Epithelial Mesothelioma Research Articles

Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study

AbstractMalignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From March 2017 until August 2023, 55 patients with localized pleural mesothelioma underwent pleurectomy and decortication. Thirty patients performed only surgery while 25 consecutive patients had surgery followed by HITOC with cisplatin (125 mg/m2) infused for 70 min at a temp of 40–43 °C. We analyzed postoperative morbidity, HITOC-related complications, and the influence of HITOC on survival. The trial was registered on 19/08/2022 as NCT05508555. The HITOC group had a mean age of 53.1 ± 8.2 years while the surgery group (non-HITOC) had a mean age of 52.1 ± 8.6 years. The HITOC group had 17 (68%) men, whereas the surgery group included 18 (60%) males. The 30-day mortality in the HITOC group was 0% vs 1 case (3.3%) in the surgery group. HITOC-related transient complications occurred in 4/25 (16%) of the HITOC group (atrial fibrillation, renal impairment and transient hypotension). Progression-free survival in the HITOC group was 8 months (95% CI 4.3–11.6) vs 6 months (95% CI 2.5–9.9) in the surgery-only group (p = 0.79). The overall survival time in the HITOC group was 28 months (95% CI 21.5–34.5) vs 22 months (95% CI 17.5–26.5) in the surgery-only group (p = 0.75). Risk factors analysis for recurrence in the HITOC group confirmed a significant role for early stages (p = 0.03). HITOC following pleurectomy and decortication is a safe therapeutic option that may improve survival for selected patients with localized epithelial pleural mesothelioma. Patients with earlier-stage mesothelioma are more likely to benefit from radical surgery and HITOC.

Isolation and whole genomic analysis of mesophilic bacterium Pseudoglutamicibacter cumminsii in epithelial mesothelioma

The relationship between bacteria and tumors has been the hot spot of clinical research in recent years. Pseudoglutamicibacter cumminsii is an aerobic Gram-positive bacterium commonly found in soil. Recent studies have identified P. cumminsii in patients with cutaneous and urinary tract infections. However, little is known on its pathogenesis as well as involvement in other clinical symptoms. In this study, we first report the isolation of P. cumminsii in blood of an epithelial mesothelioma patient. The clinical and laboratory characteristics of P. cumminsii were first described and evaluated. The pure colony of P. cumminsii was then identified using automated microorganism identification system and mass spectrum. The whole genome of the newly identified strain was sequenced with third generation sequencing (TGS). The assembled genome was further annotated and analyzed. Whole genomic and comparative genomic analysis revealed that the isolated P. cumminsii strain in this study had a genome size of 2,179,930 bp and had considerable unique genes compared with strains reported in previous findings. Further phylogenetic analysis showed that this strain had divergent phylogenetic relationship with other P. cumminsii strains. Based on these results, the newly found P. cumminsii strain was named P. cumminsii XJ001 (PC1). Virulence analysis identified a total of 71 pathogenic genes with potential roles in adherence, immune modulation, nutrition/metabolism, and regulation in PC1. Functional analysis demonstrated that the annotated genes in PC1 were mainly clustered into amino acid metabolism (168 genes), carbohydrate metabolism (107 genes), cofactor and vitamin metabolisms (98 genes), and energy metabolism (68 genes). Specifically, six genes including yodJ, idh, katA, pyk, sodA, and glsA were identified within cancer pathways, and their corresponding homologous genes have been documented with precise roles in human cancer. Collectively, the above results first identified P. cumminsii in the blood of tumor patients and further provide whole genomic landscape of the newly identified PC1 strain, shedding light on future studies of bacteria in tumorigenesis.

The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30–40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

Correlation between prognostic nutritional index and pleural thickness with survival time of epithelial malignant pleural mesothelioma patients

