-
Journal of Nuclear Medicine : Official... Aug 2023The F-labeled fibroblast activation protein inhibitor (FAPI) [F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than Ga-labeled FAPI. We...
The F-labeled fibroblast activation protein inhibitor (FAPI) [F]FAPI-74 has the benefit of a higher synthetic yield and better image resolution than Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. We enrolled 31 patients (17 men and 14 women) with lung cancer ( = 7), breast cancer ( = 5), gastric cancer ( = 5), pancreatic cancer ( = 3), other cancers ( = 5), and benign tumors ( = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [F]FAPI-74 PET scanning was performed 60 min after the intravenous injection of [F]FAPI-74 (240 ± 31 MBq). The [F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors ( = 21) and nonmalignant lesions ( = 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [F]FAPI-74 PET were also compared with those on [F]FDG PET for available patients ( = 19). [F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUV, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; = 0.053), but some of the nonmalignant lesions showed high uptake. [F]FAPI-74 PET also showed significantly higher uptake than [F]FDG PET (median SUV, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [ = 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [ = 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [ = 0.046], respectively). In 6 patients, [F]FAPI-74 PET detected more metastatic lesions than [F]FDG PET. [F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [F]FDG PET. [F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, F-labeled FAPI ligand might serve a higher demand in clinical care in the future.
Topics: Male; Humans; Female; Fluorodeoxyglucose F18; Breast Neoplasms; Pancreatic Neoplasms; Lung Neoplasms; Stomach Neoplasms; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Quinolines
PubMed: 37268427
DOI: 10.2967/jnumed.123.265486 -
Histopathology Jan 2024The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations,... (Review)
Review
The epithelial and lymphoid compartments of the thymus can give rise to a wide variety of tumours, including thymomas, thymic carcinomas, lymphoreticular proliferations, germ cell tumours, and sarcomas. While some of these have close similarity to their counterparts in other organs, both in terms of histology and immunohistochemistry, as well as molecular features, others are unique to the thymus. The epithelial tumours, which can develop in the thymus, will be discussed in this review, with a particular emphasis on resolving differential diagnosis by means of morphology, immunohistochemical profiles, and molecular diagnostics.
Topics: Humans; Diagnosis, Differential; Thymus Neoplasms; Thymoma; Neoplasms, Glandular and Epithelial
PubMed: 37994555
DOI: 10.1111/his.15097 -
Neurology Jun 2024The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the... (Review)
Review
The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.
Topics: Humans; Thymectomy; Myasthenia Gravis; Thymus Gland; Thymus Neoplasms; Thymoma; Postoperative Complications; Autoimmune Diseases
PubMed: 38781559
DOI: 10.1212/WNL.0000000000209482 -
Survey of Ophthalmology 2024Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It... (Review)
Review
Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.
Topics: Humans; Cytomegalovirus Retinitis; Thymoma; Agammaglobulinemia; Thymus Neoplasms
PubMed: 38176471
DOI: 10.1016/j.survophthal.2023.12.004 -
JAMA Network Open Nov 2023Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are...
IMPORTANCE
Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure.
OBJECTIVE
To evaluate the outcomes of guideline-based follow-up in low-risk GIST.
DESIGN, SETTING, AND PARTICIPANTS
This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up.
EXPOSURES
All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines.
MAIN OUTCOMES AND MEASURES
The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed.
RESULTS
A total of 737 patients (377 men [51.2%]; median age at diagnosis, 63 [range, 18-86] years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio [HR], 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients.
