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.

Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.

The new surgical robot Hugo™ RAS for total hysterectomy: a pilot study.

Background: With the rising popularity of robotic surgery, Hugo™ RAS is one of the newest surgical robotic platforms. Investigating the reliability of this tool is the first step toward validating its use in clinical practice; and presently there arelimited data available regarding this. The literature is constantly enriched with initial experiences, however no study has demonstrated the safety of this platform yet. Objectives: This study aimed to investigate its reliability during total hysterectomy. Materials and Methods: A series of 20 consecutive patients scheduled for minimally invasive total hysterectomy with or without salpingo-oophorectomy for benign disease or prophylactic surgery were selected to undergo surgery with Hugo™ RAS. Data regarding any malfunction or breakdown of the robotic system as well as intra- and post-operative complications were prospectively recorded. Results: Fifteen of the twenty patients (75.0%) underwent surgery for benign uterine diseases, and five (25.0%) underwent prophylactic surgery. Among the entire series, an instrument fault occurred in one case (5.0%). The problem was solved in 4.8 minutes and without complications for the patient. The median total operative time was 127 min (range, 98-255 min). The median estimated blood loss was 50 mL (range:30-125 mL). No intraoperative complications were observed. One patient (5.0%) developed Clavien-Dindo grade 2 post-operative complication. Conclusions: In this pilot study, Hugo™ RAS showed high reliability, similar to other robotic devices. What is new?: Present findings suggest that Hugo™ RAS is a viable option for major surgical procedures and deserves further investigation in clinical practice.

Subjective assessment and IOTA ADNEX model in evaluation of adnexal masses in patients with history of breast cancer.

OBJECTIVE: To evaluate the performance of subjective assessment and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in discriminating between benign and malignant adnexal tumors and between metastatic and primary adnexal tumors in patients with a personal history of breast cancer. METHODS: This was a retrospective single-center study including patients with a history of breast cancer who underwent surgery for an adnexal mass between 2013 and 2020. All patients had been examined with transvaginal or transrectal ultrasound using a standardized examination technique and all ultrasound reports had been stored and were retrieved for the purposes of this study. The specific diagnosis suggested by the original ultrasound examiner in the retrieved report was analyzed. For each mass, the ADNEX model risks were calculated prospectively and the highest relative risk was used to categorize each into one of five categories (benign, borderline, primary Stage I, primary Stages II-IV or metastatic ovarian cancer) for analysis of the ADNEX model in predicting the specific tumor type. The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal tumors and between primary and metastatic adnexal tumors was evaluated, using final histology as the reference standard. RESULTS: Included in the study were 202 women with a history of breast cancer who underwent surgery for an adnexal mass. At histology, 93/202 (46.0%) masses were benign, 76/202 (37.6%) were primary malignancies (four borderline and 72 invasive tumors) and 33/202 (16.3%) were metastases. The original ultrasound examiner classified correctly 79/93 (84.9%) benign adnexal masses, 72/76 (94.7%) primary adnexal malignancies and 30/33 (90.9%) metastatic tumors. Subjective ultrasound evaluation had a sensitivity of 93.6%, specificity of 84.9% and accuracy of 89.6%, while the ADNEX model had higher sensitivity (98.2%) but lower specificity (78.5%), with similar accuracy (89.1%), in discriminating between benign and malignant ovarian masses. Subjective evaluation had a sensitivity of 51.5%, specificity of 88.8% and accuracy of 82.7% in distinguishing metastatic and primary tumors (including benign, borderline and invasive tumors), and the ADNEX model had a sensitivity of 63.6%, specificity of 84.6% and similar accuracy (81.2%). CONCLUSIONS: The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal masses in this series of patients with history of breast cancer was relatively similar. Both subjective assessment and the ADNEX model demonstrated good accuracy and specificity in discriminating between metastatic and primary tumors, but the sensitivity was low. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program.

BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.

Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study.

BACKGROUND: Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. METHODS: We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700 mg defined low (LCD) or high (HCD) cumulative dosing during the 90 days before starting ICIs. At least one 5-day course of ≥ 10 mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5 days) or continuous (CCD, > 5 days). RESULTS: We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1-2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6 months (95%CI: 3.9-6.3) and median OS was 6.9 months (95% CI: 6.0-8.9) after a median follow-up time of 43.5 months (95% CI: 32.6-54.4). Multivariate analysis of survival confirmed ECOG PS 1-2 (p = 0.005), negative PD-L1 expression (p = 0.002), and CCD (p = 0.001) significantly correlated with an increased risk of mortality. CONCLUSIONS: These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results.

Antineoplastic treatment class modulates COVID-19 mRNA-BNT162b2 vaccine immunogenicity in cancer patients: a secondary analysis of the prospective Vax-On study.

BACKGROUND: Preliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity. METHODS: The Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties. RESULTS: Three hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine. CONCLUSIONS: Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.

