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Purpose: To assess the efficacy and safety of computed tomography (CT)-guided high-dose-rate HDR) brachytherapy in treating recurrent hepatocellular carcinoma (HCC) not amenable to repeated resection or radiofrequency ablation., Materials and Methods: From January 2010 to January 2022, 38 patients (mean age, 70.1 years; SD ± 9.0 years) with 79 nodular and four diffuse intrahepatic HCC recurrences not amenable to repeated resection or radiofrequency ablation underwent CT-guided HDR brachytheapy in our department. Tumor response was evaluated by cross-sectional imaging 6 weeks after CT-guided HDR brachytherapy and every 3 months thereafter. Local tumor control (LTC), progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves (KPCs). Severity of procedure-related complications (PRCs) was classified as recommended by the Society of Interventional Radiology (SIR)., Results: Patients were available for MRI evaluation for a mean follow-up of 33.1 months (SD, ±21.6 mm, range 4-86 months; median 29 months). Patients had a mean of 2.3 (SD, ±1.4) intrahepatic tumors. Mean tumor diameter was 43.2 mm (SD, ±19.6 mm). 13 of 38 (34.2%) patients showed local tumor progression after CT-guided HDR brachytherapy. Mean LTC was 29.3 months (SD, ±22.1). Distant tumor progression was seen in 12 patients (31.6%). The mean PFS was 20.8 months (SD, ±22.1). Estimated 1-, 3-, and 5-year PFS rates were 65.1%, 35.1% and 22.5%, respectively. 13 patients died during the follow-up period. Mean OS was 35.4 months (SD, ±21.7). Estimated 1-, 3-, and 5-year OS rates were 91.5%, 77.4% and 58.0%, respectively. SIR grade 1 complications were recorded in 8.6% (5/38) and SIR grade 2 complications in 3.4% (2/58) of interventions., Conclusion: CT-guided HDR brachytherapy is a safe and efficient therapeutic option for managing large or critically located HCC recurrences in the remaining liver after prior hepatic resection., Competing Interests: Declaration of competing Interest None., (© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: This study aims to better characterize potential responders of Y-90-radioembolization at baseline through analysis of clinical variables and contrast enhanced (CE) MRI tumor volumetry in order to adjust therapeutic regimens early on and to improve treatment outcomes., Methods: Fifty-eight HCC patients who underwent Y-90-radioembolization at our center between 10/2008 and 02/2017 were retrospectively included. Pre- and post-treatment target lesion volumes were measured as total tumor volume (TTV) and enhancing tumor volume (ETV). Survival analysis was performed with Cox regression models to evaluate 65% ETV reduction as surrogate endpoint for treatment efficacy. Univariable and multivariable logistic regression analyses were used to evaluate the combination of baseline clinical variables and tumor volumetry as predictors of ≥ 65% ETV reduction., Results: Mean patients' age was 66 (SD 8.7) years, and 12 were female (21%). Sixty-seven percent of patients suffered from liver cirrhosis. Median survival was 11 months. A threshold of ≥ 65% in ETV reduction allowed for a significant (p = 0.04) separation of the survival curves with a median survival of 11 months in non-responders and 17 months in responders. Administered activity per tumor volume did predict neither survival nor ETV reduction. A baseline ETV/TTV ratio greater than 50% was the most important predictor of arterial devascularization (odds ratio 6.3) in a statistically significant (p = 0.001) multivariable logistic regression model. The effect size was strong with a Cohen's f of 0.89., Conclusion: We present a novel approach to identify promising candidates for Y-90 radioembolization at pre-treatment baseline MRI using tumor volumetry and clinical baseline variables., Key Points: • A decrease of 65% enhancing tumor volume (ETV) on follow-up imaging 2-3 months after Y-90 radioembolization of HCC enables the early prediction of significantly improved median overall survival (11 months vs. 17 months, p = 0.04). • Said decrease in vascularization is predictable at baseline: an ETV greater than 50% is the most important variable in a multivariable logistic regression model that predicts responders at a high level of significance (p = 0.001) with an area under the curve of 87%., (© 2022. The Author(s).)

