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•Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma.•Addition of selective internal radiation therapy did not significantly ...improve overall survival compared to sorafenib alone.•Subgroup analyses provided results that will guide future clinical trial designs for this combination therapy.
Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) – with yttrium-90 (90Y) resin microspheres – to sorafenib alone in patients with advanced HCC.
SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population.
In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio HR 1.01; 95% CI 0.81–1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25–0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3–4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT.
Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies.
Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed.
Study Registration: EudraCT 2009-012576-27, NCT0112 6645.
Time-resolved volumetric magnetic resonance imaging (4D MRI) could be used to address organ motion in image-guided interventions like tumor ablation. Current 4D reconstruction techniques are ...unsuitable for most interventional settings because they are limited to specific breathing phases, lack temporal/spatial resolution, and have long prior acquisitions or reconstruction times. Deep learning-based (DL) 4D MRI approaches promise to overcome these shortcomings but are sensitive to domain shift. This work shows that transfer learning (TL) combined with an ensembling strategy can help alleviate this key challenge. We evaluate four approaches: pre-trained models from the source domain, models directly trained from scratch on target domain data, models fine-tuned from a pre-trained model and an ensemble of fine-tuned models. For that the data base was split into 16 source and 4 target domain subjects. Comparing ensemble of fine-tuned models (N = 10) with directly learned models, we report significant improvements (P < 0.001) of the root mean squared error (RMSE) of up to 12% and the mean displacement (MDISP) of up to 17.5%. The smaller the target domain data amount, the larger the effect. This shows that TL + Ens significantly reduces beforehand acquisition time and improves reconstruction quality, rendering it a key component in making 4D MRI clinically feasible for the first time in the context of 4D organ motion models of the liver and beyond.
Histogram analysis can better reflect tumor heterogeneity than conventional imaging analysis. The present study analyzed possible correlations between histogram analysis parameters derived from ...Intravoxel-incoherent imaging (IVIM) and histopathological features in rectal cancer (RC).
Seventeen patients with histopathologically proven rectal adenocarcinomas were retrospectively acquired. In all cases, pelvic MRI was performed. Diffusion weighted imaging was obtained using a multi-slice single-shot echo-planar imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm2. Simplified IVIM analysis was performed using the IntelliSpace portal, version 10 and the following images were generated: f (perfusion fraction) map, D (true diffusion coefficient) map, and ADC map utilizing all b-values. Histogram based analysis of signal intensities was performed for every IVIM map using an in-house matlab tool. Histopathology was investigated using Ki 67 specimens with calculation of Ki 67-index and cellularity. CD31 stained specimens were used for calculation of microvessel density (MVD).
There were statistically significant correlations between Ki 67 index and mode derived from ADC as well as entropy from f, r=−0.50, p=.04 and r=−0.55, p=.02, respectively. MVD correlated well with parameters derived from f.
IVIM histogram analysis parameters can reflect histopathology in RC. ADC and D values are associated with proliferation potential. Perfusion fraction f is associated with MVD.
Purpose
To search for abscopal effects (AE) distant to the site of radiation after sequential Yittrium-90 (Y-90) radioembolization (RE) of liver malignancies.
Methods and Materials
In this ...retrospective analysis, all patients treated by RE between 2007 and 2018 (
n
= 907) were screened for the following setting/conditions: sequential RE of left and right liver lobe in two sessions, liver-specific MRI (MRI1) acquired max. 10 days before or after first RE (RE1), liver-specific MRI (MRI2) acquired with a minimum time interval of 20 days after MRI1, but before second RE (RE2). No systemic tumor therapies between MRI1 and MRI2. No patients with liver cirrhosis. Metastases > 5 mm in untreated liver lobes were compared in MRI1 and MRI2 and rated as follows: same size or larger in MRI2 = no abscopal effect (NAE); > 30% shrinkage without Y-90 contamination in SPECT/CT = abscopal effect (AE).
Results
Ninety six of 907 patients met aforementioned criteria. Median time-frame between RE1 and MRI2 was 34 (20–64) days. These 96 cases had 765 metastases which were evaluable (median 5(1–40) metastases per patient). Four patients could be identified with at least one shrinking metastasis of the untreated site: one patient with breast cancer (3 metastases: 0 NAE; 3 AE), one patient with prostate cancer (6 metastases: 3 NAE; 3 metastases > 30% shrinkage but possible Y-90 contamination) and two patients with shrinkage of one metastasis each but less than 30%.
Conclusion
Our retrospective study documents AE after RE of liver tumors in 1 out of 96 cases, 3 other cases remain unclear.
Incidence of hepatocellular carcinoma (HCC) is increasing globally. Radioembolization (RE)/selective internal radiotherapy (SIRT) is a promising treatment for inoperable HCC. RE triggers an immune ...response, involving extracellular vesicles (EVs) which are crucial for cell communication and tumor development. This study explores EV immune profiles and origins in patients with inoperable HCC before and after SIRT/RE. Blood samples from 50 HCC-patients treated with SIRT/RE were collected before and after therapy to determine cytokines and isolate EVs using size exclusion chromatography. The dynamic range and EV quality required for detecting variations in surface markers were assessed. Thirty-seven EV surface markers were analyzed using flow cytometry and correlated with clinical parameters. Several immunological markers (CD4, CD2, CD40, CD45, CD49e, CD69, CD209-EVs) were present in the circulation of HCC patients. These markers positively correlated with therapy response and survival. Conversely, B cell CD20, endothelial cell CD146, platelet CD49e, and CD41b EV markers negatively correlated with 60-day survival. Elevated levels of IL-6 and IL-8 before therapy correlated negatively with patient survival, coinciding with a positive correlation with CD20-positive EVs. Plasma EVs from HCC patients exhibit immunological, cancer, and coagulation markers, including potential biomarkers (CD4, CD20, CD49e, CD146). These may enhance our understanding of cancer biology and facilitate SIRT therapy monitoring.
Background
Our aim was to provide data regarding use of diffusion-weighted imaging (DWI) for distinguishing metastatic and non-metastatic lymph nodes (LN) in rectal cancer.
Methods
MEDLINE library, ...EMBASE, and SCOPUS database were screened for associations between DWI and metastatic and non-metastatic LN in rectal cancer up to February 2021. Overall, 9 studies were included into the analysis. Number, mean value, and standard deviation of DWI parameters including apparent diffusion coefficient (ADC) values of metastatic and non-metastatic LN were extracted from the literature. The methodological quality of the studies was investigated according to the QUADAS-2 assessment. The meta-analysis was undertaken by using RevMan 5.3 software. DerSimonian, and Laird random-effects models with inverse-variance weights were used to account the heterogeneity between the studies. Mean DWI values including 95% confidence intervals were calculated for metastatic and non-metastatic LN.
Results
ADC values were reported for 1376 LN, 623 (45.3%) metastatic LN, and 754 (54.7%) non-metastatic LN. The calculated mean ADC value (× 10
−3
mm
2
/s) of metastatic LN was 1.05, 95%CI (0.94, 1.15). The calculated mean ADC value of the non-metastatic LN was 1.17, 95%CI (1.01, 1.33). The calculated sensitivity and specificity were 0.81, 95%CI (0.74, 0.89) and 0.67, 95%CI (0.54, 0.79).
Conclusion
No reliable ADC threshold can be recommended for distinguishing of metastatic and non-metastatic LN in rectal cancer.
Objectives
The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and ...safety aspects of MRI-guided single-fraction HDR.
Methods
Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned.
Results
So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far.
Conclusions
MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary.
Key Points
• MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor.
• No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure.
• Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy.
Liquid biopsy based on cell-free DNA circulating in plasma has shown solid results as a non-invasive biomarker. In the present study we evaluated the utility of circulating free DNA (cfDNA) and the ...sub-type tumor DNA (ctDNA) in hepatocellular cancer (HCC) patients to assess therapy response and clinical outcome.
A cohort of 13 patients recruited in the context of the SORAMIC trial with unresectable, advanced HCC and different etiological and clinicopathological characteristics was included in this exploratory study. Plasma samples were collected between liver micro-intervention and beginning of sorafenib-based systemic therapy and then in correspondence of three additional follow-ups. DNA was isolated from plasma and next generation sequencing (NGS) was performed on a panel of 597 selected cancer-relevant genes.
cfDNA levels showed a significant correlation with the presence of metastases and survival. In addition cfDNA kinetic over time revealed a trend with the clinical history of the patients, supporting its use as a biomarker to monitor therapy. NGS-based analysis on ctDNA identified 28 variants, detectable in different combinations at the different time points. Among the variants, HNF1A, BAX and CYP2B6 genes showed the highest mutation frequency and a significant association with the patients' clinicopathological characteristics, suggesting a possible role as driver genes in this specific clinical setting.
Taken together, the results support the prognostic value of cfDNA/ctDNA in advanced HCC patients with the potential to predict therapy response. These findings support the clinical utility of liquid biopsy in advanced HCC improving individualized therapy and possible earlier identification of treatment responders.
Purpose We aim to develop a robust 4D MRI method for large FOVs enabling the extraction of irregular respiratory motion that is readily usable with all MRI machines and thus applicable to support a ...wide range of interventional settings. Method We propose a 4D MRI reconstruction method to capture an arbitrary number of breathing states. It uses template updates in navigator slices and search regions for fast and robust vessel cross-section tracking. It captures FOVs of 255 mm x 320 mm x 228 mm at a spatial resolution of 1.82 mm x 1.82 mm x 4mm and temporal resolution of 200ms. A total of 37 4D MRIs of 13 healthy subjects were reconstructed to validate the method. A quantitative evaluation of the reconstruction rate and speed of both the new and baseline method was performed. Additionally, a study with ten radiologists was conducted to assess the subjective reconstruction quality of both methods. Results Our results indicate improved mean reconstruction rates compared to the baseline method (79.4% vs. 45.5%) and improved mean reconstruction times (24s vs. 73s) per subject. Interventional radiologists perceive the reconstruction quality of our method as higher compared to the baseline (262.5 points vs. 217.5 points, p = 0.02). Conclusions Template updates are an effective and efficient way to increase 4D MRI reconstruction rates and to achieve better reconstruction quality. Search regions reduce reconstruction time. These improvements increase the applicability of 4D MRI as a base for seamless support of interventional image guidance in percutaneous interventions.
To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC).
Patients with advanced HCC ...from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression.
Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD.
Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.
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