bims-mesote 2024-12-08 papers

Issue of 2024–12–08
five papers selected by
Laura Mannarino, Humanitas Research

Asian J Surg. 2024 Nov 29. pii: S1015-9584(24)02726-X. [Epub ahead of print]

Comparison of surgical treatment and systemic chemotherapy in patients with non-epithelioid malignant pleural mesothelioma.

Hacı Arak, Ahmet Feridun Işık, Maruf Şanlı, Ahmet Uluşan, Bekir Elma, Aydın Aytekin.

OBJECTIVE: This study aimed to investigate the most appropriate treatment options for patients with non-epithelioid malignant pleural mesothelioma.
METHODS: We retrospectively analyzed patients with non-epithelioid malignant pleural mesothelioma who received treatment at our center.
RESULTS: Forty-two patients were included in this study. Hyperthermic intrathoracic chemotherapy (HITHOT) was performed in 20 (47.6 %) patients. There were 20 (47.6 %) patients in the macroscopic complete resection (MCR) group and 22 (52.4 %) patients in the non-MCR group. The median overall survival (mOS) of patients in the MCR group was 16 (95 % CI,7.2-24.8) months, and the mOS of patients in the non-MCR group was 6 (95 % CI,2.9-9.1) months (p = 0.001). The mOS of patients who underwent HITHOT was 12 (95%CI,5.4-18.6) months, and the mOS of non-HITHOT patents was 6 (95%CI,2.6-9.4) months (p = 0.007). The mOS of patients who did and did not undergo the HITHOT in the MCR group was 21 and 15 months, respectively (p = 0.161). The mOS of biphasic subtype patients was 11 (95%CI,6.8-15.2) months and sarcomatoid subtype patients was 6 (95%CI,3.1-8.9) months (p = 0.179). In the OS analysis, performing MCR (p = 0.003), applying HITHOT (p = 0.012), TNM stage (p = 0.006), and receiving adjuvant chemotherapy (p = 0.001) were found to be significant factors. In the multivariate analysis for OS, the HITHOT application was found to be a significant parameter (p = 0.035).
CONCLUSIONS: The mOS of patients who achieved MCR in non-epithelioid malignant pleural mesothelioma was better than that of patients who did not achieve MCR. However, the OS of patients who underwent the HITHOT was better than that of patients who did not.

Keywords: HITHOT; Non-epithelioid; Pleural mesothelioma; surgical treatment

DOI: https://doi.org/10.1016/j.asjsur.2024.11.099

Pharm Res. 2024 Dec 04.

Development and In-Vitro Evaluation of Doxorubicin-Loaded Methacrylate Gelatin (GelMa)-Acrylamide Hydrogels for the Treatment of Malignant Pleural Mesothelioma.

Nishant S Kulkarni, Gautam Chauhan, Mural Quadros, Dnyandev G Gadhave, Vivek Gupta.

OBJECTIVE: Malignant pleural mesothelioma (MPM) is the most prevalent subtype of malignant mesothelioma that affects the pleural lining of the lungs. Conventionally, chemotherapy via systemic injections has shown limited efficacy due to off-target effects, and inefficacious deposition at the disease site. In our previous study, we reported the development and optimization of UV-initiated methacrylate gelatin (GelMa)-acrylamide based hydrogel formulation for local intracavitary administration of therapies. The current study utilizes a pre-established GelMa formulation for delivering a small molecule chemotherapeutic agent, Doxorubicin (Dox), against in-vitro MPM models.
METHODS: Dox-loaded hydrogel (DLH) precursor solution was prepared by dissolving Dox in the precursor solution. The gels were characterized for physical properties such as gelling time, swelling index, bio adhesion, and injectability and were compared to blank hydrogels. Dox-loaded hydrogels were also tested for therapeutic efficacy in MPM cells in various 2D and 3D cell culture models.
RESULTS: It was revealed that Dox-loaded hydrogels retained similar physical properties, including gelling time (< 25 s), swelling index (~ 1,200%), bio-adhesion (> 20 g detachment force), and injectability (< 2N force for injecting precursor), compared to blank hydrogels. Moreover, the gel formulation effectively sustained the release of hydrophilic Dox HCl over a period of 12 days by increasing the degree of crosslinking between GelMa and its crosslinkers. Further, the therapeutic efficacy of Dox was retained even after loading into hydrogels, indicating that no chemical interactions took place between gel excipients and the drug. Studies in MPM cell-based models revealed that DLH showed excellent potential in inhibiting 2D and 3D cell growth, with DLH being more effective than plain Dox in suppressing tumor growth in 3D spheroid models.
CONCLUSIONS: Overall, the results of the present study suggest that Dox-loaded hydrogels (DLH) may be a good candidate for efficacy study in preclinical mesothelioma models, with strong potential for clinical translation.

Keywords: doxorubicin hydrochloride; hydrogel; intracavitary; local delivery; malignant pleural mesothelioma; methacrylate gelatin (GelMa)

DOI: https://doi.org/10.1007/s11095-024-03794-z

JTO Clin Res Rep. 2024 Dec;5(12): 100735

Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment.

Sabine Schmid, Lisa Holer, Katrin Gysel, Kira-Lee Koster, Sacha I Rothschild, Laura A Boos, Lorenz Frehner, Sabine Cardoso Almeida, Christian Britschgi, Yannis Metaxas, Michael Mark, Patrizia Froesch, Wolf-Dieter Janthur, Anna Allemann, Christine Waibel, Catherine Von der Mühll-Schill, Martin Früh, Laetitia A Mauti.

Objectives: On the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi-nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi-nivo for patients with MPM in Switzerland.
Methods: Twelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators.
Results: Of the 109 patients with MPM treated with ipi-nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi-nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi-nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients.
Conclusion: In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

Keywords: Ipilimumab; Malignant pleural mesothelioma; Nivolumab; Outcome; Real-world

DOI: https://doi.org/10.1016/j.jtocrr.2024.100735

Clin Epigenetics. 2024 Dec 03. 16(1): 176

Genome-wide DNA methylation analysis reveals a unique methylation pattern for pleural mesothelioma compared to healthy pleura and other lung diseases.

Janah Vandenhoeck, Joe Ibrahim, Nele De Meulenaere, Dieter Peeters, Jo Raskin, Jeroen M H Hendriks, Paul Van Schil, Jan van Meerbeeck, Guy Van Camp, Ken Op de Beeck.

BACKGROUND: Pleural mesothelioma (PM) is a rare and aggressive cancer type, typically diagnosed at advanced stages. Distinguishing PM from other lung diseases is often challenging. There is an urgent need for biomarkers that can enable early detection. Interest in the field of epigenetics has increased, particularly in the context of tumour development and biomarker discovery. This study aims to identify specific changes in DNA methylation from healthy pleural tissue to PM and to compare these methylation patterns with those found in other lung diseases.
RESULTS: EPIC methylation array data (850 K) were generated for 11 PM and 29 healthy pleura in-house collected samples. This is the first time such a large dataset of healthy pleura samples has been generated. Additional EPIC methylation array data (850 K) for pleural mesothelioma and other lung-related diseases were downloaded from public databases. We conducted pairwise differential methylation analyses across all tissue types, which facilitated the identification of significantly differentially methylated CpG sites. Extensive differential methylation between PM and healthy pleura was observed, identifying 81,968 differentially methylated CpG sites across all genomic regions. Among these, five CpG sites located within four genes (MIR21, RNF39, SPEN and C1orf101) exhibited the most significant and pronounced methylation differences between PM and healthy pleura. Moreover, our analysis delineated distinct methylation patterns specific to PM subtypes. Finally, the methylation profiles of PM were distinctly different from those of other lung cancers, enabling accurate differentiation.
CONCLUSIONS: DNA methylation analyses provide a robust method for distinguishing PM from healthy pleural tissues, and specific methylation patterns exist within PM subtypes. These methylation differences underscore their importance in understanding disease progression and may serve as viable biomarkers or therapeutic targets. Moreover, differential methylation patterns between PM and other lung cancers highlights its diagnostic potential. These findings necessitate further translational studies to explore their clinical applications.

Keywords: DNA methylation; Epigenetics; Healthy pleura; Lung cancer; Pleural mesothelioma

DOI: https://doi.org/10.1186/s13148-024-01790-z

Cureus. 2024 Dec;16(12): e74998

Diffuse Pleural Mesothelioma: A Challenge in Early Diagnosis.

Ancuta-Alina Constantin, Florin Dumitru Mihaltan, Angela-Stefania Marghescu, Gabriela Andreea Craciunica.

We present the clinical case of a 58-year-old female patient, a smoker with occupational exposure to respiratory toxins, who was admitted to our clinic following evaluation in an emergency department, where she was diagnosed with a moderate right pleural effusion. Upon admission, the patient exhibited respiratory symptoms, including progressive dyspnea with a moderate exertion threshold, right posterior pleuritic chest pain radiating anteriorly, occasional episodes of low-grade fever, and persistent febrile symptoms lasting approximately two weeks. In this clinical context, the diagnostic process was guided by the presence of right pleural effusion syndrome, which was refractory to conservative medical therapy. This necessitated a careful and stepwise expansion of investigations, ultimately leading to the diagnosis of malignant pleural mesothelioma. This case underscores the diagnostic challenges posed by pleural effusion, the necessity of adhering to the diagnostic algorithm, and the critical role of the multidisciplinary team. The diagnostic approach, often complex and challenging, necessitates a multidimensional strategy that integrates the correlation and synthesis of data obtained through anamnesis, alongside advanced diagnostic procedures such as pleural biopsy, which remains the gold standard. This comprehensive process is essential for formulating a diagnostic suspicion, with the final diagnosis intended to be one of exclusion.

Keywords: adjuvant polychemotherapy; biopsy; malignant pleural mesothelioma; pleural effusion; pleurectomy

DOI: https://doi.org/10.7759/cureus.74998