Malignant Peritoneal Mesothelioma Research Articles

Desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma: a case report of two rare diseases

BackgroundDesmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma.Case presentationAn early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis.ConclusionsNo adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.

CT Differentiation of Diffuse Malignant Peritoneal Mesothelioma, Tuberculous Peritonitis, and Peritoneal Carcinomatosis

Objective: To investigate the significance of computed tomography findings in diffuse malignant peritoneal mesothelioma (DMPeM), tuberculous peritonitis (TBP), and peritoneal carcinomatosis (PC) to differentiate the three diseases. Methods: The clinical manifestation and computed tomography scans of 147 patients with diffuse malignant peritoneal mesothelioma (n = 60), tuberculous peritonitis (n = 32), and peritoneal carcinomatosis (n = 55) were retrospectively reviewed, while taking into account of ascites, pleural plaques, viscera infiltration; abnormalities in the peritoneum; involvement of the mesentery and omentum; as well as the presence and location of enlarged lymph nodes. Results: There was no significant difference among all three groups in terms of clinical manifestation, peritoneum, omentum, and mesentery involvement, ascites, as well as the presence and location of enlarged lymph nodes. The study found that 95% of DMPeM patients had been exposed to asbestos in the past. The patients showed significant differences in the following aspects: (1) irregular peritoneum thickening, caked omentum thickening, pleural plaques, visceral infiltration, and asbestos exposure were more common in peritoneal mesothelioma patients; (2) nodular peritoneum thickening and visceral metastasis were more common in patients with peritoneal carcinomatosis; (3) smooth peritoneal thickening, pleural effusion, and extraperitoneal tuberculosis were more common in patients with tuberculous peritonitis. Conclusion: A combination of computed tomography findings could improve our ability in differentiating the three diseases.

Malignant Epithelioid Peritoneal Mesothelioma in a middle-aged lady with extensive travel history and longstanding abdominal symptoms

Malignant peritoneal mesothelioma (MPM) is a rare type of mesothelioma, the most common site of mesothelioma being the pleura. It is a malignancy of the peritoneal linings and is sometimes associated with exposure to asbestos. Clinical presentation is usually vague and Imaging (Magnetic resonance imaging (MRI), computed tomography (CT) and positron-emission tomography (PET) is key in evaluation of these patients. Definitive diagnosis is by histopathology/immunohistochemistry and first line treatment is cytoreductive surgery and intraperitoneal chemotherapy.

Long-term Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma

In the United States malignant peritoneal mesothelioma (MPM) is a rare disease with approximately 300 new cases each year. The malignancy progresses within the peritoneal space throughout its natural history so that a majority of patients die as a result of massive disease within the abdomen and pelvis.

Hyperthermic Intraperitoneal Chemotherapy After Cytoreductive Surgery; Experience and Short Term Outcomes

Purpose: Cytoreductive surgery + hyperthermic intraperitoneal chemotherapy is an important treatment option in patients with primary diagnosis of colorectal cancer, ovarian cancer, appendix cancer, gastric cancer (selected cases), malignant peritoneal mesothelioma and peritoneal pseudomyxoma in the presence of peritoneal involvement and resectable lesions limited to the abdomen. In this study, it is aimed to discuss cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) in the light of literature. Patients and methods: The data of patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy between June 2017 and September 2020 at Eskisehir Osmangazi University Medical Faculty Surgical Oncology and Gastroenterology Surgery Departments were analyzed. The study was designed retrospectively, and all patients who were discussed at the oncology council and decided on CRS + HIPEC were included in the study. Results: 31 patients were included in the study. Primary diagnoses of the patients were colorectal cancer in 15 (48%), ovarian cancer in 9 (29%), stomach cancer in 3 (10%), mesothelioma in 2 (7%), appendix cancer in 1 (3%), and also peritoneal pseudomyxoma in 1 (3%). Therapeutic HIPEC was performed in 30 patients, prophylactic HIPEC was performed in 1 patient. Cytoreduction score was 0 in all patients. The median peritoneal cancer index was 15 (7-29). the median number of resected organs was 3(1-6). Stoma formation was performed in 14 patients (45%). During the postoperative 30 days, mortality was observed in 1 patient (3%) and morbidity in 5 patients (16%). Conclusion: The early postoperative mortality and morbidity results which were reported in our study are compatible to those in the literature.

Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study.

Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM. Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%. Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival. MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.

