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

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.

[Erionite, an exposure factor linked to pleural mesothelioma]. / L'érionite, un facteur expositionnel lié au mésothéliome pleural.

Mesotheliomas are neoplasia developed from the mesothelium, a layer covering the viscera (visceral layer) and the cavity where the organs are (parietal layer). The best known, and the most frequently encountered is the pleural mesothelioma. This disease has a close link with exposure to asbestos, a mineral fibre now banned in several countries. However, other exposure factors have also been incriminated, including another one recognised as a certain carcinogenic agent for several years now : erionite. We present the case of a patient with pleural mesothelioma whose exposure to erionite could be demonstrated. The presentation of this clinical case will be complemented by a literature review on this less known and mostly environmental exposure, contrary to asbestos which is mostly professional.

Les mésothéliomes sont des néoplasies se développant à partir du mésothélium, feuillet recouvrant, d'une part, les viscères (feuillet viscéral) et, d'autre part, la cavité où se trouvent les organes (feuillet pariétal). Le plus connu, et le plus fréquemment rencontré, est le mésothéliome pleural. Cette maladie a un lien étroit avec l'exposition à l'amiante, fibre minérale maintenant interdite dans plusieurs pays. Cependant, d'autres facteurs expositionnels ont également été incriminés, dont un autre reconnu comme cancérogène certain depuis plusieurs années : l'érionite. Nous présentons le cas d'un patient atteint d'un mésothéliome pleural pour lequel une exposition à l'érionite a pu être étayée. La présentation du cas clinique sera complétée d'une revue de la littérature sur cette exposition particulière moins connue et majoritairement environnementale, contrairement à l'amiante dont l'exposition est majoritairement professionnelle.

[Malignant mesothelioma of the vaginal testis: diagnostic and therapeutic considerations]. / Le mésothéliome malin de la vaginale testiculaire : aspects diagnostiques et thérapeutiques.

Mesothelioma of the testicular vagina is a rare malignant tumour, most often discovered by chance. The rarity of this type of tumour has not led to the development of specific guidelines. Median survival is estimated at 30 months. The lack of data and official recommendations makes surgical and medical management and follow-up difficult. Men who have not undergone radical orchiectomy die very rapidly after diagnosis. The remission rate at 1 year post-orchidectomy is 47 %, the recurrence rate at 1 year is 53 % and 92 % of relapses occur within 5 years post-operatively. The treatment option of hemiscrotectomy in the first instance has rarely been used; a second-look resection with negative margins may be proposed. The usefulness of adjuvant chemotherapy and/or radiotherapy has not been clearly demonstrated. Local recurrence is accompanied by metastasis in 85 % of cases. In the case of metastatic cancer (15 %), the retro-peritoneal, inguinal and iliac lymph nodes may be invaded. Follow-up by injected thoraco-abdomino-pelvic CT scan is recommended every 3 months for 2 years, then once a year for 3 years, for a total of 5 years of close follow-up. The long-term recurrence rate is 3 %.

Le mésothéliome de la vaginale testiculaire est une tumeur maligne rare et souvent de découverte fortuite. Sa rareté d'apparition n'a pas permis de développer des recommandations spécifiques. La survie médiane est estimée à 30 mois. Le manque de recommandations officielles rend sa prise en charge chirurgicale, médicale et son suivi difficiles. Les hommes n'ayant pas bénéficié d'orchidectomie radicale décèdent très rapidement après le diagnostic. Le taux de rémission à 1 an post-orchidectomie est de 47 %, le taux de récurrence à 1 an est de 53 % et 92 % des rechutes se font endéans les 5 ans post-opératoires. L'option thérapeutique par hémi-scrotectomie en première intention a rarement été pratiquée, une résection de «second look¼ en marges saines peut être proposée. L'utilité d'une chimiothérapie et/ou d'une radiothérapie adjuvante n'a pas été clairement démontrée. Une rechute locale est accompagnée de métastases dans 85 % des cas. En cas de cancer d'emblée métastatique (15 %), les relais ganglionnaires rétro-péritonéaux, inguinaux et iliaques peuvent être envahis. Un suivi par scanner thoraco-abdomino-pelvien injecté est recommandé tous les 3 mois pendant 2 ans, puis 1 fois par an pendant 3 ans pour un total de 5 ans. Le taux de récidive au long cours est de 3 %.

Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors.

The immunogenicity of cancer cells is influenced by several factors, including the expression of the major histocompatibility complex class I (MHC-I), antigen expression, and the repertoire of proteasome-produced epitope peptides. The malignant pleural mesothelioma cell line ACC-MEOS-4 (MESO-4) expresses high levels of MHC-I and Wilms tumor 1 (WT1) tumor antigens. Using a functional T cell reporter assay specific for the HLA-A*24:02 restricted WT1 epitope (WT1235, CMTWNQMNL), we searched for factors that augmented the immunogenicity of MESO-4, focusing on proteasomes, which have a central role in the antigen processing machinery. ONX-0914, a selective inhibitor of the immunoproteasome subunit ß5i, enhanced immunogenicity dose-dependently at low concentrations without cytotoxicity. In addition, CD8+ T lymphocytes recognizing WT1 showed greater cytotoxicity against MESO-4 pre-treated with ONX-0914. MESO-4 expresses a standard proteasome (SP) and immunoproteasome (IP). Notably, IP has distinct catalytic activity from SP, favoring the generation of antigenic peptides with high affinity for MHC-I in antigen-presenting cells and cancer cells. In vitro, immunoproteasome digestion assay and mass spectrometry analysis showed that IP cleaved WT1235 internally after the hydrophobic residues. Importantly, this internal cleavage of the WT1235 epitope was mitigated by ONX-0914. These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.

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.

Incidental Diagnosis of Malignant Peritoneal Mesothelioma During Liver Transplantation Surgery: A Case Report.

BACKGROUND Malignant peritoneal mesothelioma (MPM) is a rare, lethal tumor of serous membranes. The most common factor reported in association with MPM is asbestos exposure, while viral infections, genetic predisposition, paraneoplastic syndrome, and altered immunity have been described as well. The diagnosis can be challenging among those with lower tumor burden as well as nonspecific symptoms, and it is not unusual to discover the diagnosis incidentally. CASE REPORT A middle-aged woman with decompensated cirrhosis underwent extensive pre-transplant workup, showing no evidence of malignancy. She had a personal history of asbestos exposure and family history of MPM in the extended family. During transplant surgery, a few peritoneal nodules were noted, leading to termination of the procedure. Pathological analysis confirmed malignant MPM. A multidisciplinary discussion led to following a conservative treatment approach without any intervention, due to higher risk of worsening hepatic decompensation associated with peritonectomy and intraperitoneal chemotherapy. The patient's hepatic decompensation resolved 6 months after the aborted liver transplant operation. Since the diagnosis of MPM, positron emission tomography scans have shown no recurrence of MPM for 3 consecutive years. CONCLUSIONS This is the first case of MPM diagnosed incidentally during a liver transplantation surgery. This case highlights the challenges in the diagnosis and management of MPM in a patient with decompensated liver disease. A multidisciplinary approach and following a consensus decision led to prolonged survival in the described patient.

Real-World efficacy and safety of combination nivolumab plus ipilimumab for Untreated, Unresectable, pleural Mesothelioma: The Meso-Immune (GFPC 04-2021) trial.

BACKGROUND: First-line standard-of-care for unresectable, pleural mesothelioma (PM) changed with the phase 3 CheckMate 743 study results, showing that nivolumab plus ipilimumab (Nivo + Ipi) significantly extended overall survival (OS) versus platinum + pemetrexed chemotherapy for PM (median OS 18.1 versus 14.1 months; hazard ratio: 0.74; p = 0.002). Efficacy and safety data in real-world (rw) settings are needed to confirm these results. METHODS: This French multicenter, retrospective cohort study was undertaken to assess the outcomes of treatment-naïve PM patients given Nivo + Ipi via an early-access program (EAP). The primary objective was investigator-assessed real world -progression-free survival (PFS). The secondary objectives were the combination's -overall survival (OS) and safety. RESULTS: From 1 April 2021 to 15 Feb 2022, the analysis included 201 of the 305 EAP-enrolled patients treated in 63 centers (79.6 % men; median age: 75 years; 91.8 % Eastern Cooperative Oncology Group performance status (ECOG-PS) 0/1; 74.5 % epithelioid histology). With median (95 % CI) follow-up for all patients of 18.4 (17.7-19.2) months, -PFS and OS were 6.3 (5.3-7.5) and 18.9 (17.6-not reached (NR)) months, with 1-year OS at 66.4 % (60.1-73.3 %). Median OS and 1-year survival rates were 21.0 (18.7-NR) and 70.8 % (63.9 %-780.6 %), and 14.1 (10.9-21.0) months and 54.9 % (42.8 %-70.4 %) for epithelioid and non-epithelioid PM subgroups, respectively. PFS was equal between the two subgroups. Grade 3-4 adverse events occurred in 23.3 % of patients and three deaths were treatment-related. CONCLUSIONS: For this unselected PM population, efficacy and safety outcomes compared favorably with CheckMate 743 trial results.

Evaluating the anticancer potential of Polygonum multiflorum root-derived stilbenes against H2452 malignant pleural mesothelioma cells.

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.

Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.

Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers.

OBJECTIVES: Mesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review's aims were to identify/synthesise international evidence on mesothelioma's MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness. DESIGN: Systematic review. DATA SOURCES: Databases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA. ELIGIBILITY CRITERIA: We included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002. DATA EXTRACTION AND SYNTHESIS: A team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews. RESULTS: Forty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma's causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support. CONCLUSIONS: Most qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions' effectiveness in mesothelioma. PROSPERO REGISTRATION NUMBER: CRD42022302187.

Clinical investigation of former workers exposed to asbestos: the health surveillance experience of an Italian University Hospital.

Background: The need for health surveillance of former workers exposed to asbestos was provided by law in Italy after the asbestos ban in 1992. Objectives: We describe the results of the health surveillance of former workers exposed to asbestos, conducted over 27 years, from 1994 to 2020, at the Operative Unit of Occupational Medicine of the University Hospital of Bari. Materials and methods: We adopted the health surveillance protocol, which was validated at the national level in 2018. Results: A total of 1,405 former workers exposed to asbestos were examined. We proceeded with diagnosing pathologies in 339 cases (24% of the cohort subjected to surveillance), with diagnoses of some cases involving multiple pathologies. Specifically, pleural plaques were diagnosed in 49.2% of the 339 cases, asbestosis in 35.9%, malignant pleural mesothelioma (MPM) in 20.3%, mesothelioma of the vaginal tunic of the testis (MTVT) in 9.1%, lung cancer in 5.8%, and laryngeal cancer in 0.8%. Conclusion: Despite the 1992 asbestos ban, asbestos-related diseases remain a serious public health issue. It is important to establish criteria that ensure the health surveillance of formerly exposed workers minimizes costs, reduces the number of invasive examinations, and optimizes achievable results.

Germline BARD1 variants predispose to mesothelioma by impairing DNA repair and calcium signaling.

We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 (BARD1) gene that were predicted to be damaging by computational analyses. We conducted functional assays, essential for accurate interpretation of missense variants, in primary fibroblasts that we established in tissue culture from a patient carrying the heterozygous BARD1V523A mutation. We found that these cells had genomic instability, reduced DNA repair, and impaired apoptosis. Investigating the underlying signaling pathways, we found that BARD1 forms a trimeric protein complex with p53 and SERCA2 that regulates calcium signaling and apoptosis. We validated these findings in BARD1-silenced primary human mesothelial cells exposed to asbestos. Our study elucidated mechanisms of BARD1 activity and revealed that heterozygous germline BARD1 mutations favor the development of mesothelioma and increase the susceptibility to asbestos carcinogenesis. These mesotheliomas are significantly less aggressive compared to mesotheliomas in asbestos workers.

Female Adnexal Tumor of Probable Wolffian Origin (Wolffian Tumor): A Potential Mimic of Peritoneal Mesothelioma.