Objective: To explore the role of prognostic nutritional index (PNI) and pleural thickness in the prognostic evaluation of patients with epithelial malignant pleural mesothelioma (MPM) . Methods: In April 2022, a retrospective analysis was conducted on the data and laboratory data of 41 patients with epithelial MPM admitted to the cardiothoracic surgery department of Chuxiong Yi Autonomous Prefecture People's Hospital from January 2018 to May 2021. Univariate and multivariate analysis were used to evaluate the relationships between total survival time, clinical characteristics, PNI and pleural thickness in patients. Results: The 41 patients were mostly male (26 cases, 63.4%) , with a median age of 55 years old. The main clinical manifestations were chest pain (53.7%) , bloody pleural effusion (75.6%) , and chest pain combined with bloody pleural effusion (36.6%) . The median survival time of patients with different TNM stage, efficacy after 4 cycles of chemotherapy, PNI, maximum pleural thickness after chemotherapy (post max) , sum of post max in 3 zones after chemotherapy (post sum) were statistically different (χ(2)=3.89, 14.51, 15.33, 4.33, 12.05, P<0.05) . Compared with patients with high PNI and post sum<32.26 mm, MPM patients with low PNI and post sum≥32.26 mm have higher risk of death, and the differences were statistically significant (HR=1.52, 95%CI: 1.75-11.93, P=0.002; HR=1.70, 95%CI: 1.84-16.23, P=0.002) . Conclusion: PNI and post sum can be used to predict the prognosis of patients with epithelial MPM.

Second pleurectomy/decortication for a contralateral relapse of epithelial mesothelioma revealed by pneumothorax: a case report

Second pleurectomy/decortication for a contralateral relapse of epithelial mesothelioma revealed by pneumothorax: a case report

Analysis of clinicopathological features of 68 cases of malignant pleural mesothelioma

Objective: To analyze the clinicopathological characteristics of diffuse malignant pleural mesothelioma (MPM), and explore the diagnostic methods in order to improve the early diagnosis rate. Methods: In January 2019 to January 2022, the clinical features, auxiliary examination and immunohistochemical results of 68 cases of MPM were analyzed retrospectively. The pathogenic features, histopathological morphology and the expression of related antibodies including Calretinin (CR), D2-40 and WT-1 were summarized. Results: Among the 68 patients, 40 male (58.82%), 28 female (41.18%), male to female ratio was 1.43%, median age was 58 years old; 50% of patients in Dayao County, epithelial mesothelioma 59 cases (86.76%), occurred in right chest in 39 cases (57.35%), left chest in 25 cases (36.76%), and 4 cases in both sides (5.89%). The most common initial clinical manifestations were pleural effusion (95.59%), chest pain (36.75%), chest tightness and shortness of breath (30.88%). The main imaging findings were pleural effusion in 49 cases (98.00%) and pleural thickening in 46 cases (92.00%). MPM tumor cells often expressed Calretinin, CK5/6, WT1 and D2-40, while TTF-1, NapsinA and CEA, the main markers differentiated from lung adenocarcinoma were negative. Serum CYFRA21-1 and CEA have high value in differential diagnosis of benign and malignant pleural effusions. Conclusion: Diffuse MPM has diverse histological and cytological morphology, which needs to be differentiated from a variety of diseases. Correct diagnosis of diffuse MPM through immunohistochemistry requires the combined application of a group of Mesothelium related antibodies.

Mesotelioma epitelial maligno em vacas senis Sindi do Brasil

ABSTRACT: Mesotheliomas in cattle are often described as isolated case reports, and investigations of multiple cases within the same bovine herd are lacking. A series of cases of malignant epithelial mesothelioma, tubulopapilary type, is described in five 15 to 21-year-old Red Sindhi cows from the same herd. Clinical signs included three to eight months of progressive emaciation, dehydration, subcutaneous edema of the lower extremities, and abdominal distension. Grossly, severe subcutaneous edema and hydroperitoneum were noted. Multiple organs’ parietal and visceral serosal surfaces had multifocal to coalescing yellow, firm, sessile nodules ranging from 0.1 to 29.0cm. Similar free nodules floated in the peritoneal fluid. Histologically, the masses comprised a layer of cubic to columnar neoplastic cells forming papillary or cystic proliferation supported by a dense fibrovascular stroma. Neoplastic cells had strong and diffuse cytoplasmic immunolabeling for pan-cytokeratin but were negative for cytokeratin 7 and vimentin. Ultrastructurally, neoplastic cells had delicate microvilli and tight and anchoring junctions. Within the cytoplasm, a moderate amount of loose aggregate of intermediary filament with small mitochondria was observed. Epidemiological investigation evidenced endogamy in this herd. Asbestos exposure was not detected. The diagnosis was based on clinical, gross, histological, and immunohistochemical findings and confirmed by transmission electron microscopy features. A definitive underlying etiology remains unknown.

Long-term outcomes after lung-sparing surgery for epithelial mesothelioma.

BackgroundThis observational study evaluates retrospectively the long-term outcomes after pleurectomy/decortication for pleural mesothelioma, with and without the resection/reconstruction of diaphragm and pericardium.MethodsData from 155 consecutive patients undergoing lung-sparing surgery for epithelial pleural mesothelioma were reviewed. Selection criteria for surgery were cT1-3, cN0-1, good performance status, age <80 years. Perioperative Pemetrexed-Platinum regimen was administered as induction in 101 cases (65.2%) and as adjuvant treatment in 54 cases (34.8%). Extended pleurectomy/decortication was performed in 87 cases (56.12%). In 68 patients (43.87%) standard pleurectomy/decortication was performed without resection/reconstruction of diaphragm and pericardium, when tumour infiltration was deemed absent after intraoperative frozen section. The log-rank test and Cox regression model were used to assess the factors affecting overall survival and recurrence free survival.ResultsMedian follow-up was 20 months. The 2- and 5-year survival rate was 60.9% and 29.2% with a median survival of 34 months. An improved survival was observed when standard pleurectomy/decortication was carried out (P=0.007). A significant impact on survival was found comparing the TNM-stages (P=0.001), pT (P=0.002) and pN variables (P=0.001). Multivariate analysis identified the pN-status (P=0.003) and standard pleurectomy/decortication (P=0.017) as predictive for longer survival. The recurrence-free survival >12 months was strongly related to the overall survival (P<0.001). The macroscopic complete resection (P=0.001), TNM-stage (P=0.003) and pT-status (P=0.001) are related to relapse.ConclusionsWithin multimodal management of pleural mesothelioma, lung-sparing surgery is a valid option even with more conservative technique. A benefit for a longer survival was observed in the early stage of disease, with pN0 and when pleurectomy/decortication is carried out, preserving diaphragm and pericardium. Recurrence is not affected by the type of surgery, and a recurrence-free interval >12 months is predictive of an increased survival when the macroscopic complete resection is achieved.

Does the LENT score risk‐stratify patients with malignant pleural mesothelioma? An observational study

BackgroundMalignant pleural mesothelioma (MPM) is a rare, highly aggressive and deadly disease with a poor patient life expectancy. A few years ago, the main challenge was the histological diagnosis of this disease; at present, the search for the best therapeutic strategy is now a priority. However, an optimal therapeutic strategy is not yet clear, despite growing efforts in the treatment armamentarium and research, and at the era of tailored and individualized treatment, tools to predict patient survival are needed for therapeutic decision‐making. Among them, the LENT scoring system was developed to predict prognosis in patients with malignant pleural effusion. The aim of this study was to assess the performance of the LENT score in predicting prognosis in patients with MPM.MethodsA retrospective observational study was conducted by analyzing the prospective collected databases of patients undergoing medical thoracoscopy in a single center with a final diagnosis of MPM confirmed by the MESOPATH National Reference Center.ResultsA total of 41 patients with MPM were studied. All patients underwent platinum‐based chemotherapy combined with pemetrexed ± bevacizumab. No high‐risk category patients were found using the LENT scoring system in this cohort. The median (range) LENT score at the time of medical thoracoscopy was 0 (0–3) and the median survival was 15.5 (2–54) months for the entire cohort. The median survival of low‐risk and moderate‐risk category patients was 21.4 months (2–54, 32 patients) and 6.7 months (2–19, nine patients), respectively. A total of 27 patients with MPM of epithelial subgroup had a median LENT score of 1 (0–2) with a 26 (2–54) months median survival. The median LENT score and median survival of nonepithelial mesothelioma patients (biphasic MPM subgroup, eight patients; sarcomatoid MPM subgroup, six patients) were 0 (0–3) and 11 (2–52) months, respectively.ConclusionsApplied to a homogenous cohort of MPM patients, the LENT score underestimated prognosis and was not useful per se for the management of this disease, as evidenced in the epithelial mesothelioma subgroup of patients in our study.

