bims-mesote 2024-08-11 papers

Issue of 2024–08–11
five papers selected by
Laura Mannarino, Humanitas Research

J Coll Physicians Surg Pak. 2024 Aug;34(8): 904-909

Comparison of First-Line Chemotherapeutics and Validation of the EORTC Prognostic Index in Malignant Pleural Mesothelioma: Retrospective Single-Centre Experience.

Yasin Sezgin, Ogur Karhan, Serdar Ileri, Senar Ebinc, Sezai Tunc, Zuhat Urakci.

OBJECTIVE: To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma.
STUDY DESIGN: An observational study. Place and Duration of the Study: Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017.
METHODOLOGY: Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival.
RESULTS: Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009).
CONCLUSION: The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival.
KEY WORDS: Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.

DOI: https://doi.org/10.29271/jcpsp.2024.08.904

Sci Rep. 2024 Aug 06. 14(1): 18206

Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.

Darya Karatkevich, Tereza Losmanova, Philipp Zens, Haibin Deng, Christelle Dubey, Tuo Zhang, Corsin Casty, Yanyun Gao, Christina Neppl, Sabina Berezowska, Wenxiang Wang, Ren-Wang Peng, Ralph Alexander Schmid, Patrick Dorn, Thomas Michael Marti.

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

Keywords: Capecitabine; Chemotherapy; Cisplatin; Cytidine deaminase; Mesothelioma; Pemetrexed

DOI: https://doi.org/10.1038/s41598-024-69347-x

Acta Oncol. 2024 Aug 08. 63 649-657

Patient characteristics, treatment patterns, and survival outcomes for patients with malignant pleural mesothelioma in Denmark between 2011 and 2018: a nationwide population-based cohort study.

Jens Benn Sørensen, Paul Baas, Szimonetta Komjáthiné Szépligeti, Alma B Pedersen, Søren P Johnsen, Robert Carroll, Minouk J Schoemaker, Caroline Rault, Melinda J Daumont, Vera Ehrenstein.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments.
METHODS: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors.
RESULTS: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31-111) overall, 40 days (28-77) in patients with advanced MPM, and 53 days (35-121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage.
INTERPRETATION: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.

DOI: https://doi.org/10.2340/1651-226X.2024.34802

Lung Cancer. 2024 Jul 25. pii: S0169-5002(24)00433-1. [Epub ahead of print]195 107899

Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers.

Nelly Otte, Ellen Fraune, Yildiz Cetiner, Michael K Felten, Timm Dirrichs, Julia Krabbe, Thomas Kraus.

BACKGROUND: The time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos.
RESEARCH QUESTION: How does asbestos exposure patterns affect cancer mortality and the duration of latency until death?
METHODS: A mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis.
RESULTS: The mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62-29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89-1.17). Median latency until death was 46 (15-63) years for mesothelioma and 44 (15-70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking.
CONCLUSION: Cumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.

Keywords: Asbestos; Cancer mortality; Latency; Lung cancer; Mesothelioma

DOI: https://doi.org/10.1016/j.lungcan.2024.107899