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Bidirectional chemotherapy allowing surgery and HIPEC for malignant peritoneal mesothelioma.

ABSTRACT: Background:This case report aims to describe the impact of the bidirectional chemotherapy (BDC) on resecability for initially unresectable malignant peritoneal mesothelioma (MPM). Methods:We report a case of 55-year-old male with the diagnosis of initially unresecable MPM. The BDC combined intravenous (IV) chemotherapy (Cisplatin-Pemetrexed) and intra peritoneal (IP) chemotherapy (Cisplatin). The response to chemotherapy was assessed by CT - scan and laparoscopy. Results:Initial evaluation classed the disease as unresecable with PCI at 39. At the reevaluation, CT - scan and laparoscopy showed a macroscopic response, allowing surgery consisting of cytoreductive surgery and hyperthermic intra peritoneal chemotherapy (Doxorubicin and Cisplatin). Conclusions:BDC (IV and IP) has promising results and allows to undergo surgery for selected patients with borderline or initially unresectable MPM.

SUBMITTER: Noiret B

PROVIDER: S-EPMC6693479 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Bidirectional chemotherapy allowing surgery and HIPEC for malignant peritoneal mesothelioma.

Noiret Barbara B Eveno Clarisse C

Pleura and peritoneum 20190621 2

<h4>Background</h4>This case report aims to describe the impact of the bidirectional chemotherapy (BDC) on resecability for initially unresectable malignant peritoneal mesothelioma (MPM).<h4>Methods</h4>We report a case of 55-year-old male with the diagnosis of initially unresecable MPM. The BDC combined intravenous (IV) chemotherapy (Cisplatin-Pemetrexed) and intra peritoneal (IP) chemotherapy (Cisplatin). The response to chemotherapy was assessed by CT - scan and laparoscopy.<h4>Results</h4>In ...[more]

PMID: 31417959

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Project description:ImportanceMalignant peritoneal mesothelioma is a rare, aggressive tumor arising from the peritoneal lining, induced by asbestos, therapeutic radiation, or germline mutations. Nevertheless, the molecular features remain largely unknown.ObjectiveTo investigate anaplastic lymphoma kinase (ALK) rearrangements in a large series of peritoneal mesothelioma and characterize the mutational landscape of these tumors.Design, setting, and participantsWe studied 88 consecutive patients (39 men, 49 women; median age 61, range 17-84 years) with peritoneal mesotheliomas diagnosed at a single institution between 2005 and 2015. We identified ALK-positive mesotheliomas by immunohistochemistry and confirmed ALK rearrangement by fluorescence in situ hybridization (FISH). In ALK-rearranged cases, we characterized the fusion partners using targeted next-generation sequencing of both tumor DNA and RNA. In select cases, we quantified asbestos fibers by combined scanning electron microscopy and x-ray spectroscopy. We also explored ALK rearrangement in a separate series of 205 patients with pleural mesothelioma.Main outcomes and measuresIdentification and characterization of novel ALK rearrangements and correlations with clinicopathologic characteristics.ResultsAnaplastic lymphoma kinase was positive by immunohistochemistry in 11 (13%) peritoneal mesotheliomas (focal weak in 8, diffuse strong in 3). In focal weak ALK-positive cases, no ALK rearrangement was detected by FISH or next-generation sequencing. In strong diffuse ALK-positive cases, FISH confirmed ALK rearrangements, and next-generation sequencing identified novel fusion partners ATG16L1, STRN, and TPM1. Patients with ALK-rearranged peritoneal mesotheliomas were women and younger than patients without ALK rearrangement (median age 36 vs 62; Mann-Whitney test, P?=?.02), but all other clinicopathologic characteristics (size of tumor nodules, histology, treatment, and survival) were not different. No asbestos fibers were detected in ALK-rearranged cases. Furthermore, loss of chromosomal region 9p or 22q or genetic alterations in BAP1, SETD2, or NF2 typically present in peritoneal mesothelioma were absent in the ALK-rearranged cases. All pleural mesotheliomas were ALK-negative by immunohistochemistry.Conclusions and relevanceWe identified unique ALK rearrangements in a subset of patients with peritoneal mesothelioma, each lacking asbestos fibers, therapeutic radiation, and cytogenetic and molecular alterations typically found in these tumors. Identification of clinically actionable ALK rearrangements may represent a novel pathogenetic mechanism of malignant peritoneal mesothelioma with promise for targeted therapy.

Project description:IntroductionMalignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma.Methods and analysisThe MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma.Intervention4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy.Ethics and disseminationPermission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal.Trial registration numberNTR7060. EudraCT: 2017-000897-12; Pre-Results.

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Bidirectional chemotherapy allowing surgery and HIPEC for malignant peritoneal mesothelioma.

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Bidirectional chemotherapy allowing surgery and HIPEC for malignant peritoneal mesothelioma.

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