Role of artificial intelligence applied to ultrasound in gynecology oncology: A systematic review.

The aim of this paper was to explore the role of artificial intelligence (AI) applied to ultrasound imaging in gynecology oncology. Web of Science, PubMed, and Scopus databases were searched. All studies were imported to RAYYAN QCRI software. The overall quality of the included studies was assessed using QUADAS-AI tool. Fifty studies were included, of these 37/50 (74.0%) on ovarian masses or ovarian cancer, 5/50 (10.0%) on endometrial cancer, 5/50 (10.0%) on cervical cancer, and 3/50 (6.0%) on other malignancies. Most studies were at high risk of bias for subject selection (i.e., sample size, source, or scanner model were not specified; data were not derived from open-source datasets; imaging preprocessing was not performed) and index test (AI models was not externally validated) and at low risk of bias for reference standard (i.e., the reference standard correctly classified the target condition) and workflow (i.e., the time between index test and reference standard was reasonable). Most studies presented machine learning models (33/50, 66.0%) for the diagnosis and histopathological correlation of ovarian masses, while others focused on automatic segmentation, reproducibility of radiomics features, improvement of image quality, prediction of therapy resistance, progression-free survival, and genetic mutation. The current evidence supports the role of AI as a complementary clinical and research tool in diagnosis, patient stratification, and prediction of histopathological correlation in gynecological malignancies. For example, the high performance of AI models to discriminate between benign and malignant ovarian masses or to predict their specific histology can improve the diagnostic accuracy of imaging methods.

Diagnostic performance of ultrasound in assessing the extension of disease in advanced ovarian cancer.

BACKGROUND: Surgical exploration remains the gold standard for evaluating the extension of disease and predicting resectability. A laparoscopy-based scoring model was developed by Fagotti and colleagues in 2006 and updated in 2015, based on the intraoperative presence or absence of some specific cancer features. The model proved an overall accuracy rate of 77% to 100% and is considered the reference test for assessing resectability in our institution. OBJECTIVE: The primary aim of the study was to analyze the agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intraabdominal disease using 6 parameters described by Fagotti's score. STUDY DESIGN: This was a prospective single-center observational study. Between January 2019 and June 2020, consecutive patients with clinical or radiological suspicion of ovarian or peritoneal cancer were assessed with preoperative ultrasound examination and assigned a score based on the 6 Fagotti score parameters (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel disease). Presence of mesenteral retraction of the small bowel and miliary carcinomatosis on the serosa were also evaluated. Each parameter was correlated with laparoscopic findings. Concordance was calculated between ultrasound and laparoscopic parameters using Cohen's kappa. RESULTS: Cohen's kappa ranged from 0.70 to 0.90 for carcinomatosis on the small or large bowel, supracolic omentum, liver surface, and diaphragms. Cohen's kappa test was lower for carcinomatosis on the parietal peritoneum (k=0.63) and on the lesser omentum or lesser curvature of the stomach or spleen (k=0.54). The agreement between ultrasound and surgical predictive index value (score) was k=0.74. For the evaluation of mesenteral retraction and miliary carcinomatosis, the agreement was low (k=0.57 and k=0.36, respectively). CONCLUSION: The results of ultrasound and laparoscopy in the assessment of intraabdominal tumor spread were in substantial agreement for almost all the parameters. Ultrasound examination can play a useful role in the preoperative management of patients with ovarian cancer when used in dedicated referral centers.

Practice changes in Italian Gynaecologic Units during the COVID-19 pandemic: a survey study.

