Helen Addley

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 patients 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.

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.

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.

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.

Pelvic Imaging Following Chemotherapy and Radiation Therapy for Gynecologic Malignancies

Gynecologic malignancies account for 10%-15% of all malignancies in females. A variety of oncologic options are available depending on organ of origin, histologic diagnosis, and disease grade and stage. Gynecologic malignancies are usually treated with surgery, chemotherapy, or radiation therapy. Posttreatment imaging plays a crucial role in the assessment of treatment response and tumor recurrence. Imaging of the female pelvis following chemotherapy and radiation therapy is particularly challenging due to alteration of the normal anatomy and loss of tissue planes. Expected changes in appearance occur following chemotherapy-radiation therapy, as do complications such as fistulas, proctitis, enteritis, typhlitis, cystitis, and insufficiency fractures. Radiologists should be familiar with both the expected posttreatment imaging findings and the imaging features of common complications to help make the correct interpretation and avoid possible pitfalls.

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.

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.

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.

Radiological Staging of Ovarian Carcinoma

Ovarian cancer is the sixth most commonly diagnosed cancer in the world, accounting for 4% of all female cancers. An estimated 1 in 71 women in the United States will develop ovarian cancer in their lifetime. Accurate staging of ovarian carcinoma is vital in the appropriate management and counseling of patients. The surgical staging proposed by the International Federation of Obstetrics and Gynaecology is the most universally used, and International Federation of Obstetrics and Gynaecology encourages the use of imaging techniques to assess prognostic factors, such as resectable disease and lymph node status. Identifying the volume and locations of tumor is valuable in planning percutaneous tissue biopsy, triaging patients to either primary cytoreductive surgery, or primary platinum-based chemotherapy. Contrast-enhanced computed tomography is the modality of choice for the staging of ovarian carcinoma, with magnetic resonance imaging being used as a problem-solving tool. In this article we discuss and illustrate the staging of ovarian carcinoma, with emphasis on the current imaging modalities and optimal image acquisition.

Diffusion-weighted imaging in gynaecological malignancy

Diffusion weighted imaging (DWI) has become an essential part of the gynaecological magnetic resonance imaging (MRI) protocol. DWI is used as an adjunct to conventional MRI sequences and has been shown to improve reporting accuracy in the imaging of gynaecological malignancy. In this review, we discuss the role of DWI in the diagnosis, staging, and assessment of treatment response of endometrial, cervical, and ovarian cancer. We also review the role of DWI in the assessment of the sonographically indeterminate ovarian lesion. Further, we highlight potential pitfalls that can beset the accurate interpretation of DWI in patients with gynaecological malignancy.