Maura Miccò

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

OBJECTIVE To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer. METHODS AND MATERIALS Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADCmean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS. RESULTS Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADCmean, SUVmax, MTV and TLG according to FIGO stage (p<0.001-0.025). There were significant correlations between ADCmean, MTV, TLG and LN metastasis (p=0.017-0.032). SUVmax was not associated with LN metastasis. FIGO stage (p=0.017/0.033), LN metastases (p=0.001/0.020), ADCmean (p=0.007/0.020) and MTV (p=0.014/0.026) were adverse predictors of both DFS/OS. maxTD (p=0.005) and TLG (p=0.024) were adverse predictors of DFS. PE and SUVmax did not correlate with DFS or OS (p=0.18-0.72). CONCLUSIONS Quantitative parameters derived from pre-treatment DW-MRI (ADCmean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.

Association between Morphologic CT Imaging Traits and Prognostically Relevant Gene Signatures in Women with High-Grade Serous Ovarian Cancer: A Hypothesis-generating Study

PURPOSE To investigate associations among imaging traits observed on computed tomographic (CT) images, Classification of Ovarian Cancer (CLOVAR) gene signatures, and survival in women with high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS The institutional review board approved this HIPAA-compliant retrospective study of CT images obtained before cytoreductive surgery in 46 women with HGSOC, whose tumors were subjected to molecular analysis performed by the Cancer Genome Atlas Research Network. Two readers independently evaluated the CT features of the primary ovarian mass and sites of metastatic spread if present, including size, outline, and texture. Fisher exact test was used to examine the relationship between imaging traits and CLOVAR subtypes (CLOVAR differentiated, immunoreactive, mesenchymal, and proliferative). Kaplan-Meier and Cox proportional hazards regression survival analyses were performed. RESULTS The presence of mesenteric infiltration and diffuse peritoneal involvement by tumor at CT were significantly associated with CLOVAR subtype (P = .002-.004 for reader 1 and P = .005-.012 for reader 2). Mesenteric infiltration at CT was associated with CLOVAR mesenchymal subtype. Patients with mesenteric infiltration had shorter median progression-free survival than patients without mesenteric involvement (14.7 months vs 25.6 months according to both readers; P = .019 for reader 1 and .015 for reader 2) and overall survival (49.0 vs 58.2 months; P = .014 [reader 1] and 50.0 vs 59.1 months; P = .015 [reader 2]). No other imaging features were significantly associated with CLOVAR subtype or survival. CONCLUSION Specific CT imaging traits were associated with the CLOVAR subtypes and survival in patients with HGSOC.

Complementary Prognostic Value of Pelvic Magnetic Resonance Imaging and Whole-Body Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Pretreatment Assessment of Patients With Cervical Cancer

Objective The aim of this study was to evaluate the incremental prognostic value of pelvic magnetic resonance imaging (MRI) and whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings compared with clinical-histopathologic factors in patients with newly diagnosed cervical cancer. Methods The institutional review board approved this retrospective study of 114 patients (median age, 40.6 years) with International Federation of Gynecology and Obstetrics (FIGO) stage I-IVB cervical cancer who underwent pretreatment MRI and PET/CT. All scans were reviewed for locoregional tumor extent, pelvic or/and para-aortic lymphadenopathy, and distant metastases. Univariate Cox proportional hazard regression was performed to evaluate associations between clinical-histopathologic factors, imaging findings, and progression-free survival (PFS). Multivariate models were built using independent predictors for PFS. Harrell C was used to measure concordance (C index). Results Forty patients progressed within a median time of 10.4 months (range, 0.4–40.3 months). At univariate analysis, age, FIGO stage, tumor histology, tumor grade, and all MRI and PET/CT features were significantly associated with PFS (P < 0.0001 to P = 0.0474). A multivariate model including clinical and imaging parameters (parametrial invasion on MRI and para-aortic lymphadenopathy/distant metastases on PET/CT) had significantly higher concordance for predicting PFS than a model including clinical parameters only (C index: 0.81 [95% confidence interval, 0.75–0.87] vs 0.68 [95% confidence interval, 0.59–0.78]; P < 0.001). The comparison of C indices for the combined clinical and imaging model approached significance when compared with a FIGO stage model (C index: 0.81 [95% confidence interval, 0.75–0.87] vs 0.75 [95% confidence interval, 0.69–0.82]; P = 0.058). Conclusions In patients with newly diagnosed cervical cancer, a prognostic model including combined MRI and PET/CT findings provides information that complements clinical and histopathologic factors.

A novel representation of inter-site tumour heterogeneity from pre-treatment computed tomography textures classifies ovarian cancers by clinical outcome

AbstractPurposeTo evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC).MethodsIRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model. Pairwise inter-site similarities were computed, generating an inter-site similarity matrix (ISM). Inter-site texture heterogeneity metrics were computed from the ISM and compared to clinical outcomes.ResultsOf the 12 inter-site texture heterogeneity metrics evaluated, those capturing the differences in texture similarities across sites were associated with shorter overall survival (inter-site similarity entropy, similarity level cluster shade, and inter-site similarity level cluster prominence; p ≤ 0.05) and incomplete surgical resection (similarity level cluster shade, inter-site similarity level cluster prominence and inter-site cluster variance; p ≤ 0.05). Neither the total number of disease sites per patient nor the overall tumour volume per patient was associated with overall survival. Amplification of 19q12 involving cyclin E1 gene (CCNE1) predominantly occurred in patients with more heterogeneous inter-site textures.ConclusionQuantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC.Key Points• Calculating inter-site texture-based heterogeneity metrics was feasible • Metrics capturing texture similarities across HGSOC sites were associated with overall survival • Heterogeneity metrics were also associated with incomplete surgical resection of HGSOC.

