Longitudinal Changes in Bone Mineral Measurements Inside and Outside Radiation Fields Used for Cervical Cancer Treatment.

PURPOSE: We compared the magnitude of changes in bone mineral density (BMD), within and outside the radiation field, among women who received pelvic radiation therapy (RT) with or without chemotherapy for cervical cancer. METHODS AND MATERIALS: In this secondary analysis of a prospective study, we analyzed serial computed tomography scans and dual-energy x-ray absorptiometry scans from 78 patients who received definitive RT or chemoradiation therapy (CRT) for cervical cancer at a single institution from 2008 to 2015. BMD values at L1, L2, L3, and L4 were measured. We compared changes in BMD within the radiation field (ie, at L4) with those outside the field (ie, at L1). Linear mixed models were also used to examine the effect of RT on changes in BMD over time and covariate adjustment. RESULTS: The median age of the 78 patients was 45.5 years (range, 23-88 years); all received RT and 76 (97%) received concurrent CRT. Treatment was associated with significant declines in BMD in all 4 lumbar vertebral bodies over time (P < .05), with nadir at 3 months for L4 and at 1 year for L1. Pairwise comparisons at 3 months and 2 years after treatment indicated that BMD in L4 (within the RT field) had improved (P = .037), but BMD in L1 (outside the RT field) was no different at 3 months and 2 years. CONCLUSIONS: Significant BMD declines were observed in all lumbar vertebral bodies immediately after RT. However, in-field vertebral bodies reached nadir BMD earlier than those located outside the RT field. Our results suggest that treatment and patient-related factors other than RT may contribute to declines in BMD after treatment for cervical cancer. Routine bone density screening and post-RT therapy with hormones may be beneficial for selected patients who receive CRT for cervical cancer.

Comprehensive review of imaging features of sex cord-stromal tumors of the ovary.

Sex cord-stromal tumors of the ovary (SCST) are uncommon ovarian tumors arising from sex cord and/or stromal cells of the ovaries. They may be nonfunctional and asymptomatic or functional presenting with hyperestrogenic, hyperandrogenic or cushingoid symptoms. They present in a wide age group of women, mostly in early stages and follow a nonaggressive clinical course after surgical resection. They differ from more prevalent epithelial ovarian tumors which tend to present in older women in advanced stages with poor prognosis. Some of SCSTs are associated with clinical syndromes. We will review imaging features on ultrasound, computed tomography and magnetic resonance imaging, epidemiology and clinical presentations of these tumors.

Ovarian teratomas: clinical features, imaging findings and management.

Ovarian teratomas are the most common type of germ cell tumors. There are three major subtypes of ovarian teratomas including mature, immature, and monodermal teratomas. Ultrasound, computed tomography and magnetic resonance imaging can demonstrate specific imaging findings for mature teratoma. Imaging features of immature and monodermal teratomas are less specific, but a combination of clinical features and imaging findings can help in the diagnosis. Imaging is also very helpful in guiding management. In this article, we review the epidemiology, histopathology, clinical presentation, imaging features and management of ovarian teratomas.

Diagnostic performance of PET/CT and PET/MR in the management of ovarian carcinoma-a literature review.

Ovarian cancer is a challenging disease. It often presents at an advanced stage with frequent recurrence despite optimal management. Accurate staging and restaging are critical for improving treatment outcomes and determining the prognosis. Imaging is an indispensable component of ovarian cancer management. Hybrid imaging modalities, including positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (MRI), are emerging as potential non-invasive imaging tools for improved management of ovarian cancer. This review article discusses the role of PET/CT and PET/MRI in ovarian cancer.

The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: Further evidence of relative chemoresistance.

OBJECTIVE: Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC). METHODS: Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed. RESULTS: All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p < 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p < 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months. CONCLUSIONS: This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.

Pelvic fractures and changes in bone mineral density after radiotherapy for cervical, endometrial, and vaginal cancer: A prospective study of 239 women.

