Radiomics analysis of ultrasound images to discriminate between benign and malignant adnexal masses with solid ultrasound morphology.

OBJECTIVE: Our primary aim was to identify radiomic ultrasound features that can distinguish benign from malignant adnexal masses with solid ultrasound morphology, and primary invasive from metastatic solid ovarian masses, and to develop ultrasound-based machine learning models that include radiomics features to discriminate between benign and malignant solid adnexal masses. Our secondary aim was to compare the diagnostic performance of our radiomics models with that of the ADNEX model and subjective assessment by an experienced ultrasound examiner. METHODS: This is a retrospective observational single center study. Patients with a histological diagnosis of an adnexal tumor with solid morphology at preoperative ultrasound examination performed between 2014 and 2021 were included. The patient cohort was split into training and validation sets with a ratio of 70:30 and with the same proportion of benign and malignant (borderline, primary invasive and metastatic) tumors in the two subsets. The extracted radiomic features belonged to two different families: intensity-based statistical features and textural features. Models to predict malignancy were built based on a random forest classifier, fine-tuned using 5-fold cross-validation over the training set, and tested on the held-out validation set. The variables used in model building were patient's age, and those radiomic features that were statistically significantly different between benign and malignant adnexal masses (Wilcoxon-Mann-Whitney Test with Benjamini-Hochberg correction for multiple comparisons) and assessed as not redundant based on the Pearson correlation coefficient. We describe discriminative ability as area under the receiver operating characteristics curve (AUC) and classification performance as sensitivity and specificity. RESULTS: 326 patients were identified and 775 preoperative ultrasound images were analyzed. 68 radiomic features were extracted, 52 differed statistically significantly between benign and malignant tumors in the training set, and 18 features were selected for inclusion in model building. The same 52 radiomic features differed statistically significantly between benign, primary invasive malignant and metastatic tumors. However, the values of the features manifested overlap between primary malignant and metastatic tumors and did not differ statistically significantly between them. In the validation set, 25/98 tumors (25.5%) were benign, 73/98 (74.5%) were malignant (6 borderline, 57 primary invasive, 10 metastases). In the validation set, a model including only radiomics features had an AUC of 0.80, and 78% sensitivity and 76% specificity at its optimal risk of malignancy cutoff (68% based on Youden's index). The corresponding results for a model including age and radiomics features were 0.79, 86% and 56% (cutoff 60% based on Youden's method), while those of the ADNEX model were 0.88, 99% and 64% (at 20% malignancy cutoff). Subjective assessment had sensitivity 99% and specificity 72%. CONCLUSIONS: Even though our radiomics models had discriminative ability inferior to that of the ADNEX model, our results are promising enough to justify continued development of radiomics analysis of ultrasound images of adnexal masses. This article is protected by copyright. All rights reserved.

A cost-effectiveness analysis of an integrated clinical-radiogenomic screening program for the identification of BRCA 1/2 carriers (e-PROBE study).