Background: To improve therapy outcome of Yttrium-90 selective internal radiation therapy ( 90 Y SIRT), patient-specific post-therapeutic dosimetry is required. For this purpose, various dosimetric approaches based on different available imaging data have been reported. The aim of this work was to compare post-therapeutic 3D absorbed dose images using Technetium-99m ( 99m Tc) MAA SPECT/CT, Yttrium-90 ( 90 Y) bremsstrahlung (BRS) SPECT/CT, and 90 Y PET/CT., Methods: Ten SIRTs of nine patients with unresectable hepatocellular carcinoma (HCC) were investigated. The 99m Tc SPECT/CT data, obtained from 99m Tc-MAA-based treatment simulation prior to 90 Y SIRT, were scaled with the administered 90 Y therapy activity. 3D absorbed dose images were generated by dose kernel convolution with scaled 99m Tc/ 90 Y SPECT/CT, 90 Y BRS SPECT/CT, and 90 Y PET/CT data of each patient. Absorbed dose estimates in tumor and healthy liver tissue obtained using the two SPECT/CT methods were compared against 90 Y PET/CT., Results: The percentage deviation of tumor absorbed dose estimates from 90 Y PET/CT values was on average -2 ± 18% for scaled 99m Tc/ 90 Y SPECT/CT, whereas estimates from 90 Y BRS SPECT/CT differed on average by -50 ± 13%. For healthy liver absorbed dose estimates, all three imaging methods revealed comparable values., Conclusion: The quantification capabilities of the imaging data influence 90 Y SIRT tumor dosimetry, while healthy liver absorbed dose values were comparable for all investigated imaging data. When no 90 Y PET/CT image data are available, the proposed scaled 99m Tc/ 90 Y SPECT/CT dosimetry method was found to be more appropriate for HCC tumor dosimetry than 90 Y BRS SPECT/CT based dosimetry., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Patients with increased liver stiffness have a higher risk of developing cancer, however, the role of fluid-solid tissue interactions and their contribution to liver tumor malignancy remains elusive. Tomoelastography is a novel imaging method for mapping quantitatively the solid-fluid tissue properties of soft tissues in vivo . It provides high resolution and thus has clear clinical applications. In this work we used tomoelastography in 77 participants, with a total of 141 focal liver lesions of different etiologies, to investigate the contributions of tissue stiffness and fluidity to the malignancy of liver tumors. Shear-wave speed (c) as surrogate for tissue stiffness and phase-angle (φ) of the complex shear modulus reflecting tissue fluidity were abnormally high in malignant tumors and allowed them to be distinguished from nontumorous liver tissue with high accuracy [c: AUC = 0.88 with 95% confidence interval (CI) = 0.83-0.94; φ: AUC = 0.95, 95% CI = 0.92-0.98]. Benign focal nodular hyperplasia and hepatocellular adenoma could be distinguished from malignant lesions on the basis of tumor stiffness (AUC = 0.85, 95% CI = 0.72-0.98; sensitivity = 94%, 95% CI = 89-100; and specificity = 85%, 95% CI = 62-100), tumor fluidity (AUC = 0.86, 95% CI = 0.77-0.96; sensitivity = 83%, 95% CI = 72-93; and specificity = 92%, 95% CI = 77-100) and liver stiffness (AUC = 0.84, 95% CI = 0.74-0.94; sensitivity = 72%, 95% CI = 59-83; and specificity = 88%, 95% CI = 69-100), but not on the basis of liver fluidity. Together, hepatic malignancies are characterized by stiff, yet fluid tissue properties, whereas surrounding nontumorous tissue is dominated by solid properties. Tomoelastography can inform noninvasively on the malignancy of suspicious liver lesions by differentiating between benign and malignant lesions with high sensitivity based on stiffness and with high specificity based on fluidity. SIGNIFICANCE: Solid-fluid tissue properties measured by tomoelastography can distinguish malignant from benign masses with high accuracy and provide quantitative noninvasive imaging biomarkers for liver tumors., (©2019 American Association for Cancer Research.)

