bims-mesote 2026-06-28 papers

Issue of 2026–06–28
three papers selected by
Laura Mannarino, Humanitas Research

Cancers (Basel). 2026 Jun 19. pii: 2000. [Epub ahead of print]18(12):

FDG PET/CT for Postoperative Surveillance in Malignant Pleural Mesothelioma: Temporal Evolution of Postsurgical Metabolic Activity and Diagnostic Performance for Recurrence Detection.

Sun Ha Boo, Soo Jin Kwon, Seok Whan Moon, Yeon-Sil Kim, Sook-Hee Hong, Ie Ryung Yoo.

Background/Objectives: Differentiating recurrent disease from postsurgical changes on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) remains challenging in malignant pleural mesothelioma (MPM). This study aimed to characterize the temporal patterns of postsurgical FDG uptake and evaluate the diagnostic performance of FDG PET/CT for detecting recurrent disease after radical surgery. Methods: We retrospectively analyzed 91 postsurgical PET/CT scans from 45 patients with MPM who underwent extrapleural pneumonectomy (EPP; n = 29) or pleurectomy/decortication (P/D; n = 16). Scans were stratified into four postoperative time intervals: <6 months, 6 to <12 months, 12 to <24 months, and ≥24 months. FDG uptake in the postsurgical bed and local recurrent lesions was quantified using maximum standardized uptake value ratios normalized to the mediastinal blood pool and liver. Recurrence was confirmed by histopathology or follow-up imaging. Results: Postsurgical FDG uptake showed a time-dependent decline, with significantly lower uptake beyond 24 months postoperatively (p < 0.05). EPP patients demonstrated significantly higher postsurgical FDG uptake than P/D patients (p < 0.01). FDG PET/CT identified occult recurrence in 23.4% of CT-negative scans. Local recurrent lesions showed significantly higher FDG uptake than postsurgical changes across all postoperative intervals (p < 0.001). Conclusions: Postsurgical FDG uptake in MPM demonstrates a time-dependent decline, and surgical extent is an important determinant of background metabolic activity. Despite this variable background, FDG PET/CT demonstrated high diagnostic accuracy for detecting recurrent disease, including CT-occult recurrences. Incorporating surgical type and postoperative interval into PET/CT interpretation may improve diagnostic accuracy in postoperative MPM surveillance.

Keywords: FDG PET/CT; malignant pleural mesothelioma; postoperative surveillance; postsurgical change; recurrence

DOI: https://doi.org/10.3390/cancers18122000

J Thorac Oncol. 2026 Jun 20. pii: S1556-0864(26)00446-6. [Epub ahead of print] 103993

Amivantamab induces immune-mediated cytotoxicity in mesothelioma via EGFR and MET engagement.

Shinichiro Suzuki, Kaushal Parikh, Ezequiel Tolosa, Kuan-Li Wu, Rohini Mopuri, Jennifer Ayers-Ringler, Lin Yang, Kim P Lauer, Katherine E R Smith, Yan W Asmann, Anja Roden, Farhad Kosari, Aaron S Mansfield.

INTRODUCTION: Diffuse pleural mesothelioma (DPM) is a lethal malignancy with no approved therapies directly targeting tumor cells. Based on reports that epidermal growth factor receptor (EGFR) and MET proto-oncogene (MET) are frequently expressed in DPM, we sought to systematically assess their co-expression and determine the preclinical activity of amivantamab, a bispecific antibody that targets EGFR and MET.
METHODS: We evaluated EGFR and MET expression in patient cohorts and cell lines using transcriptomic analysis, immunohistochemistry, and biochemical assays. The mechanistic actions of amivantamab, including receptor internalization, signaling blockade, and immune-mediated cytotoxicity, were assessed using in vitro co-culture systems with peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells. In vivo efficacy was evaluated in mesothelioma patient-derived xenograft (PDX) models using immunodeficient mice reconstituted with human NK cells.
RESULTS: Transcriptomic and single-cell RNA sequencing analyses of DPM patient cohorts revealed frequent co-expression of EGFR and MET, predominantly in malignant cells. Immunohistochemical analyses confirmed EGFR and MET protein expression across mesothelioma histologic subtypes. In vitro, amivantamab preferentially bound to DPM cells, inhibited ligand-induced EGFR and MET signaling, and promoted receptor internalization. Co-culture experiments demonstrated that amivantamab induced dose-dependent cytotoxicity via NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In multiple mesothelioma PDX models, the combination of amivantamab and NK cells significantly reduced tumor growth without overt toxicity.
CONCLUSIONS: Amivantamab demonstrates robust preclinical antitumor activity in mesothelioma primarily through innate immune-mediated cytotoxicity associated with EGFR and MET engagement. These findings support the clinical evaluation of bispecific EGFR/MET-targeting antibodies in mesothelioma.

Keywords: ADCC; EGFR; MET; Mesothelioma; amivantamab

DOI: https://doi.org/10.1016/j.jtho.2026.103993

Radiol Oncol. 2026 Jun 01. 60(2): 271-281

Genetic variability of immune checkpoints in asbestos-related diseases.

Irma Zeljkovic, Katja Goricar, Tanja Blagus, Alenka Franko, Viljem Kovac, Vita Dolzan.

BACKGROUND: Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying the development of asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases.
SUBJECTS AND METHODS: We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed using logistic regression.
RESULTS: Our study showed that the CTLA4 rs4553808 polymorphism was associated with a decreased risk of asbestosrelated diseases (OR = 0.34, 95% CI = 0.15-0.74, P = 0.007). Homozygous carriers of polymorphic rs4553808 G allele had a lower risk of developing pleural plaques as well as MM compared to the control group (OR = 0.28, 95% CI = 0.11-0.68, P = 0.01, and OR = 0.38, 95% CI = 0.16 -0.93, P = 0.03, respectively). However, carriers of polymorphic CTLA4 rs231775 GG genotype had a higher risk of developing MM compared to the group of subjects with pleural plaques (OR = 1.79, 95% CI = 1.10-2.89, P = 0.02). The other investigated polymorphisms were not associated with any of the asbestos-related diseases.
CONCLUSIONS: CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases.

Keywords: asbestos; immune checkpoints; malignant mesothelioma; single nucleotide polymorphism

DOI: https://doi.org/10.2478/raon-2026-0035