The impact of Coronavirus disease 2019 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown. Therefore, a survey was conducted among all Italian Gynaecological Units Directors in April 2020. The response rate was 90% (135/150). 77.8% of centres performed surgery only for oncologic or not deferrable pathologies, and 9.6% was closed. 68.7% of directors were at least moderately satisfied by published guidelines/recommendations, but 94.8% of respondents identified limitations, mainly (83%) the absent definition of benign non-deferrable pathology. Responders considered as non-deferrable severe endometriosis (69.6%), endometriosis with organ failure/dysfunction (74.1%), and unresponsive symptomatic fibroids (89.6%). Despite guidelines/recommendations, respondents treated ovarian (77%) and endometrial (71.6%) cancer as usual. Only a minority of respondents reduced the laparoscopic approach (11.2%) and adopted all recommended surgical precautions (9.6%). Compliance with available guidelines/recommendations appears incomplete. Reconsidering guidelines/recommendations regarding oncological cases and specify non-deferrable benign pathologies would improve guidelines/recommendations compliance.Impact statementWhat is already known on this subject? The SARS-CoV-2 pandemic has profoundly influenced medical routine practice worldwide. Surgery units have been forced to reduce or even completely restrict their activity to re-allocate human resources. Many major international gynaecological societies have released statements and guidelines, providing various recommendations to guide practice changes. However, the impact of the SARS-CoV-2 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown.What do the results of this study add? Study results provide evidence showing how the SARS-CoV-2 pandemic has changed surgical activity in the Italian Gynaecological Units. Most centres reduced surgical activity, limiting surgery only for oncologic or not deferrable pathologies. Moreover, our research shows the level of compliance and satisfaction with available guidelines/recommendations and where they need to be improved. Most directors were at least moderately satisfied but identified different limitations. Guidelines/recommendations do not provide enough details, such as the absent definition of benign non-deferrable pathologies.What are the implications of these findings for clinical practice and/or further research? The limited compliance with available guidelines/recommendations and identified limitations suggest reconsidering guidelines/recommendations focussing on identified gaps. Provide more details, such as specifying non-deferrable benign pathologies, would improve guidelines/recommendations compliance.

Clinical and ultrasound characteristics of vaginal lesions.

OBJECTIVE: Ultrasound examination represents the most important diagnostic method to preoperatively assess gynecological diseases. However, the ultrasound characteristics of vaginal pathologies are poorly investigated. The aim of this study was to describe the clinical and ultrasound characteristics of vaginal lesions detected at ultrasound. METHODS: This was a single center, prospective, observational study including patients with vaginal masses examined from January 2017 to May 2019. Morphologic sonographic characteristics of the lesions were described as unilocular, multilocular, unilocular-solid, multilocular-solid, and solid. For the analysis, patients were grouped into a 'malignant group', including patients with confirmed malignancy at final histology, and a 'benign group', including patients with a confirmed benign pathology at final histology and patients without a histological diagnosis but with a lesion that manifested no changes during follow-up. RESULTS: 44 patients were enrolled. 22 (50%) of 44 lesions were benign: 12 (54.5%) of these underwent ultrasound follow-up and did not show any changes at the 12 month follow-up whereas 10 (45.5%) lesions had surgical excision which confirmed the benign nature. The remaining 22 (50%) of 44 lesions underwent surgery because of suspicion of malignancy: histology confirmed a malignancy in 20 (90.9%) of 22 cases. Benign lesions were described as follow: 11/24 (45.8%) unilocular, 3/24 (12.5%) multilocular with two locules, and 10/24 (41.7%) solid lesions. Malignant lesions were solid in 19/20 (95%) cases and multilocular-solid in 1/20 (5%). Most benign lesions had a color score of 1-2 (20/24, 83.4%) while malignant lesions had a color score of 3-4 (18/20, 90%). CONCLUSION: A typical ultrasound image of a benign lesion was a unilocular cyst or hypoechoic solid mass with no or minimal vascularization on color Doppler examination. Malignant vaginal lesions were hypoechoic solid tumors with irregular margins and moderate/rich vascularization or multilocular-solid. Ultrasound should be used to supplement the clinician in the management of vaginal lesions.

Emerging role of immune checkpoint inhibitors in the treatment of ovarian cancer.

INTRODUCTION: In recent years, ovarian cancer (OC) treatment has been enriched with many new target therapies, most of all antiangiogenic drugs and PARP inhibitors (PARPis), which have literally changed the natural history of the disease. The impressive results of immunotherapy in other malignancies, mainly melanoma and lung cancer, and the good signals of activity in gynecological neoplasms like cervical and microsatellite instable (MSI-H) endometrial cancer, opened the space to the introduction of immune-stimulatory drugs in ovarian cancer. AREA COVERED: The goal of this article is to summarize the newest evidence on the use of immune check point inhibitors in OC trying to explain why, at present, this strategy has failed to improve clinical outcome and focusing on the possible strategies to overcome treatment failure. EXPERT OPINION: Although numerous trials have been undertaken, only scanty results have been obtained so far with immune check-point inhibitors (ICIs) in OC either when used as single agents or in combination with antiangiogenic therapy and ongoing trials are exploring the association of ICIs with PARPis and other ICIs. A better knowledge of predictive biomarkers of response and mechanisms of immunotherapy resistance, will help in identifying the most appropriate population to treat with ICIs.

Clinical outcome of recurrent endometrial cancer: analysis of post-relapse survival by pattern of recurrence and secondary treatment.