Social distress among medical oncologists and other healthcare professionals during the first wave of COVID-19 pandemic in Italy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread to every country around the world taking on pandemic proportions. Since 8 March 2020, the Italian government ordered a nationwide lockdown with unavoidable social isolation. Healthcare professionals (HCPs) represent the most physically and emotionally involved category. The aim of this study is to assess the social distress among HCPs in Italy. PATIENTS AND METHODS: In this online, totally anonymous survey, 24 multiple choice questions were posed to medical staff employed in the Italian Healthcare System during the COVID-19 pandemic. Data collection was performed from 30 March to 24 April 2020. RESULTS: A total of 600 HCPs completed the questionnaire. The majority of respondents expressed the fear of being at higher risk of contagion than the general population (83.3%) and the weighty concern of infecting their families (72.5%). An insufficient supply of personal protective equipment (PPE; P = 0.0003) and inadequate training about procedures to follow (P = 0.0092) were seen to significantly coincide with these worries. More than two-thirds declared a change in family organisation, which showed a significant correlation with the concern of infecting their relatives (P < 0.0001). CONCLUSIONS: This is the first Italian survey on social distress among HCPs during the COVID-19 pandemic. The unavailability of PPE, screening procedures and adequate training strongly affected HCPs' emotional status. Although there was a predominance of oncologists (especially from the North of Italy), which impairs the generalisation of our findings, this survey underlined the social impact that this health emergency has had on HCPs.

Nickel dermatitis from earrings 15 years after EU directive implementation: a clinical-epidemiological study and a market survey in Rome, Italy.

BACKGROUND: Nickel (Ni) dermatitis remains a highly prevalent allergic condition in Italy. There is a continuous need for clinical and epidemiological surveillance to evaluate whether or not European Ni Directive has been effective in contact allergy prevention. OBJECTIVES: To assess the prevalence of Ni dermatitis among patch-tested patients and self-interviewed school students and to analyse Ni release from earlobe jewellery. METHODS: Results of patch tests performed in 2006-2007, 2015-2016 and 2017-2018 were retrieved. A questionnaire was compiled by 315 secondary school students. Ni release from earring parts was analysed with the EN1811:2015 method. RESULTS: A significant time trend of decreasing Ni positivity from 2006-2007 to 2017-2018 was observed both in the overall population (44.1% in 2006-2007, 33.0% in 2015-2016, 31.6% in 2017-2018, P < 0.0001) and in female patients (P < 0.0001). Conversely, change was not significant in males (P = 0.16). Decrease was significant for all age groups, except for those aged >60 years (P = 0.51). Among 242 students who reported earring use, 130 (54%) reported symptoms at earlobes, mostly associated with jewellery of materials other than gold and silver (59% of those with earlobe symptoms). Ni release exceeded the migration limit in 4/21 (20%) earring parts. CONCLUSIONS: A high prevalence of Ni dermatitis and earlobe symptoms were found in Rome. A decreasing time trend was noted, with a significant decline in Ni sensitivity compared to the situation observed right after Ni Directive implementation. This most likely represents the consequence of reduced Ni content in earring parts, although a major care in the use of Ni-containing objects could contribute to explain these findings.

Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: A pilot randomised controlled trial.

Chemo-induced oral mucositis (OM) is associated with significant symptoms, treatment delays and increased costs. This pilot randomised controlled trial aimed at evaluating the safety, tolerability and compliance with propolis in breast cancer patients receiving doxorubicin and cyclophosphamide, testing preliminary clinical efficacy of propolis in the prevention of OM, and prospectively evaluating the incidence of OM. Sixty patients were randomised to receive either a dry extract of propolis with 8%-12% of galangin plus mouth rinsing with sodium bicarbonate (experimental arm), or mouth rinsing with sodium bicarbonate (control arm). OM was evaluated with the NCI-CTCAE v4.0 after 5, 10, 15 and 21 days of treatment. Compliance with, tolerability of propolis and adverse events were recorded. The incidence of OM was also prospectively evaluated for 6 months. Two patients (6.7%) manifested a suspected skin reaction to propolis. No patient in the experimental arm developed OM > G1, while in the control arm OM > G1 was 16.7% (p = .02). The incidence of OM ≥ G1 at the end of cycles 2-8 was higher at the second (25%) and fifth cycles (45.8%). Propolis plus bicarbonate was safe, well tolerated and promisingly effective in the prevention of OM in patients with breast cancer.

Comparison of Two Questionnaires on Informed Consent in "Marginal" Donor Liver.

The necessity of liver donors has contributed to overcoming the traditional criteria and to propose new ones for the acceptance of livers for transplantation. For this reason expanded or extended criteria donation (ECD) or even overextended criteria for marginal or high-risk organ donors have been developed. Ethical, Legal and Psychological Aspects of Organ Transplantation (ELPAT) and European Liver and Intestine Transplant Association (ELITA) - European Liver Transplantation Registry (ELTR) coordinated the distribution of a previously reported questionnaire that was sent to 53 European liver transplant centers. Criteria were divided based on the response rate. Donor criteria such as steatosis and serum sodium >165 mmol/L, as well as recipient criteria such as previous history of cancer, were not considered contraindications to transplantation in more than 60% of cases. Criteria such as ICU (intensive care unit) stay, body mass index >30, serum bilirubin >3 mg/dL, and HIV infection or critical illness were not considered adequate for transplantation in 30% to 59% of cases. On the other hand, there was no agreement on other extended liver donor and recipient criteria, such as age up to 80 years, serum glutamic oxaloacetic transaminase >90 U/L, serum glutamic pyruvic transaminase >105 U/L, high-risk sex practices, drug users, patients older than 65 years, and patients younger than 65 years, respectively. Criteria such as serum sodium could not be considered ECD criteria. In conclusion, development of more studies and inclusion of more liver transplantation centers are required to confirm these data.