Detection of TP53 Clonal Variants in Papanicolaou Test Samples Collected up to 6 Years Prior to High-Grade Serous Epithelial Ovarian Cancer Diagnosis.

Importance: The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease. Objective: To determine whether the presence of the clonal pathogenic TP53 variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis. Design, Setting, and Participants: This cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women's Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the TP53 variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019. Main Outcomes and Measures: The presence of tumor pathogenic TP53 variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings. Results: Among 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched TP53 variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the TP53 clonal variant was detected at all time points. Conclusions and Relevance: These findings suggest that noninvasive early molecular diagnosis of HGS-EOC is potentially achievable through detection of TP53 clonal variants in the DNA purified from Papanicolaou tests performed during cervical cancer screening.

Radiomics of the primary tumour as a tool to improve 18F-FDG-PET sensitivity in detecting nodal metastases in endometrial cancer.

BACKGROUND: A radiomic approach was applied in 18F-FDG PET endometrial cancer, to investigate if imaging features computed on the primary tumour could improve sensitivity in nodal metastases detection. One hundred fifteen women with histologically proven endometrial cancer who underwent preoperative 18F-FDG PET/CT were retrospectively considered. SUV, MTV, TLG, geometrical shape, histograms and texture features were computed inside tumour contours. On a first group of 86 patients (DB1), univariate association with LN metastases was computed by Mann-Whitney test and a neural network multivariate model was developed. Univariate and multivariate models were assessed with leave one out on 20 training sessions and on a second group of 29 patients (DB2). A unified framework combining LN metastases visual detection results and radiomic analysis was also assessed. RESULTS: Sensitivity and specificity of LN visual detection were 50% and 99% on DB1 and 33% and 95% on DB2, respectively. A unique heterogeneity feature computed on the primary tumour (the zone percentage of the grey level size zone matrix, GLSZM ZP) was able to predict LN metastases better than any other feature or multivariate model (sensitivity and specificity of 75% and 81% on DB1 and of 89% and 80% on DB2). Tumours with LN metastases are in fact generally characterized by a lower GLSZM ZP value, i.e. by the co-presence of high-uptake and low-uptake areas. The combination of visual detection and GLSZM ZP values in a unified framework obtained sensitivity and specificity of 94% and 67% on DB1 and of 89% and 75% on DB2, respectively. CONCLUSIONS: The computation of imaging features on the primary tumour increases nodal staging detection sensitivity in 18F-FDG PET and can be considered for a better patient stratification for treatment selection. Results need a confirmation on larger cohort studies.