Pathogenic germline variants in SMARCA4 and further cancer predisposition genes in early onset ovarian cancer

Herold N, Schmolling J, Ernst C, et al. Pathogenic germline variants in SMARCA4 and further cancer predisposition genes in early onset ovarian cancer. Cancer Medicine . 2023.To assess the role of germline pathogenic variants (PVs) in SMARCA4 and further established ovarian cancer (OC) predisposition genes in early onset OC, we investigated a clinical cohort of 206 unrelated OC index patients with an age at diagnosis of OC & LE;40 years using an extended panel of 24 (candidate) cancer predisposition genes. PVs in established OC predisposition genes were most frequent in patients with high grade serous OC (21/62, 33.9%), comparatively rare in patients with epithelial OC other than high grade serous (5/74, 6.8%) or borderline ovarian tumours (2/39, 5.1%) and absent in mucinous OC (0/27). We demonstrate that germline PVs in SMARCA4 unlikely predispose for early onset OC other than SCCOHT

Artificial intelligence for tumour tissue detection and histological regression grading in oesophageal adenocarcinomas: a retrospective algorithm development and validation study

Background: Oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction are among the most common malignant epithelial tumours. Most patients receive neoadjuvant therapy before complete tumour resection. Histological assessment after resection includes identification of residual tumour tissue and areas of regressive tumour, data which are used to calculate a clinically relevant regression score. We developed an artificial intelligence (AI) algorithm for tumour tissue detection and tumour regression grading in surgical specimens from patients with oesophageal adenocarcinoma or adenocarcinoma of the oesophagogastric junction. Methods: We used one training cohort and four independent test cohorts to develop, train, and validate a deep learning tool. The material consisted of histological slides from surgically resected specimens from patients with oesophageal adenocarcinoma and adenocarcinoma of the oesophagogastric junction from three pathology institutes (two in Germany, one in Austria) and oesophageal cancer cohort of The Cancer Genome Atlas (TCGA). All slides were from neoadjuvantly treated patients except for those from the TCGA cohort, who were neoadjuvant-therapy naive. Data from training cohort and test cohort cases were extensively manually annotated for 11 tissue classes. A convolutional neural network was trained on the data using a supervised principle. First, the tool was formally validated using manually annotated test datasets. Next, tumour regression grading was assessed in a retrospective cohort of post-neoadjuvant therapy surgical specimens. The grading of the algorithm was compared with that of a group of 12 board-certified pathologists from one department. To further validate the tool, three pathologists processed whole resection cases with and without AI assistance. Findings: Of the four test cohorts, one included 22 manually annotated histological slides (n=20 patients), one included 62 sides (n=15), one included 214 slides (n=69), and the final one included 22 manually annotated histological slides (n=22). In the independent test cohorts the AI tool had high patch-level accuracy for identifying both tumour and regression tissue. When we validated the concordance of the AI tool against analyses by a group of pathologists (n=12), agreement was 63·6% (quadratic kappa 0·749; p<0·0001) at case level. The AI-based regression grading triggered true reclassification of resected tumour slides in seven cases (including six cases who had small tumour regions that were initially missed by pathologists). Use of the AI tool by three pathologists increased interobserver agreement and substantially reduced diagnostic time per case compared with working without AI assistance. Interpretation: Use of our AI tool in the diagnostics of oesophageal adenocarcinoma resection specimens by pathologists increased diagnostic accuracy, interobserver concordance, and significantly reduced assessment time. Prospective validation of the tool is required. Funding: North Rhine-Westphalia state, Federal Ministry of Education and Research of Germany, and the Wilhelm Sander Foundation

FungiScope - Registre Mondial d’Infections Fongiques Invasives

FungiScopeTM - Enregistrement Global d‘Infections Fongiques Émergentes a été créé en 2003 avec l’objectif d‘améliorer la connaissance de l‘épidémiologie, les manifestations cliniques et les stratégies pour le traitement des infections invasives appelées «fonge émergents». Depuis sa création, des centres de 64 pays se sont associés à l‘initiative FungiScopeTM et plus de 650 cas ont été documentés. Les résultats du projet ont été présentés lors de conférences internationales et publiés dans multiples revues scientifiques. Mais FungiScopeTM est plus qu‘un simple outil pour l´enregistrement des cas cliniques: cette initiative offre un soutien pour le diagnostic, le recueilet l‘identification d’échantillons et fournit un moteur de recherche pour la base de données

First Clinical Experience With [68Ga]Ga-FAPI-46-PET/CT Versus [18F]F-FDG PET/CT for Nodal Staging in Cervical Cancer

In several solid tumors, fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts in the tumor microenvironment. Preliminary evidence suggests that detection and staging are feasible with PET/CT imaging using [(68)Ga]-radiolabeled inhibitors of FAP also in cervical cancer (CC). Our study aims to explore the accuracy of [(68)Ga]Ga–fibroblast activation protein inhibitor (FAPI)-46 PET/CT and [(18)F]F-FDG PET/CT compared with histopathological results of surgical lymph node (LN) staging before primary chemoradiation. METHODS: Seven consecutive women with treatment-naive and biopsy-proven locally advanced CC underwent both whole-body [(68)Ga]Ga-FAPI-46- and [(18)F]F-FDG PET/CT, for imaging nodal staging before systematic laparoscopic lymphadenectomy of the pelvic and para-aortic region. Location and number of suspicious LNs in PET imaging were recorded and compared with the results of histopathological analysis, including immunohistochemical staining for FAP. RESULTS: All 7 patients had focal uptake above background in their tumor lesions in [(68)Ga]Ga-FAPI-46 PET/CT. [(68)Ga]Ga-FAPI-46 PET/CT showed a higher tumor-to-background ratio (TBR) in primary tumor as well as in LN metastasis. Median TBR(max) values using liver were 32.02 and 5.15 for [(68)Ga]Ga-FAPI-46 PET/CT and [(18)F]F-FDG PET/CT, respectively. Median TBR(max) using blood pool was 18.45 versus 6.85 for [(68)Ga]Ga-FAPI-46 PET/CT and [(18)F]F-FDG PET/CT, respectively. Higher TBR also applies for nodal metastasis: TBR(max) was 14.55 versus 1.39 (liver) and 7.97 versus 1.8 (blood pool) for [(68)Ga]Ga-FAPI-46 PET/CT and [(18)F]F-FDG PET/CT, respectively. Overall, [(68)Ga]Ga-FAPI-46 PET/CT detected more lesions compared with [(18)F]F-FDG PET/CT. Following surgical staging, a total of 5 metastatic LNs could be pathologically confirmed, of which 2 and 4 were positive by [(18)F]F-FDG PET/CT and [(68)Ga]Ga-FAPI-46 PET/CT, respectively. CONCLUSION: [(68)Ga]Ga-FAPI-46 PET/CT seems useful to improve detection of nodal metastasis in patients with CCs. Future studies should aim to compare [(68)Ga]Ga-FAPI-46 PET/CT to surgical staging of pelvic and para-aortic LNs in patients with locally advanced CC

FungiScope - Registro de Enfermedades Fúngicas Emergentes

FungiScopeTM - Registro Global de Infecciones Fúngicas Emergentes, fue establecido en el año 2003 con el objetivo de mejorar el conocimiento de la epidemiología, las manifestaciones clínicas y las estrategias para el tratamiento de infecciones invasivas CAUSADAS por los llamados “hongos emergentes”. Desde sus inicios, centros de 64 países se han unido a la iniciativa de FungiScopeTM y se han documentado más de 650 casos. Los resultados del proyecto han sido presentados en conferencias internacionales y publicados en revistas científicas indexadas. FungiScopeTM es más que un simple registro de casos clínicos dado que ofrece apoyo para el diagnóstico, recolección e identificación de muestras y proporciona una base de datos clínicos de acceso público

FungiScope - Registro Globale delle Infezioni Fungine Invasive

FungiScopeTM - Registro Globale delle Infezioni Fungine Emergenti è stato fondato nel 2003 con l‘obiettivo di migliorare le conoscenze di epidemiologia, la conoscenza delle manifestazioni cliniche e le strategie per il trattamento delle infezioni da funghi emergenti. Fin dalla sua istituzione, centri di 64 paesi hanno aderito all‘iniziativa FungiScopeTM e più di 650 casi sono stati documentati. I risultati del progetto sono stati presentati in conferenze internazionali e pubblicati su riviste scientifiche. FungiScopeTM è più di una semplice registrazione di casi clinici perché fornisce supporto per la diagnosi, la raccolta e l‘identificazione dei funghi, e offre un motore di ricerca per i dati clinici