Metastatic Mesothelioma Research Articles

1517P - Cisplatin-raltitrexed vs cisplatin-pemetrexed in the treatment of advanced pleural mesothelioma. Final results of a network meta-analysis

To compare efficacy and safety of cisplatin-pemetrexed and cisplatin-raltitrexed in the treatment of advanced pleural mesothelioma. An indirect comparison of efficacy and safety of cisplatin-pemetrexed and cisplatin-raltitrexed was performed. The indirect comparison and the network meta-analysis were performed on data extracted from cisplatin-pemetrexed vs cisplatin, and cisplatin-raltitrexed vs cisplatin comparisons in the treatment of metastatic pleural mesothelioma. The Odds Ratios of 10, 15, and 20 month survival rate and response rate were assumed as indexes of efficacy; the Odds Ratio of grade III-IV side effects, and the absolute risk of overall, hematologic and non-hematologic toxicity, were assumed as indexes of safety. The outcome of 352 patients were analyzed. 226 patients were treated with cisplatin-pemetrexed and 126 with cisplatin-raltitrexed. The Odds Ratios and 95% Confidence Interval (95% CI) of 10, 15, and 20 months survival rate and response rate were 1.204 (95% CI 0.646-2.244, p = 0.559), 1.022 (95% CI 0.492-2.123, p = 0.953), 1.127 (95% CI 0.437-2.907, p = 0.805) and 0.559 (95% CI 0.258-1.212, p = 0.141), respectively. An absolute increased risk of grade III-IV side effects was observed for cisplatin-pemetrexed: 5.8% (95% CI 2.6%-9%, p < 0.001), 9% (95% CI 2.3%-15.7%, p = 0.008) and 2.8% (95% CI 0.2%-5.4%, p = 0.035) for overall toxicity, hematological toxicity and non-hematological toxicity, respectively. Cisplatin-pemetrexed and cisplatin-raltitrexed can be considered comparable in terms of efficacy in the treatment of metastatic pleural mesothelioma, with a modest increased risk of grade III-IV side effects for cisplatin-pemetrexed. The comparability in terms of efficacy and safety of the two schedules may support clinicians in decision making at the time of planning strategies against metastatic pleural mesothelioma.

Metastatic pleural mesothelioma presenting in a breast fine needle aspiration specimen

This is an unusual presentation of metastatic mesothelioma presenting as a breast lump and mimicking a primary tumour at that site.

Abstract CT083: A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140)

Abstract Background: Mesothelioma is a rare but aggressive cancer with a 5-year survival rate less than 10%. Mesothelin is a protein normally present on mesothelial cells and overexpressed in the majority of mesotheliomas. Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to ravtansine, an antitubulin cytotoxic agent. In a phase I study, anetumab ravtansine at 6.5 mg/kg on a q3w IV schedule was well tolerated and showed encouraging durable tumor responses in patients with previously treated mesothelioma. Design: A randomized, open-label, active-controlled, 2-arm, multicenter, phase II trial to evaluate the efficacy and safety of anetumab ravtansine at 6.5 mg Q3W versus vinorelbine 30 mg/m2 QW in patients with advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin and who have progressed on first-line platinum/pemetrexed-based chemotherapy. Objectives: The primary objective is to test the superiority of anetumab ravtansine monotherapy over vinorelbine in progression-free survival (PFS). The secondary objectives of this study include overall survival, patient-reported outcomes (PRO), tumor response, and safety. Exploratory objectives include immunogenicity of anetumab ravtansine, pharmacokinetics, and biomarkers of response. Methods: Biomarker sampling will be performed on all patients to measure tumor mesothelin expression levels at prescreening. Biomarker-positive patients with moderate (2+) and/or strong (3+) level in at least 30% of tumor cells will be randomized and start study treatment following progression after 1st line treatment of platinum/pemetrexed (with or without bevacizumab). Approximately 183 patients meeting eligibility criteria will berandomized in a 2:1 ratio to receive anetumab ravtansine or vinorelbine. Randomization will be stratified by geographic region (Rest of World v. Asia) and time to progression on 1st line treatment (? 6 months vs &amp;lt; 6 months). The primary endpoint, PFS per modified RECIST criteria for metastatic pleural mesothelioma per central review, will be tested using a log-rank test stratified by randomization strata, with 1-sided significance level 0.0125. The primary analysis will occur after approximately 117 PFS events. Assuming true median PFS of 3.6 months under vinorelbine treatment, the primary hypothesis test is designed to detect a 100% prolongation of true PFS (median 7.2 months) with 90% power. Novel study methods include a grading system for AEs of special interest and the PRO instrument. Results: This trial is open and currently accruing patients. Citation Format: Raffit Hassan, John J. Nemunaitis, Jan P. van Meerbeeck, Ross Jennens, George R. Blumenschein, Jr, Dean A. Fennell, Hedy L. Kindler, Silvia Novello, Cem Elbi, Annette Walter, Danila Serpico, Emma Fountain, Sandra Vingerhoedt, Christine Brown, Jonathan Siegel, Barrett H. Childs. A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT083.