Current approach to identify BRCA 1/2 carriers in the general population is ineffective as most of the carriers remain undiagnosed. Radiomics is an emerging tool for large scale quantitative analysis of features from standard diagnostic imaging and has been applied also to identify gene mutational status. The objective of this study was to evaluate the clinical and economic impact of integrating a radiogenomics model with clinical and family history data in identifying BRCA mutation carriers in the general population. This cost-effective analysis compares three different approaches to women selection for BRCA testing: established clinical criteria/family history (model 1); established clinical criteria/family history and the currently available radiogenomic model (49% sensitivity and 87% specificity) based on ultrasound images (model 2); same approach used in model 2 but simulating an improvement of the performances of the radiogenomic model (80% sensitivity and 95% specificity) (model 3). All models were trained with literature data. Direct costs were calculated according to the rates currently used in Italy. The analysis was performed simulating different scenarios on the generation of 18-year-old girls in Italy (274,000 people). The main outcome was to identify the most effective model comparing the number of years of BRCA-cancer healthy life expectancy (HLYs). An incremental cost-effectiveness ratio (ICER) was also derived to determine the cost in order to increase BRCA carriers-healthy life span by 1 year. Compared to model 1, model 2 increases the detection rate of BRCA carriers by 41.8%, reduces the rate of BRCA-related cancers by 23.7%, generating over a 62-year observation period a cost increase by 2.51 €/Year/Person. Moreover, model 3 further increases BRCA carriers detection (+ 68.3%) and decrease in BRCA-related cancers (- 38.4%) is observed compared to model 1. Model 3 increases costs by 0.7 €/Year/Person. After one generation, the estimated ICER in the general population amounts to about 3800€ and 653€ in model 2 and model 3 respectively. Model 2 has a massive effect after only one generation in detecting carriers in the general population with only a small cost increment. The clinical impact is limited mainly due to the current low acceptance rate of risk-reducing surgeries. Further multicentric studies are required before implementing the integrated clinical-radiogenomic model in clinical practice.

Targeting the hallmarks of ovarian cancer: The big picture.

OBJECTIVE: As a result of relevant achievements in the field of translational research, several active drugs and multiple biological targets are available in ovarian cancer (OC). In this complex scenario, there is an urgent need to effectively summarize the available data in order to update conclusions, and outline perspectives. METHODS: The results in terms of target identification and drug development have been summarized using the well-known hallmarks of cancer firstly described, and recently modified by Hanahan and Weinberg [1-2]. Published data from clinical trials have been retrieved from PubMed, Embase, CINAHL and Cochrane database. Ongoing clinical trials were searched using clinicaltrials.gov web platform, and identified using NCT number. RESULTS: Genomic instability and angiogenesis are the most actively investigated hallmarks in high-grade serous OC, and the inhibition of tumor immune evasion appears as the emerging strategy for molecularly-driven therapy. Targeting sustained proliferative signaling through MEK and mTOR inhibitors seems the most promising approach in clear cell, and low-grade serous OC. CONCLUSIONS: This substantial amount of data suggests that targeted therapies are already part of the clinical and therapeutic management of OC patients. The expectations of getting from translational research a better knowledge of tumor biology and therefore personalized drugs are high and worthy of maximum effort from referral centers.

A laparoscopic risk-adjusted model to predict major complications after primary debulking surgery in ovarian cancer: A single-institution assessment.

OBJECTIVE: To develop and validate a simple adjusted laparoscopic score to predict major postoperative complications after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (AEOC). METHODS: From January 2006 to June 2015, preoperative, intraoperative, and post-operative outcome data from patients undergoing staging laparoscopy (S-LPS) before receiving PDS (n=555) were prospectively collected in an electronic database and retrospectively analyzed. Major complications were defined as levels 3 to 5 of MSKCC classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n=370) and was validated on the remaining one-third patients (n=185). RESULTS: Major complication rate was 18.3% (102/555). Significant predictors included in the scoring system were: poor performance status, presence of ascites (>500cm(3)), CA125 serum level (>1000U/ml), and high laparoscopic tumor load (predictive index value, PIV ≥8). The mean risk of developing major postoperative complications was 3.7% in patients with score 0 to 2, 13.2% in patients with score 3 to 5, 37.1% in patients with score 6 to 8. In the validation population, the predicted risk of major complications was 17.8% (33/185) versus a 16.7% (31/185) observed risk (C-statistic index=0.790). CONCLUSION: This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt tailored strategies on individual basis.

Timing and pattern of recurrence in ovarian cancer patients with high tumor dissemination treated with primary debulking surgery versus neoadjuvant chemotherapy.