Role of MR Imaging and FDG PET/CT in Selection and Follow-up of Patients Treated with Pelvic Exenteration for Gynecologic Malignancies

Pelvic exenteration (PE) is a radical surgical procedure used for the past 6 decades to treat locally advanced malignant diseases confined to the pelvis, particularly persistent or recurrent gynecologic cancers in the irradiated pelvis. The traditional surgical technique known as total PE consists of resection of all pelvic viscera followed by reconstruction. Depending on the tumor extent, the procedure can be tailored to remove only anterior or posterior structures, including the bladder (anterior exenteration) or rectum (posterior exenteration). Conversely, more extended pelvic resection can be performed if the pelvic sidewall is invaded by cancer. Preoperative imaging evaluation with magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is central to establishing tumor resectability and therefore patient eligibility for the procedure. These imaging modalities complement each other in diagnosis of tumor recurrence and differentiation of persistent disease from posttreatment changes. MR imaging can accurately demonstrate local tumor extent and show adjacent organ invasion. FDG PET/CT is useful in excluding nodal and distant metastases. In addition, FDG PET/CT metrics may serve as predictive biomarkers for overall and disease-free survival. This pictorial review describes different types of exenterative surgical procedures and illustrates the central role of imaging in accurate patient selection, treatment planning, and postsurgical surveillance.

Imaging Features of Uncommon Gynecologic Cancers

OBJECTIVE The role of imaging in patients with suspected gynecologic malignancies is to provide an accurate diagnosis to achieve the best and most tailored treatment plan. Uncommon cancers pose a distinct challenge, because current knowledge of these diseases is still limited. Our purpose is to highlight the role of cross-sectional imaging techniques, including ultrasound, CT, MRI, and PET/CT, in the diagnosis and pretreatment stratification of patients with rare gynecologic cancers. CONCLUSION This review shows the relevance of imaging findings for diagnosis, staging, and treatment planning in patients with uncommon uterine, cervical, vaginal, vulvar, and ovarian cancers.

Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery. The PRICE (PRospective Imaging of CErvical cancer and neoadjuvant treatment) study 2: the role of ultrasound after chemoradiation to assess residual tumor

To determine the diagnostic performance of two‐dimensional (2D) ultrasound parameters, three‐dimensional (3D) power Doppler and contrast‐enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery.

High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features. Associations between CT features, BRCA mutation status, cytoreductive outcome, and progression-free survival (PFS) were evaluated by using logistic regression and Cox proportional hazards regression, respectively. Results Peritoneal disease (PD) pattern, presence of PD in gastrohepatic ligament, mesenteric involvement, and supradiaphragmatic lymphadenopathy at CT were associated with BRCA mutation status (multiple regression: P < .001 for each CT feature). While clinical and CT features were not associated with cytoreductive outcome for patients with BRCA-mutant HGSOC, presence of PD in lesser sac (odds ratio [OR] = 2.40) and left upper quadrant (OR = 1.19), mesenteric involvement (OR = 7.10), and lymphadenopathy in supradiaphragmatic (OR = 2.83) and suprarenal para-aortic (OR = 4.79) regions were associated with higher odds of incomplete cytoreduction in BRCA wild-type HGSOC (multiple regression: P < .001 each CT feature). Mesenteric involvement at CT was associated with significantly shorter PFS for both patients with BRCA-mutant HGSOC (multiple regression: hazard ratio [HR] = 26.7 P < .001) and those with BRCA wild-type HGSOC (univariate analysis: reader 1, HR = 2.42, P < .001; reader 2, HR = 2.61; P < .001). Conclusion Qualitative CT features differed between patients with BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC. CT indicators of cytoreductive outcome varied according to BRCA mutation status. Mesenteric involvement at CT was an indicator of significantly shorter PFS for both patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC.

OC24.03: *A possible role of 3D-ultrasound in the assessment of parametrial infiltration in cervical cancer

E. Epstein1, A. Testa2, A. Gaurilcikas3, A. Di Legge2, L. Ameye4, V. Atstupenaite5, A. Valentini6, B. Gui6, N. Wallengren7, S. Pudaric7, A. Cizauskas8, A. Masback9, G. Zannoni10, P. Kannisto11, M. Zikan12, I. Pinkavova12, A. Burgetova13, P. Dundr14, K. Nemejcova14, D. Cibula12, D. Fischerova12 1Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden; 2Oncology, Catholic University of Sacred Heart, Rome, Italy; 3Obstetrics and Gynecology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 4Department of Electrical Engineering, ESAT-SCD, Katholieke Universiteit, Leuven, Belgium; 5Radiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 6Radiology, Catholic University of Sacred Heart, Rome, Italy; 7Radiology, Skane University Hospital, Lund, Sweden; 8Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 9Pathology, Skane University Hospital, Lund, Sweden; 10Pathology, Catholic University of Sacred Heart, Rome, Italy; 11Obstetrics and Gynecology, Skane University Hospital, Lund, Sweden; 12Gynecological Oncology Centre, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic; 13Radiology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic; 14Pathology, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic