Treatment Of Malignant Peritoneal Mesothelioma Research Articles

Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.

Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM. An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies. NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice. NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

Effect of postoperative normothermic intraperitoneal chemotherapy on the prognosis of MPM patients receiving CRS+HIPEC: A single-center case-control study

BackgroundThe comprehensive treatment strategy, mainly cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), combined with systemic and intraperitoneal chemotherapy, is the standard treatment for malignant peritoneal mesothelioma (MPM), which can significantly prolong the survival of patients. The aim of this study is to investigate the clinical significance of postoperative normothermic intraperitoneal chemotherapy (NIPEC) in MPM patients. MethodsData of 152 MPM patients who underwent CRS + HIPEC and postoperative intravenous chemotherapy were retrospectively analyzed. Patients were divided into the Non-NIPEC group and the NIPEC group according to whether they received NIPEC after surgery. The baseline characteristics of the two groups were compared, and the survival outcome was analyzed in subgroups according to completeness of cytoreduction (CC) score. Multivariate survival analysis was used to determine the independent prognostic factors. ResultsIn CC 0–1 and CC 2–3 subgroups, there was no significant difference in baseline characteristics between Non-NIPEC and NIPEC groups. Survival analysis showed that for CC 0–1 patients, there was no significant difference in overall survival (OS) between Non-NIPEC and NIPEC groups (P = 0.503). However, for CC 2–3 patients, the median OS of the NIPEC group was significantly longer than that of the Non-NIPEC group (24.5 vs. 10.3 months, P = 0.005). Pathological type, preoperative thrombosis and postoperative NIPEC (HR = 0.423, 95%CI: 0.228–0.786, P = 0.006) were independent prognostic factors for CC 2–3 patients. ConclusionsFor MPM patients receiving CRS + HIPEC, postoperative intraperitoneal combined with intravenous chemotherapy may improve the survival of CC 2–3 patients, but CC 0–1 patients do not seem to derive the same benefit.

Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma

BackgroundMalignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment.MethodsMPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients.ResultsWe successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients.ConclusionThis study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma: A case report and review of literature

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.

National Practice Patterns in Malignant Peritoneal Mesothelioma: Updates in Management and Survival.

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.

Immunotherapy in malignant peritoneal mesothelioma (Review).

Over the last decade, there has been a movement in cancer treatment away from cytotoxic therapies toward strategies that enhance the immune system against cancer. Immune checkpoint inhibitors (ICIs) have been incorporated into the treatment regimens for patients with various solid tumors. Mesothelioma trials revealed encouraging efficacy; however, patients with peritoneal mesothelioma are usually excluded, slowing the progress of improving the treatment of this aggressive cancer and compelling oncologist to rely on retrospective studies despite their flaws and limitations. Currently, there is no consensus on the role of ICIs in the treatment of malignant peritoneal mesothelioma (MPeM). The present review discusses data from clinical studies that examined immunotherapy in MPeM and evaluates what is known about the relevance of the tumor microenvironment and clinically validated biomarkers for ICIs efficacy. Furthermore, a proposed strategy for utilizing immunotherapy in treating MPeM is discussed.

Efficacy of second-line treatment and prognostic factors in patients with advanced malignant peritoneal mesothelioma: a retrospective study

BackgroundStandard treatment for malignant peritoneal mesothelioma has not been established, and systemic chemotherapy is administered according to malignant pleural mesothelioma. We previously reported the efficacy of cisplatin plus pemetrexed as first-line chemotherapy; however, the efficacy of second-line chemotherapy remains unknown.MethodsWe retrospectively evaluated patients with malignant peritoneal mesothelioma who started first-line systemic chemotherapy with platinum plus pemetrexed between March 2007 and February 2019 at the National Cancer Center Hospital. Patients who received second-line chemotherapy after failure of platinum plus pemetrexed were identified. We evaluated the efficacy of first- and second-line chemotherapy, and explored the prognostic factors. Survival outcomes were estimated using the Kaplan–Meier method, and between-group differences were compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models.ResultsA total of 54 and 26 patients received platinum plus pemetrexed as first- and second-line chemotherapy, respectively (gemcitabine in 12 patients; taxane, six; nivolumab, three; and others, five). In all patients, the median overall survival and progression-free survival after first-line chemotherapy were 16.6 and 7.3 months, respectively. Among patients who received second-line chemotherapy, the median overall survival, progression-free survival, and second-line overall survival were 16.9, 3.2, and 9.9 months, respectively. Patients who received ≥6 cycles of platinum plus pemetrexed as first-line chemotherapy had longer overall survival after second-line chemotherapy than those who did not (hazard ratio, 0.23; 95% confidence interval: 0.06–0.82; p = 0.02).ConclusionsSecond-line chemotherapy may be an option for refractory malignant peritoneal mesothelioma, especially in patients who have completed 6 cycles of platinum plus pemetrexed as first-line chemotherapy.

Unusual radiologic presentations of malignant peritoneal mesothelioma.

BACKGROUNDMalignant peritoneal mesothelioma is an unusual disease process characterized radiologically by ascites and infiltration of the peritoneum by multiple small tumor nodules. Both parietal and visceral peritoneum are involved by the multiple malignant tumor nodules. Computed tomography (CT) has been used to identify the anatomic pathology induced by the progression of this malignant process. AIMTo identify and then describe unusual CT images in patients with malignant peritoneal mesothelioma. Recognition of these unusual radiologic findings can cause the radiologist to be suspicious of this rare malignant process.METHODSIn 100 patients who were to undergo definitive treatment of malignant peritoneal mesothelioma, the findings on preoperative CT scans were catalogued. Many of these changes were repeatedly noted on the CT scans. Other pathologic CT images were less common. These unusual radiologic presentations were specially studied in this manuscript. RESULTSEight unusual radiologic presentations of malignant peritoneal mesothelioma were selected for study. These unusual findings included a mass occurring within a Spigelian hernia, infiltration of the splenic parenchyma by spherical mesothelioma masses, infiltration of the lower mediastinum by tumor, a mesothelioma mass within a left inguinal canal, enlarged cardiophrenic angle lymph nodes, pleural plaques associated with the progression of malignant peritoneal mesothelioma, splenic notches caused by disease surrounding the spleen, and a mass greater than 5 cm associated with the proximal jejunum and directly adjacent to the anatomic location of the Treitz ligament.CONCLUSIONThere are unusual radiologic presentations of malignant peritoneal mesothelioma that are important to recognize in order to accurately diagnose this disease by CT.

Current Status and Progress on Diagnosis and Treatment of Malignant Peritoneal Mesothelioma

Current Status and Progress on Diagnosis and Treatment of Malignant Peritoneal Mesothelioma

Treatment of Malignant Peritoneal Mesothelioma.

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.

MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma.

BackgroundMalignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The standard frontline treatment of MPM is cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) unless the peritoneal disease is considered unresectable. For unresectable patients the standard frontline treatment is a combination of cisplatin and pemetrexed but the prognosis remains ominous with only 13 months of overall survival (OS).MethodsThe proposed study is a multicenter randomized non-comparative study evaluating the association of Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) and systemic chemotherapy vs. systemic chemotherapy alone as first-line treatment of MPM. Patients will be randomized with a 2:1 ratio using a minimization technique. Sixty-six patients have to be enrolled. Stratification will be performed according to histology (epithelioid vs. sarcomatoid and biphasic), presence of extraperitoneal disease and center. Primary objective is OS and secondary objectives include progression-free survival (PFS), safety, compliance, feasibility, conversion to resectability, histological response to treatment and quality of life.ConclusionsWe expect to show that intensification of the first line treatment with PIPAC for initially unresectable MPM patients increases OS.Trial registrationProspective study. Clinicaltrials.gov: NCT03574493 EudraCT: 2019–001515-23.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: patient selection and special considerations.