BACKGROUND: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers; however, the long-term effects and survivorship implications need further evaluation. The purpose of this study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) after pelvic RT. METHODS: Two hundred thirty-nine women who had pelvic RT for cervical, endometrial, or vaginal cancer between 2008 and 2015 were prospectively studied. BMD scans and biomarkers of bone turnover were obtained at the baseline and 3 months, 1 year, and 2 years after RT. Imaging studies were assessed for pelvic fractures for up to 5 years. Patients with osteopenia, osteoporosis, or pelvic fractures at any point were referred to the endocrinology service for evaluation and treatment. RESULTS: The median age at diagnosis was 51 years; 132 patients (56%) were menopausal. The primary diagnoses were cervical (63.6%), endometrial (30.5%), and vaginal cancer (5.9%). Sixteen patients (7.8%; 95% confidence interval, 4.5%-12.4%) had pelvic fractures with actuarial rates of 3.6%, 12.7%, and 15.7% at 1, 2, and 3 years, respectively. Fractures were associated with baseline osteoporosis (P < .001), higher baseline bone-specific alkaline phosphatase (P < .001), and older age (P = .007). The proportion of patients with osteopenia/osteoporosis increased from 50% at the baseline to 58%, 59%, and 70% at 3 months, 1 year, and 2 years, respectively. CONCLUSIONS: A high proportion of women had significant decreases in BMD after pelvic RT, with 7.8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered for these high-risk women.

Ovarian Cancer Genetics and Implications for Imaging and Therapy.

Ovarian cancer is the second most common gynecologic malignancy in the United States. Ovarian cancer has a dismal prognosis when diagnosed at an advanced stage. Therapy for these cancers is determined not only by stage but also by their heterogeneous pathologic features, genetic mutations, and biology. In this review, we will discuss types of epithelial ovarian cancer, and their associated genetic mutations and the implications for imaging and treatment.

The Role of Positron Emission Tomography/Magnetic Resonance Imaging in Gynecological Malignancies.

Accurate oncological staging for early detection is of utmost importance in patient care and increasing the overall patient survival outcome. Hybrid imaging in the form of positron emission tomography (PET)/computed tomography has been successfully implemented in oncological imaging and, where available, has been used consistently in patients with gynecologic malignancies. The implementation of PET/magnetic resonance imaging (MRI) enables high-quality assessment of gynecological malignancies by combining the diagnostic advantages of metabolic information of PET along with the high-resolution anatomical and functional information from the MRI to provide precise information about staging, recurrence, and metastases. This article will review the various applications of PET/MRI in gynecological cancer.

Esophageal pneumatosis: Case report and review of literature.

Pneumatosis of the gastrointestinal tract is defined as presence of air in the wall of the gastrointestinal tract and can occur in any part of the gastrointestinal tract. It is most commonly seen in the intestine and very rarely in the esophagus. The exact pathogenesis is still unknown. It is managed primarily by conservative and non-surgical therapy, unless there are findings to suggest an acute abdomen or other co-morbidities. On review of literature, very few case reports of esophageal pneumatosis have been published. We present a rare case of pneumatosis of the esophagus with cytomegalovirus (CMV) infection.

Patterns of treatment failure in patients undergoing adjuvant or definitive radiotherapy for vulvar cancer.

OBJECTIVES: Knowledge of the detailed pattern of failure can be useful background knowledge in clinical decision making and potentially drive the development of new treatment strategies by increasing radiotherapy dose prescription to high-risk sub-regions of the target. Here, we analyze patterns of recurrence in patients with vulvar cancer treated with radiotherapy according to original planning target volumes and radiation dose delivered. METHODS: We analyzed dose-planning and post-treatment recurrence scans from patients with vulvar cancer treated at two institutions from January 2009 through October 2014. We delineated the recurrences and merged the dose-planning and recurrence scans for each patient by using deformable co-registration. We estimated the center of each recurrence on the merged scans with the goal of relating them to the original dose plan. RESULTS: We evaluated 157 patients who received radiotherapy for vulvar cancer. Median age was 68 years (range 29-91). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVB were included. Twenty-nine patients had recurrent disease; 156 patients had squamous cell carcinoma and one patient had adenosquamous carcinoma of the vulva. Among the 157 patients, 37 patients with recurrent disease had recurrence scans available for review, for a total of 80 recurrence sites; 53% of the recurrences were located in the region to which the highest dose (60-70 Gy) had been prescribed. Patients who received definitive radiotherapy developed failure primarily in the high-dose region (80.5%), whereas patients who received adjuvant radiotherapy had a more scattered failure pattern (p<0.0001). Among the latter group, 29.5% failed in the high-dose region. CONCLUSIONS: Patients who received definitive versus adjuvant radiotherapy had different failure patterns, indicating that separate approaches are needed to improve both adjuvant and definitive radiotherapy for vulvar cancer.

