bims-mesote Biomed News
on Mesothelioma
Issue of 2022–03–27
twelve papers selected by
Laura Mannarino, Humanitas Research
  1. 3-year CheckMate743 outcomes: ringing in immunotherapy for the treatment of malignant pleural mesothelioma.
  2. Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.
  3. Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.
  4. Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study.
  5. Prognostic impact of inflammation in malignant pleural mesothelioma: A large-scale analysis of consecutive patients.
  6. Prognostic value of 18F-FDG PET/CT in malignant pleural mesothelioma: a meta-analysis.
  7. Cancer-Associated Fibroblasts Regulate Kinase Activity in Mesothelioma Cell Lines via Paracrine Signaling and Thereby Dictate Cell Faith and Behavior.
  8. Informative Power Evaluation of Clinical Parameters to Predict Initial Therapeutic Response in Patients with Advanced Pleural Mesothelioma: A Machine Learning Approach.
  9. Force-feeding malignant mesothelioma stem-cell like with exosome-delivered miR-126 induces tumour cell killing.
  10. Gene Expression Analysis of Biphasic Pleural Mesothelioma: New Potential Diagnostic and Prognostic Markers.
  11. Radiation Induced Abscopal Effect in a Patient With Malignant Pleural Mesothelioma on Pembrolizumab.
  12. Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study.
  1. Ann Oncol. 2022 Mar 16. pii: S0923-7534(22)00381-7. [Epub ahead of print]
    3-year CheckMate743 outcomes: ringing in immunotherapy for the treatment of malignant pleural mesothelioma.
    S Cedres, E Felip.
      
    DOI:  https://doi.org/10.1016/j.annonc.2022.03.004
  2. Int J Environ Res Public Health. 2022 Mar 13. pii: 3390. [Epub ahead of print]19(6):
    Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.
    Andrea Spinazzè, Dario Consonni, Francesca Borghi, Sabrina Rovelli, Andrea Cattaneo, Carolina Zellino, Barbara Dallari, Angela Cecilia Pesatori, Hans Kromhout, Susan Peters, Luciano Riboldi, Domenico Maria Cavallo, Carolina Mensi.
      The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen's kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.
    Keywords:  SYN-JEM; asbestos; job-exposure matrix (JEM); mesothelioma; occupational exposure; retrospective exposure assessment
    DOI:  https://doi.org/10.3390/ijerph19063390
  3. Biomedicines. 2022 Mar 14. pii: 673. [Epub ahead of print]10(3):
    Recent Advances of Immune Checkpoint Inhibition and Potential for (Combined) TIGIT Blockade as a New Strategy for Malignant Pleural Mesothelioma.
    Sophie Rovers, Annelies Janssens, Jo Raskin, Patrick Pauwels, Jan P van Meerbeeck, Evelien Smits, Elly Marcq.
      Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs, and is causally associated with asbestos exposure. Until recently, the first-line treatment consisted of a combination of chemotherapeutics that only had a limited impact on survival, and had not been improved in decades. With the recent approval of combined immune checkpoint inhibition for MPM, promising new immunotherapeutic strategies are now emerging for this disease. In this review, we describe the current preclinical and clinical evidence of various immune checkpoint inhibitors in MPM. We will consider the advantages of combined immune checkpoint blockade in comparison with single agent checkpoint inhibitor drugs. Furthermore, recent evidence suggests a role for T cell immunoglobulin and ITIM domain (TIGIT), an inhibitory immunoreceptor, as a novel target for immunotherapy. As this novel immune checkpoint remains largely unexplored in mesothelioma, we will discuss the potential of TIGIT blockade as an alternative therapeutic approach for MPM. This review will emphasize the necessity for new and improved treatments for MPM, while highlighting the recent advances and future perspectives of combined immune checkpoint blockade, particularly aimed at PD-L1 and TIGIT.
    Keywords:  PD-L1; TIGIT; cancer immunotherapy; immune checkpoint blockade; mesothelioma
    DOI:  https://doi.org/10.3390/biomedicines10030673
  4. Cancers (Basel). 2022 Mar 15. pii: 1498. [Epub ahead of print]14(6):
    Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study.