22 - Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma

22 - Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma

A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140).

TPS8576Background: Mesothelioma is a rare but aggressive cancer with a poor prognosis. Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to the mytan...

Metastatic malignant pleural mesothelioma masquerading as a case of acute abdomen secondary to small bowel perforation

Metastatic pleural mesothelioma is a rare disease. The present study aimed to report a rare presentation of metastatic malignant mesothelioma (MM). The patient was an elderly man who presented with small bowel (jejunal) perforation secondary to metastatic pleural mesothelioma deposits. This was a rare presentation of a rare disease and the first reported case in the published studies in which MM masqueraded as bowel perforation prior to the primary diagnosis.

Métastases révélatrices de mésothéliomes malins du péritoine : difficultés diagnostiques à propos de deux cas et conduite à tenir

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers.

Pattern of treatment and clinico-epidemiological analysis of 804 lung and pleura cancer patients treated in radiation oncology department, NCI-Egypt

BackgroundEpidemiological profile and treatment outcomes of Lung and pleural malignancies vary among different geographical regions. The aim of the study is to analyze the clinico-pathological profile and pattern of treatment of lung and pleural cancers at the Radiation Oncology department, NCI, Cairo University. Materials and methodsA review of 804 clinical patient records with 770 pathologically/cytologically confirmed patients from Jan 2008-December 2012 was performed. Patients were evaluated (clinical, demographic and pathological profiles) in addition to the treatment adopted. ResultsMedian age was 56years with a male: female ratio of 4:1. Smoking was reported in 63% of patients. Dyspnea and chest pain were the most presenting symptoms (53%). Among lung cancer patients; 78% were NSCLC and 12% SCLC with mesothelioma comprising 10%. Among NSCLCs, adenocarcinoma and large cell undifferentiated carcinoma were the commonest histological subtype (72%). Among NSCLC, 58% cases were of stage IV while among SCLC 73% cases had extensive stage disease. Chemotherapy was administered to 47% (55% vs. 67%, and 35% vs. 31% among non-metastatic lung cancer, mesothelioma patients and metastatic lung cancer and mesothelioma patients respectively). Distant metastases (brain 48%, bone 36%) were reported in 45% of patients. The pattern of treatment intent was palliative (88%) vs. 12% treated with radical intent. ConclusionsAdvanced stages at presentation reflect the palliative pattern of treatment. Hypo-fractionated radiotherapy for lung and pleura malignancies as a palliative measure is the current practice. Implementation of early palliative care should be considered for metastatic patients.

Spenules Masquerader of Metastatic Disease

Splenosis is heterotopic auto transplantation of splenic tissue usually following splenectomy and traumatic rupture of spleen. They result from seeding of the Splenosis is heterotopic autotransplantation of splenic tissue usually following splenectomy and traumatic rupture of spleen. They result from seeding of the peritoneal cavity with splenic tissue which recruits local blood supply. Splenules typically are rounded well-marginated soft tissue structures that measure less than 2 centimeters. A 52 year old female with past medical history of splenectomy in 1980 due to MVA, presented to our clinic with history of abdominal bloating last 5 months, decrease appetite and weight loss about 12lb for 6 months, constipation. She had guaiac positive stool, was admitted to the hospital and had colonoscopy that was suggestive of inflammation of sigmoid colon. CT scan abdomen was suggestive of diverticulosis with minimal inflammation. She was treated with antibiotics but her symptoms did not improve completely. A repeat CT was done which showed pelvic lymphadenopathy, peritoneal nodules and severe sigmoid inflammatory changes more suggestive of extrinsic compression and peritoneal disease. Patient had positive family history of breast and ovarian cancers. CEA, CA 19-9 and CA 125 were unremarkable. Based on her clinical presentation and family history ovarian cancer was suspected and gynecologist was consulted and thought that inflammation of sigmoid secondary to peritoneal disease. Surgery was consulted for possible pelvic malignancy with possible peritoneal metastasis. Patient underwent surgery, peritoneal nodule with frozen section showed splenules (remnant of spleen) with calcification, biopsy of sigmoid showed inflammatory bowel disease. Splenules are incidental findings of little clinical significance in most patients. However, they must be properly identified in various situations, such as: differentiating them from metastatic lesions, torsion, infarction, endometriosis, mesenchymal tumors and peritoneal mesothelioma. These differential diagnoses can be differentiated using clinical history and radiological appearance. On noncontract CT, the attenuation of splenules is comparable to that of the spleen. However, small splenules may be hypodense and if calcified as in our patient can be mistaken for metastatic disease. Fused SPECT/CT imaging with Tc-99m labeled denatured red blood cells facilitates the definitive diagnosis of a splenule and may also helpful in identifying splenules that have relocated within the abdominal cavity.Figure 1Figure 2

5. Benign mesothelial inclusions in a mediastinal lymph node in association with previous cardiac surgery: a case report

Mesothelial inclusions in mediastinal lymph nodes are uncommon and are a great mimic of metastatic carcinoma or malignant mesothelioma. Several studies have shown that inclusions are mostly found in lymph nodes draining regions of pleural effusions or pericardial effusions from various causes. Our case report illustrates that the finding of mesothelial inclusions can also be associated with previous cardiac surgery. The mechanism of lymph node seeding by these benign mesothelial cells is thought to be migration of the mesothelial cells via lymphatics as part of post surgical inflammatory processes. It is important to be aware of the possibility of mesothelial inclusions in lymph nodes to avoid overdiagnosis of metastatic carcinoma or malignant mesothelioma.

Clinicopathological characteristics of pulmonary epithelioid hemangioendothelioma: A report of four cases and review of the literature.

This study aimed to investigate the clinicopathological characteristics, differential diagnosis and prognosis of pulmonary epithelioid hemangioendothelioma (PEH). PEH is a rare low-grade malignant vascular tumor. The cause of PEH remains unclear. Patient prognosis is unpredictable, with life expectancy ranging from 1 to 15 years due to the fact that estrogenic receptors behave inconsistently within the tumor and the occurence of the disease in male patients does not support the usual hormonal hypothesis. The clinical manifestations, imaging findings, histopathological characteristics and immunohistochemical phenotypes of four cases of epithelioid hemangioendothelioma occurring in the lung were retrospectively analyzed, and a review of the associated literature was conducted. The age of onset for the four PEH cases was 25–54 years, and the disease manifested as multiple nodules in the lungs or pleura. All of the patients underwent lobectomy or pulmonary wedge resection. The morphology of the tumor cells was epithelioid or spindle-shaped with abundant eosinophilic cytoplasm in which lumina or vacuoles containing erythrocytes were observed. The cells were arranged in nests and cords with degenerated interstitial mucoid. The morphology of the majority of the tumor cells was moderate, including mild atypia and little mitosis or necrosis. Immunohistochemical staining showed positive results for CD31, CD34 and F8. PEH is a rare low- to moderate-level tumor occurring in the lungs with differentiation toward vascular endothelial cells. Clinically, it is difficult to distinguish from a variety of other benign and malignant lung diseases. For diagnosis, a distinction must be made from other diseases such as chronic granulomatous disease, amyloid nodules, hamartoma, primary and metastatic lung cancers, malignant mesothelioma and vascular sarcoma. In the present study, the clinicopathological features of four cases of PEH were investigated and the associated literature was reviewed. The results of this study may improve understanding with regards to the diagnosis and therapeutic options for patients with PEH.

Metastatic Peritoneal Mesothelioma in a 21-Year-Old Female with Chronic Myelogenous Leukemia

We report the case of a 21-year-old female who presented with cervical lymphadenopathy and subsequently diagnosed with peritoneal mesothelioma. She had a medical history of Ph+ chronic myelogenous leukemia, treated with total body radiation and bone marrow transplant 13 years earlier, then 10 years of imatinib for a relapse 3 years later. The mesothelioma responded well to combination therapy but recurred locally 3 years after diagnosis. This case report emphasizes that even without asbestos exposure, mesothelioma can present as a second malignancy in survivors of childhood cancer who were exposed to radiation therapy as part of their initial treatment.

Gingival Metastasis as First Sign of Multiorgan Dissemination of Epithelioid Malignant Mesothelioma

Metastatic malignant mesothelioma to the oral cavity is extremely rare. They are more common in the jaw bones than the soft tissue. Occurrence of the malignant disease typically carries an average survival rate of 9-12 months : Thirteen patients underwent neoadjuvant chemotherapy and radical pleurectomy decortication, followed by radiotherapy from August 2012 to September 2013. Patients were followed up with computed tomography of the chest and the abdomen every 3 months. All patients were followed up until February 2014. In January 2014, 11 patients were still alive with a median survival of 11 months, eight patients developed a recurrence and two patients died at 8 and 9 months after surgery. After 1 year from macroscopic radical pleurectomy decortication, a 68-year-old man suffered from gingival mass turned out to be a metastatic deposit of biphasic malignant mesothelioma as first sign of multiorgan recurrence. The patient underwent chemotherapy and local radiotherapy in the oral cavity. This case points out the relevance of biopsy to all new growing lesions, even in uncommon anatomical sites, whenever a history of mesothelioma is on record.

Metastasis of mesothelioma to the maxillary gingiva.

Malignant mesothelioma predominantly arises from the serosal surfaces of the pleural or peritoneal cavity. There is currently no effective standard treatment for mesothelioma and the prognosis for patients is poor; the majority of patients with malignant mesothelioma succumb between 12 and 17 months following diagnosis. The association of all forms of malignant mesothelioma with asbestos exposure has been well documented. However, metastasis to the oral gingiva is rare, as only four cases have previously been reported; two cases of metastasis to the tongue and four cases to the jaw bone. In the current report, the case of a 62-year-old male with metastatic mesothelioma is presented. To the best of our knowledge, this is the first report regarding the metastasis of this type of neoplasm to the maxillary gingiva.

A phase I/II study of azacitidine in combination with temozolomide in patients with unresectable or metastatic soft tissue sarcoma or malignant mesothelioma.

10560 Background: Soft tissue sarcomas are rare tumors, for which complete surgical resection offers the best chance of survival. However, two thirds of diagnosed tumors are unresectable and/or met...

Desmoplastic small round cell tumor with sphere‐like clusters mimicking adenocarcinoma

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere-like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients.

Diagnostic and prognostic value of soluble syndecan-1 in pleural malignancies.

Background. The distinction between malignant and benign pleural effusions is a diagnostic challenge today and measuring soluble biomarkers could add to the diagnostic accuracy. Syndecan-1 is a proteoglycan involved in various cellular functions and is cleaved from the cell surface in a regulated manner. The shed fragment, which can be recovered in effusion supernatant and in serum, retains its binding capacities, but often with different functions and signalling properties than the cell-bound form. Aim. This study aimed to investigate the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera from patients with pleural malignancies. Study Design. Using two cohorts of patients, we assessed the diagnostic and prognostic value of soluble syndecan-1 in pleural effusions and sera, using enzyme-linked immunosorbent assays. Results. In pleural effusions, syndecan-1 distinguished malignant and benign diseases, with an odds ratio of 8.59 (95% CI 3.67 to 20.09). Furthermore, syndecan-1 in pleural effusions predicted a survival difference for patients with pleural metastatic disease and malignant mesothelioma of 11.2 and 9.2 months, respectively. However, no such effects were seen when syndecan-1 was measured in serum. Conclusion. Soluble syndecan-1 is a promising candidate biomarker for the cytopathological diagnosis and prognostication of malignant pleural effusions.

Neurosurgical Management of Intracranial Metastatic Mesothelioma

Mesothelioma is a relatively rare tumor arising from the pleura, most notably associated with exposure to asbestos. Typically, mesothelioma is a locally aggressive tumor with a poor outcome in the order of months from the time of diagnosis. Although cases of distant metastases of mesothelioma have been documented in the literature, this tumor has less reported cases of metastases than other malignancies of the chest, and most reported cases of metastases have been identified in autopsy studies, likely related to the short survival times of patients harboring these tumors.

The diagnostic performance of chest ultrasonography in the up-to-date work-up of the critical care setting

BackgroundManagement of patients in the critical care setting is crucial. The availability, the absence of ionizing radiation and the non invasive nature of chest ultrasonography (US) have currently increased its use in the up-to-date work-up of various pleuropulmonary abnormalities in the critical care setting. ObjectiveTo evaluate the sensitivity, specificity and diagnostic accuracy of chest US for various pleuropulmonary abnormalities in intensive care unit (ICU) patients. Materials and methodsNinety consecutive patients admitted in chest ICU with respiratory distress were assessed clinically and by chest radiography (CXR). They were suspected to have a provisional diagnosis of any of the following pathological entities: pneumonic consolidation, bronchogenic carcinoma, metastatic pulmonary nodules, pleural effusion, pneumothorax, hydropneumothorax and mesothelioma. These patients were scheduled for chest computed tomography (CT) and prospectively reviewed using chest US. The results of chest US were compared with these of chest CT for each encountered pathological entity using chest CT as the diagnostic standard of reference to subsequently calculate the sensitivity, specificity and diagnostic accuracy of chest US. ResultsThe sensitivity, specificity and diagnostic accuracy of chest US were 100%, 96% and 97% for pneumonic consolidation, 71%, 100% and 98% for bronchogenic carcinoma and 92%, 100% and 99% for pneumothorax respectively. The sensitivity, specificity and diagnostic accuracy of 100% for the rest of the included pathological entities were obtained. ConclusionChest ultrasonography has a considerable diagnostic performance for various pleuropulmonary pathological conditions that may be encountered in the ICU patients making it as an adjunct tool in the up-to-date work-up of the ICU setting.

Uroplakin IB and IIIb Are Two Novel Markers for Mesothelioma

Mesotheliomas can present a wide variety of cytomorphologic features and histologic patterns. The definitive diagnosis can be challenging, particularly for those metastatic mesothelioma or other tumors metastatic to the pleura and lung. A long list of antibodies can be used to different mesothelioma from other malignant tumors. Howerver, none of them are specific and …