INTRODUCTION: Recurrence of endometrial cancer is an important clinical challenge, with median survival rarely exceeding 12 months. The aim of this study was to analyze patterns of endometrial cancer recurrence and associations of these patterns with clinical outcome. METHODS: The study included patients with endometrial cancer who underwent primary surgical treatment with or without adjuvant treatment between July 2004 and June 2017 at the Gynaecologic Oncology Unit of one of three tertiary hospitals of the Catholic University Network in Italy with complete follow-up data available. Information on the date and pattern of recurrence was retrieved for each relapse. Post-relapse survival was recorded as the time from the date of recurrence to the date of death or last follow-up. Survival probabilities were compared using log rank tests, and associations of clinico-pathological characteristics with post-relapse survival were tested using Cox's regression models. RESULTS: A total of 1503 patients were included in the analysis. We identified 210 recurrences (14.0%) and 105 deaths (7.0%) at a median follow-up of 34 months (range 1-162). One hundred and fifty-eight recurrences (78.1%) occurred during the first two years of follow-up. Most recurrences were multifocal (n=121, 57.6%) and involved extrapelvic sites (n=38, 65.7%). Parameters associated with post-relapse survival in the univariate analysis included histotype, grade, time to recurrence, pattern of recurrence, number of relapsing lesions, and secondary radical surgery. Only the pattern of recurrence and secondary radical surgery were independent predictors of post-relapse survival in the multivariate analysis (p=0.025 and p=0.0001, respectively). CONCLUSION: Lymph node recurrence and the feasibility of secondary radical surgery were independent predictors of post-relapse survival in patients with recurrent endometrial cancer.

Mesenteric lymph node involvement in advanced ovarian cancer patients undergoing rectosigmoid resection: prognostic role and clinical considerations.

BACKGROUND: The aim of this retrospective study was to investigate the incidence of mesenteric lymph node (MLN) involvement, and its prognostic role in advanced ovarian cancer (OC). METHODS: OC patients undergoing rectosigmoid resection during primary debulking surgery or interval debulking surgery were recorded. Progression-free survival (PFS) and overall survival were calculated from the date of diagnosis to the date of relapse/progression, death of disease, or the date of last follow-up. RESULTS: MLNs were detected in 102/148 cases (68.9 %); the rate of MLN involvement was 47.0 %. The percentage of metastatic MLNs was higher in cases with >5 MLNs removed compared with cases with ≤ 5 MLNs removed (62.7 % vs. 31.3 %; p = 0.0027). A progressive increase in the rate of metastatic MLNs was documented in association with depth of bowel infiltration (p = 0.026). Cases with metastatic MLNs experienced isolated celiac trunk or aortic lymph node recurrences more frequently than patients without MLN involvement (44.8 % vs. 10.7 %; p = 0.0008). PFS did not differ between cases with positive versus negative MLN involvement (2-year PFS = 31 % vs. 43 %; p = 0.58). CONCLUSION: OC patients undergoing rectosigmoid resection showed metastatic MLN involvement in 47.0 % of cases. Metastatic MLN status is associated with a high rate of isolated aortic and celiac trunk lymph node recurrences.

Innovative Ultrasound Criteria for the Diagnosis of Adenomyosis and Correlation with Symptoms: A Retrospective Re-Evaluation.

The 2022 Delphi revision of the MUSA (Morphological Uterus Sonographic Assessment) criteria for the ultrasound diagnosis of adenomyosis divides the ultrasound signs for diagnosis into direct and indirect ones, considering the presence of at least one direct sign as a mandatory criterion. This study aimed to reclassify the patients referred to the Pelvic Pain specialist outpatient clinic of the Gynecological Clinic of Udine according to the new criteria, evaluating the number of overdiagnoses and the possible correlation between the direct and indirect signs and the patients' symptoms. 62 patients affected by adenomyosis were retrospectively recruited. The patients were then re-evaluated by ultrasound and clinically. At least one direct sign of adenomyosis was found in 52 patients, while 16% of the population examined did not present any. There was no statistically significant difference between patients presenting direct signs and those presenting none for the symptoms considered. According to the new criteria, 16% of the patients examined were not affected by adenomyosis; applying the new consensus to symptomatic patients could increase false negatives. In a population of symptomatic patients, the diagnosis of adenomyosis is still highly probable even without direct ultrasound signs, given the clinical symptoms and having ruled out other causes of such symptoms.

Optimizing the Angiography Protocol to Reduce Radiation Dose in Uterine Artery Embolization: The Impact of Digital Subtraction Angiographies on Radiation Exposure.

