Non-contrast MRI can accurately characterize adnexal masses: a retrospective study.

OBJECTIVE: To determine the accuracy of interpretation of a non-contrast MRI protocol in characterizing adnexal masses. METHODS AND MATERIALS: Two hundred ninety-one patients (350 adnexal masses) who underwent gynecological MRI at our institution between the 1st of January 2008 and the 31st of December 2018 were reviewed. A random subset (102 patients with 121 masses) was chosen to evaluate the reproducibility and repeatability of readers' assessments. Readers evaluated non-contrast MRI scans retrospectively, assigned a 5-point score for the risk of malignancy and gave a specific diagnosis. The reference standard for the diagnosis was histopathology or at least one-year imaging follow-up. Diagnostic accuracy of the non-contrast MRI score was calculated. Inter- and intra-reader agreement was analyzed with Cohen's kappa statistics. RESULTS: There were 53/350 (15.1%) malignant lesions in the whole cohort and 20/121 (16.5%) malignant lesions in the random subset. Good agreement between readers was found for the non-contrast MRI score (к = 0.73, 95% confidence interval [CI] 0.58-0.86) whilst the intra-reader agreement was excellent (к = 0.81, 95% CI 0.70-0.88). The non-contrast MRI score value of ≥ 4 was associated with malignancy with a sensitivity of 84.9%, a specificity of 95.9%, an accuracy of 94.2% and a positive likelihood ratio of 21 (area under the receiver operating curve 0.93, 95% CI 0.90-0.96). CONCLUSION: Adnexal mass characterization on MRI without the administration of contrast medium has a high accuracy and excellent inter- and intra-reader agreement. Our results suggest that non-contrast studies may offer a reasonable diagnostic alternative when the administration of intravenous contrast medium is not possible. KEY POINTS: • A non-contrast pelvic MRI protocol may allow the characterization of adnexal masses with high accuracy. • The non-contrast MRI score may be used in clinical practice for differentiating benign from malignant adnexal lesions when the lack of intravenous contrast medium precludes analysis with the O-RADS MRI score.

Ultrasound-guided targeted biopsies of CT-based radiomic tumour habitats: technical development and initial experience in metastatic ovarian cancer.

PURPOSE: To develop a precision tissue sampling technique that uses computed tomography (CT)-based radiomic tumour habitats for ultrasound (US)-guided targeted biopsies that can be integrated in the clinical workflow of patients with high-grade serous ovarian cancer (HGSOC). METHODS: Six patients with suspected HGSOC scheduled for US-guided biopsy before starting neoadjuvant chemotherapy were included in this prospective study from September 2019 to February 2020. The tumour segmentation was performed manually on the pre-biopsy contrast-enhanced CT scan. Spatial radiomic maps were used to identify tumour areas with similar or distinct radiomic patterns, and tumour habitats were identified using the Gaussian mixture modelling. CT images with superimposed habitat maps were co-registered with US images by means of a landmark-based rigid registration method for US-guided targeted biopsies. The dice similarity coefficient (DSC) was used to assess the tumour-specific CT/US fusion accuracy. RESULTS: We successfully co-registered CT-based radiomic tumour habitats with US images in all patients. The median time between CT scan and biopsy was 21 days (range 7-30 days). The median DSC for tumour-specific CT/US fusion accuracy was 0.53 (range 0.79 to 0.37). The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76-0.79) while it was lower for the smaller omental metastases (DSC: 0.37-0.53). CONCLUSION: We developed a precision tissue sampling technique that uses radiomic habitats to guide in vivo biopsies using CT/US fusion and that can be seamlessly integrated in the clinical routine for patients with HGSOC. KEY POINTS: • We developed a prevision tissue sampling technique that co-registers CT-based radiomics-based tumour habitats with US images. • The CT/US fusion accuracy was high for the larger pelvic tumours (DSC: 0.76-0.79) while it was lower for the smaller omental metastases (DSC: 0.37-0.53).

Recurrent ovarian immature teratoma in a 12-year-old girl: Implications for management.

Immature teratomas (IT) are rare and recurrences uncommon. A 12-year-old female with grade 3 (high-grade) ovarian IT underwent surgical resection but experienced early recurrences; the first was treated with surgery but the second was metastatic and managed with chemotherapy, resulting in growing-teratoma-syndrome and need for further surgery. She now remains well in uneventful clinical follow-up. We believe chemotherapy could be reserved for very carefully selected recurrent IT cases, which may alter the natural history of disease.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

BACKGROUND: Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). METHODS AND FINDINGS: We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, p = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. CONCLUSIONS: In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.

Endometrial Cancer: Combined MR Volumetry and Diffusion-weighted Imaging for Assessment of Myometrial and Lymphovascular Invasion and Tumor Grade.

PURPOSE: To investigate magnetic resonance (MR) volumetry of endometrial tumors and its association with deep myometrial invasion, tumor grade, and lymphovascular invasion and to assess the value of apparent diffusion coefficient (ADC) histographic analysis of the whole tumor volume for prediction of tumor grade and lymphovascular invasion. MATERIALS AND METHODS: The institutional review board approved this retrospective study; patient consent was not required. Between May 2010 and May 2012, 70 women (mean age, 64 years; range, 24-91 years) with endometrial cancer underwent preoperative MR imaging, including axial oblique and sagittal T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted imaging. Volumetry of the tumor and uterus was performed during the six sequences, with manual tracing of each section, and the tumor volume ratio (TVR) was calculated. ADC histograms were generated from pixel ADCs from the whole tumor volume. The threshold of TVR associated with myometrial invasion was assessed by using receiver operating characteristic curves. An independent sample Mann Whitney U test was used to compare differences in ADCs, skewness, and kurtosis between tumor grade and the presence of lymphovascular invasion. RESULTS: No significant difference in tumor volume and TVR was found among the six MR imaging sequences (P = .95 and .86, respectively). A TVR greater than or equal to 25% allowed prediction of deep myometrial invasion with sensitivity of 100% and specificity of 93% (area under the curve, 0.96; 95% confidence interval: 0.86, 0.99) at axial oblique diffusion-weighted imaging. A TVR of greater than or equal to 25% was associated with grade 3 tumors (P = .0007) and with lymphovascular invasion (P < .0001). There was no significant difference in the ADCs between grades 1 and 2 tumors (P > .05). The minimum, 10th, 25th, 50th, 75th, and 90th percentile ADCs were significantly lower in grade 3 tumors than in grades 1 and 2 tumors (P < .02). CONCLUSION: The combination of whole tumor volume and ADC can be used for prediction of tumor grade, lymphovascular invasion, and depth of myometrial invasion.

Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience.

PURPOSE: To evaluate rectal cancer volumetry in predicting initial neoadjuvant chemotherapy response. MATERIALS AND METHODS: Sixteen consecutive patients who underwent neoadjuvant chemotherapy (CX) before chemoradiotherapy (CRT) and surgery were enrolled in this retrospective study. Tumor volume was evaluated at the first magnetic resonance imaging (MRI), after CX and after CRT. Tumor volume regression (TVR) and downstaging were compared with histological results according to Tumor Regression Grade (TRG) to assess CX and CRT response, respectively. RESULTS: The mean tumor volume was 132 cm(3) ± 166 before and 56 cm(3) ± 71 after CX. TVR after CX was significantly different between patients with poor histologic response (TRG1/2) and those with good histologic response (TRG3/4) (P = 0.001). An optimal cutoff of TVR >68% (area under the curve [AUC]: 0.9, 95% confidence interval [CI]: 0.65-0.98, P = 0.0001) to predict good histology response after CX was assessed by receiver operating characteristic curve. According to previous data and this study, we defined 70% as the best cutoff values according to sensitivity (86%), specificity (100%) of TVR for predicting good histology response. In contradistinction, MRI downstaging was associated with TRG only after CRT (P = 0.04). CONCLUSION: Our pilot study showed that MRI volumetry can predict early histological response after CX and before CRT. MRI volumetry could help the clinician to distinguish early responders in order to aid appropriate individually tailored therapies.

Pearls and pitfalls in MRI of gynecologic malignancy with diffusion-weighted technique.

OBJECTIVE: Developments in MRI techniques have increased the role of MRI in assessment of the pelvis in women. The aims of this review are a short overview of pelvic MRI with an emphasis on diffusion-weighted MRI (DWI) and presentation of a practical approach that includes the pearls and pitfalls of DWI. CONCLUSION: DWI provides indispensable information in the evaluation of gynecologic malignancies. Prudent application of this technique requires knowledge of the optimal protocols and pitfalls in interpretation.

Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer.

High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.

FIGO staging system for endometrial cancer: added benefits of MR imaging.

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. This pathologic condition is staged with the International Federation of Gynecology and Obstetrics (FIGO) system. The FIGO staging system recently underwent significant revision, which has important implications for radiologists. Key changes incorporated into the 2009 FIGO staging system include simplification of stage I disease and removal of cervical mucosal invasion as a distinct stage. Magnetic resonance (MR) imaging is essential for the preoperative staging of endometrial cancer because it can accurately depict the depth of myometrial invasion, which is the most important morphologic prognostic factor and correlates with tumor grade, presence of lymph node metastases, and overall patient survival. Diffusion-weighted MR imaging and dynamic contrast medium-enhanced MR imaging are useful adjuncts to standard morphologic imaging and may improve overall staging accuracy.

The revised FIGO staging system for uterine malignancies: implications for MR imaging.