Malignant peritoneal mesothelioma (MPM) is a rare, aggressive malignancy that typically presents with vague symptoms, ascites, and/or diffuse peritoneal studding. Despite findings of advanced disease within the peritoneal cavity, spread beyond the abdomen is uncommon. Although advances in systemic chemotherapy have been made, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remain the mainstay of treatment. Median overall survival of approximately 50 months with CRS/HIPEC has been demonstrated, with age, gender, histologic subtype, peritoneal carcinomatosis index, comorbidities, nodal and extra-abdominal metastases, and completeness of cytoreduction all playing a role in prognosis. In patients with refractory malignant ascites and unresectable disease, complete resolution of ascites and improvement in quality of life have been demonstrated with palliative HIPEC. In appropriately selected patients, CRS/HIPEC plays a critical role in the treatment and palliation of MPM.

Malignant Peritoneal Mesothelioma: Treatment Options and Survival.

Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland. The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure. Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009). Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.

The impact of chemotherapy and its timing on survival in malignant peritoneal mesothelioma treated with complete debulking

The current standard of treatment for malignant peritoneal mesothelioma (MPM) is cytoreductive surgery when the disease distribution is favorable. The role of chemotherapy, as an adjunct to surgery, remains unclear. The national database of mesothelioma was used to identify MPM patients who were treated with curative intent. Patients were divided into treatment groups: (1) chemotherapy only, (2) surgery only, (3) neoadjuvant chemotherapy + surgery, and (4) surgery + adjuvant chemotherapy. A negative control group of patients who did not receive any treatment was added (group 0). Totally, 1740 patients were included. Mean age was 63.04 ± 14.58 and 60.7% were males. The patients' distribution into the treatment groups was 604, 684, 169, 55, and 228 patients in groups 0-4, respectively, with a median survival of 3.61 ± 0.37, 11.10 ± 0.73, 57.41 ± 11.91, 52.30 ± 7.20, and 55.00 ± 9.19months. The addition of chemotherapy, in any setting, to surgery provided an improved survival at 1year (p = 0.006). This survival benefit ceased at the 2-, 3-, and 5-year checkpoints. The multivariate analysis identified age, sarcomatoid/biphasic histologies, nodal and distant metastasis, and offering no treatment or chemotherapy only as poor prognostic factors for overall survival. No difference in overall survival was noted with the addition of chemotherapy to complete debulking regardless of the timing. Complete debulking remains the standard treatment for MPM. The addition of systemic chemotherapy provides a short-term survival improvement at 1year only and was similar whether given in the neoadjuvant or adjuvant setting. Nevertheless, it did not add a survival benefit beyond the 1-year time point.

Malignant peritoneal mesothelioma

Malignant mesothelioma is one of the rare disease. It is an aggressive tumor arising from the mesothelial lining of the pleura or peritoneum. In our country there is no reported data or known incidence rate. It has an association with exposure to asbestos and usually has a poor prognosis. Early diagnosis and establishment of a standard treatment for malignant peritoneal mesothelioma is difficult. We report on a case of malignant peritoneal mesothelioma in a 59-year-old man with huge abdominal swelling, ascites and respiratory distress.KYAMC Journal Vol. 8, No.-2, Jan 2018, Page 40-42

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM. The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly.Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is<1year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1year. The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

Recent advances in diagnosis and treatment of malignant peritoneal mesothelioma

Recent advances in diagnosis and treatment of malignant peritoneal mesothelioma

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma.

