Search

Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti‐vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine‐protein kinase erbB‐2‐negative breast cancers, we measured metabolites and inflammation‐related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation‐regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth‐differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy. What's new? How inflammatory markers and metabolites mold the tumor microenvironment, especially angiogenesis, is still poorly understood. Here the authors tested the response of patients with breast cancer to neoadjuvant chemotherapy with or without the angiogenesis inhibitor bevacizumab. They identified 10 non‐invasive biomarkers that predict therapy response, including the acute phase protein pentraxin‐3 and hemostasis regulator von Willebrand factor that were specifically upregulated by bevacizumab treatment. The authors suggest that these factors could be further targeted to potentiate antiangiogenic therapies in breast cancer and beyond. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations of metabolite levels derived from magnetic resonance spectroscopic imaging (MRSI) and 18F-fluciclovine positron emission tomography (PET) with prostate tissue characteristics. Methods: In a cohort of 19 high-risk prostate cancer patients that underwent simultaneous PET/MRI, we evaluated the diagnostic performance of MRSI and PET for discrimination of aggressive cancer lesions from healthy tissue and benign lesions. Data analysis comprised calculations of correlations of mean standardized uptake values (SUVmean), maximum SUV (SUVmax), and the MRSI-derived ratio of (total choline + spermine + creatine) to citrate (CSC/C). Whole-mount histopathology was used as gold standard. Results: The results showed a moderate significant correlation between both SUVmean and SUVmax with CSC/C ratio. Conclusions: We demonstrated that the simultaneous acquisition of 18F-fluciclovine PET and MRSI with an integrated PET/MRI system is feasible and a combination of these imaging modalities has potential to improve the diagnostic sensitivity and specificity of prostate cancer lesions. [ABSTRACT FROM AUTHOR]

Background: Breast cancer treatment has metabolic side effects, potentially affecting risk of cardiovascular disease (CVD) and recurrence. We aimed to compare alterations in serum metabolites and lipoproteins during treatment between recipients and non-recipients of chemotherapy, and describe metabolite profiles associated with treatment-related weight gain.Methods: This pilot study includes 60 stage I/II breast cancer patients who underwent surgery and were treated according to national guidelines. Serum sampled pre-surgery and after 6 and 12 months was analysed by MR spectroscopy and mass spectrometry. In all, 170 metabolites and 105 lipoprotein subfractions were quantified.Results: The metabolite and lipoprotein profiles of chemotherapy recipients and non-recipients changed significantly 6 months after surgery (p < 0.001). Kynurenine, the lipid signal at 1.55-1.60 ppm, ADMA, 2 phosphatidylcholines (PC aa C38:3, PC ae C42:1), alpha-aminoadipic acid, hexoses and sphingolipids were increased in chemotherapy recipients after 6 months. VLDL and small dense LDL increased after 6 months, while HDL decreased, with triglyceride enrichment in HDL and LDL. At baseline, weight gainers had less acylcarnitines, phosphatidylcholines, lyso-phosphatidylcholines and sphingolipids, and showed an inflammatory lipid profile.Conclusion: Chemotherapy recipients exhibit metabolic changes associated with inflammation, altered immune response and increased risk of CVD. Altered lipid metabolism may predispose for treatment-related weight gain. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic potential of simultaneous 18F-fluciclovine PET/MRI for pelvic lymph node (LN) staging in patients with high-risk prostate cancer.Methods: High-risk prostate cancer patients (n=28) underwent simultaneous 18F-fluciclovine PET/MRI prior to surgery. LNs were removed according to a predefined template of eight regions. PET and MR images were evaluated for presence of LN metastases according to these regions. Sensitivity/specificity for detection of LN metastases were calculated on patient and region basis. Sizes of LN metastases in regions with positive and negative imaging findings were compared with linear mixed models. Clinical parameters of PET-positive and -negative stage N1 patients were compared with the Mann-Whitney U test.Results: Patient- and region-based sensitivity/specificity for detection of pelvic LN metastases was 40 %/87.5 % and 35 %/95.7 %, respectively, for MRI and 40 %/100 % and 30 %/100 %, respectively, for PET. LN metastases in true-positive regions were significantly larger than metastases in false-negative regions. PET-positive stage N1 patients had higher metastatic burden than PET-negative N1 patients.Conclusion: Simultaneous 18F-fluciclovine PET/MRI provides high specificity but low sensitivity for detection of LN metastases in high-risk prostate cancer patients. 