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

OBJECTIVE: To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy. METHODS: Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6-20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02). CONCLUSIONS: While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancer patients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.

[18F]-2-Fluoro-2-Deoxy-D-glucose-PET Assessment of Cervical Cancer.

This article provides an overview of PET in cervical cancer, primarily with regard to the use of 18F-2-fluoro-2-deoxy-d-glucose-PET/computed tomography. A brief discussion of upcoming technologies, such as PET/MR imaging, is presented.

A multicenter assessment of the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease at primary debulking for advanced epithelial ovarian cancer.

OBJECTIVE: To assess the ability of preoperative computed tomography scan and CA-125 to predict gross residual disease (RD) at primary cytoreduction in advanced ovarian cancer. METHODS: A prospective, non-randomized, multicenter trial of patients who underwent primary debulking for stage III-IV epithelial ovarian cancer previously identified 9 criteria associated with suboptimal (>1cm residual) cytoreduction. This is a secondary post-hoc analysis looking at the ability to predict any RD. Four clinical and 18 radiologic criteria were assessed, and a multivariate model predictive of RD was developed. RESULTS: From 7/2001-12/2012, 350 patients met eligibility criteria. The complete gross resection rate was 33%. On multivariate analysis, 3 clinical and 8 radiologic criteria were significantly associated with the presence of any RD: age≥60years (OR=1.5); CA-125≥600U/mL (OR=1.3); ASA 3-4 (OR=1.6); lesions in the root of the superior mesenteric artery (OR=4.1), splenic hilum/ligaments (OR=1.4), lesser sac >1cm (OR=2.2), gastrohepatic ligament/porta hepatis (OR=1.4), gallbladder fossa/intersegmental fissure (OR=2); suprarenal retroperitoneal lymph nodes (OR=1.3); small bowel adhesions/thickening (OR=1.1); and moderate-severe ascites (OR=2.2). All ORs were significant with p<0.01. A 'predictive score' was assigned to each criterion based on its multivariate OR, and the rate of having any RD for patients who had a total score of 0-2, 3-5, 6-8, and ≥9 was 45%, 68%, 87%, and 96%, respectively. CONCLUSIONS: We identified 11 criteria associated with RD, and developed a predictive model in which the rate of having any RD was directly proportional to a predictive score. This model may be helpful in treatment planning.

Potential Application of Dual-Energy CT in Gynecologic Cancer: Initial Experience.

OBJECTIVE: The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer. CONCLUSION: DECT has the potential to improve diagnostic performance, may improve the ability to differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.

Can reduced field-of-view diffusion sequence help assess microsatellite instability in FIGO stage 1 endometrial cancer?

PURPOSE: To determine if a reduced-field-of-view (rFOV) diffusion intravoxel incoherent motion (IVIM) sequence can differentiate the imaging characteristics of tumors with microsatellite instability (MSI) from those that are microsatellite stable (MSS) in patients with clinical FIGO stage IA endometrial cancer and if MRI can be used to determine MSI status. MATERIALS AND METHODS: Sagittal rFOV diffusion-weighted images were obtained in 12 patients on a 3T scanner using six b-values (0, 50, 100, 150, 200, and 600). These images were used to derive apparent diffusion coefficient (ADC), true diffusion coefficient (Dt ), pseudodiffusion (D*), and perfusion fraction (f). Regions of interest (ROIs) were drawn on the dynamic contrast-enhanced magnetic resonance imaging (MRI) sequence on an Advantage Windows workstation and were copied to the same location on IVIM-derived images. The ROI mean of these images was recorded and compared with the microsatellite status. The depth of myometrial invasion and IVIM-derived parameters were tabulated by microsatellite status. The Wilcoxon rank sum test was used to compare T1 postcontrast images and IVIM-derived images and microsatellite status. RESULTS: Six patients had MSS tumors and six had MSI tumors. MSS tumors had a significantly higher ADC value (P = 0.03) and Dt (P = 0.045) than the MSI tumors. There was no association between < and ≥ 50% depth of myometrial invasion (measured on pathology and MRI analysis) and MSI stability P > 0.99. CONCLUSION: IVIM, ADC and Dt may be able to determine microsatellite status noninvasively in patients with clinical FIGO stage I endometrial cancer. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1216-1224.

