Dynamic contrast-enhanced MRI to characterize angiogenesis in primary epithelial ovarian cancer: An exploratory study.

PURPOSE: Angiogenesis is essential for tumor growth. Currently, there are no established imaging biomarkers to show angiogenesis in tumor tissue. The aim of this prospective study was to evaluate whether semiquantitative and pharmacokinetic DCE-MRI perfusion parameters could be used to assess angiogenesis in epithelial ovarian cancer (EOC). METHOD: We enrolled 38 patients with primary EOC treated in 2011-2014. DCE-MRI was performed with a 3.0 T imaging system before the surgical treatment. Two different sizes of ROI were used to evaluate semiquantitative and pharmacokinetic DCE perfusion parameters: a large ROI (L-ROI) covering the whole primary lesion on one plane and a small ROI (S-ROI) covering a small solid, highly enhancing focus. Tissue samples from tumors were collected during the surgery. Immunohistochemistry was used to measure the expression of vascular endothelial growth factor (VEGF), its receptors (VEGFRs) and to analyse microvascular density (MVD) and the number of microvessels. RESULTS: VEGF expression correlated inversely with Ktrans (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.390, (p = 0.010)), Ve (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.412 (p = 0.006)) and Vp (L-ROI, r = -0.388 (p = 0.011), S-ROI, r = -0.339 (p = 0.028)) values in EOC. Higher VEGFR-2 correlated with lower DCE parameters Ktrans (L-ROI, r = -0.311 (p = 0.040), S-ROI, r = -0.337 (p = 0.025)) and Ve (L-ROI, r = -0.305 (p = 0.044), S-ROI, r = -0.355 (p = 0.018)). We also found that MVD and the number of microvessels correlated positively with AUC, Peak and WashIn values. CONCLUSIONS: We observed that several DCE-MRI parameters correlated with VEGF and VEGFR-2 expression and MVD. Thus, both semiquantitative and pharmacokinetic perfusion parameters of DCE-MRI represent promising tools for the assessment of angiogenesis in EOC.

Greater increases in intratumoral apparent diffusion coefficients after chemoradiotherapy predict better overall survival of patients with cervical cancer.

PURPOSE: To evaluate whether 1) the intratumoral apparent diffusion coefficients (ADCs) change during cervical cancer treatment and 2) the pretreatment ADC values or their change after treatment predict the treatment outcome or overall survival of patients with cervical cancer. METHODS: We retrospectively enrolled 52 patients with inoperable cervical cancer treated with chemoradiotherapy, who had undergone diffusion weighted MRI before treatment and post external beam radiotherapy (EBRT) and concurrent chemotherapy. A subgroup of patients (n = 28) underwent altogether six consecutive diffusion weighted MRIs; 1) pretreatment, 2) post-EBRT and concurrent chemotherapy; 3-5) during image-guided brachytherapy (IGBT) and 6) after completing the whole treatment course. To assess interobserver and intertechnique reproducibility two observers independently measured the ADCs by drawing freehand a large region of interest (L-ROI) covering the whole tumor and three small ROIs (S-ROIs) in areas with most restricted diffusion. RESULTS: Reproducibility was equally good for L-ROIs and S-ROIs. The pretreatment ADCs were higher in L-ROIs (883 mm2/s) than in S-ROIs (687 mm2/s, P < 0.001). The ADCs increased significantly between the pretreatment and post-EBRT scans (L-ROI: P < 0.001; S-ROI: P = 0.001). The ADCs remained significantly higher than pretreatment values during the whole IGBT. Using S-ROIs, greater increases in ADCs between pretreatment and post-EBRT MRI predicted better overall survival (P = 0.018). CONCLUSION: ADC values significantly increase during cervical cancer treatment. Greater increases in ADC values between pretreatment and post-EBRT predicted better overall survival using S-ROIs. Standardized methods for timing and delineation of ADC measurements are advocated in future studies.

Neoadjuvant chemotherapy induces an elevation of tumour apparent diffusion coefficient values in patients with ovarian cancer.

OBJECTIVES: Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). METHODS: We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient's disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. RESULTS: The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71-0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p < 0.001, S-ROIs p < 0.01), and the increase after NACT was associated with sensitivity to platinum-based chemotherapy. The changes in the ADC values of the omental mass were associated with a response to NACT. CONCLUSION: The mean ADC values of the primary tumour increased significantly after NACT in the OC patients, and the amount of increase in omental mass was associated with the response to platinum-based NACT. Our study indicates that quantitative analysis of ADC values with a single slice and a whole tumour ROI placement is a reproducible method that has a potential role in the evaluation of NACT response in patients with OC. TRIAL REGISTRATION: Retrospectively registered (institutional permission code: 5302501; date of the permission: 31.7.2020).

Robotic-assisted laparoscopy is a feasible method for resection of deep infiltrating endometriosis, especially in the rectosigmoid area.