Sugarbaker et al are to be congratulated for their comprehensive review of the management of malignant peritoneal mesothelioma using cytoreductive surgery (CRS) and perioperative chemotherapy. Their report encompasses the entirety of care for patients with malignant peritoneal mesothelioma, from diagnosis and treatment to morbidity and mortality resulting from CRS, and the role of hyperthermic intraperitoneal chemotherapy (HIPEC). The authors also describe patient and operative risk factors to improve patient outcomes in this rare disease. Peritoneal mesothelioma was first described in 1908 byMiller andWynn. It is a rare cancer that is increasing in incidence and affects approximately 800 people per year in the United States. It was once a rapidly fatal tumor secondary to obstruction, with a median survival of 6 to 12 months. One of the first published treatment strategies for malignant peritoneal mesothelioma was by Antman et al in 1983, when they described a multidisciplinary regimen including CRS, with a median survival in responding patients of 22 months. CRS and HIPEC then quickly became the treatments of choice, with an improvement in median overall survival of 30 to 92 months. As detailed in the report by Sugarbaker et al, it is widely accepted that CRS and HIPEC represent the standards of care for peritoneal mesothelioma. Unfortunately, not everyone is a candidate for these treatments, and certain prognostic indicators are important to discuss. Although there are three histologic types of peritoneal mesothelioma, only the epithelial type has a favorable prognosis. In general, sarcomatoid and biphasic tumor types do not fare well enough to warrant treatment with CRS and HIPEC. Additionally, there is little doubt that completeness of cytoreduction plays a major role in a patient’s prognosis. Although there is some controversy, as the authors mention, between selective peritonectomy and complete parietal peritonectomy, there is broad consensus that patients with cytoreduction completeness of 0 or 1 (no disease or disease , 2.5 mm) have significantly improved survival compared with patients left with gross disease. Finally, patientsmust have the overall fitness to withstand a physically taxing surgery, where the approximate mortality is a 2% to 4%, and morbidity approaches 30% to 40%. There is some consensus about the treatment of malignant peritoneal mesothelioma with HIPEC; however, there are also many unanswered questions, which Sugarbaker et al highlight. Table 2 in their report is adapted from one of the largest multi-institutional reviews, encompassing 405 patients withmalignant peritoneal mesothelioma from 29 centers

Survival and fertility in women with malignant peritoneal mesothelioma.

111 Background: The prognosis of malignant peritoneal mesothelioma (MPM) has improved over the past decade in patients undergoing operative extirpation and intraperitoneal chemotherapy (IC). This study investigates the time from diagnosis to treatment intervention in premenopausal women and its impact on fertility and childbearing options. Methods: A retrospective analysis of 195 patients diagnosed with peritoneal mesothelioma between 1995 and 2015. Patients with unresectable or bicavity disease were not excluded. Kaplan-Meier curves and univariate cox proportional hazards model were used to estimate survival and significant treatment and prognosis factors. Results: The median survival time of all peritoneal mesothelioma patients (n = 195) was 3.21 years with (95% CI: 2.38- 5.53), with median follow-up of 3.44 years (SD = 3.4, minimum = 0.014 and maximum = 16.752) years from first operation. Patient set included 111 men (57%) and 84 women (43.1%) with female sex having favorable survival [HR: 0.442 95% CI: 0.296-0.659), p &lt; 0.001] of 110.1 months with (95% CI: lower bond: 48.3). Of these women, their mean age at diagnosis was 52 years, (SD = 14.5, minimum = 14.7 – maximum = 79.9), with a mean time of 8.20 months from diagnosis to the start of treatment (SD = 18.6, minimum = 0 and maximum = 128.6 months). Overall survival of premenopausal women (N = 23) during follow-up was 72.2% (SE = 27.8%). Mean age at time of diagnosis was 34.7 years, (SD = 9.26, minimum = 14.7, maximum = 48.1), with a mean time of 10.6 months from diagnosis to treatment (SD = 17.9, minimum = 0.63, maximum = 86.7). Of the 195 patients who received a full treatment course, 66 (33.8% CI: 95%) were still alive at the median follow-up, of those alive 37 are female: 7 are premenopausal and have presented with gynecological symptoms, and 17 are premenopausal and have presented with abdominal discomfort. Conclusions: This data suggests that women preparing for treatment of MPM should not be precluded from exploring fertility options. With a mean time of 10.6 months from diagnosis to treatment, it is possible for premenopausal women to take advantage of fertility preservation before starting treatment.

Oncolytic Vaccinia Virus as an Adjuvant Treatment to Cytoreductive Surgery for Malignant Peritoneal Mesothelioma

Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery. Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy. The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed. VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.