    Jean-Baptiste Assié, Florian Crépin, Emmanuel Grolleau, Anthony Canellas, Margaux Geier, Aude Grébert-Manuardi, Nabila Akkache, Aldo Renault, Pierre-Alexandre Hauss, Marielle Sabatini, Valentine Bonnefoy, Alexis Cortot, Marie Wislez, Clément Gauvain, Christos Chouaïd, Arnaud Scherpereel, Isabelle Monnet.
       BACKGROUNDS: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10-25% objective response rate (ORR) and 40-70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response.
    METHODS: This retrospective study included (September 2017-July 2021) all MPM patients managed in 11 French centers.
    RESULTS: The 109 enrolled patients' characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2-5.9) and 12.8 (9.2-16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52-7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22-0.99), progression on the line preceding nivolumab: 2.1 (1.11-3.9) and age > 70 years: 2.5 (1.5-4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08-11.8) and albumin < 25 g/L: 10.28 (1.5-70.7) as significant and independent predictors.
    CONCLUSIONS: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.
    Keywords:  immune-checkpoint inhibitors; malignant pleural mesothelioma; nivolumab; real-world study; second-line regimen
    DOI:  https://doi.org/10.3390/cancers14061498
  5. Lung Cancer. 2022 Mar 19. pii: S0169-5002(22)00383-X. [Epub ahead of print]166 221-227
    Prognostic impact of inflammation in malignant pleural mesothelioma: A large-scale analysis of consecutive patients.
    Ludovic Fournel, Thomas Charrier, Maxime Huriet, Amedeo Iaffaldano, Audrey Lupo, Diane Damotte, Jennifer Arrondeau, Marco Alifano.
       BACKGROUND: Prediction of prognosis is a key step of malignant pleural mesothelioma (MPM) management and treatment assignment. Aim of this study was to identify simple prognostic factors, focusing on inflammation-related parameters.
    METHODS: Baseline clinical and laboratory data were extracted from a single-center 20-year cohort of consecutive patients exhibiting a proven MPM. Inflammation-related ratios and composite scores were evaluated as prognostic indicators.
    RESULTS: 468 patients were identified. Mean age and BMI were 73.0 years and 25.1 kg/m2. The histologic subtype was epithelioid, sarcomatoid, or biphasic in 80.3%, 6.2%, and 13.5% of cases, respectively. Mean Neutrophil to Lymphocyte Ratio (NLR), systemic Inflammation Index (SII) and Advanced Lung cancer inflammation Index (ALI) were 5.8, 1,836.6, and 29.6. Median survival was 13.0 months. Univariate analyses revealed that age > 70 years, persistent asthenia, hemoglobin < 13 g/dL, and non-epithelioid histologic type were associated with poorer survival, as well as the following high-inflammation-related criteria: CRP > 25 mg/L, white blood cell count (WBC) > 109/dL, NLR > 5, SII > 1,270, and ALI < 18. Multivariate regression showed that age, histology, hemoglobin, and WBC were independent predictors of survival. Also, the inflammation-related factors ALI and NLR were independently associated with survival. Interestingly, hemoglobin was statistically significant predictor of survival in all multivariate models. We found higher proportion of survival > 18 months (66th percentile) in patients exhibiting SII < 2,000 and NLR < 5.
    CONCLUSION: The prognosis of MPM is strongly influenced by systemic inflammation and patients exhibiting higher NLR, SII and lower ALI have shorter survival, which strengthens the level of evidence about the major role played by inflammation in MPM.
    Keywords:  Cancer; Inflammation; Mesothelioma; Nutrition; Prognosis
    DOI:  https://doi.org/10.1016/j.lungcan.2022.03.014
  6. Acta Radiol. 2022 Mar 22. 2841851221085378
    Prognostic value of 18F-FDG PET/CT in malignant pleural mesothelioma: a meta-analysis.
    Yu Wang, Yanfeng Xu, Ying Kan, Wei Wang, Jigang Yang.
       BACKGROUND: Several FDG PET/CT parameters have been utilized to evaluate the prognosis in malignant pleural mesothelioma (MPM). However, there are still controversial results due to the low incidence of MPM.
    PURPOSE: To assess the prognostic value of 18F-FDG PET/CT in MPM.