Cancers of the uterine corpus and cervix are the most common gynecologic malignancies worldwide. The International Federation of Gynecology and Obstetrics (FIGO) staging system was first established in 1958, when it was recognized that the recurrence rate and patient outcomes were directly related to the degree of tumor spread at the patient's initial presentation. Changes in understanding of tumor biology led to a recent update in the FIGO staging system that reflects the variation in treatment strategies between endometrial and cervical cancer. Patients with endometrial cancer are primarily treated with hysterectomy; thus, staging is done at surgery and histologic analysis. Magnetic resonance (MR) imaging may accurately depict the extent of endometrial cancer at diagnosis and, in conjunction with the tumor grade and histologic subtype, help stratify risk, which determines the therapeutic course. Cervical carcinoma is staged at clinical examination because many tumors are inoperable at the time of patient presentation. Preoperative MR imaging criteria are not formally included in the revised FIGO staging system because cervical carcinoma is most prevalent in developing countries, where imaging resources are limited. However, MR imaging is highly sensitive and specific for depicting important prognostic factors and, when available, is recommended as an adjunct to clinical examination. The MR imaging findings of uterine carcinoma should be discussed in a multidisciplinary setting in conjunction with clinical and histologic findings, an approach that provides accurate staging and risk stratification and allows for individualized treatment.

T2-hypointense adnexal lesions: an imaging algorithm.

T2-weighted sequences are an integral part of magnetic resonance (MR) imaging performed for the characterization of adnexal lesions. A relatively small number of these lesions demonstrate low signal intensity on T2-weighted MR images. In the majority of cases, a specific diagnosis can be made by interpreting the signal intensity of the lesion with respect to certain pathologic correlates, including blood products, smooth muscle, fibrous tissue, and calcification, as well as high lesion cellularity. For example, lesions that are at least as dark as skeletal muscle are almost always benign, whereas those whose T2 signal intensity is higher than that of skeletal muscle constitute a more heterogeneous group composed of benign, borderline, and malignant disease entities. The authors propose a diagnostic algorithm that takes these features into account, as well as the appearances of the lesion with additional pulse sequences, to aid in the correct interpretation of T2-hypointense adnexal lesions. Knowledge of the anatomy, the T1-weighted imaging features, and the enhancement characteristics of adnexal lesions allows accurate characterization of these lesions, resulting in appropriate patient management.

Ovarian carcinomatosis: how the radiologist can help plan the surgical approach.

Ovarian carcinoma is the most common cause of death due to gynecologic malignancy. Peritoneal involvement is present in approximately 70% of patients at the time of initial diagnosis. The disease spreads abdominally by direct extension, exfoliation of tumor cells into the peritoneal space, and dissemination of tumor cells along lymphatic pathways. Carcinomatosis characterizes an advanced stage of disease in which peritoneal disease has spread throughout the upper abdomen (stage IIIC) or in which diffuse peritoneal disease is accompanied by malignant pleural infiltration or visceral metastases (stage IV). Common sites of intraperitoneal seeding of ovarian carcinoma include the pelvis, omentum, paracolic gutters, liver capsule, and diaphragm. Soft-tissue thickening, nodularity, and enhancement are all signs of peritoneal involvement. Advanced-stage disease is treated either with initial cytoreductive surgery (debulking) followed by adjuvant chemotherapy, or with initial neoadjuvant chemotherapy followed by debulking. Radiologic imaging plays an important role in the selection of patients who may benefit from neoadjuvant chemotherapy before debulking. However, accurate interpretation of the imaging findings is challenging and requires a detailed knowledge of the complex peritoneal anatomy, directionality of flow of peritoneal fluid, and specific disease sites that are likely to present particular difficulties with regard to surgical access and technique. Although there is as yet no clear consensus on the criteria for resectability of peritoneal lesions, extensive involvement of the small bowel or mesenteric root, involved lymph nodes superior to the celiac axis, pleural infiltration, pelvic sidewall invasion, bladder trigone involvement, and hepatic parenchymal metastases or implants near the right hepatic vein are considered indicative of potential nonresectability. Implants larger than 2 cm in diameter in the diaphragm, lesser sac, porta hepatis, intersegmental fissure, gallbladder fossa, or gastrosplenic or gastrohepatic ligament also may represent nonresectable disease.

Placental MRI: Identification of radiological features to predict placental attachment disease regardless of reader expertise.

PURPOSE: To compare the accuracy of placental MRI in reporting placental adhesive disease in readers with different expertise and to identify the most reliable MRI features that predict placental pathology regardless of reader expertise. METHODS: Retrospective analysis of 27 placental MRI studies by six radiologists with different expertise levels; specificity, sensitivity, and accuracy were used to quantify the predictive performance of eight radiological features previously described in the literature. Histopathological evaluation was used as a diagnostic gold standard when available and the presence of the radiological features was decided by consensus. Features with higher sensitivity and specificity were identified and the optimal cut-off was calculated to obtain the resulting accuracy. RESULTS: The accuracy for seniors with expertise was non-statistically higher (0.83) compared to senior with no expertise (SWE) (0.65) and juniors (0.74) with SWE having tendency to over-estimate the severity of abnormality (26% vs 17%), whilst junior underestimated the degree of placental infiltration when compared to seniors with expertise (18.5% vs 0%, p = 0.006). Dark bands was the criteria with the highest sensitivity (95%) and high specificity (74%), followed by myometrial thinning (89%-76%) and uterine bulging (86%-81%). These three features demonstrated substantial (K) agreement. Using these features with optimal diagnostic cut-off, the accuracy increased to 0.91 for both the seniors and SWE and to 0.93 for the juniors. CONCLUSION: Placental MRI is most accurately interpreted by experienced radiologists; however, less experienced readers can obtain an accurate diagnosis relying on set criteria that are easier to be identified.

Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy.

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT). Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment. Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06). Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding. Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Clinically Interpretable Radiomics-Based Prediction of Histopathologic Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma.

Background: Pathological response to neoadjuvant treatment for patients with high-grade serous ovarian carcinoma (HGSOC) is assessed using the chemotherapy response score (CRS) for omental tumor deposits. The main limitation of CRS is that it requires surgical sampling after initial neoadjuvant chemotherapy (NACT) treatment. Earlier and non-invasive response predictors could improve patient stratification. We developed computed tomography (CT) radiomic measures to predict neoadjuvant response before NACT using CRS as a gold standard. Methods: Omental CT-based radiomics models, yielding a simplified fully interpretable radiomic signature, were developed using Elastic Net logistic regression and compared to predictions based on omental tumor volume alone. Models were developed on a single institution cohort of neoadjuvant-treated HGSOC (n = 61; 41% complete response to NCT) and tested on an external test cohort (n = 48; 21% complete response). Results: The performance of the comprehensive radiomics models and the fully interpretable radiomics model was significantly higher than volume-based predictions of response in both the discovery and external test sets when assessed using G-mean (geometric mean of sensitivity and specificity) and NPV, indicating high generalizability and reliability in identifying non-responders when using radiomics. The performance of a fully interpretable model was similar to that of comprehensive radiomics models. Conclusions: CT-based radiomics allows for predicting response to NACT in a timely manner and without the need for abdominal surgery. Adding pre-NACT radiomics to volumetry improved model performance for predictions of response to NACT in HGSOC and was robust to external testing. A radiomic signature based on five robust predictive features provides improved clinical interpretability and may thus facilitate clinical acceptance and application.

Differentiating uterine sarcoma from leiomyoma: BET1T2ER Check!

Although rare, uterine sarcoma is a diagnosis that no one wants to miss. Often benign leiomyomas (fibroids) and uterine sarcomas can be differentiated due to the typical low T2 signal intensity contents and well-defined appearances of benign leiomyomas compared to the suspicious appearances of sarcomas presenting as large uterine masses with irregular outlines and intermediate T2 signal intensity together with possible features of secondary spread. The problem is when these benign lesions are atypical causing suspicious imaging features. This article provides a review of the current literature on imaging features of atypical fibroids and uterine sarcomas with an aide-memoire BET1T2ER Check! to help identify key features more suggestive of a uterine sarcoma.

Serous borderline ovarian tumours: an extensive review on MR imaging features.

Serous borderline ovarian tumours (SBOTs) are an intermediate group of neoplasms, which have features between benign and malignant ovarian tumours and for which, fertility-sparing surgery can be offered. MRI in imaging of SBOTs is, therefore, crucial in raising the possibility of the diagnosis, in order to present the patient with the most appropriate treatment options. There are characteristic MRI features that SBOTs demonstrate. In addition, recent advanced techniques, and further classification into subtypes within the borderline group have been developed. The aim of this article is to review the MRI features of SBOT and provide the reporter with an awareness of the imaging tips and tricks in the differential diagnosis of SBOT.

MRI of the endometrium - from normal appearances to rare pathology.

MRI was recently included as a standard pre-operative diagnostic tool for patients with endometrial cancer. MR findings allow a better risk assessment and ultimately guides the surgical planning. Therefore, it is vital that the radiological interpretation is as accurate as possible. This requires essential knowledge regarding the appropriate MRI protocol, as well as different appearances of the endometrium, ranging from normal peri- and post-menopausal changes, benign findings (e.g. endometrial hyperplasia, polyp, changes due to exogenous hormones) to common and rare endometrium-related malignancies. Furthermore, this review will emphasize the role of MRI in staging endometrial cancer patients and highlight pitfalls that could result in the underestimation or overestimation of the disease extent.