CONCLUSIONS AND RELEVANCE
In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Gastrointestinal Stromal Tumors; Cohort Studies; Follow-Up Studies; Retrospective Studies; Neoplasm Recurrence, Local; Recurrence; Sarcoma; Italy
PubMed: 37930700
DOI: 10.1001/jamanetworkopen.2023.41522 -
Kardiochirurgia I Torakochirurgia... Dec 2023Mediastinal tumors encompass a diverse range of malignancies, originating within or spreading to the mediastinum. The administration of radiotherapy within the... (Review)
Review
Mediastinal tumors encompass a diverse range of malignancies, originating within or spreading to the mediastinum. The administration of radiotherapy within the anatomical confines of the mediastinum presents unique challenges owing to the close proximity of critical organs, including the heart, lungs, esophagus, and spinal cord. However, recent progress in imaging techniques, treatment modalities, and our understanding of tumor biology has significantly contributed to the development of effective and safe therapeutic strategies for mediastinal diseases. This review article aims to explore the latest innovations in radiotherapy and their practical applications in the management of mediastinal tumors, with a primary focus on lymphomas, thymomas, and thymic carcinomas. By examining these advancements, we seek to provide valuable insights into the current state of the art in radiotherapy for mediastinal malignancies, ultimately fostering improved patient outcomes and clinical decision-making.
PubMed: 38283558
DOI: 10.5114/kitp.2023.134132 -
Clinical Neurology and Neurosurgery Nov 2023Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH)....
INTRODUCTION
Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized.
OBJECTIVE
To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre.
METHODS
Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021.
RESULTS
Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort.
CONCLUSION
Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.
Topics: Female; Humans; Male; Autoantibodies; Limbic Encephalitis; Retrospective Studies; Seizures; Syndrome
PubMed: 37797365
DOI: 10.1016/j.clineuro.2023.107994 -
ESMO Open Oct 2023Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the...
BACKGROUND
Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting.
METHODS
We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.
RESULTS
A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma.
CONCLUSIONS
To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Genomics
PubMed: 37703595
DOI: 10.1016/j.esmoop.2023.101627 -
Neurological Research Mar 2024Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the...
BACKGROUND
Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs.
METHODS
The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C.
RESULTS
A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage.
CONCLUSIONS
A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival. A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma.
Topics: Male; Female; Humans; Melanoma; Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Uterine Cervical Neoplasms; Pancreatic Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Glioma; Glioblastoma; Biomarkers; Peptides; RNA; RNA, Messenger; Apolipoproteins; Prognosis; Cytidine Deaminase
PubMed: 38007705
DOI: 10.1080/01616412.2023.2287340 -
Journal of Cancer Research and Clinical... Nov 2023To explore the efficiency of a contrast-enhanced CT-based radiomics nomogram integrated with radiomics signature and clinically independent predictors to distinguish... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To explore the efficiency of a contrast-enhanced CT-based radiomics nomogram integrated with radiomics signature and clinically independent predictors to distinguish mass-like thymic hyperplasia (ml-TH) from low-risk thymoma (LRT) preoperatively.
METHODS
135 Patients with histopathology confirmed ml-TH (n = 65) and LRT (n = 70) were randomly divided into training set (n = 94) and validation set (n = 41) at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) algorithm was used to obtain the optimal features. Based on the selected features, four machine learning models, support vector machine (SVM), logistic regression (LR), extreme gradient boosting (XGBOOST), and random forest (RF) were constructed. Multivariate logistic regression was used to establish a radiomics nomogram containing clinically independent predictors and radiomics signature. Receiver operating characteristic (ROC), DeLong test, and calibration curves were used to detect the performance of the radiomics nomogram in training set and validation set.
RESULTS
In the validation set, the area under the curve (AUC) value of LR (0.857; 95% CI: 0.741, 0.973) was the highest of the four machine learning models. Radiomics nomogram containing radiomics signature and clinically independent predictors (including age, shape, and net enhancement degree) had better calibration and identification in the training set (AUC: 0.959; 95% CI: 0.922, 0.996) and validation set (AUC: 0.895; 95% CI: 0.795, 0.996).
CONCLUSION
We constructed a contrast-enhanced CT-based radiomics nomogram containing clinically independent predictors and radiomics signature as a noninvasive preoperative prediction method to distinguish ml-TH from LRT. The radiomics nomogram we constructed has potential for preoperative clinical decision making.
Topics: Humans; Thymoma; Nomograms; Thymus Hyperplasia; Thymus Neoplasms; Tomography, X-Ray Computed
PubMed: 37604939
DOI: 10.1007/s00432-023-05263-3