Case of a 57-Year-Old Man With Malignant Mesothelioma Presenting With Miliary Nodules on Chest Imaging.

CASE PRESENTATION: A 57-year-old man with history of stage IIIB right-sided malignant pleural mesothelioma was admitted from his oncologist's office for progressive dyspnea of two weeks duration. He had associated dyspnea at rest and a new dry cough. He denied sputum production, hemoptysis, or fevers, but he did endorse chills, fatigue, and weight loss. The patient was a veteran of the Navy and had extensive international travel in his 20s. He had never been incarcerated and denied any sick contacts or recent travels. He had received a diagnosis of mesothelioma 11 months earlier after presenting to his physician's office with complaints of shortness of breath on exertion. Initial imaging revealed a large right-sided pleural effusion with irregular pleural thickening. He underwent right-sided thoracoscopy, and the pleural biopsy result was consistent with epithelioid mesothelioma. Because of invasion of his seventh rib, he was not a candidate for surgery and underwent palliative radiation and chemotherapy with cisplatin, pemetrexed, and bevacizumab. He was undergoing his eighth cycle of chemotherapy at the time of presentation.

SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020).

Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

Gender-based Disparities in Receipt of Care and Survival in Malignant Pleural Mesothelioma.

BACKGROUND: Despite accounting for a minority of malignant pleural mesothelioma (MPM) diagnoses, females may experience differential survival relative to males. It is unclear if there are gender-based differences in receipt of treatment or disease-related outcomes for patients with MPM. We therefore utilized the National Cancer Database (NCDB) to assess patterns-of-care and overall survival (OS) among patients with MPM by gender. MATERIALS AND METHODS: Patients with histologically confirmed MPM treated from 2004 to 2013 were identified from the NCDB. The association between female gender and OS was assessed using multivariable Cox proportional hazards models with propensity score matching. Patterns-of-care were assessed using multivariable logistic regression. The overall treatment effect was tested in subsets of patients by treatment strategy, histology, and clinical stage. RESULTS: A total of 18,799 patients were identified, of whom 14,728 (78%) were male and 4071 (22%) were female. Females were statistically more likely to present at a younger age, with fewer comorbidities, and with epithelioid histology. Despite these favorable prognostic features, women were less likely to receive surgery (P ≤ .001) or chemotherapy (P ≤ .001) compared with males. On multivariable analysis, female gender was associated with improved OS (hazard ratio, 0.83; 95% confidence interval, 0.80-0.86; P ≤ .001). Gender-based survival differences were seen across all stages, but only among patients with epithelioid (P ≤ .001) and not biphasic (P = .17) or sarcomatoid (P = 1.00) histology. CONCLUSIONS: Surgery and chemotherapy are disproportionately underutilized in female patients with MPM. Despite this concerning disparity, female gender is independently associated with improved survival relative to males. Further research to understand factors that lead to gender disparities in MPM is warranted.

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.