1636P Prognostic indication for malignant peritoneal mesothelioma with tumor-specific and inflammatory biomarkers

Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer of the peritoneal lining of the abdominal cavity. Though early stage MPeM has better outcomes with multimodal treatment, advanced, non-resectable disease has a poor prognosis. No prognostic indicators are available to inform clinical decision-making. We hypothesize inflammatory biomarkers may provide a means of survival assessment.

Molecular Characterization of Mesothelioma: Impact of Histologic Type and Site of Origin on Molecular Landscape.

Mesothelioma is an aggressive malignancy with heterogeneous outcomes that are partly driven by the differential efficacy of existing therapies across histologic types and sites of origin. Large-scale molecular analysis of mesothelioma and its subtypes has the potential to inform future therapeutic strategies. We analyzed 1,294 mesotheliomas {980 pleural (malignant pleural mesothelioma [MPM]) and 314 peritoneal (malignant peritoneal mesothelioma [MPeM])} using next-generation sequencing, determined programmed death ligand-1 (PD-L1) expression and histology in a subset of cases, and assessed MTAP/CDKN2A copy-number status by fluorescence in situ hybridization and T-cell infiltration in an independent cohort. The molecular landscape of MPM was characterized by inactivating alterations in CDKN2A (49%), BAP1 (44%), CDKN2B (42%), MTAP (34%), and NF2 (33%). Compared with epithelioid MPM, nonepithelioid (ie, biphasic and sarcomatoid) MPM had identical tumor mutational burden (median 1.25 mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss (P < .05). Fluorescence in situ hybridization confirmed that homozygous MTAP loss was enriched in nonepithelioid MPM. Relative to MPM, MPeM had comparable tumor mutational burden and PD-L1 expression. The molecular profile of MPeM was similar to MPM, with the distinction that PBRM1 alterations occurred at higher frequency (16% v 7%, P < .01). ALK rearrangements were only observed in MPeM. Regardless of histology and location, the molecular landscape of mesothelioma primarily consists of inactivating alterations in tumor suppressor genes, with enrichment of certain alterations in distinct subsets (eg, MTAP loss in nonepithelioid tumors). Given the limited efficacy of current therapies for this disease, novel approaches targeting recurring alterations should be explored.

Efficacy and Adverse Events of Apatinib Salvage Treatment for Refractory Diffuse Malignant Peritoneal Mesothelioma: A Pilot Study

ObjectiveTo investigate the clinical efficacy and adverse events (AEs) of apatinib salvage treatment for diffuse malignant peritoneal mesothelioma (DMPM) that has failed to respond to the recommended treatments.Methods27 patients with refractory DMPM were treated with apatinib at our center from April 2014 to October 2020, at the initial dose of 250 mg/d. The dose was reduced to 125 mg/d when serious adverse events (SAEs) occurred. 28-day was set as a treatment cycle. The frequency of follow up was once every 28 days. The efficacy evaluation was conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the serum tumor markers before and after apatinib treatment. The safety assessment was performed with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were AEs.ResultsThe 27 patients completed a median treatment-cycle of 15.0, ranging from 5.1 to 39.4 cycles. At the median follow-up of 14.3 (4.8-51.8) months, median overall survival (OS) was 59.4 months, median apatinib-treatment-related survival (ATRS) was 14.0 (4.8-36.8) months. Complete response (CR) was observed in 0 case (0.0%), partial response (PR) in 4 cases (14.8%), stable disease (SD) in 12 cases (44.4%), and progression disease (PD) in 11 cases (40.7%). The ORR was 14.8%, and DCR was 59.3%. The median serum CA125 values before and after apatinib treatment were 32.9 (7.0-4592.4) U/mL and 29.7 (6.1-4327.4) U/mL, respectively (P=0.009). The common AEs were hypertension (6/27; 22.2%), hand-foot syndrome (5/27; 18.5%), albuminuria (4/27; 14.8%), anemia (4/27; 14.8%), leukopenia (4/27; 14.8%), rash (2/27; 7.4%), fatigue (2/27; 7.4%), oral ulcers (2/27; 7.4%), hoarseness (2/27; 7.4%), nausea/vomiting (2/27; 7.4%), diarrhea (2/27; 7.4%), headache (1/27; 3.7%), and fever (1/27; 3.7%). The incidence rate of grade III/IV AEs was 16.2%.ConclusionsApatinib is effective in treating refractory DMPM, with promising efficacy and acceptable safety.

Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.

Prognostic factors of malignant peritoneal mesothelioma: a retrospective study of 52 female patients

BackgroundPrognosis in malignant peritoneal mesothelioma (MPM) remains poor, and the associated factors are unclear. Therefore, this study aimed to investigate the prognostic factors of MPM.MethodsA total of 52 female MPM patients treated in 2012–2017 were retrospectively analyzed. Kaplan-Meier survival curves were generated for survival analysis by the log-rank test. The Cox regression model was used for univariate and multivariate analyses.ResultsUnivariate analysis showed that median survival time (MST) was longer in the epithelioid type compared with the sarcomatoid type (12 months vs 5 months); cumulative survival rates at 12 months were 45.7% and 0%, respectively (P=0.005). MST was longer in patients with proliferating cell nuclear antigen (Ki67) ≤ 10% compared with those with Ki67 > 10% (15 months vs 11 months). Cumulative survival rates at 12 months were 60.0% and 28.1%, respectively (P=0.036). MSTs in patients administered peritoneal biopsy or adnexectomy + paclitaxel + platinum perfusion, peritoneal biopsy (or adnexectomy) + pemetrexed + platinum perfusion, cytoreductive surgery + paclitaxel + platinum perfusion, and cytoreductive surgery + pemetrexed + platinum perfusion were 6, 11, 12, and 24 months, respectively, with cumulative survival rates at 12 months of 0%, 35.7%, 45.5%, and 73.3%, respectively. Survival time after cytoreductive surgery combined with pemetrexed + platinum was the longest. In multivariate analysis, pathological type, T staging, and therapeutic regimen were independent prognostic factors of MPM (P < 0.05).ConclusionsPrognosis in MPM is associated with pathological subtype, clinical staging, cytoreductive surgery, and subsequent pemetrexed use. Radical cytoreductive surgery and postoperative use of pemetrexed prolong survival.

Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60min or 90min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. The median follow-up was 5.0years (95%-CI 4.6-5.5). The median age was 59.2years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60min and 14 patients (16.7%) received it for 90min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.

Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases.

Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients' median age was 55 years (y) (range: 33 to 79y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.

Improved Survival and Quality of Life Through an Integrative, Multidisciplinary Oncological Approach: Pathophysiological Analysis of Four Clinical Cancer Cases and Review of the Literature.

Objectives: According to the National Cancer Institute, the integrative medicine (IM) approach to medical care combines standard medicine with complementary and alternative medicine practices that have proved safe and effective. Methods: We describe the clinical cases of four patients with malignant pleural mesothelioma (MPM), diffuse malignant peritoneal mesothelioma (DMPM), intrahepatic cholangiocarcinoma, and breast cancer (BC) who received supportive treatment (ST) according to an IM approach after the failure of standard cancer treatments or the appearance of serious adverse events caused by antiblastic chemotherapy. The critical role of complementary drugs in reducing the side effects of cancer treatments and normalizing the white cell count is especially apparent in the case of the patient with metastatic BC, who experienced prolonged neutropenia. Results: The IM approach was well-tolerated and had no adverse side effects. It improved the quality of life (QoL) of all patients and in two cases extended overall survival. Conclusion: The extended clinical and instrumental response to IM of the patients with malignant mesothelioma and the improved health-related QoL and good tolerance of the ST demonstrated in all cases support the value of this approach in patients whose cancer therapies have failed but who show a good performance status. Our data require confirmation in a well-designed prospective clinical trial.

Functional Anatomy in Relation to Peritoneal Surface Malignancies (PSM): Lessons Learnt after 254 Cases of Peritonectomy at a Tertiary Oncology Centre in India

Introduction: Peritoneal Surface Malignancies (PSMs) are a heterogenous group of diseases. They are still considered terminal in many tertiary care centers in India. Cytoreductive Surgery (CRS) including peritonectomy has been the main stay of treatment of PSMs. In this article, we elaborate the applied anatomy of peritoneum from macroscopic to microscopic structure, the mechanism of spread, common sites of involvements and the techniques of perfection in CRS leading to better surgical outcomes based on our experience. Methods: We have performed 254 cases of peritonectomy-Total Parietal Peritonectomy (TPP) in 104 cases (40.9%) and disease selective in 150 cases (59.1%) from 2014 to 2021. We have performed TPP in cases of Pseudomyxoma Peritonei (PMP), Malignant Peritoneal Mesothelioma (MPM) and post NACT cytoreduction in all patients of PSMs Results: In all cases of CRS we removed the primary tumor as per standard oncological principles. Apart from this we removed total greater omentum, lesser omentum, omental bursa and all lymph nodes pertaining to respective diseases. The distribution of our patients was Ovarian carcinoma (n = 152), Colorectal (n = 43), PMP (n = 34), MPM (n = 11), Sarcomatosis (n = 7), Gastric Cancer (n = 3) and Miscellaneous (n = 4). With our 7 years’ experience we share our inputs on the anatomical basis of peritoneal carcinomatosis and sarcomatosis. Conclusion: We have performed 254 peritonectomy procedures. On the basis of our experience and evidence, we conclude that anatomy of peritoneum is very important as it is the most common site of recurrence in PSMs after CRS. We recommend TPP in all cases of PMP, MPM and in interval cytoreduction setting. Keywords: CRS; HIPEC; Peritoneum; Peritoneal carcinomatosis; Sarcomatosis

Abstract 2276: High frequency of pathogenic germline variants in patients with malignant mesothelioma

Abstract Background: Malignant mesothelioma (MM) is associated with asbestos exposure, tumor heterogeneity and aggressive clinical behavior. Identification and characterization of germline variants in malignant mesothelioma is relevant for identifying potential actionable targets and genetic counseling of family members. Methods: Patients referred to the Phase I Unit at Rigshospitalet were prospectively enrolled into the Copenhagen Prospective Personalized Oncology trial and underwent whole exome sequencing for somatic and germline variants. Between January 2014 and September 2021, 45 patients with MM were identified and 40 patients underwent whole exome sequencing. Germline variants were selected according to association to inherited cancer using a 168-gene panel and variants were classified according to ACMG/AMP classification as pathological (class 5) or likely pathogenic (class 4). Results: 34 males (85%) and 6 females (15%) with a median age of 64 years (range: 43-77) were available for analysis. The majority (85%) had malignant pleural mesothelioma whilst the rest (15%) had malignant peritoneal mesothelioma. Histological subtypes were distributed between epithelioid type (N=24, 60%), biphasic type (N=12, 30%) and the sarcomatoid type (N=4, 10%). A pathogenic or likely pathogenic variant was found in 16 patients (40%). In total 13 different germline variants were identified (ATM, BAP1, BRCA2, CDKN2A, FANCA, FANCC, FANCD2, FANCM, MUTYH, NBN, RAD51B, SDHA and XPC). The variants included five frameshifts (33%), four missenses (25%), four nonsenses (25%), one splice site (6%), one start loss (6%) and one synonymous (6%). The pathogenic germline variants were found in DNA repair pathways, including homologous recombination repair (69%), nucleotide excision repair (13%), cell cycle regulatory (6%), DNA damage checkpoint control (6%) and hypoxic pathway (6%). Three (19%) of the patients with a germline variant had a second cancer. A previously undiagnosed BRCA2 germline mutation was found in 2 patients. A potential treatment target based on the pathogenic germline variant could be suggested in four patients (10%). Conclusion: The current analysis revealed a high frequency of pathogenic germline variants in patients with malignant mesothelioma. These data support germline testing in these patients and provide a rationale for additional investigation of the homologous recombination pathway as a potential target for precision medicine. Citation Format: Laila Belcaid, Birgitte Bertelsen, Karin A. Wadt, Ida V. Tuxen, Iben Spanggaard, Martin Højgaard, Jens B. Sørensen, Ulrik Lassen, Finn C. Nielsen, Kristoffer Rohrberg, Christina W. Yde. High frequency of pathogenic germline variants in patients with malignant mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2276.

Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly

BackgroundMalignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in elderly individuals. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in elderly MPM patients.MethodsFrom the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥ 65) and the adult group (< 65). We compared the clinical-pathological characteristics and treatment methods of the elderly group (N = 665) and the adult group (N = 827). At the same time, we analysed specific selected clinicopathological parameters and prognostic factors for elderly MPM patients.ResultsCompared with the adult group, the elderly group had higher percentages of male patients (P = 0.017) and white patients (P = 0.043) and lower proportions of insured patients (P < 0.001) married patients (P < 0.001), patients with peritoneal tumours (P = 0.006) and patients who underwent surgery (P < 0.001) and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). Elderly patients had a shorter median survival time than adult patients (6 months vs. 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR 3.913, P < 0.001), poorly differentiated (HR 3.900, P < 0.001), distant metastasis (HR 1.735, P = 0.001), no cancer-directed surgery (HR 1.733, P < 0.001), and no chemotherapy (HR 1.532, P < 0.001) were independently associated with poorer prognosis in elderly MPM patients.ConclusionCompared with adult patients, elderly MPM patients had a higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.