18F-Fluciclovine PET/MRI scan positive for LN metastases indicates higher metastatic burden than negative scan.Key Points: • 18F-Fluciclovine PET/MRI has high specificity for detection of lymph node metastasis. • 18F-Fluciclovine PET/MRI lacks sensitivity to replace ePLND. • 18F-Fluciclovine PET/MRI may be used to aid surgery and select adjuvant therapy. • 18F-Fluciclovine PET-positive patients have more extensive disease than PET-negative patients. • Size of metastatic lymph nodes is an important factor for detection. [ABSTRACT FROM AUTHOR]

Background: Steady state susceptibility contrast (SSC)-MRI provides information on vascular morphology but is a rarely used method.Purpose: To investigate the utility of the ultrasmall superparamagnetic iron oxide particles (USPIOs) GEH121333 for measuring tumor response to bevacizumab and compare this with gadolinium-based DCE-MRI.Study Type: Prospective preclinical animal model study.Animal Model: Mice bearing subcutaneous TOV-21G human ovarian cancer xenografts treated with bevacizumab (n = 9) or saline (n = 9).Field Strength/sequence: Imaging was performed on a 7T Bruker Biospec. For SSC-MRI with GEH121333 we acquired R1 -maps (RARE-sequence with variable TR), R2 -maps (multi-spin echo), and R2*-maps (multi-gradient echo). Additionally, R1 and R2 maps were measured on the days after USPIO injection. For DCE-MRI with gadodiamide we acquired 200 T1 -weighted images (RARE-sequence).Assessment: ΔR1 , ΔR2 , and ΔR2* maps were computed from SSC-MRI. DCE-MRI was analysed using the extended Tofts model.Statistical Tests: Results from pre- and 3 days posttreatment SSC-MRI were compared using paired-sample t-tests. Treatment and control groups were compared using independent sample t-tests. Performance of SSC- and DCE-MRI was compared using multivariate partial least squares discriminant analysis.Results: Already one day after treatment and USPIO injection, R1 and R2 values were lower in treated (R1  = 0.49 ± 0.03s-1 , R2  = 23.07 ± 1.49s-1 ) compared with control tumors (R1  = 0.52 ± 0.02s-1 , R2  = 24.98 ± 1.01s-1 ), indicating lower USPIO accumulation. Posttreatment SSC-MRI displayed significantly decreased tumor blood volume (change in ΔR2  = -0.43 ± 0.26s-1 , P = 0.001) and vessel density (change in Q = -0.032 ± 0.020s-1/3 , P = 0.002). DCE-MRI showed among others lower Ktrans in treated tumors (control = 0.064 ± 0.011min-1 , tx = 0.046 ± 0.008min-1 , P = 0.002). Multivariate analysis suggests that SSC-MRI was slightly inferior to DCE-MRI in distinguishing treated from control tumors (accuracy = 75%, P = 0.058 versus 80%, P = 0.028), but a combination of both was best (accuracy = 85%; P = 0.003).Data Conclusion: SSC-MRI with GEH121333 is sensitive to early (<24 h) and late changes in tumor vasculature. SSC-MRI and DCE-MRI provide complementary information and can be used to assess different aspects of vascular responses to anti-angiogenic therapies.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1589-1600. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between relative enhanced diffusivity (RED) and intravoxel incoherent motion (IVIM), as well as the impact of noise and the choice of intermediate diffusion weighting (b value) on the RED parameter.Materials and methods: A mathematical derivation was performed to cast RED in terms of the IVIM parameters. Noise analysis and b value optimization was conducted by using Monte Carlo calculations to generate diffusion-weighted imaging data appropriate to breast and liver tissue at three different signal-to-noise ratios.Results: RED was shown to be approximately linearly proportional to the IVIM parameter f, inversely proportional to D and to follow an inverse exponential decay with respect to D*. The choice of intermediate b value was shown to be important in minimizing the impact of noise on RED and in maximizing its discriminatory power. RED was shown to be essentially a reparameterization of the IVIM estimates for f and D obtained with three b values.Conclusion: RED imaging in the breast and liver should be performed with intermediate b values of 100 and 50 s/mm2, respectively. Future clinical studies involving RED should also estimate the IVIM parameters f and D using three b values for comparison. [ABSTRACT FROM AUTHOR]

Background: Diffusion-weighted MRI (DWI) is currently one of the fastest developing MRI-based techniques in oncology. Histogram properties from model fitting of DWI are useful features for differentiation of lesions, and classification can potentially be improved by machine learning.Purpose: To evaluate classification of malignant and benign tumors and breast cancer subtypes using support vector machine (SVM).Study Type: Prospective.Subjects: Fifty-one patients with benign (n = 23) and malignant (n = 28) breast tumors (26 ER+, whereof six were HER2+).Field Strength/sequence: Patients were imaged with DW-MRI (3T) using twice refocused spin-echo echo-planar imaging with echo time / repetition time (TR/TE) = 9000/86 msec, 90 × 90 matrix size, 2 × 2 mm in-plane resolution, 2.5 mm slice thickness, and 13 b-values.Assessment: Apparent diffusion coefficient (ADC), relative enhanced diffusivity (RED), and the intravoxel incoherent motion (IVIM) parameters diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f) were calculated. The histogram properties (median, mean, standard deviation, skewness, kurtosis) were used as features in SVM (10-fold cross-validation) for differentiation of lesions and subtyping.Statistical Tests: Accuracies of the SVM classifications were calculated to find the combination of features with highest prediction accuracy. Mann-Whitney tests were performed for univariate comparisons.Results: For benign versus malignant tumors, univariate analysis found 11 histogram properties to be significant differentiators. Using SVM, the highest accuracy (0.96) was achieved from a single feature (mean of RED), or from three feature combinations of IVIM or ADC. Combining features from all models gave perfect classification. No single feature predicted HER2 status of ER + tumors (univariate or SVM), although high accuracy (0.90) was achieved with SVM combining several features. Importantly, these features had to include higher-order statistics (kurtosis and skewness), indicating the importance to account for heterogeneity.Data Conclusion: Our findings suggest that SVM, using features from a combination of diffusion models, improves prediction accuracy for differentiation of benign versus malignant breast tumors, and may further assist in subtyping of breast cancer.Level Of Evidence: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1205-1216. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of correction for B0 inhomogeneity‐induced geometric distortion in echo‐planar diffusion‐weighted imaging on quantitative apparent diffusion coefficient (ADC) analysis in multiparametric prostate MRI. Methods: Geometric distortion correction was performed in echo‐planar diffusion‐weighted images (b = 0, 50, 400, 800 s/mm2) of 28 patients, using two b0 scans with opposing phase‐encoding polarities. Histology‐matched tumor and healthy tissue volumes of interest delineated on T2‐weighted images were mapped to the nondistortion‐corrected and distortion‐corrected data sets by resampling with and without spatial coregistration. The ADC values were calculated on the volume and voxel level. The effect of distortion correction on ADC quantification and tissue classification was evaluated using linear‐mixed models and logistic regression, respectively. Results: Without coregistration, the absolute differences in tumor ADC (range: 0.0002–0.189 mm2/s×10−3 (volume level); 0.014–0.493 mm2/s×10−3 (voxel level)) between the nondistortion‐corrected and distortion‐corrected were significantly associated (P < 0.05) with distortion distance (mean: 1.4 ± 1.3 mm; range: 0.3–5.3 mm). No significant associations were found upon coregistration; however, in patients with high rectal gas residue, distortion correction resulted in improved spatial representation and significantly better classification of healthy versus tumor voxels (P < 0.05). Conclusions: Geometric distortion correction in DWI could improve quantitative ADC analysis in multiparametric prostate MRI. Magn Reson Med 79:2524–2532, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Background In vivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. In vivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer. [ABSTRACT FROM AUTHOR]