Prognostic Role of PD-L1 in Malignant Pleural Mesothelioma: Unraveling the Complexity of the Tumor Microenvironment in Mesothelioma

In this issue of The Annals of Thoracic Surgery, Lee and colleagues1 observed that high programmed death-ligand 1 (PD-L1) expression characterized by PD-L1 expression in 50% or more of tumor cells in malignant pleural mesothelioma (MPM) was associated with worse survival both in epithelial and nonepithelial histology. This high level of PD-L1 expression was seen in 50% of sarcomatoid mesothelioma and in 14% of epithelial mesothelioma treated with complete macroscopic resection. Ingenuity pathway analysis demonstrated that high PD-L1 expression was associated with genes expression related to T cell exhaustion, dendritic cell maturation, interferon signaling, and JAK/Stat signaling, suggesting that high expression of PD-L1 is associated with the presence of reactive, but exhausted tumor-specific T cells.

Well-Differentiated Papillary Mesothelioma of the Peritoneum Is Genetically Distinct from Malignant Mesothelioma.

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial proliferation that is most commonly encountered as an incidental finding in the peritoneal cavity. There is controversy in the literature about whether WDPM is a neoplasm or a reactive process and, if neoplastic, whether it is a variant or precursor of epithelial malignant mesothelioma or is a different entity. Using whole exome sequencing of five WDPMs of the peritoneum, we have identified distinct mutations in EHD1, ATM, FBXO10, SH2D2A, CDH5, MAGED1, and TP73 shared by WDPM cases but not reported in malignant mesotheliomas. Furthermore, we show that WDPM is strongly enriched with C > A transversion substitution mutations, a pattern that is also not found in malignant mesotheliomas. The WDPMs lacked the alterations involving BAP1, SETD2, NF2, CDKN2A/B, LASTS1/2, PBRM1, and SMARCC1 that are frequently found in malignant mesotheliomas. We conclude that WDPMs are neoplasms that are genetically distinct from malignant mesotheliomas and, based on observed mutations, do not appear to be precursors of malignant mesotheliomas.

Mesotelioma deciduoide pleural: presentación de 3 casos y revisión de la literatura

Deciduoid mesothelioma is an uncommon histological variant of epithelial mesothelioma which is extremely clinically aggressive. We report 3 cases of pleural caducoid mesothelioma in women of 75, 74 and 23 years of age. All patients presented with dyspnoea, vomiting and pelvic pain. Their imaging studies showed nodular pleuropericardic thickening, a parietal pleuropericardic solid mass and a large thoracic mass, respectively. Only one of them could be treated with chemotherapy, surgery and radiotherapy. Post diagnostic survival was 24 days, 1 month and 17 months respectively (mean 6.2 months).We describe the clinicopathological and immunohistochemical findings together with a review of the relevant literature.

Establishment and characterization of patient derived xenograft model of malignant peritoneal mesothelioma in nude mice

Objective: To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM. Methods: Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 μL, others were inoculated at a dose of 200 μL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed. Results: The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 μL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations. Conclusions: The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.

Study of characteristics and behavior of patients with malignant pleural mesothelioma in Cairo and Fayoum University Hospitals

Background Malignant pleural mesothelioma (MPM) is a challenging disease regarding diagnosis and treatment; early diagnosis is important. MPM develops after a long latency period of asbestos exposure. Objectives To study the behavior and characteristics of MPM in Cairo and Fayoum University Hospitals. Patients and methods A total of 90 patients with MPM were examined from December 2015 to May 2017 and were subjected to history taking, clinical and radiological assessment, biopsy of the pleura for histopathological assessment, and immunohistochemical staining whenever needed. Results Mean age of the studied patients was 60.57, and males were 65.6%. Occupational asbestos exposure was present in 13.3%. Radiological pleural affection was in the form of pleural effusion (93.3%), pleural thickening (52.2%), pleural nodules (11%), and pleural plaques (1.1%). Overall, 80% of the cases were diagnosed by thoracoscopic pleural biopsy, 18.9% by ultrasound-guided biopsy, and 1.1% by surgery. The main histopathological subtype was epithelial mesothelioma (86.7%). Immunohistochemical marker staining was done for 25 cases. Calretinin was positive in 83.3%, cytokeratin (CK7) was positive in 88.9%, CK5/6 was positive in 62.5%, and D2-40 was positive in 50% of cases. Conclusion MPM had a male predominance (65.6%) and occupational hazards of exposure to asbestos. Thoracoscopic pleural biopsy is a good option for diagnosis. The main histopathological subtype was epithelial mesothelioma. Immunohistochemical markers that were frequently associated with the diagnosis of mesothelioma were calretinin (83.3%) and CK7 (88.9%).