PURPOSE: To compare the timing and pattern of recurrence in patients with advanced ovarian cancer (AOC) receiving primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). METHODS: We retrospectively evaluated a consecutive series of 175 stage IIIC-IV epithelial ovarian cancer patients, with diffuse peritoneal carcinomatosis documented at initial surgical exploration. Forty patients received complete PDS, and the remaining 135 were treated with NACT followed by IDS with absent residual tumor after surgery. RESULTS: No differences were observed in the distribution of clinical pathological characteristics at the time of diagnosis between the two groups. The median follow-up was 31 months (range 9-150 months). We observed 20 (50.0%) recurrences in the PDS group compared to 103 (76.3%) in the IDS group (p = 0.001). Duration of primary platinum-free interval (PFI) was shorter in IDS compared to PDS group (13 vs. 21 months, respectively; p = 0.014). A significantly higher percentage of patients in the IDS group experienced platinum-resistant recurrences (35.9 vs. 5.0%; p = 0.006) and carcinomatosis at the time of relapse (57.3 vs. 20.0%; p = 0.0021). Finally, in women with platinum-sensitive recurrence, we observed a shorter secondary PFI in the IDS compared to PDS group (p = 0.006). CONCLUSIONS: We documented a better behavior of recurrent disease in AOC patients with diffuse peritoneal carcinomatosis treated with complete PDS compared to women submitted to NACT followed by IDS with no residual tumor after surgery.

Ovarian cancer patients with localized relapse: clinical outcome and prognostic factors.

OBJECTIVE: We evaluated the clinical outcome and prognostic factors for post-relapse survival (PRS) in a large retrospective series of ovarian cancer patients with localized relapse. PATIENTS AND METHODS: The following radiological inclusion criteria were adopted: relapse in single anatomic site and ≤ 3 nodules. All cases were followed for at least 24 months after recurrent disease. RESULTS: Two hundred twenty ovarian cancer patients met the inclusion criteria. Serous histotype and G3 tumors were observed in 173 (78.6%) and 151 (77.4%) cases, respectively. All women received platinum-based first-line chemotherapy. Overall, the median follow-up was 46 (8-249) months, and platinum-resistant relapse was documented in 51 women (23.2%). Eighty-one patients (36.8%) recurred in the peritoneum (LPeR), 76 patients (34.5%) in the abdominal lymph nodes (LLNR), and 63 patients (28.7%) in parenchymal organs (LPaR); 142 patients (64.5%) recurred with a single nodule; and 78 patients (35.5%) recurred with 2-3 nodules. Secondary cytoreductive surgery (SCS) was attempted in 73 cases (33.2%), and complete debulking was achieved in all patients. On multivariate analysis, platinum-free interval (PFI, χ(2)=13.457, p value=0.001), complete SCS (median PRS, 69 months vs 25 months, p=0.001), anatomic site of relapse (median PRS, 41months in LPeRs, 63 months in LLNRs and 24 months in LPaRs, p=0.001), and number of nodules (median PRS, 58months in patients with one nodule, 24months in patients with 2-3 nodules, p=0.001) were identified as predictors of PRS. CONCLUSIONS: Beside the duration of PFI, the complete SCS, the anatomic site of relapse, and the number of nodules were independent prognostic factor for duration of PRS.

Comparison of mutagenic activities of several peroxyacyl nitrates.

Salmonella typhimurium, strain TA100 was exposed to a series of peroxyacyl nitrates including peroxyacetyl nitrate (PAN), peroxypropionyl nitrate (PPN), peroxybutyryl nitrate (PBN), peroxybenzoyl nitrate (PBzN), and chloroperoxyacetyl nitrate (CPAN). Gas-phase concentrations for the individual exposures were in the high part per billion by volume ppbv range. The dose was determined from the deposition rate and measured from the net decrease of the test compound in the exposure chamber and the exposure time. The mutagenic activity for each compound determined from the dose-response relationship gave values ranging from 250 (PBN) to 6,500 (PBzN) revertants/mumols. The mutagenic activity for CPAN could not be determined, due to an interference from chloroacetaldehyde. The difficulties of quantifying the actual gas-phase chemical dose the bacteria are exposed to in this variant of the Ames test are delineated.