawbacks in terms of non-standardised methodology, low viable cell numbers and accuracy of CTC identification. In this pilot study, we report that chemosensitivity assays using liquid biopsy-derived metastatic EOC CTCs, from 10 patients, nine with stage IIIC and one with stage IV disease, in progression after systemic chemotherapy, submitted for hypoxic isolated abdominal perfusion (HAP), are both feasible and useful in predicting response to therapy. Viable metastatic EOC CTCs (>5 cells/mL for all 10 blood samples), enriched by transient culture and identified by reverse transcription polymerase chain reaction (RT-PCR) and indirect immunofluorescence (IF), were subjected to flow cytometry-based Annexin V-PE assays for chemosensitivity to several chemotherapeutic agents and by RT-PCR for tumour gene expression profiling. Using a cut-off value of >80% cell death, CTC chemosensitivity tests were predictive of patient RECIST 1.1 responses to HAP therapy associated with 100% sensitivity, 50% specificity, 33% positive predictive, 100% negative predictive and 60% accuracy values. We propose that the methodology employed in this study is feasible and has the potential to predict response to therapy, setting the stage for a larger study.

Multidisciplinary palliative treatment including isolated thoracic perfusion for progressive malignant pleural mesothelioma: a retrospective observational study.

PURPOSE: To investigate the relative importance of isolated thoracic perfusion (ITP) in the multidisciplinary palliative treatment of progressive malignant pleural mesothelioma (MPM) patients. METHODS: Fifty-two MPM patients with progressive disease after systemic chemotherapy with cisplatin and pemetrexed were submitted to 112 ITP using mitomycin C (25 mg/m2) and cisplatin (70 mg/m2) between 2000 and 2017. Isolation of the chest was achieved by insertion of stop-flow balloon catheters via femoral or iliac access. Primary endpoints were adverse events, tumor response rate, progression-free survival (PFS) and overall survival (OS) from initial ITP. RESULTS: Median interval-time from MPM diagnosis was 9 months. There were no perfusion-related postoperative deaths. The main procedure-related complication was persistent leakage of lymphatic fluid from the incision in less than 10% of ITP. No severe perfusion-related toxicity was reported, with grade 3 haematological toxicity and platinum-induced neurotoxicity in less than 8% of the patients. Following initial ITP, overall tumor response rate was 25%, median PFS was 7 months (IQR 5-10.5), and median OS was 16 months (IQR 12.5-21). After the last ITP, 14 patients received further therapies, including targeted therapy with cetuximab or bevacizumab. Non-epithelioid histology, stage III, and ECOG performance status 3 pre-ITP were prognostic factors with a significant influence on OS. Median OS, calculated from the diagnosis of MPM, was 26.5 months (IQR 22.5-28). CONCLUSIONS: ITP is safe, tolerable, and useful but its inclusion in the multidisciplinary palliative treatment of progressive MPM patients should be investigated in a larger multicentre controlled study.