PURPOSE: The aim was to compare a protocol of uterine artery embolization (UAE) consisting in three digital subtraction angiographies (DSAs)-Group A, with a protocol based on a single DSA-Group B. MATERIALS AND METHODS: This is a single-center prospective randomized study enrolling 20 women (mean age 41 years, range 22-55 years) with uterine fibroids treated with UAE, from January 2015 to February 2016. All UAEs were performed by two interventional radiologists using the same angiography machine. Protocol of Group A consisted in three DSA runs (non-selective pelvic view and selective uterine views before and after embolization). Protocol of Group B consisted in 1 DSA run: selective UA angiography before embolization. (Fluoroscopic roadmap was used for UA catheterization; fluoroscopy storage was used as control after embolization.) Each patient was randomized to receive Protocol A in one pelvic side and Protocol B on the other. RESULTS: All patients received bilateral UAE. Mean fluoroscopy time for UA catheterization was 11.3 ± 3.7 s. (Protocol A) and 9.93 ± 2.99 s. (Protocol B) (p = 0.19). Fluoroscopy dose for catheterization and embolization was not different between both protocols (p = 0.14). Identification of the UA origin score was similar in both protocols (median error = 0, p = 0.79). Mean dose area product (DAP) was 40859 mGy/cm2 (Protocol A) and 28839 mGy/cm2 (Protocol B) (p = 0.003). Mean effective dose (ED) decreased from Protocol A (14.6 mSv) to Protocol B (9.2 mSv; - 37%). Mean absorbed dose (AD) to ovaries and uterus, respectively, decreased of 53% and 55% from Protocol A to Protocol B. CONCLUSION: Reducing the number of DSA runs from 3 to 1 during UAE allows at least a 30% reduction on radiation exposure, without compromising technical outcomes.

Role of Homologous Recombination Repair (HRR) Genes in Uterine Leiomyosarcomas: A Retrospective Analysis.

Uterine leiomyosarcomas (uLMS) is a very rare disease, and patients experience a dismal prognosis even when treated with chemotherapy. Therefore, a more in-depth molecular characterization of this disease could provide suitable data for the identification of potential target-based drugs. This retrospective, single institutional study aimed to define the frequencies of gene alterations in uLMS, especially regarding the somatic mutations of BRCA and Homologous Recombination Repair (HRR) genes, and the impact of molecular alterations on clinical outcomes. The 16-genes Next-Generation Sequencing (NGS) panel, Homologous Recombination Solution TM (HRS, Sophia Genetics, Saint Sulpice, Switzerland), was used for the molecular evaluation of samples. The majority of patients (66/105, 63%) carried at least one sequence alteration, with a prevalence of TP53 involvement followed by RAD51B, BRCA1/2, and FANCL. Patients with TP53 gene alterations experienced a significantly worse prognosis for progression free survival (PFS) and overall survival (OS) versus wild-type patients. Given the number of patients with the BRCA1/2 mutation (N = 12), we included them in the HRR patient group; there was no difference in clinical outcomes with HRR versus non-HRR. The Cox's multivariate analysis showed that stage and TP53 gene alterations resulted in a significantly worse OS. The integration of gene networking data, such as tumor mutation burdens and cancer driver gene identification, could show a clearer discrimination of gene distribution patterns, and lead to the implementation of therapeutic targets.

PARP Inhibitors Resistance: Mechanisms and Perspectives.

PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke "synthetic lethality" in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.

Preoperative Tumor Texture Analysis on MRI for High-Risk Disease Prediction in Endometrial Cancer: A Hypothesis-Generating Study.

OBJECTIVE: To develop and validate magnetic resonance (MR) imaging-based radiomics models for high-risk endometrial cancer (EC) prediction preoperatively, to be able to estimate deep myometrial invasion (DMI) and lymphovascular space invasion (LVSI), and to discriminate between low-risk and other categories of risk as proposed by ESGO/ESTRO/ESP (European Society of Gynaecological Oncology-European Society for Radiotherapy & Oncology and European Society of Pathology) guidelines. METHODS: This retrospective study included 96 women with EC who underwent 1.5-T MR imaging before surgical staging between April 2009 and May 2019 in two referral centers divided into training (T = 73) and validation cohorts (V = 23). Radiomics features were extracted using the MODDICOM library with manual delineation of whole-tumor volume on MR images (axial T2-weighted). Diagnostic performances of radiomic models were evaluated by area under the receiver operating characteristic (ROC) curve in training (AUCT) and validation (AUCV) cohorts by using a subset of the most relevant texture features tested individually in univariate analysis using Wilcoxon-Mann-Whitney. RESULTS: A total of 228 radiomics features were extracted and ultimately limited to 38 for DMI, 29 for LVSI, and 15 for risk-classes prediction for logistic radiomic modeling. Whole-tumor radiomic models yielded an AUCT/AUCV of 0.85/0.68 in DMI estimation, 0.92/0.81 in LVSI prediction, and 0.84/0.76 for differentiating low-risk vs other risk classes (intermediate/high-intermediate/high). CONCLUSION: MRI-based radiomics has great potential in developing advanced prognostication in EC.

[Clinical applications of bevacizumab in the treatment of colorectal and ovarian cancer.] / Applicazioni cliniche di bevacizumab nel trattamento del tumore del colon-retto e dell'ovaio.

The development of biological drugs, which began in the 1980s, has revolutionized the treatment of numerous oncological diseases and severely disabling autoimmune diseases, with widely demonstrated evidence of benefit. Today, biological drugs represent an important and continuously developing category and are used both as a support therapy in onco-hematology and as molecules with their own therapeutic activity, such as monoclonal antibodies. Among these, bevacizumab represents a drug of relevant clinical value, used as antiangiogenic therapy in numerous cancers, in particular colorectal and ovarian cancers. The expiry of the patent period of monoclonal antibodies, including bevacizumab, has opened up to the development of biosimilar drugs, represented by structurally similar molecules with pharmacokinetic, pharmacodynamic and clinical characteristics equivalent to a biological drug already present in clinical use (originator biologic). The development process of these drugs is contained in the guidelines of the major regulatory bodies (FDA/EMA) and is faster than that provided for the originator biologic. Since biosimilars have a lower cost than reference drugs, their use represents a possibility of containing health care costs and of satifying the growing demand in terms of efficacy and personalization of pharmacological therapies. Considering the particular severity of the diseases treated, including colorectal and ovarian cancers, biosimilar drugs must be used with full awareness, in terms of efficacy and safety, since their approval is based on a rigorous analytical process, as well as preclinical and clinical evaluation.

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment.

Adjuvant therapy recommendations for endometrial cancer were historically based on the individual patient's risk of disease recurrence using clinicopathologic factors such as age, stage, histologic subtype, tumor grade, and lymphovascular space invasion. Despite the excellent prognosis for early stages, considerable under- and overtreatment remains. Integrated genomic characterization by the Cancer Genome Atlas (TCGA) in 2013 defined four distinct endometrial cancer subgroups (POLE mutated, microsatellite instability, low copy number, and high copy number) with possible prognostic value. The validation of surrogate markers (p53, Mismatch repair deficiency, and POLE) to determine these subgroups and the addition of other molecular prognosticators (CTNNB1, L1CAM) resulted in a practical and clinically useful molecular classification tool. The incorporation of such molecular alterations into established clinicopathologic risk factors resulted in a refined, improved risk assessment. Thus, the ESGO/ESTRO/ESP consensus in 2020 defined for the first time different prognostic risk groups integrating molecular markers. Finally, the feasibility and clinical utility of molecular profiling for tailoring adjuvant therapy in the high-intermediate-risk group is currently under investigation (NCT03469674).

Role of Immune Checkpoint Inhibitors in Cervical Cancer: From Preclinical to Clinical Data.

Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor. The aim of this review is to analyze the possible role of immune checkpoint inhibitors in cervical cancer treatment, with a particular focus on the rationale and on the results of phase I and II clinical trials. An overview of ongoing phase III studies with possible future areas of development is also provided.

Disseminated peritoneal leiomyomatosis and malignant transformation: A case series in a single referral center.

OBJECTIVE: The aim of this study was to describe one of the largest series of disseminated peritoneal leiomyomatosis (DPL) and its malignant counterpart, evaluating possible risk factors for both the benign and malignant condition, and highlighting any differences between them in terms of surgical and clinical management. STUDY DESIGN: Clinical, surgical and histopathological characteristics of patients diagnosed with DPL (group 1) and malignant-DPL (group 2), between July 2010 and July 2020, were retrospectively retrieved. RESULTS: A total of 14 benign and 5 malignant cases were selected. The duration of preoperative hormonal therapy was significantly longer in the benign condition while malignant DPL showed significantly larger lesions (median nodule size: 12 cm). However, surgical procedures and surgical outcomes did not differ among the two conditions, with highly complex surgery and relatively high post-operative complications in both groups. CONCLUSION: Preoperative discrimination between benign and malignant DPL is challenging. Given the high surgical complexity required in both cases, addressing patients to referral cancer centers is strictly recommend, in order to offer them the best possible treatment and allowing a continuous and accurate collection of clinical information that might be crucial for further studies.