Ovarian Cancer, the Revised FIGO Staging System, and the Role of Imaging.

OBJECTIVE: It is now recognized that ovarian cancer includes a heterogeneous group of malignant epithelial tumors originating from the ovaries, fallopian tubes, or peritoneum. This development has prompted the International Federation of Gynecology and Obstetrics (FIGO) to issue a revised staging system that can provide prognostic information and guidance on personalized management of ovarian cancer. CONCLUSION: We review the epidemiology of ovarian cancer, the new FIGO staging system, and the role of imaging in the assessment, staging, and follow-up of ovarian cancer.

Increase in post-therapy tumor calcification on CT scan is not an indicator of response to therapy in low-grade serous ovarian cancer.

PURPOSE: The aim of the study was to determine if increasing post-therapy calcification in peritoneal metastases in recurrent low-grade serous ovarian carcinomas indicated response to therapy. MATERIALS AND METHODS: Retrospective analysis of patients with histologically confirmed, recurrent low-grade serous ovarian carcinoma who received treatment at our institution between 2000 and 2014 was performed. Only patients who had calcified tumor implants and showed either interval increase or decrease in tumor calcification following therapy were included in the study. Pre- and post-therapy CT scans of these patients were reviewed by 2 radiologists independently. Changes in the tumor calcification status and tumor deposits size were correlated with serum CA-125 levels. Fisher's exact test was used to assess the association between peritoneal deposit and calcification status with serum CA-125 status. RESULTS: 35 Patients were included in the study. Based on serial serum CA 125 levels, 22 patients (63%) had progressive disease, 12 (34%) had partial response and 1 (3%) had stable disease. Using RECIST 1.1, 16 had progressive disease, 3 had partial response and 16 had stable disease. In the patients with progressive disease, post-therapy tumor calcification increased in 77% and decreased in 23%. Fischer's exact test showed that serum CA 125 change was significantly associated with change in size of peritoneal deposits and calcification change. CONCLUSIONS: This preliminary study shows that post-therapy increase in peritoneal implant calcification in low-grade serous ovarian carcinomas is not an indicator of response to therapy.

Feasibility of a reduced field-of-view diffusion-weighted (rFOV) sequence in assessment of myometrial invasion in patients with clinical FIGO stage I endometrial cancer.

PURPOSE: To compare the clinical usefulness of reduced field-of-view diffusion-weighted imaging (rFOV) with other imaging techniques in determining the depth of myometrial invasion (DMI) in endometrial cancer. MATERIALS AND METHODS: In this prospective study we reviewed 3T magnetic resonance images of 51 patients with clinical Stage I endometrial cancer who underwent total abdominal hysterectomy with bilateral salphingoopherectomy within 3 days after imaging. rFOV with apparent diffusion coefficient reconstruction was obtained in three standard planes followed by sagittal T2 -weighted (T2 WI) images and 3D dynamic T1 -weighted and contrast-enhanced imaging (DCE MRI). Two radiologists with expertise in imaging gynecologic cancers evaluated images independently. The DMI was recorded on imaging and correlated with surgical pathology results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for DMI were calculated (<50% vs. >50%). RESULTS: Compared with sagittal T2 WI + DCE MRI, rFOV imaging yielded greater specificity (82.2% vs. 90.0%, positive predictive value (42.8% vs. 60.0%), and accuracy (84.0% vs. 92%) for DMI determined by reader 1 and greater the sensitivity (83.3% vs. 100%) for DMI determined by reader 2. The error of measurement of DMI as a continuous variable in millimeters did not differ significantly between the rFOV and pathology results (P < 0.21). However, there was a statistically significant difference for the DMI measured on the dynamic sequence. The DMI on DCE was greater than that seen on pathology at P = 0.02. CONCLUSION: rFOV can be used to assess DMI in clinical Stage I endometrial cancer.

Survival outcomes for patients with stage IVB vulvar cancer with grossly positive pelvic lymph nodes: time to reconsider the FIGO staging system?

OBJECTIVE: To evaluate treatment outcomes for patients with vulvar cancer with grossly positive pelvic lymph nodes (PLNs). METHODS: From a database of 516 patients with vulvar cancer, we identified patients with grossly positive PLNs without distant metastasis at initial diagnosis. We identified 20 patients with grossly positive PLNs; inclusion criteria included PLN 1.5cm or larger in short axis dimension on CT/MRI (n=11), FDG-avid PLN on PET/CT (n=3), or biopsy-proven PLN disease (n=6). Ten patients were treated with chemoradiation therapy (CRT), 4 with RT alone, and 6 with various combinations of surgery, RT or CRT. Median follow-up time for patients who had not died of cancer was 47months (range, 4-228months). RESULTS: Mean primary vulvar tumor size was 6.4cm; 12 patients presented with 2009 AJCC T2 and 8 with T3 disease. All patients had grossly positive inguinal nodes, and the mean inguinal nodal diameter was 2.8cm. The 5-year overall survival and disease specific survival rates were 43% and 48%, respectively. Eleven patients had recurrences, some at multiple sites. There were 9 recurrences in the vulva, but no isolated nodal recurrences. Four patients developed distant metastasis within 6months of starting radiation therapy. CONCLUSIONS: Aggressive locoregional treatment can lead to favorable outcomes for many patients with grossly involved PLNs that is comparable to that of grossly involved inguinal nodes only. We recommend modification of the FIGO stage IVB classification to more accurately reflect the relatively favorable prognosis of patients with PLN involvement.

CT colonography for the detection of nonpolypoid adenomas: sensitivity assessed with restricted national CT colonography trial criteria.

OBJECTIVE: The purpose of this study was to determine the prevalence of nonpolypoid adenomas and the sensitivity of CT colonography (CTC) in their detection by use of the restricted criteria of height-to-width ratio<50% and height elevation≤3 mm. MATERIALS AND METHODS: In the National CT Colonography Trial (American College of Radiology Imaging Network protocol 6664), a cohort of 2531 participants without symptoms underwent CTC and screening colonoscopy. The CTC examinations were interpreted with both 2D and 3D techniques. Nonpolypoid adenomatous polyps identified with CTC or colonoscopy were retrospectively reviewed to determine which polyps met the restricted criteria. The prevalence of nonpolypoid adenomas and the prospective sensitivity of CTC were determined. Descriptive statistics were used to report the prevalence, size, and histologic features. The sensitivities (with 95% CIs) for nonpolypoid and polypoid lesions were compared by two-sided Z test for independent binomial proportions. RESULTS: The retrospective review confirmed 21 nonpolypoid adenomas, yielding a prevalence of 0.83% (21 of 2531 participants). Eight (38.1%) were advanced adenomas, many (50% [4/8]) only because of large size (≥10 mm). The overall per polyp sensitivity of CTC (combined 2D and 3D interpretation) for detecting nonpolypoid adenomas≥5 mm (n=21) was 0.76; ≥6 mm (n=16), 0.75; and ≥10 mm (n=5), 0.80. These values were not statistically different from the sensitivity of detecting polypoid adenomas (p>0.37). CONCLUSION: In this large screening population, nonpolypoid adenomas had a very low prevalence (<1%), and advanced pathologic features were uncommon in polyps<10 mm in diameter. Most nonpolypoid adenomas are technically visible at CTC. The prospective sensitivity is similar to that for polypoid adenomas when the interpretation combines both 2D and 3D review.