    MATERIAL AND METHODS: A systematic literature search was performed in PubMed, Embase, Medline, and The Cochrane Library to identify eligible studies from inception to 12 February 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of several variables, such as maximum standardized uptake value (SUVmax), the reduction of SUVmax after treatment (ΔSUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the reduction of TLG after treatment (ΔTLG), were calculated. Meta-regression with subsequent subgroup analyses were conducted to determine the heterogeneity of cutoff values, treatment regimen, study design, uptake time, and scanners across various studies.
    RESULTS: In total, 19 eligible studies including 1819 patients were enrolled in the meta-analysis. The univariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, TLG, and ΔTLG were 1.29 (1.16-1.42), 1.12 (1.05-1.19), 1.15 (1.00-1.33), 1.47 (1.23-1.76), and 1.27 (1.12-1.45), respectively. The multivariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, and TLG for overall survival (OS) were 1.20 (1.08-1.33), 1.10 (1.02-1.19), 0.95 (0.81-1.11), and 1.13 (1.08-1.18), respectively.
    CONCLUSION: SUVmax, ΔSUVmax, TLG, and ΔTLG are significant prognostic indicators for OS, while more clinical studies are needed to confirm the prognostic value of MTV in MPM.
    Keywords:  Positron emission tomography; mesothelioma; meta-analysis; prognosis
    DOI:  https://doi.org/10.1177/02841851221085378
  7. Int J Mol Sci. 2022 Mar 18. pii: 3278. [Epub ahead of print]23(6):
    Cancer-Associated Fibroblasts Regulate Kinase Activity in Mesothelioma Cell Lines via Paracrine Signaling and Thereby Dictate Cell Faith and Behavior.
    Alexander Mathilakathu, Michael Wessolly, Elena Mairinger, Hendrik Uebner, Daniel Kreidt, Luka Brcic, Julia Steinborn, Kristina Greimelmaier, Jeremias Wohlschlaeger, Kurt Werner Schmid, Fabian D Mairinger, Sabrina Borchert.
       BACKGROUND: Malignant pleural mesothelioma (MPM) has an infaust prognosis due to resistance to systemic treatment with platin-analoga. MPM cells modulate the immune response to their benefit. They release proinflammatory cytokines, such as TGF-ß, awakening resting fibrocytes that switch their phenotype into activated fibroblasts. Signaling interactions between cancer cells and cancer-associated fibroblasts (CAFs) play an integral part in tumor progression. This study aimed to investigate the role CAFs play in MPM progression, analyzing the impact this complex, symbiotic interaction has on kinase-related cell signaling in vitro.
    METHODS: We simulated paracrine signaling in vitro by treating MPM cell lines with conditioned medium (CM) from fibroblasts (FB) and vice versa. NCI-H2052, MSTO-211H, and NCI-H2452 cell lines representing the three mayor MPM subtypes, while embryonal myofibroblast cell lines, IMR-90 and MRC-5, provide a CAFs-like phenotype. Subsequently, differences in proliferation rates, migratory behavior, apoptosis, necrosis, and viability were used as covariates for data analysis. Kinase activity of treated samples and corresponding controls were then analyzed using the PamStation12 platform (PamGene); Results: Treatment with myofibroblast-derived CM revealed significant changes in phosphorylation patterns in MPM cell lines. The observed effect differs strongly between the analyzed MPM cell lines and depends on the origin of CM. Overall, a much stronger effect was observed using CM derived from IMR-90 than MRC-5. The phosphorylation changes mainly affected the MAPK signaling pathway.; Conclusions: The factors secreted by myofibroblasts in fibroblasts CM significantly influence the phosphorylation of kinases, mainly affecting the MAPK signaling cascade in tested MPM cell lines. Our in vitro results indicate promising therapeutic effects by the use of MEK or ERK inhibitors and might have synergistic effects in combination with cisplatin-based treatment, improving clinical outcomes for MPM patients.
    Keywords:  MAPK signaling; MEK and ERK inhibitors; cancer-associated fibroblasts; kinases; microenvironment; phosphorylation; pleural mesothelioma
    DOI:  https://doi.org/10.3390/ijms23063278
  8. J Clin Med. 2022 Mar 16. pii: 1659. [Epub ahead of print]11(6):
    Informative Power Evaluation of Clinical Parameters to Predict Initial Therapeutic Response in Patients with Advanced Pleural Mesothelioma: A Machine Learning Approach.
    Raffaella Massafra, Annamaria Catino, Pia Maria Soccorsa Perrotti, Pamela Pizzutilo, Annarita Fanizzi, Michele Montrone, Domenico Galetta.
      Malignant pleural mesothelioma (MPM) is a rare neoplasm whose early diagnosis is challenging and systemic treatments are generally administered as first line in the advanced disease stage. The initial clinical response may represent a useful parameter in terms of identifying patients with a better long-term outcome. In this report, the initial therapeutical response in 46 patients affected with advanced/unresectable pleural mesothelioma was investigated. The initial therapeutic response was assessed by CT scan and clinical examination after 2-3 treatment cycles. Our preliminary evaluation shows that the group of patients treated with regimens including antiangiogenetics and/or immunotherapy had a significantly better initial response as compared to patients only treated with standard chemotherapy, exhibiting a disease control rate (DCR) of 100% (95% IC, 79.40-100%) and 80.0% (95% IC, 61.40-92.30%), respectively. Furthermore, the therapeutic response was correlated with the disease stage, blood leukocytes and neutrophils, high albumin serum levels, and basal body mass index (BMI). Specifically, the patients with disease stage III showed a DCR of 95.7% (95% IC, 78.1-99.9%), whereas for disease stage IV the DCR decreased to 66.7% (95% IC, 34.9-9.1%). Moreover, a better initial response was observed in patients with a higher BMI, who reached a DCR of 96.10% (95% IC, 80.36-99.90%). Furthermore, in order to evaluate in the predictive power of the collected features a multivariate way, we report the preliminary results of a machine learning model for predicting the initial therapeutic response. We trained a state-of-the-art algorithm combined to a sequential forward feature selection procedure. The model reached a median AUC value, accuracy, sensitivity, and specificity of 77.0%, 75%, 74.8%, and 83.3%, respectively. The features with greater informational power were gender, histotype, BMI, smoking habits, packs/year, and disease stage. Our preliminary data support the possible favorable correlation between innovative treatments and therapeutic response in patients with unresectable/advanced pleural mesothelioma. The small sample size does not allow concrete conclusions to be drawn; nevertheless, this work is the basis of an ongoing study that will also involve radiomics in a larger dataset.
    Keywords:  clinical parameters; early prediction; initial therapeutic response; machine learning; pleural mesothelioma
    DOI:  https://doi.org/10.3390/jcm11061659
  9. Transl Oncol. 2022 Mar 22. pii: S1936-5233(22)00062-6. [Epub ahead of print]20 101400
    Force-feeding malignant mesothelioma stem-cell like with exosome-delivered miR-126 induces tumour cell killing.
    Federica Monaco, Laura De Conti, Simone Vodret, Nunzia Zanotta, Manola Comar, Sandra Manzotti, Corrado Rubini, Laura Graciotti, Gianluca Fulgenzi, Massimo Bovenzi, Marco Baralle, Marco Tomasetti, Lory Santarelli.
      Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach is proposed. MPM-derived spheroids have been treated with exosome-delivered miR-126 (exo-miR) and evaluated for their anticancer effect. The exo-miR treatment increased MPM stem-cell like stemness and inhibited cell proliferation. However, at a prolonged time, the up taken miR-126 was released by the cells themselves through exosomes; the inhibition of exosome release by an exosome release inhibitor GW4869 induced miR-126 intracellular accumulation leading to massive cell death and in vivo tumour growth arrest. Autophagy is involved in these processes; miR-126 accumulation induced a protective autophagy and the inhibition of this process by GW4869 generates a metabolic crisis that promotes necroptosis, which was associated with PARP-1 over-expression and cyt-c and AIF release. Here, for the first time, we proposed a therapy against CSCs, a heterogeneous cell population involved in cancer development and relapse.
    Keywords:  Mesothelioma; exosome; miR-126; miRNA-based therapy; spheroids
    DOI:  https://doi.org/10.1016/j.tranon.2022.101400
  10. Diagnostics (Basel). 2022 Mar 10. pii: 674. [Epub ahead of print]12(3):
    Gene Expression Analysis of Biphasic Pleural Mesothelioma: New Potential Diagnostic and Prognostic Markers.
    Rossella Bruno, Anello Marcello Poma, Greta Alì, Claudia Distefano, Agnese Proietti, Antonio Chella, Marco Lucchi, Franca Melfi, Renato Franco, Gabriella Fontanini.
      Biphasic is the second most common histotype of pleural mesothelioma (PM). It shares epithelioid and sarcomatoid features and is challenging to diagnose. The aim of this study was to identify biphasic PM markers to improve subtyping and prognosis definition. The expression levels of 117 cancer genes, evaluated using the nanoString system, were compared between the three major histotypes (epithelioid, sarcomatoid, and biphasic), and expression differences within biphasic PM were evaluated in relation to the percentage of epithelioid components. Biphasic PM overexpressed CTNNA1 and TIMP3 in comparison to sarcomatoid, and COL16A1 and SDC1 in comparison to epithelioid PM. CFB, MSLN, CLDN15, SERPINE1, and PAK4 were deregulated among all histotypes, leading to the hypothesis of a gradual expression from epithelioid to sarcomatoid PM. According to gene expression, biphasic PM samples were divided in two clusters with a significant difference in the epithelioid component. ADCY4, COL1A1, and COL4A2 were overexpressed in the biphasic group with a low percentage of epithelioid component. Survival analysis using TCGA data showed that high COL1A1 and COL4A2 expression levels correlate with poor survival in PM patients. Herein, we identified markers with the potential to improve diagnosis and prognostic stratification of biphasic PM, which is still an orphan tumor.
    Keywords:  biomarkers; biphasic pleural mesothelioma; diagnosis; gene expression; nanoString system; prognosis
    DOI:  https://doi.org/10.3390/diagnostics12030674
  11. Cureus. 2022 Feb;14(2): e22159
    Radiation Induced Abscopal Effect in a Patient With Malignant Pleural Mesothelioma on Pembrolizumab.
    Rebekah Rittberg, Elisa Chan, Stephen Yip, Deepu Alex, Cheryl Ho.
      Abscopal effect is a rare phenomenon in which treatment benefit from radiotherapy (RT) is seen outside the target field due to activation of the immune system inducing an anti-tumor effect. This phenomenon has been reported in cancer patients receiving immune checkpoint inhibitors (ICI). Here we report a case of presumed abscopal effect in malignant mesothelioma. The patient received second-line single-agent pembrolizumab however had disease progression after four cycles leading to palliative RT (20 Gray) to the right mainstem bronchus. Follow-up radiographic imaging confirmed benefit and pembrolizumab was continued. Follow-up computed tomography (CT) five months after RT, showed marked radiographic improvement of all measurable diseases with improvement in right-sided aerated lung volume. Because of the original disease progression on pembrolizumab, with marked improvements within and outside the RT field after RT, treatment response was presumed due to the abscopal effect.
    Keywords:  abscopal effect; immune modulation; immunotherapy; mesothelioma; pembrolizumab; radiotherapy
    DOI:  https://doi.org/10.7759/cureus.22159
  12. Oncologist. 2022 Mar 24. pii: oyab077. [Epub ahead of print]
    Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study.
    Takumi Sakurada, Hiroshi Nokihara, Tadashi Koga, Yoshito Zamami, Mitsuhiro Goda, Kenta Yagi, Hirofumi Hamano, Fuka Aizawa, Hirokazu Ogino, Seidai Sato, Yasushi Kirino, Hisatsugu Goto, Yasuhiko Nishioka, Keisuke Ishizawa.
       BACKGROUND: Rash eruptions are a common side-effect of pemetrexed, for which the administration of 8 mg/day of dexamethasone for 3 days from the day preceding pemetrexed administration is recommended. This study aimed to prospectively assess the effectiveness of prophylactic administration of low-dose dexamethasone for pemetrexed-induced rashes.
    METHODS: This single-arm, phase II study recruited patients with non-squamous non-small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions.
    RESULTS: Twenty-five patients were enrolled between September 2017 and May 2019. The incidence of rash after 3 weeks was 16.7%. Rashes erupted mainly on the upper half of the body, such as the chest and neck, and were of grades 1 and 2 in 2 patients each. No rashes of grade 3 or higher were observed, and there were no adverse events associated with additional corticosteroids.
    CONCLUSION: Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666).
    Keywords:  Rash prevention; low-dose dexamethasone; malignant pleural mesothelioma; non-squamous non–small cell lung cancer; pemetrexed
    DOI:  https://doi.org/10.1093/oncolo/oyab077
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