Malignant peritoneal mesothelioma literature review: past, present, and future.

Background and Objective:Malignant peritoneal mesothelioma (MPM) is an insidious neoplasm that arises from the mesothelial lining of the abdominal cavity. Historically, outcomes of MPM were dismal, as MPM is relatively resistant to cytotoxic chemotherapy. However, with advances in technology and improved understanding of tumor pathophysiology, treatments for MPM have produced encouraging 5-year survival. The standard of care for patients with resectable disease remains cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with inoperable MPM can be offered several systemic treatments, including chemotherapy, immune checkpoint inhibitors, or investigational treatments. Our objective is to provide an overview of our current knowledge concerning MPM and latest advances in treatment.Methods:Narrative overview of the literature published in English from database origin until January 31, 2022 relating to MPM was searched in PubMed database, Google Scholar, and ClinicalTrials.gov.Key Content and Findings:CRS-HIPEC has offered improved survival for surgical candidates, however outcomes for inoperable MPM remains dismal. With advancements in technology and better understanding of underlying MPM biology, new treatment approaches are arising and imperative.Conclusions:MPM is a rare and lethal disease of the peritoneum. CRS-HIPEC remains the standard of care for resectable disease. In 2022, several clinical trials are available for patients with MPM offering future advances in therapy and further understanding of this rare disease process.

Clinical activity of pembrolizumab monotherapy in diffuse malignant peritoneal mesothelioma.

8557 Background: Among patients with malignant mesothelioma, pembrolizumab has demonstrated activity in diffuse pleural mesothelioma (DPM), with limited data available for those with diffuse malignant peritoneal mesothelioma (DMPM). DMPM represents a clinically distinct entity from DPM and disease specific outcomes data is needed. We present real world data on the efficacy of pembrolizumab in DMPM. Methods: In this retrospective study, we identified patients with DMPM treated with pembrolizumab at two tertiary care cancer centers between 1/1/2009 and 1/1/2021. Clinicopathologic features were annotated. Median progression free survival (mPFS) and median overall survival (mOS) were calculated using Kaplan-Meier curves. Best overall response rate (BOR) was determined using RECIST 1.1 criteria. Association of partial response with disease characteristics was evaluated using Fisher’s exact test. Results: We identified 24 patients with DMPM who received pembrolizumab (median age 62 years, 63% never smokers, 58% female, 75% had epithelioid histology). All patients received systemic chemotherapy prior to pembrolizumab (median prior lines of therapy: 3). BOR was 17% (3 partial responses, 10 stable disease, 5 progressive disease, 6 lost to follow-up). With a median follow up time of 29.2 months, mPFS was 4.9 months and mOS 20.9 months from pembrolizumab initiation. Three patients experienced PFS of &gt; 2 years. Among the 14 patients who underwent next generation sequencing of tumor tissue, there were 8 somatic BAP1 alterations. Among the 17 patients tested for PDL1, 6 had positive PDL1 expression (1-80%). There was no association between partial response and presence of a BAP1 somatic alteration (p = 0.453), PDL1 positivity (p = 0.7) or non-epithelioid histology (p = 0.55). Conclusions: Pembrolizumab is active in a PDL1 unselected cohort of patients with DMPM. The overall response rate of 17% and mPFS of 4.9 months in this 75% epithelioid histology cohort warrants further investigation to identify those most likely to respond to immunotherapy, especially among epithelioid histology.

Cytoreductive Surgery and HIPEC for Malignant Peritoneal Mesothelioma: Outcomes and Survival From an Australian Centre

The aim of the study was to determine outcomes and overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for malignant peritoneal mesothelioma (MPM). This was a retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for MPM from April 1999 to December 2021. A total of 81 patients were identified with MPM. Median OS was 53 months with a 1-, 3- and 5-year OS of 76%, 55% and 49% respectively. Multivariate analysis identified lymph node status, PCI and CC score as statistically significant prognostic factors that impact survival. Median OS for PCI 0-20 was 103 months vs. 33 months for PCI 21-39 (p=0.005). Median OS for CC0, CC1 and CC2 were 104, 30 and 2.7 months respectively (p<0.001). Hazard ratio for node-positive disease over node-negative was 2.14 (95% CI=1.07-4.31, p<0.033). Grade III/IV complication rate was 43.2% and mortality 4.9%. CRS/HIPEC remains the gold standard for treating patients with MPM with excellent patient OS. Lymph node status, PCI and CC score were independent prognostic factors that affect OS.