Cyclin D1 immunohistochemical staining to separate benign from malignant mesothelial proliferations.

The separation of benign from malignant mesothelial proliferations is a morphologically difficult problem. Mutations/deletions of components of the Hippo pathway are frequent in malignant mesotheliomas, and one downstream effect of aberrant Hippo signaling is increased production of cyclin D1. We examined expression of cyclin D1 nuclear staining in two tissue microarrays containing 52 reactive epithelial mesothelial proliferations, 51 reactive spindle cell mesothelial proliferations, 54 epithelial mesotheliomas, and 22 sarcomatous/desmoplastic mesotheliomas. When present, cyclin D1 staining was always strong, hence the arrays were scored as 0, 1-25%, 26-50%, 51-75%, and 76-100% staining. Both arrays showed a similar pattern. Reactive epithelial proliferations generally showed no staining (42/52 cases) or 1-25% staining (10/52 cases) with no cases showing >25% staining. Overall for reactive epithelial proliferations the maximum staining was 14.8% and mean 1.1 ± 2.9%. For epithelial mesotheliomas 39/54 (72%) cases demonstrated >25% staining, with 8/54 in the 26-50% staining range, 9/54 in the 51-75% range, and 22/54 in the >75% range. Combinations of staining using cyclin D1 >50% plus BAP1 or MTAP loss in epithelial mesotheliomas produced about a 10% increase in sensitivity. Reactive spindle cell proliferations showed a broader range of staining with 27/51 in the 1-25% range, 5/51 in the 26-50% range, and 1/51 >50%. Eleven of 22 sarcomatous/desmoplastic mesotheliomas scored 50% or greater. We conclude that for epithelial mesothelial proliferations, the finding of >50% of tumor cells staining supports a diagnosis of epithelial mesothelioma with 100% specificity but only modest (57%) sensitivity.

2577 Dysdiadochokinesia, Ataxia, and Anemia: A Sign of Intraluminal Malignant Mesothelioma in the Small Bowel?

INTRODUCTION: Malignant mesothelioma (MM) is a rare cancer of the serosal membranes, the pleura and peritoneum, and causes significant morbidity and mortality. While implants of the bowel wall are common, only two case reports on intraluminal involvement exist. We present a case of an elderly male with dysdiadochokinesia found to have abdominal lymphadenopathy, and a jejunal mass from peritoneal mesothelioma (PM). CASE DESCRIPTION/METHODS: An 87 year-old male with a family history (FH) of colon cancer in one first-degree relative presented with one month of unintentional weight loss, gait instability, and trouble performing alternating movements. Two months prior to admission, evaluation included a negative MRI of the brain but positive CSF analysis for neuron-restricted autoantibody treated empirically with five days of intravenous immunoglobulin (IVIG) and three days of pulse dose steroids. Physical examination was notable for ataxia and dysdiadochokinesia and a benign abdominal exam. He had normal electrolytes and liver chemistries, but was anemic. PET/CT revealed intensely FDG-avid abdominal and mesenteric lymph nodes, one inseparable from the small bowel (Figures 1 and 2). Lymph nodes were not accessible by IR-guided biopsy, so he underwent push enteroscopy and colonoscopy, in light of his FH, to evaluate for anemia. A large, oozing ulcerated mass was found in the jejunum and biopsied (Figure 3). Immunostaining was positive for cytokeratin, CK7, WT1, and calretinin consistent with PM. His neurologic decline was then linked to PNS secondary to PM. He was discharged with plans for carboplatin therapy. DISCUSSION: MM is strongly associated with asbestos exposure, and is four to five times more prevalent in men than women. PM limited to the small bowel is exceedingly rare. Only one previous case report describes a mass spanning the entire small bowel, identified as mucin-positive epithelial mesothelioma. PNS affects 1 in 10,000 patients with cancer; more than 85% of cases are linked to gynecologic and breast cancers causing cerebellar dysfunction via purkinje cell destruction by anti-Yo antibody (Ab). Two cases of PM associated PNS with anti-Yo Ab in the CSF have been reported; one was treated with IVIG and high dose steroids. The treatment of PM is key to stabilizing neurologic symptoms, such as dysdiadochokinesia. The prognosis of PM and associated PNS remains poor. Anemia with cerebellar symptoms should trigger a search for malignancy and rarer causes such as PM.

Role of Immunotherapy in Small Cell Lung Cancer, Thymic Epithelial Tumors, and Mesothelioma.

The introduction of programmed death receptor ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) inhibitors into the field of non-small cell lung cancer (NSCLC) was practice changing. The pivotal trials consistently showed a clinically meaningful improvement in overall survival (OS) for patients with driver mutation-negative NSCLC, a field in which outcomes had been stagnant for decades. The success of immune checkpoint inhibitor (ICI) therapy in NSCLC has led to enthusiasm to expand the reach of these drugs into other thoracic malignancies such as thymic epithelial tumors (TETs), mesothelioma, and small cell lung cancer (SCLC). Unfortunately, the improvement in outcomes with ICI therapy in these rarer thoracic tumors has been somewhat modest, and in the case of thymoma, rates of adverse events are too high to routinely justify their use. Although the response rates seen in ICI therapy in these tumor types are similar to those seen with other available single-agent therapies for advanced disease, ICIs do present another option for clinicians treating patients with mesothelioma, small cell carcinoma, and thymic carcinoma (TC), diseases in which approved treatment options are limited. Here we review the latest trials of ICI therapy in mesothelioma, SCLC, and TETs.

Pleurectomy/decortication and hyperthermic intrathoracic chemoperfusion using cisplatin and doxorubicin for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITHOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITHOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. From 2009 until 2013, 71 patients with localized pleural mesothelioma underwent pleurectomy and decortication followed by HITHOC with cisplatin and doxorubicin. We analyzed postoperative morbidity, age, overall survival and influence of macroscopic resection on survival. Median patient age was 70 years (range, 65-73 years). Patients having the sarcomatoid subtype of mesothelioma showed a poor median survival of 9.2 months. In contrast, patients having the epithelioid subtype had a median survival of 17.9 months. Patients following macroscopic complete resection had a significantly better survival with 28.2 months compared to 13.1 months in patients with incomplete resection of the mesothelioma (P<0.0001). HITHOC was performed in all patients after tumor resection using cisplatin and doxorubicin. Taken together, HITHOC following pleurectomy and decortication is supposed to be a safe therapeutic option for selected patients with localized epithelial pleural mesothelioma.

Disparities in Compliance With National Guidelines for the Treatment of Malignant Pleural Mesothelioma

Current guidelines support cancer-directed surgery, chemotherapy, or active surveillance for clinical stages 1 to 3 of epithelial malignant pleural mesothelioma (MPM). Definitive chemotherapy is recommended for sarcomatoid/biphasic histologies. Our objective is to assess compliance with recommendations, measuring their impact on overall survival. The National Cancer Database participant user file (2004 to 2014) was queried for patients diagnosed with MPM clinical stages 1 to 3. Multivariable logistic regression model identified factors independently associated with guideline compliance. Kaplan-Meier analysis and Cox proportional hazards were used for overall survival comparison with histologic subgroup analysis. A total of 3419 patients with clinical stages 1 to 3 met criteria for analysis and comprised epithelial (68.5%), sarcomatoid (17.2%), and biphasic subtypes (14.3%). Cancer-directed surgery was significantly underutilized in epithelial MPM, with 29.3% having no treatment. On multivariable analysis, insurance status and facility type were the strongest predictors of guideline compliance. High-volume hospitals were the most compliant with guidelines (odds ratio 3.58, 95% confidence interval (CI), 2.34 to 5.49, P < .001). Median survival estimates for no treatment, chemotherapy alone, surgery plus chemotherapy, and trimodal therapy were 10.2, 15.4, 21.1, and 21.7 months, respectively (log rank P < .001). In epithelial MPM, a significant increase in overall survival was observed in surgery plus chemotherapy (hazard ratio 0.62, 95% CI, 0.53 to 0.73, P < .001) and trimodality (hazard ratio 0.61, 95% CI, 0.49 to 0.76, P < .001; reference: no treatment). There is a suboptimal compliance with national guidelines for the treatment of MPM, particularly in low-volume nonacademic settings. Adherence to recommended surgery-based multimodal therapy is associated with an overall survival improvement.

Prognostic factors of survival in patients with malignant pleural mesothelioma: an analysis of the National Cancer Database.

Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis.