Fibroblast Activation Protein-Directed Imaging Outperforms 18F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial.

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a 68Ga-FAPI46 PET observational trial (NCT04571086). Methods: Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the 68Ga-FAPI46 PET observational trial. All patients underwent 68Ga-FAPI46 PET/CT, contrast-enhanced CT, and 18F-FDG PET/CT. The primary study endpoint was the association of 68Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with 18F-FDG PET/CT. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI46 SUVmax or SUVpeak and histopathologic FAP expression was significant (SUVmax: r = 0.49, P = 0.037; SUVpeak: r = 0.51, P = 0.030).68Ga-FAPI46 and 18F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher 68Ga-FAPI46 than 18F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). Conclusion: We confirm an association of 68Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for 68Ga-FAPI46 versus 18F-FDG.

Thoracic SMARCA4-Deficient Undifferentiated Tumor Mimicking Malignant Pleural Mesothelioma on FDG PET/CT.

ABSTRACT: We describe contrast-enhanced CT and FDG PET/CT findings in a case of thoracic SMARCA4-deficient undifferentiated tumor with extensive pleural involvement and mediastinal lymph node metastases. Contrast-enhanced CT showed multiple enhancing right-sided pleural masses and soft tissue plaques and enlarged mediastinal lymph nodes. The pleural lesions and mediastinal lymph nodes showed intense FDG uptake mimicking malignant pleural mesothelioma with mediastinal lymph node metastases.

Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.

OBJECTIVES: Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction. RESULTS: imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST p < 0.0001 and p = 0.015, respectively; mRECIST p < 0.0001 and p = 0.015, respectively). METHODS: Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2-4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods. CONCLUSION: For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).

Imaging in pleural Mesothelioma: A review of the 16th International Conference of the International Mesothelioma Interest Group.

Imaging continues to gain a greater role in the assessment and clinical management of patients with mesothelioma. This communication summarizes the oral presentations from the imaging session at the 2023 International Conference of the International Mesothelioma Interest Group (iMig), which was held in Lille, France from June 26 to 28, 2023. Topics at this session included an overview of best practices for clinical imaging of mesothelioma as reported by an iMig consensus panel, emerging imaging techniques for surgical planning, radiologic assessment of malignant pleural effusion, a radiomics-based transfer learning model to predict patient response to treatment, automated assessment of early contrast enhancement, and tumor thickness for response assessment in peritoneal mesothelioma.

Thoracic SMARCA4-Deficient Undifferentiated Tumor Mimicking a Pleural Mesothelioma on 18 F-FDG PET/CT.

ABSTRACT: A 72-year-old woman, who was a nonsmoker, presented with chest distress persisting for over 10 days. Plain chest CT revealed thickening of the left pleura accompanied by hydrothorax. Subsequent 18 F-FDG PET/CT showed irregular thickening involving the visceral, parietal, and interlobular pleura on the left side, with diffuse high avidity of 18 F-FDG. The left pleural mesothelioma was suspected initially, but pathological examination from biopsied specimen later confirmed a thoracic SMARCA4-deficient undifferentiated tumor.

Predictive potential of MRI in differentiating the predominant component in biphasic pleural mesothelioma.

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.

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography. MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis. RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%. CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma.

ABSTRACT: A 66-year-old man with local prostate adenocarcinoma underwent radical prostatectomy (Gleason score 3 + 4 = 7, pT2c) in 2016. Four years later, he presented with a hydrocele and cystic atypical change in the left scrotum and soft tissue in the left groin. Final histopathology revealed spermatic cord mesothelioma and left hemangiosis carcinomatosa. A bone biopsy of the sacrum revealed infiltrates of a prostatic adenocarcinoma with small cell neuroendocrine differentiation. Dual-tracer PET/CT imaging using 18F-FDG and 68Ga-PSMA was able to identify local recurrence of scrotal mesothelioma and differentiate metastases of prostate cancer from malignant mesothelioma.

Epithelial Malignant Pleural Mesothelioma Mimics Lymphoma on 18 F-FDG PET/MRI : A Case Report.

ABSTRACT: Malignant pleural mesothelioma is a rare tumor with a poor prognosis. We describe a case of 55-year-old man without asbestos exposure history presenting with extensive lymph nodes with high 18 F-FDG uptake in PET/MRI but atypical pleural manifestations thereby being misdiagnosed for lymphoma. Pathological examination concludes for an epithelioid mesothelioma-associated lymph node metastasis. This case emphasizes that with the extensive lymph node abnormalities shown in PET imaging, in addition to the general consideration of lymphoma, it is still necessary to be vigilant about the possibility of mesothelioma and emphasizes the necessity of pathological examination.

Testicular mesothelioma disguised as hydrocele: a case report.

BACKGROUND: Testicular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis. CASE PRESENTATION: We present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up. CONCLUSION: Although hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.

Malignant Peritoneal Mesothelioma Complicating Familial Mediterranean Fever on 18 F-FDG PET/CT.

ABSTRACT: A 77-year-old man with a personal history of familial Mediterranean fever presented with a slowly enlarging tumefaction of the left abdominal wall and persistent inflammatory syndrome despite good adherence to colchicine. 18 F-FDG PET/CT showed a hypermetabolic muscular mass of the abdominal wall along with other hypermetabolic lesions including a peritoneal mass and several subcutaneous soft tissue nodules. CT-guided needle biopsy led to the diagnosis of a muscular localization of a malignant peritoneal mesothelioma, which is an extremely rare complication of familial Mediterranean fever. Six courses of chemotherapy with carboplatin and pemetrexed allowed an almost complete response.

The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.

INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters. METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle. RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis. CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.

An overview on multimodal imaging for the diagnostic workup of pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.

Clinical Response of Primary Malignant Pericardial Mesothelioma with Peritoneal Dissemination to Nivolumab.

Malignant pericardial mesothelioma (MPM) is extremely rare, and peritoneal dissemination has not yet been reported. There is no consensus regarding appropriate pharmacological treatment for MPM, including immune checkpoint inhibitors (ICIs). We herein report a 36-year-old man with MPM diagnosed by peritoneal dissemination and treated with an ICI. Cytology of the ascites revealed malignant peritonitis, and a re-evaluation of a pericardial biopsy performed at the previous hospital led to a diagnosis of MPM. The patient was treated with nivolumab and showed a clinical response despite several complications, such as renal dysfunction and performance status deterioration. This case report provides suggestive information for the diagnosis and ICI therapy of a rare type of mesothelioma.

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).