OBJECTIVE: This study aimed to compare outcomes of mini-invasive surgical treatment of endometriosis, especially conventional laparoscopy with robotic-assisted laparoscopy, and to evaluate the quality of life. METHODS: One hundred three consecutive patients with endometriosis who had surgery from 2014 to 2017 owing to an indication of pain were enrolled in this retrospective study. The majority (n = 77, 75%) of patients underwent conventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. The quality of life was postoperatively assessed with a questionnaire. RESULTS: The rates of parametrectomy (76% vs. 45%,) and rectovaginal resection (28% vs. 4%) were significantly higher in robotic-assisted laparoscopy than in laparoscopy. Additionally, the rate of bowel operations (50% vs. 17%), especially the shaving technique, was higher in robotic-assisted laparoscopy surgery than in laparoscopy (39% vs. 8%). There was no difference in the rate of postoperative complications between laparoscopy and robotic-assisted laparoscopy. Most (91%) of the patients who answered the questionnaire felt that surgical treatment had relieved their pain. In the laparoscopic and robotic-assisted groups, 88% of respondents felt that their quality of life had improved after surgery. CONCLUSIONS: This study suggests that robotic-assisted laparoscopy is a feasible method to resect deep infiltrating endometriosis, especially in the rectosigmoid area.

Dynamic contrast-enhanced perfusion parameters in ovarian cancer: Good accuracy in identifying high HIF-1α expression.

BACKGROUND: Hypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1α) in ovarian cancer (OC). MATERIALS AND METHODS: Thirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (Ktrans) and a rate constant from EES to plasma (Kep), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal-Wallis, Mann-Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1α expression. RESULTS: Pharmacokinetic perfusion parameters Ktrans and Kep were inversely associated with HIF-1α expression (Ktrans L-ROI P = 0.021; Ktrans S-ROI P = 0.018 and Kep L-ROI P = 0.032; Kep S-ROI P = 0.033). Ktrans and Kep showed good accuracy in identifying high HIF-1α expression (AUC = 0.832 Ktrans L-ROI; 0.840 Ktrans S-ROI; 0.808 Kep L-ROI and 0.808 Kep L-ROI). CONCLUSION: This preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1α in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation.

Prognostic value of preoperative dynamic contrast-enhanced magnetic resonance imaging in epithelial ovarian cancer.

OBJECTIVES: To investigate whether semi-quantitative and pharmacokinetic perfusion dynamic contrast-enhanced (DCE) parameters are associated with traditional prognostic factors and can predict clinical outcome in ovarian cancer (OC). METHODS: This prospective study, approved by local ethical committee, enrolled 38 patients with primary OC, 2011-2014. After preoperative DCE-MRI (3.0 T), two observers measured perfusion (Ktrans, Kep, Ve, Vp) and semi-quantitative parameters (area under the curve, peak, time-to-peak) by drawing regions of interest (ROIs) covering the large solid lesion (L-ROI) and the most enhancing small area (S-ROI) (NordicICE platform). Kruskal-Wallis was used to analyze associations between MRI parameters and classified prognostic factors. RESULTS: Mean Ktrans values were higher in high-grade serous OC than in other types (L-ROI, P = 0.041; S-ROI, P = 0.018), and lower mean Ktrans values predicted residual tumor (L-ROI P = 0.030; S-ROI, P = 0.012). Higher minimum Vp values were associated with higher International Federation of Gynecology and Obstetrics (FIGO) stage (S-ROI, P = 0.023).Shorter recurrence-free survival was predicted by higher Ve (minimum L-ROI, P = 0.035; maximum S-ROI, P = 0.046), Vp (maximum S-ROI, P = 0.033), and lower time-to-peak (maximum S-ROI, P = 0.047) in Kaplan-Meier analysis. Multiparametric MRI variables combining DCE and diffusion weighted data were also predictive for survival. CONCLUSION: DCE-MRI parameters may represent imaging biomarkers for predicting tumor aggressiveness and prognosis in OC. Higher Ktrans levels were associated with better results in cytoreductive surgery but with earlier recurrence.

Primary and metastatic ovarian cancer: Characterization by 3.0T diffusion-weighted MRI.

OBJECTIVES: We aimed to investigate whether apparent diffusion coefficients (ADCs) measured by 3.0T diffusion-weighted magnetic resonance imaging (DWI) associate with histological aggressiveness of ovarian cancer (OC) or predict the clinical outcome. This prospective study enrolled 40 patients with primary OC, treated 2011-2014. METHODS: DWI was performed prior to surgery. Two observers used whole lesion single plane region of interest (WLsp-ROI) and five small ROIs (S-ROI) to analyze ADCs. Samples from tumours and metastases were collected during surgery. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure the expression of vascular endothelial growth factor (VEGF) and its receptors. RESULTS: The interobserver reliability of ADC measurements was excellent for primary tumours ICC 0.912 (WLsp-ROI). Low ADCs significantly associated with poorly differentiated OC (WLsp-ROI P = 0.035). In primary tumours, lower ADCs significantly associated with high Ki-67 (P = 0.001) and low VEGF (P = 0.001) expression. In metastases, lower ADCs (WLsp-ROI) significantly correlated with low VEGF receptors mRNA levels. ADCs had predictive value; 3-year overall survival was poorer in patients with lower ADCs (WLsp-ROI P = 0.023, S-ROI P = 0.038). CONCLUSION: Reduced ADCs are associated with histological severity and worse outcome in OC. ADCs measured with WLsp-ROI may serve as a prognostic biomarker of OC. KEY POINTS: • Reduced ADCs correlate with prognostic markers: poor differentiation and high Ki-67 expression • ADCs also significantly correlated with VEGF protein expression in primary tumours • Lower ADC values are associated with poorer survival in ovarian cancer • Whole lesion single plane-ROI ADCs may be used as a prognostic biomarker in OC.