Prognostic impact of inflammation in malignant pleural mesothelioma: A large-scale analysis of consecutive patients

Fournel, Ludovic; Charrier, Thomas; Huriet, Maxime; Iaffaldano, Amedeo; Lupo, Audrey; Damotte, Diane; Arrondeau, Jennifer; Alifano, Marco

doi:10.1016/j.lungcan.2022.03.014

Cited by 8 publications

(9 citation statements)

References 36 publications

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“…Nguen et al also demonstrated that inferred infiltrating immune cell fractions can be combined with genomic parameters to develop prognostic models in MPM [40]. Finally, another recent study showed that markers for higher levels of systemic inflammation correlated with shorter overall survival in MPM patients [41]. Our observations in the context of those studies obviously suggest that immune-based markers are to be included in prognostic schemes for MPM patients.…”

Section: Discussionsupporting

confidence: 56%

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

2023

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Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.

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Section: Discussionsupporting

confidence: 56%

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

2023

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“…We considered other indexes, namely SII (systemic immune-inflammation index) or ALI (advanced lung cancer inflammation Index). Fournel [ 39 ] showed the strong impact of systemic inflammation on the prognosis of malignant pleural mesothelioma and a shorter survival associated with NLR, SII, and lower ALI.…”

Section: Discussionmentioning

confidence: 99%

Systemic Inflammation and Lung Cancer: Is It a Real Paradigm? Prognostic Value of Inflammatory Indexes in Patients with Resected Non-Small-Cell Lung Cancer

Mazzella

Maiolino

Maisonneuve

et al. 2023

Cancers

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Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan–Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3): We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 (p = 0.002); histology (p = 0.002); HALP < 32.2 (p = 0.0002); SII ≥ 808.9 (p = 0.0004); ALI < 34.86 (p = 0.0005); NLr ≥ 2.29 (p = 0.01); hemoglobin < 13 g/dl (p = 0.01); PLR ≥ 196.1 (p = 0.005); pN+ (p < 0.0001); pleural invasion (p = 0.0002); and presence of vascular or lymphatic tumor emboli (p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 (p = 0.02); histology, HALP < 32.2 (p = 0.004), and pN (p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery.

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“…In MPM, the interaction of eosinophils with other immune cells such as macrophages, monocytes and neutrophils may direct pro- or anti-tumor functions as well as response to therapy ( 13 – 18 ). Consistently, inflammation markers such as lymphocyte predominance, NLR and absolute monocyte count (AMC) have been correlated with poor survival ( 52 – 57 ). Analysis of the data set of our cohort did not reveal any association of OS with NLR, AMC and monocyte-to-lymphocyte ratios.…”

Section: Discussionmentioning

confidence: 88%

Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma

et al. 2023

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BackgroundOnly a fraction of patients with malignant pleural mesothelioma (MPM) will respond to chemo- or immunotherapy. For the majority, the condition will irremediably relapse after 13 to 18 months. In this study, we hypothesized that patients’ outcome could be correlated to their immune cell profile. Focus was given to peripheral blood eosinophils that, paradoxically, can both promote or inhibit tumor growth depending on the cancer type.MethodsThe characteristics of 242 patients with histologically proven MPM were retrospectively collected in three centers. Characteristics included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). The mean absolute eosinophil counts (AEC) were determined by averaging AEC data sets of the last month preceding the administration of chemo- or immunotherapy.ResultsAn optimal cutoff of 220 eosinophils/µL of blood segregated the cohort into two groups with significantly different median OS after chemotherapy (14 and 29 months above and below the threshold, p = 0.0001). The corresponding two-year OS rates were 28% and 55% in the AEC ≥ 220/µL and AEC < 220/µL groups, respectively. Based on shorter median PFS (8 vs 17 months, p < 0.0001) and reduced DCR (55.9% vs 35.2% at 6 months), the response to standard chemotherapy was significantly affected in the AEC ≥ 220/µL subset. Similar conclusions were also drawn from data sets of patients receiving immune checkpoint-based immunotherapy.ConclusionIn conclusion, baseline AEC ≥ 220/µL preceding therapy is associated with worse outcome and quicker relapse in MPM.

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Prognostic impact of inflammation in malignant pleural mesothelioma: A large-scale analysis of consecutive patients

Cited by 8 publications

References 36 publications

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

Systemic Inflammation and Lung Cancer: Is It a Real Paradigm? Prognostic Value of Inflammatory Indexes in Patients with Resected Non-Small-Cell Lung Cancer

Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma

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