Background: Virtual monochromatic images (VMI) generated using spectral computed tomography (CT) are promising recently available tools to improve diagnostic performance in oncologic patients., Purpose: To investigate if virtual monochromatic datasets are suitable for clinical routine use in patients with hypervascularized abdominal tumors., Material and Methods: A total of 41 patients with hypervascularized hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), or neuroendocrine tumors (NET) were enrolled in the study; 451 CT series were analyzed. In an intra-individual study design, virtual monochromatic datasets of the arterial phase of each scan were computed. Image quality was assessed objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR) and subjectively by using five-point Likert-scales. The volume CT dose index (CTDI vol ) was taken from each radiation dose report. The increase in reading time was estimated from the increase in the number of images., Results: Intra-individual comparison of the spectral mode in the arterial phase with the portal venous phase revealed no significant increase in the applied dose. SNR, CNR tumor-to-liver  , and CNR tumor-to-muscle were significantly increased by lowering virtual monochromatic energy. Subjective image quality scores revealed an increase of contrast in low energy datasets, resulting in significantly higher diagnostic confidence, but an increased image noise at low energies. While diagnostic confidence improved, taking all datasets into account resulted in a significantly longer estimated reading time., Conclusion: In clinical practice, the use of low energy VMI improved diagnostic confidence without a significant increase in dose. The main disadvantage is a decrease in efficiency due to longer reading times.

Background During transarterial chemoembolization (TACE), cone-beam computed tomography (CBCT) can be used for tumor and feeding vessel detection as well as postembolization CT imaging. However, there will be additional radiation exposure from CBCT. Purpose To evaluate the additional dose raised through CBCT-assisted guidance in comparison to TACE procedures guided with pulsed digital subtraction angiography (DSA) alone. Material and Methods In 70 of 140 consecutive patients undergoing TACE for liver cancer, CBCT was used to facilitate the TACE. Cumulative dose area product (DAP), cumulative kerma(air), DAP values of DSA, total and cine specific fluoroscopy times (FT) of 1375 DSA runs, and DAP of 91 CBCTs were recorded and analyzed using Spearman's correlation, Mann-Whitney U-test, and Kruskal-Wallis test. P values < 0.05 were considered significant. Results Additional CBCT increased DAP by 2% ( P = 0.737), kerma(air) by 24.6% ( P = 0.206), and FT by 0.02% ( P = 0.453). Subgroup analysis revealed that postembolization CBCT for detection of ethiodized oil deposits added more DAP to the procedure. Performing CBCT-assisted TACE, DSA until first CBCT contributed about 38% to the total DAP. Guidance CBCT acquisitions conduced to 6% of the procedure's DAP. Additional DSA for guidance after CBCT acquisition required approximately 46% of the mean DAP. The last DSA run for documentation purposes contributed about 10% of the DAP. Conclusion CBCT adds radiation exposure in TACE. However, the capability of CBCT to detect vessels and overlay in real-time during fluoroscopy facilitates TACE with resultant reduction of DAPs up to 46%.

Due to its dual role as reporter and therapy gene, the sodium iodide symporter (NIS) allows noninvasive imaging of functional NIS expression by (123)I-scintigraphy or (124)I-PET imaging before the application of a therapeutic dose of (131)I. NIS expression provides a novel mechanism for the evaluation of mesenchymal stem cells (MSCs) as gene delivery vehicles for tumor therapy. In the current study, we stably transfected bone marrow-derived CD34(-) MSCs with NIS cDNA (NIS-MSC), which revealed high levels of functional NIS protein expression. In mixed populations of NIS-MSCs and hepatocellular cancer (HCC) cells, clonogenic assays showed a 55% reduction of HCC cell survival after (131)I application. We then investigated body distribution of NIS-MSCs by (123)I-scintigraphy and (124)I-PET imaging following intravenous (i.v.) injection of NIS-MSCs in a HCC xenograft mouse model demonstrating active MSC recruitment into the tumor stroma which was confirmed by immunohistochemistry and ex vivo γ-counter analysis. Three cycles of systemic MSC-mediated NIS gene delivery followed by (131)I application resulted in a significant delay in tumor growth. Our results demonstrate tumor-specific accumulation and therapeutic efficacy of radioiodine after MSC-mediated NIS gene delivery in HCC tumors, opening the prospect of NIS-mediated radionuclide therapy of metastatic cancer using MSCs as gene delivery vehicles.