Stereotactic body radiation therapy for hepatocellular carcinoma: From infancy to ongoing maturity.

Hepatocellular carcinoma (HCC) accounts for 90% of liver tumours and is one of the leading causes of mortality. Cirrhosis due to viral hepatitis, alcohol or steatohepatitis is the major risk factor, while liver dysfunction due to cirrhosis is a deciding factor in its treatment. The treatment modalities for HCC include liver transplant, hepatectomy, radiofrequency ablation, transarterial chemoembolisation, transarterial radioembolisation, targeted therapy, immunotherapy, and radiation therapy. The role of radiation therapy has been refined with the increasing use of stereotactic body radiation therapy (SBRT). Trials over the past two decades have shown the efficacy and safety of SBRT in recurrent and definitive HCC, leading to its acceptance and adoption in some more recent guidelines. However, high quality level I evidence supporting its use is currently lacking. Smaller randomised trials of external beam radiation therapy suggest high efficacy of radiation therapy compared to other treatments for patients with unresectable HCC, and phase III trials comparing SBRT with other modalities are ongoing. In this review, we discuss the rationale for SBRT in HCC and present evidence on its efficacy, associated toxicity, and technological advances.

Diagnostic value of integrated 18F-PSMA-1007 PET/MRI compared with that of biparametric MRI for the detection of prostate cancer.

Objective: To assess the diagnostic value of fluorine 18 (18F)-labeled prostate-specific membrane antigen (PSMA)-1007 Positron emission tomography/Magnetic resonance imaging (PET/MRI) and compared with that of biparametric MRI (bpMRI) for the detection of prostate cancer (PCa). Materials and methods: The study enrolled 29 patients with suspected PCa preoperatively who underwent 18F-PSMA-1007 PET/MRI and subsequent targeted biopsy for suspected PCa lesions. Two readers independently assessed the images of each suspected PCa lesion and determined their overall assessment category on bpMRI and 18F-PSMA-1007 PET/MRI. By using biopsy histopathology as the reference standard, the accuracies of 18F-PSMA-1007 PET/MRI and bpMRI for the detection of PCa lesion were determined. Furthermore, the receiver-operating characteristic (ROC) curves of their semi-quantitative parameters of the optimal standardized uptake value (SUVmax) and apparent diffusion coefficient (ADC) for detecting PCa lesions were derived, and their correlations with the International Society of Urological Pathology (ISUP) grade were reported. Results: Of the 48 suspected PCa lesions in 29 patients, 38 were pathologically diagnosed with clinically significant PCa and 10 with nonprostate cancer (non-PCa) lesions. Compared with the pathological results, 18F-PSMA-1007 PET/MRI demonstrated much greater diagnostic accuracy (area under the curve, AUC), sensitivity, specificity, positive predictive value, and negative predictive value than bpMRI: 0.974 versus 0.711, 94.74% versus 92.11%, 100% versus 50%, 100% versus 87.50%, and 83.33% versus 62.50%, respectively. The semi-quantitative parameters of SUVmax demonstrated a higher AUC of 0.874 than that of ADC with 0.776 for detecting PCa. The ISUP grade was positively associated with SUVmax at spearman's rho correlation coefficient (Rho) = 0.539, p = 0), but not associated with ADC (Rho = -0.105, p = 0.529). Conclusion: The diagnostic value of 18F-PSMA-1007 PET/MRI for the detection of PCa is better than that of bpMRI, and a high SUVmax may indicate a lesion with a high ISUP grade.

Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project.

Background: Sporadic cerebral small vessel disease (SVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) share clinical and neuroimaging features and possibly vascular dysfunction(s). However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre. The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres. Methods: We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) and CADASIL in Edinburgh, Maastricht and Munich. We will perform detailed clinical and neuropsychological phenotyping of the participants, and neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous and CSF flow and pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) and multishell diffusion imaging. Participants will measure their blood pressure (BP) and its variability over seven days using a telemetric device. Discussion: INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility and CSF flow in sporadic SVD and CADASIL using a multisite, multimodal MRI protocol. We aim to establish associations between these measures of vascular function, risk factors particularly BP and its variability, and brain parenchymal lesions in these two SVD phenotypes. Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures and sample size estimates for future trials.

Differentiation of prostate cancer lesions in the Transition Zone by diffusion-weighted MRI.

OBJECTIVE: To differentiate prostate cancer lesions in transition zone by diffusion-weighted-MRI (DW-MRI). METHODS: Data from a total of 63 patients who underwent preoperative DWI (b of 0-1000 s/mm2) were prospectively collected and processed by a monoexponential (DWI) model and compared with a biexponential (IVIM) model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analyses were performed by outlining entire-tumor regions of interest (ROIs). These parameters (separately and combined in a logistic regression model) were used to differentiate lesions depending on histopathological analysis of Magnetic Resonance/transrectal Ultrasound (MR/TRUS) fusion-guided biopsy. The diagnostic ability of differentiate the PCa from BHP in TZ was analyzed by ROC regression. Histogram analysis of quantitative parameters and Gleason score were assessed with Spearman correlation. RESULTS: Thirty (30 foci) cases of PCa in PZ and 33 (36 foci) cases of BPH were confirmed by pathology. Mean ADC, median ADC, 10th percentile ADC, 90th percentile ADC, kurtosis and skewness of ADC and mean D values, median D and 90th percentile D differed significantly between PCa and BHP in TZ. The highest classification accuracy was achieved by the mean ADC (0.841) and mean D (0.809). A logistic regression model based on mean ADC and mean D led to an AUC of 0.873, however, the difference is not significant. There were 7 Gleason 6 areas, 9 Gleason 7 areas, 8 Gleason 8 areas, 5 Gleason 9 areas and 2 Gleason 10 areas detected from the 31 prostate cancer areas, the mean Gleason value was(7.5 ± 1.2). The mean ADC and mean D had correlation with Gleason score(r = -0.522 and r = -0.407 respectively, P < 0.05). CONCLUSION: The diagnosis efficiency of IVIM parameters was not superior to ADC in the diagnosis of PCa in TZ. Moreover, the combination of mean ADC and mean D did not perform better than the parameters alone significantly; It is feasible to stratify the pathological grade of prostate cancer by mean ADC.

Role of 3T multiparametric-MRI with BOLD hypoxia imaging for diagnosis and post therapy response evaluation of postoperative recurrent cervical cancers.

OBJECTIVES: To assess the diagnostic value of multiparametric-MRI (MPMRI) with hypoxia imaging as a functional marker for characterizing and detecting vaginal vault/local recurrence following primary surgery for cervical cancer. METHODS: With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. RESULTS: Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). CONCLUSION: Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future.

The expression of P2X7 receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas.

In order to use endothelial progenitor cells (EPCs) as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas, how to enhance proliferation and targeting ability of transplanted EPCs is a high priority. Here, we confirmed, for the first time, the expression of P2X7 receptors in rat spleen-derived EPCs. Activation of P2X7 receptors in EPCs by BzATP promoted cells proliferation and migration, rather than apoptosis. In vivo, the homing of transplanted EPCs after long-term suppression of P2X7 receptors by persistent BBG stimulation was evaluated by MRI, immunohistochemistry and flow cytometry. Compared to the group without BBG treatment, less transplanted EPCs homed to gliomas in the group with BBG treatment, especially integrated into the vessels containing tumor-derived endothelial cells in gliomas. Moreover, western blot showed that CXCL1 expression was downregulated in gliomas with BBG treatment, which meant P2X7 receptors suppression inhibited the homing of EPCs to gliomas through down-regulation of CXCLl expression. Further, effects of P2X7 receptors on C6 glioma cells or gliomas were evaluated at the same dose of BzATP or BBG used in EPCs experiments in vitro and in vivo. MTT assay and MRI revealed that P2X7 receptors exerted no significant promoting effect on C6 glioma cells proliferation, gliomas growth and angiogenesis. Taken together, our findings imply the possibility of promoting proliferation and targeting ability of transplanted EPCs to brain gliomas in vivo through P2X7 receptors, which may provide new perspectives on application of EPCs as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas.