Survival In Mesothelioma Research Articles

Mesothelioma survival prediction based on a six-gene transcriptomic signature

Mesothelioma survival prediction based on a six-gene transcriptomic signature

Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.

Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ-Jβ rearrangements associated with MM immunotherapy efficacy. The present study reported the largest-scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR-specific clones.

Differential expression of DMD transcripts as a novel prognostic biomarker in histologically diverse mesotheliomas.

The identification of prognostic biomarkers is crucial for guiding treatment strategies in mesothelioma patients. The Duchenne muscular dystrophy (DMD) gene and its specific transcripts have been associated with patient survival in various tumours. In this study, we aimed to investigate the prognostic potential of DMD gene expression and its transcripts in mesothelioma patients. We analysed The Cancer Genome Atlas (TCGA) mesothelioma RNAseq, mutation, and clinical data to assess the association between DMD gene expression and its transcripts (Dp427, Dp71 splice variants) and mesothelioma survival. We also evaluated the specific Dp71 transcript as a unique prognostic biomarker across mesothelioma subtypes. Additionally, we performed differential gene expression analysis between high and low DMD gene/transcript expression groups. The analysis included 57 epithelioid, 23 biphasic, two sarcomatoid, and five not otherwise specified (NOS) histological subtypes of mesothelioma samples. Univariate analysis revealed that high expression of the DMD gene and its Dp71 transcript was significantly associated with shorter survival in mesothelioma patients (P=0.003 and P<0.001, respectively). In a multivariate analysis, the association between Dp71 expression and survival remained significant [hazard ratio (HR) 2.29, 95% confidence interval (CI): 1.24-4.23, P=0.008] across all mesothelioma patients, and also among patients with mesotheliomas without deep CDKN2A deletions (HR 3.58, 95% CI: 1.31-9.80, P=0.01). Pathway analysis revealed enrichment of cell cycle (P=3.01×10-4) and homologous recombination (P=0.01) pathways in differentially expressed genes (DEGs) between high and low Dp71 groups. Furthermore, there were correlations between Dp71 transcript expression and tumour microenvironment (TME) cells, including a weak positive correlation with macrophages (R=0.32, P=0.002) specifically M2 macrophages (R=0.34, P=0.001). Our findings indicate that the differential expression of specific DMD transcripts is associated with poor survival in mesothelioma patients. The specific Dp71 transcript can serve as a potential biomarker for predicting patient survival in diverse histological subtypes of mesothelioma. Further studies are needed to understand the role of specific dystrophin transcripts in cancer and TME cells, and their implications in the pathogenesis and progression of mesothelioma. Identifying patients at risk of poor survival based on DMD transcript expression can guide treatment strategies in mesothelioma, informing decisions regarding treatment intensity, follow-up schedules, eligibility for clinical trials, and ultimately, end-of-life care planning.

Prognostic significance of inflammation scores in malignant mesothelioma.

The relationship between inflammatory markers and survival in many cancers has been investigated previously. Inflammatory markers may also offer the possibility of predicting surveillance in patients with malignant mesothelioma. Our study seeks to enhance comprehension of how variables such as the nutritional status and inflammation indices of malignant mesothelioma patients impact the disease's progression and prognosis. This study included patients who were treated at the Erciyes University Medical Oncology Clinic between 2010 and 2022 and diagnosed with malignant mesothelioma. This is a retrospective single-center cohort study. Receiver Operating Characteristic (ROC) analysis was applied to determine the inflammation markers' optimal cut-off values with high sensitivity and specificity. Patients were categorized based on these values. The differences in overall survival (OS) and progression-free survival (PFS) between categorized groups were assessed using Log-rank curves and Kaplan-Meier tests. Multivariate analysis was performed using Cox regression analysis on statistically significant data. The relationship between inflammation markers and malignant mesothelioma survival was evaluated. There are 115 patients in this study. Pre-treatment high neutrophil to lymphocyte ratio (NLR) (HR: 1.34, 95% CI: 1.12-2.83, p=0.04), high pan-immune inflammation value (PIIV) (HR: 2.01, 95% CI: 1.32-4.79, p=0.03), and high systemic inflammation response index (SIRI) (HR: 1.34, 95% CI: 1.2-2.78, p=0.04) were associated with poor OS. Conversely, high advanced lung cancer inflammation index (ALI) (HR: 0.73, 95% CI: 0.53-0.84, p=0.03) and high hemoglobin-albumin-lymphocyte and platelet (HALP) (HR: 0.67, 95% CI: 0.23-0.78, p=0.02) were associated with favorable survival. Our study investigated the prognostic value of various inflammation markers in malignant mesothelioma patients and suggests that composite formulas like NLR, PIIV, SIRI, ALI, and HALP that incorporate CBC cells and nutritional parameters like albumin, height, and weight could more consistently and accurately predict malignant mesothelioma prognosis.

Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.

Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.

Laterality and survival in mesothelioma: A SEER database analysis.

e20594 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive and rare cancer type that carries dismal prognosis with a median survival of only 12 months. Often patients are diagnosed at advanced age and tend to have many co-morbid conditions. More precise prognostication should help physicians to decide on the best treatment approach for patients. Previous three studies suggest right sided involvement is associated with poorer prognosis. However, these were very small studies and estimates were not precise. We therefore decided to assess prognostic indicators, including laterality, using the large SEER database. Methods: Using SEER database, a total of 5064 cases diagnosed between 1975-2003 were included in this study. R software (4.0.5) was used. Prognostic indicators assessed included age, stage at diagnosis (distant versus regional/early), gender, and tumor laterality. We evaluated all-cause mortality using multivariate regression and introduced a competing risk regression to explore the association of clinical features and mesothelioma-related death. In analyses, we treated non-cancer related death as a competing factor. The prognostic significance of laterality was assessed at each stage of diagnosis. Results: The patients were predominantly male (81%), aged 60 years or older (79.1%) with right side predominance (58.9%). The overall median survival time was 8 months. The cumulative incidence of mesothelioma-specific death was 42% at 6 months and 62% at 12 months. In the multivariate analysis, male gender (HR = 1.23, p &lt; 0.01), age 60 year or older (HR = 1.52, p &lt; 0.01) and distant stage at diagnosis (HR = 1.2, p &lt; 0.01) were independent predictors of shorter overall survival. In subgroup analyses of different stages, right sided mesothelioma was an independent predictor of mesothelioma-related death(HR = 1.14, CI 1.00-1.28, p = 0.042) in patients with regional/early-stage disease (Table) after adjustment for age and gender. When included all cohort with both early and late stages, there was no statistically significant association between laterality and all-cause mortality(HR = 1.02, CI 0.958-1.08, p = 0.61). Conclusions: Our study confirms that right-sided involvement is independently associated with increased risk of death in early stage/localized mesothelioma patients. The lack of association between laterality and survival in those with distant spread may be explained by the overall shorter survival in that group.[Table: see text]

Survival of Korean Patients with Malignant Pleural Mesothelioma Compensated for the Asbestos Injury Relief

Background: The purpose of this study was to identify the epidemiologic characteristics and prognostic factors for malignant pleural mesothelioma in Korea, which are currently insufficient. The data were derived from malignant mesothelioma patients who registered under the Asbestos Injury Relief Act; Methods: A total of 728 patients received compensation from the Asbestos Injury Relief Act due to malignant mesothelioma between 2011 and 2015. Of these, 313 patients (43.0%) with malignant pleural mesothelioma were included in the study. The study variables were sex (male, female), age at diagnosis (&lt;59, 60–69, ≥70), smoking history (yes, no), surgery (yes, no), chemotherapy (yes, no), occupational exposure to asbestos (yes, no), and histological subtype (epithelioid, nonepithelioid); Results: Median survival of mesothelioma was 8.0 months (95% confidence interval: 6.2 to 9.8). The 1-year, 2-year, and 5-year survival rates (%) were 43.5%, 23.6%, and 12.5%, respectively. In multivariate analysis of Cox’s proportional hazards model; sex, age, smoking history, occupational asbestos exposure, and histological subtype were not significant prognostic factors, but surgery and chemotherapy combined was a significant predictor; Conclusions: Although the representativeness of these data is limited, our study estimates the epidemiologic characteristics of malignant pleural mesothelioma. Non-occupational exposure had a similar prognosis to occupational asbestos exposure, and there was no sex difference. In addition, it was found that receiving a combination of surgery and chemotherapy affects the survival rate, but there is a limitation in that factors such as performance status, comorbidities, and stage that contribute to survival are not considered.

Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China

Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998–2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan–Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.

Gender Differences in Outcomes of Patients With Mesothelioma.

Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom. Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders. There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology. The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort.

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses data and associated biospecimens for over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier's method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were younger than 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and having combination treatment of surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone.

Is pleural infection associated with longer survival in mesothelioma? A population-based cohort study using data from Hospital Episode Statistics

BackgroundHistorically pleural infection was thought to be associated with longer survival in thoracic malignancies. The aim of this population-based cohort study was to investigate this hypothesis in mesothelioma, using national data from a high incidence country. MethodsCase records for all patients with mesothelioma seen in English hospitals between 01/01/2005 and 31/12/2014 were extracted from Hospital Episode Statistics using International Classification of Diseases Tenth Edition (ICD-10) codes. Episodes of pleural infection were identified. Linked mortality data was obtained from the Office of National Statistics.The primary outcome was all-cause mortality. The explanatory variable was pleural infection. Cox proportional hazards model was used to analyse survival, with pleural infection, chemotherapy and thoracic surgery handled as time-variable co-factors. ResultsOf 22,215 patients with mesothelioma, 512 (2.3%) developed pleural infection at some point in their illness. Overall median survival was 7.0 months (IQR 2.3–16.4). Pleural infection was associated with shorter survival in the immediate post-infection period (up to 30 days – HR 1.81, 95% CI 1.45–2.22) and longer term (>30 days – HR 1.81, 95% CI 1.63–1.99). Other factors associated with increased mortality were age, male gender and being diagnosed as an inpatient. Receiving chemotherapy and being less economically deprived were associated with longer survival. ConclusionPleural infection occurred in 2.3% of people with mesothelioma and was associated with shorter survival. This refutes previous reports suggesting pleural infection may be associated with better outcomes in thoracic malignancy.

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort.

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier's method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were below the age of 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and had treatment that consisted of combining surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone.

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses data and associated biospecimens for over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier’s method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were younger than 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and having combination treatment of surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone.

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort.

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier's method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were below the age of 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and had treatment that consisted of combining surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment is associated with improved survival compared to local therapy alone.

Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis.

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1‐ and 2‐year survival according to sex, age, co‐morbidities, management, population‐density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co‐morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One‐ and 2‐year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7–15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co‐morbidities, living in rural/semi‐rural area was associated with better 2‐year survival (HR: 0.83 [95% CI: 0.73–0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co‐morbidities, sex, age, and living place appear to be significant factors of prognosis.

Is Pleural Infection Associated with Longer Survival in Mesothelioma? A Population-Based Cohort Study Using Data from Hospital Episode Statistics

Is Pleural Infection Associated with Longer Survival in Mesothelioma? A Population-Based Cohort Study Using Data from Hospital Episode Statistics

The epithelioid BAP1-negative and p16-positive phenotype predicts prolonged survival in pleural mesothelioma.

Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to guide treatment. We therefore sought to investigate the role of p16 immunohistochemistry (IHC) both alone and in combination with other markers as a potential predictor of prolonged survival in mesothelioma. P16 IHC was performed on unselected pleural mesotheliomas biopsied from 1991 to 2014; 153 of 208 (74%) cases were p16-negative, which correlated significantly with poor overall survival in both univariate (median survival 7.6 versus 13.6 months; P = 0.001) and multivariate analysis [hazard ratio (HR): 1.632; 95% confidence interval (CI): 1.103-2.415; P = 0.014]. Other independent factors associated with prolonged survival included loss of expression of BAP1 and epithelioid morphology. We therefore stratified patients further based on these three independent prognostic variables and demonstrated an unusually prolonged survival in mesotheliomas which were epithelioid, BAP1 IHC negative and p16 IHC positive (12% of cases, median survival 31.7 months, P < 0.0001). In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, patients with exceptionally prolonged survival can potentially be identified.

The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma

IntroductionResults of recent clinical studies of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) have dampened initial enthusiasm. However, the immune environment and targets of these treatments such as programmed cell death protein 1 and its ligand programmed death ligand 1 (PD-L1) have not been well characterized in MPM. Using a large cohort of patients, we investigated PD-L1 expression, immune infiltrates, and genome-wide copy number status and correlated them to clinicopathological features. MethodsTissue microarrays were constructed and stained with PD-L1(clone E1L3N [Cell Signaling Technology, Danvers, MA]), cluster of differentiation 4, cluster of differentiation 8, and forkhead box P3 antibodies. PD-L1 positivity was defined as at least 5% membranous staining regardless of intensity, and high PD-L1 positivity was defined as at least 50%. Genomic DNA from a representative subset of 113 patients was used for genome-wide copy number analysis. The percent genome alteration was computed as a proxy for genomic instability, and statistical analyses were used to relate copy number aberrations to other variables. ResultsAmong 329 patients evaluated, PD-L1 positivity was detected in 130 of 311 (41.7%), but high PD-L1 positivity was seen in only 30 of 311 (9.6%). PD-L1 positivity correlated with nonepithelioid histological subtype and increased infiltration with cluster of differentiation 4–positive, cluster of differentiation 8–positive, and forkhead box P3–positive lymphocytes. High PD-L1–positive expression correlated with worse prognosis (hazard ratio = 2.37, 95% confidence interval: 1.57–3.56, p < 0.001) in univariate analysis but not in multivariate analysis. Higher percent genome alteration was associated with epithelioid histological subtype and poorer survival (hazard ratio = 1.59, 95% confidence interval: 1.01–2.5, p = 0.04) but not PD-L1 expression. ConclusionsPD-L1 expression was associated with nonepithelioid MPM, poor clinical outcome, and increased immunological infiltrates. Increased genomic instability did not correlate with PD-L1 expression but was associated with poorer survival.

Correlation of PD-L1 expression with immune cell infiltrates, genome-wide copy number aberrations and survival in mesothelioma.

8518Background: Recent clinical studies using immune checkpoint inhibitors in mesothelioma (MM) have shown promise in shifting treatment paradigms. However, the immune environment and targets of th...

Survival in Patients With Malignant Pleural Effusions Who Developed Pleural Infection

Malignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014. Survival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics. Of 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6). This small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression.