bims-mesote 2024-11-10 papers

Issue of 2024–11–10
three papers selected by
Laura Mannarino, Humanitas Research

J Microsc Ultrastruct. 2024 Jul-Sep;12(3):12(3): 120-125

Utility of a Highly Specific and Sensitive Podoplanin/D2-40, Calretinin, Thyroid Transcription Factor-1, and Carcinoembryonic Antigen/CD66e Immunohistochemical Panel in Differentiating Malignant Pleural Mesothelioma from Metastatic Adenocarcinoma: An Egyptian Experience.

Rasha A Khairy, Eman Khaled, Samar El Sheikh, Ahmed Abdlaziz, Sara E Khalifa.

Background and Objective: Considering plentiful immunohistochemical (IHC) antibodies, a selection of highly sensitive and specific targeted panels is necessary to differentiate malignant pleural mesothelioma (MPM) from metastatic adenocarcinoma. We aimed to examine the sensitivity and specificity of four markers (podoplanin [PDPN]/D2-40, calretinin, thyroid transcription factor-1 [TTF-1], and carcinoembryonic antigen [CEA]/CD66e) as an initial IHC panel of Egyptian patients with malignant pleural biopsies.
Materials and Methods: Forty Egyptian malignant pleural biopsies with histomorphological features of mesothelioma versus adenocarcinoma were immunohistochemically stained by PDPN/D2-40, calretinin, TTF-1, and CEA/CD66e.
Results: PDPN/D2-40 and calretinin were positive in 27/27, 100% of mesothelioma cases with 100% sensitivity, 96.4% specificity for PDPN/D2-40, and 100% sensitivity and specificity for calretinin. Membranous PDPN/D2-40 expression was strong in 14 cases (53.85%), moderate in eight cases (30.77%), and weak in four cases (15.38%), while pure cytoplasmic staining was reported in one case. Calretinin was predominantly nuclear in all mesothelioma cases. TTF1 and CEA/CD66e were negative in all mesothelioma cases. In adenocarcinomas, PDPN/D2-40 was only expressed as weak cytoplasmic staining in 1/13 cases, while calretinin was negative in all 13 cases. Nuclear TTF1 and cytoplasmic CEA/CD66e immunostaining positivity were reported in all adenocarcinoma cases (13/13) with 100% sensitivity and specificity for both markers.
Conclusion: The combination of PDPN/D2-40, calretinin together with CEA/CD66e, and TTF1 may be highly valuable in differentiating MPM from metastatic adenocarcinoma.

Keywords: Adenocarcinoma; calretinin; carcinoembryonic antigen/CD66e; mesothelioma; podoplanin/D2-40; thyroid transcription factor-1

DOI: https://doi.org/10.4103/jmau.jmau_51_22

Asia Pac J Clin Oncol. 2024 Dec;20(6): 723-730

Real-world outcomes for patients with pleural mesothelioma: A multisite retrospective cohort study.

Kar Ven Cavan Chow, Cassie Turner, Brett Hughes, Zarnie Lwin, Bryan Chan.

AIM: To evaluate the real-world treatment patterns and outcomes for patients with pleural mesothelioma (PM) in the era of immunotherapy.
METHODS: This retrospective audit included patients with PM diagnosed within three tertiary referral centers in Queensland, Australia from January 2017 to July 2023. Patient and treatment characteristics and outcomes were recorded. Data was analyzed using descriptive statistics and the Kaplan-Meier survival method.
RESULTS: A total of 90 patients were included: 84% were male, the median age was 75 years (range 70-79) and 85% had baseline Eastern Group Cooperative Group of 0-1. Subtypes included 54% epithelioid, 17% biphasic, 12% sarcomatoid, and 17% unspecified/unknown. First-line treatment was received by 57/90 patients (63%) and 33/90 patients (37%) received the best supportive care (BSC). Chemotherapy was most used (63%) overall, but first-line immunotherapy was more commonly used since ipilimumab/nivolumab was reimbursed by the Australian Pharmaceutical Benefits Scheme in July 2021. After first-line treatment, only 40% received second-line treatment and 60% received BSC. 12-month overall survival (OS) and progression-free survival for all patients were 53% (95% confidence interval [CI]: 43-65) and 25% (95% CI 15-40) respectively. 12-month OS was 72%, 64%, and 29% for immunotherapy, chemotherapy, and BSC, respectively. There was no significant difference in survival between chemotherapy and immunotherapy (hazard ratio 1.28, 95% CI: 0.65-2.5, p = 0.5).
CONCLUSION: In our unselected real-world cohort, both chemotherapy and immunotherapy are active against PM, but the prognosis remains guarded. There remains a need for better treatment options, especially in the first-line setting. Enrolment in clinical trials is crucial to improving outcomes in this debilitating disease.

Keywords: Australia; immunotherapy; pleural mesothelioma; real‐world

DOI: https://doi.org/10.1111/ajco.14098

BMC Cancer. 2024 Nov 05. 24(1): 1353

Safety and efficacy of PD-1/PD-L1 immune checkpoint inhibitors in patients with pre-treated advanced stage malignant mesothelioma: a systematic review and meta-analysis.

Amjad Zafar, Asma Abdul Rashid, Abdul Moeed, Muhammad Junaid Tahir, Ahmad Jamal Khan, Oadi N Shrateh, Ali Ahmed.

BACKGROUND: Malignant mesothelioma is an aggressive cancer with poor prognosis. Programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) have recently presented as a viable option in some first line but primarily as a second-line treatment of advanced-stage malignant mesothelioma (asMM). Therefore, this systematic review and meta-analysis aims to assess the safety and efficacy of PD-1/L-1 ICIs in advanced-stage malignant mesothelioma.
METHODS: PubMed, Scopus, and Cochrane databases were searched for all studies assessing the safety and efficacy of anti PD-1/PD-L1 agents. Primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were median progression free (mPFS) and overall survival (mOS). Safety outcomes were treatment- (TRAEs) and immune-related adverse events (IRAEs). A random-effects meta-analysis was performed to pool medians and to derive event rates.
RESULTS: A total of 15 studies were included with total of 1064 asMM patients. ORR and DCR were 16% and 57%, respectively. A pooled mPFS was 4.53 (CI: 3.40-5.65) and mOS was 10.51 (CI: 9.03-12.00). Overall TRAEs had an event rate of 0.69 (0.50-0.83) whereas IRAEs had an event rate of 0.28 (0.15-0.46). There were no significant differences between pembrolizumab, nivolumab primarily, and avelumab subgroups for all the outcomes. Additionally, meta-regression found no covariate to be a significant factor in ORR and DCR.
CONCLUSION: In this meta-analysis we found that anti-PD1/PD-L1 treatment could be useful in pretreated asMM as they had at least comparable or greater mPFS, mOS, ORR, and DCR than other second-line agents currently being used.
REGISTRATION NUMBER: This systematic review was registered at PROSPERO prior to the literature search, CRD42023442350.

Keywords: Immune checkpoint inhibitors; Malignant mesothelioma; PD-1; PD-L1

DOI: https://doi.org/10.1186/s12885-024-13127-3