Wolffian tumor and its nosologic relative, the recently defined STK11 adnexal tumor are rare neoplasms thought to arise from mesonephric remnants. These tumors typically arise in the broad ligament, fallopian tube, and ovarian hilum and although most are associated with a good prognosis, up to 50% of STK11 adnexal tumors demonstrate aggressive clinical behavior. The chief differential diagnoses include endometrioid adenocarcinoma and sex cord stromal tumors. However, the morphologic and immunohistochemical features of these tumors exhibit considerable overlap with peritoneal mesothelioma. To fully characterize their immunophenotypic signature, we examined a total of 21 cases (18 Wolffian and 3 STK11 adnexal tumors) with standard markers used in the diagnosis of mesothelioma. Morphologic and immunohistochemical (IHC) features were reviewed and additional IHC performed for cases with available material. Patient age ranged from 25 to 73 (mean: 51) years. Sites included adnexa/broad ligament (6, 28%), paratubal (5, 24%), ovary/paraovarian (5, 24%), tubal (intraluminal) (2, 9.5%), pelvis (2, 9.5%), and liver (1, 5%). The mean tumor size was 9.3 cm (range: 0.2 to 22 cm). The histomorphology in most cases (14/21, 66%) consisted of tubular to solid sheets of neoplastic cells lined by columnar to cuboidal cells containing uniform round to oval nuclei. Compressed tubules with slit-like lumens and sieve-like pattern were also seen in at least 7 (33%) cases. Three cases demonstrated interanastomosing cords and trabeculae of epithelioid cells with cribriform and microacinar patterns growing within prominent myxoid stroma as described in STK11 adnexal tumors. In the cases with available IHC for 3 mesothelial markers (calretinin, WT1, D2-40), 55.5% (5 of 9) showed reactivity with all 3 markers. In cases with at least 2 available mesothelial markers, 69% (11/16) were positive for 2 markers (mostly calretinin and WT1). Claudin-4, MOC31, and BER-EP4 were negative in most cases tested (78% [7/9], 71.4% [5/7], and 100% [6/6], respectively). Given the resemblance to mesothelioma, there was initial strong consideration and/or actual misdiagnosis of mesothelioma in 3 cases (14%). In summary, the morphologic and immunohistochemical features of Wolffian tumor and its recently defined relative, STK11 adnexal tumor, can lead to misdiagnosis of mesothelioma, particularly when encountered in the disseminated or metastatic setting. Wolffian tumor and STK11 adnexal tumor should be considered in the differential diagnosis of all pelvic and peritoneal mesotheliomas.

Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

BACKGROUND: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. METHODS: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. RESULTS: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. CONCLUSION: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

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).

Confirmatory validation of the Mesothelioma Psychological Distress Tool-Patients: A brief patient-reported outcome measure assessing psychological distress in malignant mesothelioma patients.

OBJECTIVE: Psychological suffering in patients with Malignant Mesothelioma (MM) is different from the one experienced by patients with other cancers due to its occupational or environmental etiology and its peculiar symptomatology and prognosis (i.e., poor prognosis, reduced effectiveness of the therapies, poor quality of residual life, and advanced age at the time of diagnosis). Therefore, the Mesothelioma Psychological Distress Tool-Patients (MPDT-P) has been developed to evaluate the specific profile of psychological suffering in this population. This paper describes the item selection, factor analysis, and psychometric evaluation of the revised MPDT-P. METHODS: The analyses of the current work aimed to confirm the factorial structure found in the first version of the MPDT-P. In the case of nonfit, it aimed to find an alternative structure and causes of nonfit in the model. The search for the fit of the factorial model was conducted using a Bayesian approach. RESULTS: The two-factor model reported in the first version of the instrument did not fit the data. Confirmatory Bayesian analyses showed adequate fit for the three-factor solution. Based on the content of the items, we labeled the factors as dysfunctional emotions, claims for justice, and anxieties about the future. CONCLUSIONS: Integrating the MPDT-P into clinical practice could help clinicians gain insight into the specific suffering related to MM and investigate potential differences related to different occupational and environmental exposure contexts.