bims-mesote Biomed News
on Mesothelioma
Issue of 2024–06–02
eight papers selected by
Laura Mannarino, Humanitas Research
  1. FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology.
  2. Sarcomatoid malignant pleural mesothelioma: a case of long-term recurrence-free survival following curative intent surgery alone.
  3. Predictive potential of MRI in differentiating the predominant component in biphasic pleural mesothelioma.
  4. Different Frequency and Clinical Role for MTAP Loss in Pleural and Peritoneal Mesothelioma.
  5. STEREOTACTIC BODY RADIATION THERAPY FOR OLIGO-PROGRESSIVE PLEURAL MESOTHELIOMA: FINE-TUNING THE OPTIMAL DOSES.
  6. Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.
  7. A case of pleural mesothelioma with immunohistochemical staining positive for Krebs von den Lungen-6.
  8. Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.
  1. Mol Med. 2024 May 31. 30(1): 73
    FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology.
    James Mei-Lin Chan, Yuan-Ching Chang, Hua-Chen Chan, Hsiu-Chuan Chan, Wei-Chin Chang, Liu-Fang Wang, Tung-Hu Tsai, Yu-Jen Chen, Wen-Chien Huang.
      Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.
    Keywords:  Epithelioid; Human malignant pleural mesothelioma (hMPM); Non-epithelioid; Romidepsin (FK228); Sarcomatoid
    DOI:  https://doi.org/10.1186/s10020-024-00835-6
  2. Surg Case Rep. 2024 May 31. 10(1): 134
    Sarcomatoid malignant pleural mesothelioma: a case of long-term recurrence-free survival following curative intent surgery alone.
    Masatoshi Kanayama, Masaru Takenaka, Katsuma Yoshimatsu, Hiroki Matsumiya, Masataka Mori, Koji Kuroda, Aya Nawata, Manabu Yasuda, Fumihiro Tanaka.
       BACKGROUND: Curative intent surgery may be indicated for some patients with resectable early stage malignant pleural mesothelioma (MPM). However, sarcomatoid MPM is a highly aggressive subtype for which curative intent surgery is generally not recommended.
    CASE PRESENTATION: We present the case of a 63-year-old man who presented with dyspnea and chest tightness. Computed tomography revealed pleural thickening and nodular lesions. A pleural biopsy confirmed lymphohistiocytoid MPM (cT1N0M0, stage IA), prompting surgical intervention. The patient underwent left extrapleural pneumonectomy (EPP), and the final diagnosis was sarcomatoid MPM (pT2N0M0, stage IB). Although post-operative chemotherapy was planned, the patient refused additional treatment, because of the introduction of home oxygen therapy, and has remained recurrence-free for 10 years after the surgery.
    CONCLUSIONS: This case presents a noteworthy instance of achieving long-term recurrence-free survival solely through curative intent surgery for sarcomatoid MPM. It highlights the potential efficacy of surgical intervention in managing this aggressive subtype, offering a glimmer of hope for improved outcomes. Further research is warranted to better define the role of surgery in the treatment of sarcomatoid MPM.
    Keywords:  Malignant pleural mesothelioma; Sarcomatoid subtype; Surgery
    DOI:  https://doi.org/10.1186/s40792-024-01939-1
  3. Eur J Radiol. 2024 May 26. pii: S0720-048X(24)00243-2. [Epub ahead of print]176 111527
    Predictive potential of MRI in differentiating the predominant component in biphasic pleural mesothelioma.
    Ritu R Gill, William G Richards, Hillary Heiling, Emanuele Mazzola, Yin P Hung, Ravi T Seethamraju, Lucian R Chirieac, Raphael Bueno.
       PURPOSE: To assess the potential of apparent diffusion coefficient (ADC) values derived from diffusion weighted (DW) MRI preoperatively to predict the predominant histologic component among biphasic pleural mesothelioma (PM) tumors.
    METHODS: ADC maps were generated from DW MRI scans. Histology and predominant component of biphasic PM were confirmed following surgical resection. Statistical analyses were done with R (R Foundation for Statistical Computing, Vienna, Austria). Average ADC values corresponding to epithelioid- and sarcomatoid-predominant tumors were compared. ADC thresholding was accomplished by recursive partitioning and confirmed with ROC analysis.
    RESULTS: Eighty-four patients with biphasic PM's, 69 (82 %) epithelioid-predominant (BE) and 15(18 %) sarcomatoid-predominant (BS) tumors were evaluated. Thirty-eight (45 %) patients underwent extrapleural pneumonectomy (EPP), 39 (46 %) had extended pleural decortication (ePDC) and 7 (8 %) had pleural decortication (PDC). ADC values ranged between 0.696 x 10-3 to 1.921 x 10-3 mm2/s. BE tumors demonstrated significantly higher ADC values than BS tumors (p = 0.026). ADC values above 0.94 x 10-3 mm2/s were associated with a significant increase of relative risk of being in group BE over group BS (relative risk: 1.47, 95 %CI: 1.05-2.06, p = 0.027) CONCLUSION: Average ADC values of BE tumors were higher than BS tumors and the two groups can be separated by a cut off value of 0.94 X 10-3 mm2/s.
    Keywords:  Biphasic MPM; DWI; Malignant Pleural Mesothelioma
    DOI:  https://doi.org/10.1016/j.ejrad.2024.111527
  4. Appl Immunohistochem Mol Morphol. 2024 May 30.
    Different Frequency and Clinical Role for MTAP Loss in Pleural and Peritoneal Mesothelioma.
    Ben Davidson, Arild Holth, Charlotte Hummel, Kjersti Flatmark, Annette Torgunrud.
      The objective of this study was to analyze the expression and prognostic role of methylthioadenosine phosphorylase (MTAP) in mesothelioma. MTAP protein expression by immunohistochemistry was analyzed in 113 mesotheliomas (60 pleural and 53 peritoneal), consisting of 36 effusions and 77 surgical specimens. MTAP expression was fully lost in 38 tumors and partially lost in 8 tumors. Loss of expression was significantly more common in effusions compared with biopsies/surgical resection specimens (20/36 vs. 26/77; P=0.017), and in pleural compared with peritoneal mesotheliomas (35/60 vs. 11/53; P<0.001). MTAP performed less robustly than BAP1 in comparative analysis of 57 tumors previously analyzed for expression of the latter protein (46 vs. 25 cases with loss of expression). In survival analysis for 69 patients with partial clinical data, male gender was significantly associated with shorter overall survival (OS; P=0.042), whereas loss of MTAP was associated with a trend for shorter OS (P=0.058), with no prognostic role for patient age (P=0.379) or anatomic site (P=0.381). The association between loss of MTAP and poor OS became significant when survival analysis was limited to patients with pleural mesothelioma (P=0.018). In conclusion, loss of MTAP expression is more frequent in pleural compared with peritoneal mesothelioma and has limited diagnostic relevance at the latter anatomic site. More frequent loss in effusion specimens suggests a role for this marker in effusion cytology. MTAP loss in pleural mesothelioma is associated with poor survival.
    DOI:  https://doi.org/10.1097/PAI.0000000000001206
  5. Pract Radiat Oncol. 2024 May 28. pii: S1879-8500(24)00136-X. [Epub ahead of print]
    STEREOTACTIC BODY RADIATION THERAPY FOR OLIGO-PROGRESSIVE PLEURAL MESOTHELIOMA: FINE-TUNING THE OPTIMAL DOSES.
    Paolo Ghirardelli, Gianluca Costantino, Davide Franceschini, Elisa Villa, Annamaria Guaineri, Marta Scorsetti, Vittorio Vavassori, Giovanni Luca Ceresoli.
      There is growing evidence of a role of stereotactic body radiation therapy (SBRT) in the treatment of patients with oligo-progressive pleural mesothelioma (PM). The objective of this study was to investigate the optimal RT doses and schedules in this setting. The records of patients treated with SBRT (> 5 Gy per fraction) for oligo-progression of PM at two Institutions from June 2014 to September 2022 were reviewed. Patients were divided in two groups: "intermediate-dose" SBRT (i-SBRT, total dose 30-36 Gy in 5-6 fractions), and "high-dose" SBRT (h-SBRT, total dose 45-50 Gy in 4-8 fractions). The comparison between the two groups in terms of local control (LC) and toxicity was the primary endpoint of the study. Overall, 23 patients were treated on 25 pleural lesions. All had received upfront chemotherapy with platinum/pemetrexed. Fifteen patients were treated with i-SBRT and 8 patients with h-SBRT. The median equivalent dose (EQD2) was 40 Gy (range 40-49.6) in the i-SBRT group and 74.46 Gy (range 64-88) in the h-SBRT group. Six-month, 1-year and 2-year LC were 100%, 100% and 80% in the i-SBRT group and 100%, 100% and 67% in the h-SBRT group, respectively (p=0.94). Only two patients (one for each dose group) had a recurrence in the RT field, both after experiencing distant relapse. No severe acute and late toxicities were observed in the i-SBRT group, while in the h-SBRT group 2 patients experienced a G2 acute and late thoracic pain and one patient developed a G2 acute and G3 chronic thoracic pain. In our experience, SBRT is a safe and effective option for selected patients with oligo-progressive PM. Use of intermediate total doses keeping the dose per fraction high seems to offer an excellent LC, avoiding the risk of severe toxicity.
    DOI:  https://doi.org/10.1016/j.prro.2024.05.004
  6. Thorac Cancer. 2024 May 27.
    Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.
    Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai.
       BACKGROUND: 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.
    METHODS: 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.
    RESULTS: 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.
    CONCLUSIONS: 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.
    Keywords:  Chinese malignant mesothelioma; T cell receptor repertoire; genomic landscape; immunotherapy efficacy; overall survival
    DOI:  https://doi.org/10.1111/1759-7714.15326
  7. Respir Med Case Rep. 2024 ;50 102040
    A case of pleural mesothelioma with immunohistochemical staining positive for Krebs von den Lungen-6.
    Yugo Matsumura, Seidai Sato, Keiko Haji, Takeshi Masuda, Hiroto Yoneda, Hirokazu Ogino, Hirohisa Ogawa, Masaki Hanibuchi, Noboru Hattori, Yasuhiko Nishioka.
      A 71-year-old male visited a hospital with a chief complaint of exertional dyspnea. A chest CT revealed multiple nodular lesions on the parietal pleura. Thoracoscopic pleural biopsy was performed resulting in a diagnosis of pleural mesothelioma with epithelioid type. When chemotherapy was initially initiated, his serum level of Krebs von den Lungen-6 (KL-6) was high. However, once chemotherapy was started, the serum KL-6 level gradually decreased with tumor shrinkage. Immunohistochemical staining revealed the expression of KL-6 from the tumor cells. This is the first report of KL-6 production directly from tumor cells in epithelial-type pleural mesothelioma.
    Keywords:  Immunohistochemical staining; Krebs von den Lungen-6; Pleural mesothelioma
    DOI:  https://doi.org/10.1016/j.rmcr.2024.102040
  8. J Cancer Res Clin Oncol. 2024 May 28. 150(5): 282
    Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990-2019.
    Zhiming Chen, Yikuan Cai, Tongyin Ou, Hu Zhou, Huajie Li, Zhizhi Wang, Kaican Cai.
      Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312-28,622) deaths and 569,429 (95% UI 509,956-617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25-74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.
    Keywords:  Global burden of disease (GBD); Mesothelioma; Occupational asbestos exposure
    DOI:  https://doi.org/10.1007/s00432-024-05802-6
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