Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Gilani, Syeda Nadia Shah; Mehta, Akash; García-Fadrique, Alfonso; Rowaiye, Babatunde; Jenei, Veronika; Dayal, Sanjeev; Chandrakumaran, Kandiah; Carr, Norman; Mohamed, Faheez; Cecil, Tom; Moran, Brendan

doi:10.1080/02656736.2018.1434902

Cited by 23 publications

(14 citation statements)

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“…Median overall survival for selected patients with PM treated by CRS and HIPEC ranges from 29⋅5 to 95 months 8 -11 . Poor prognostic factors include age above 60 years, deep tissue invasion by tumour, residual disease after CRS, biphasic/sarcomatoid histology, metastatic lymph nodes, and mitotic count greater than 5 per 50 high-power fields 12 . Recent studies 13,14 also suggest that overall survival after CRS and HIPEC may be influenced by the Ki-67 proliferation index.…”

Section: Introductionmentioning

confidence: 99%

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting

et al. 2020

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Background Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video‐conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. Methods Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video‐conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. Results A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien–Dindo grade I–II complications occurred in 16 patients; there was no grade III–IV morbidity or 30‐day in‐hospital mortality. The median follow‐up for the whole cohort was 18·7 months, and the 2‐year survival rate from time of first review at the national PM MDT was 68·3 per cent. Conclusion The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.

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Section: Introductionmentioning

confidence: 99%

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting

et al. 2020

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“…Systemic chemotherapy is rarely effective [2], and cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the new standard of care for selected patients. This treatment has improved survival (median OS of ~100 months), however, many patients still suffer of disease recurrence, especially when CRS fails to remove tumors from inaccessible abdominal loci [3]. Thus, novel therapeutic options to implement in the current surgical and HIPEC procedures are warranted.…”

Section: Introductionmentioning

confidence: 99%

Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma

et al. 2019

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IntroductionTherapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival rates, patients eventually succumb to disease progression. We investigated splicing deregulation both as molecular prognostic factor and potential novel target in DMPM, while we tested modulators of SF3b complex for antitumor activity.MethodsTissue-microarrays of 64 DMPM specimens were subjected to immunohistochemical assessment of SF3B1 expression and correlation to clinical outcome. Two primary cell cultures were used for gene expression profiling and in vitro screening of SF3b modulators. Drug-induced splicing alterations affecting downstream cellular pathways were detected through RNA sequencing. Ultimately, we established bioluminescent orthotopic mouse models to test the efficacy of splicing modulation in vivo.ResultsSpliceosomal genes are differentially upregulated in DMPM cells compared to normal tissues and high expression of SF3B1 correlated with poor clinical outcome in univariate and multivariate analysis. SF3b modulators (Pladienolide-B, E7107, Meayamycin-B) showed potent cytotoxic activity in vitro with IC50 values in the low nanomolar range. Differential splicing analysis of Pladienolide-B-treated cells revealed abundant alterations of transcripts involved in cell cycle, apoptosis and other oncogenic pathways. This was validated by RT-PCR and functional assays. E7107 demonstrated remarkable in vivo antitumor efficacy, with significant improvement of survival rates compared to vehicle-treated controls.ConclusionsSF3B1 emerged as a novel potential prognostic factor in DMPM. Splicing modulators markedly impair cancer cell viability, resulting also in potent antitumor activity in vivo. Our data designate splicing as a promising therapeutic target in DMPM.

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“…For the treatment and in the absence of consensual therapeutic management, 7 the treatment has long been palliative. Currently, a more aggressive therapeutic management of peritoneal mesothelioma has emerged and has considerably modified the prognosis of the pathology.…”

Section: Discussionmentioning

confidence: 99%

Peritoneal mesothelioma associated with bladder cancer and occupational exposure to asbestos: A case report

Brahim

Mechergui

Said

et al. 2020

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Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Abstract: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

Cited by 23 publications

References 44 publications

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting

Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma

Peritoneal mesothelioma associated with bladder cancer and occupational exposure to asbestos: A case report

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