Efficacy of Selective Internal Radiation Therapy for Hepatocellular Carcinoma Post-Incomplete Response to Chemoembolization.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide and the third most common cause of cancer-related death. Several liver-targeted intra-arterial therapies are available for unresectable HCC, including selective internal radiation therapy (SIRT) and trans-arterial chemoembolization (TACE). Those two are the most used treatment modalities in localized non-operable HCC. TACE is the treatment option for patients with stage B, according to the BCLC staging system. In contrast, SIRT does not have an official role in the treatment algorithm, but recent studies showed promising outcomes in patients treated with SIRT. Although TACE is globally a safe procedure, it might provoke several vascular complications such as spasms, inflammatory constriction, and, in severe cases, occlusion, dissection, or collateralization. Hence, it is acclaimed that those complications could restrain the targeted response of the radio-embolization when we use it as second-line therapy post TACE. In this study, we will assess the efficacity of SIRT using Yttrium 90 Microspheres post incomplete or failure response to TACE. In our retrospective study, we had 23 patients who met the inclusion criteria. Furthermore, those patients have been followed radiologically and biologically. Then, we evaluated the therapeutic effect according to the mRECIST criteria, in addition to the personalized dose analysis. We found 8 patients were treated with TheraSphere®, with a median tumor absorbed dose of 445 Gy, while 15 received SIR-Spheres® treatment with a mean tumor dose of 268 Gy. After radiological analysis, 56.5% of the patients had a complete response, and 17.3% showed partial response, whereas 13% had stable disease and 13% had progressive disease. For patients treated with SIRT after an incomplete response or failure to TACE, we found an objective response rate of 73.8%. Despite the known vascular complications of TACE, SIRT can give a favorable response.

Personalized 90 Y-resin microspheres dose determination: a retrospective study on the impact of dosimetry software on the treatment of patients with selective internal radiotherapy.

INTRODUCTION: The calculation of resin yttrium-90 ( 90 Y-) microspheres activity for selective internal radiotherapy (SIRT) needs to be investigated. METHODS AND MATERIALS: Analyses using Simplicit 90 Y (Boston Scientific, Natick, Massachusetts, USA) dosimetry software were performed to determine the concordance between the absorbed doses to the tumor (D T1 and D T2 ) and healthy liver (D N1 and D N2 ) during the pre-treatment and the post-treatment phases. An optimized calculation of the activity of 90 Y-microspheres performed using dosimetry software was applied retrospectively to assess the impact of this calculation method on the treatment. RESULTS: D T1 ranged from 38.8 to 372 Gy, with a mean value of 128.9 ± 73.6 Gy and median of 121.2 Gy [interquartile range (IQR): 81.7-158.8 Gy]. The median D N1 and D N2 was 10.5 Gy (IQR: 5.8-17.6). A significant correlation was between D T1 and D T2 ( r = 0.88, P < 0.001) and D N1 and D N2 ( r = 0.96, P < 0.001). The optimized activities were calculated; the target dose to the tumor compartment was 120 Gy. No activity reduction was applied in accordance with the tolerance of the healthy liver. Optimization of the microspheres dosages would have resulted in a significant increase in activity for nine treatments (0.21-2.54 GBq) and a reduction for seven others (0.25-0.76 GBq). CONCLUSIONS: The development of customized dosimetry software adapted to clinical practice makes it possible to use dosimetry to optimize the dosage for each patient.

Left gastric vein embolization during TIPS placement for acute variceal bleeding has no effect on bleeding recurrence: Results of a multicenter study.

PURPOSE: The purpose of this study was to evaluate whether concomitant left gastric vein embolization (LGVE) during transjugular intrahepatic portosystemic shunt (TIPS) for acute variceal hemorrhage could reduce the risk of bleeding recurrence. MATERIAL AND METHOD: A national multicenter observational study was conducted in 14 centers between January 2019 and December 2020. All cirrhotic patients who underwent TIPS placement for acute variceal bleeding were included. During TIPS procedure, size of left gastric vein (LGV), performance of LGVE, material used for LGVE and portosystemic pressure gradient (PPG) before and after TIPS placement were collected. A propensity score for the occurrence of LGVE was calculated to assess effect of LGVE on rebleeding recurrence at six weeks and one year. RESULTS: A total of 356 patients were included (mean age 57.3 ± 10.8 [standard deviation] years; 283/356 [79%] men). Median follow-up was 11.2 months [interquartile range: 1.2, 13.3]. The main indication for TIPS was pre-emptive TIPS (162/356; 46%), rebleeding despite secondary prophylaxis (105/356; 29%), and salvage TIPS (89/356; 25%). Overall, 128/356 (36%) patients underwent LGVE during TIPS procedure. At six weeks and one year, rebleeding-free survival did not differ significantly between patients who underwent LGVE and those who did not (6/128 [5%] vs. 15/228 [7%] at six weeks, and 11/128 [5%] vs. 22/228 [7%] at one year, P = 0.622 and P = 0.889 respectively). A total of 55 pairs of patients were retained after propensity score matching. In patients without LGVE, the rebleeding rate was not different from those with LGVE (3/55 [5%] vs. 4/55 [7%], P > 0.99, and 5/55 [9%] vs. 6/55[11%], P > 0.99, at six weeks and one year respectively). Multivariable analysis identified PPG after TIPS placement as the only predictor of bleeding recurrence (hazard ratio = 1.09; 95% confidence interval: 1.02-1.18; P = 0.012). CONCLUSION: In this multicenter national real-life study, we did not observe any benefit of concomitant LGVE during TIPS placement for acute variceal bleeding on bleeding recurrence rate.

Cost Analysis of Radiofrequency Ablation for Adrenal Adenoma in Patients with Primary Aldosteronism and Hypertension: Results from the ADERADHTA Pilot Study and Comparison with Surgical Adrenalectomy.

PURPOSE: Primary Aldosteronism (PA) is increasingly considered as a common disease affecting up to 10% of the hypertensive population. Standard of care comprises laparoscopic total adrenalectomy but innovative treatment such as RadioFrequency Ablation (RFA) constitutes an emerging promising alternative to surgery. The main aim of this study is to analyse the cost of RFA versus surgery on aldosterone-producing adenoma patient from the French National Health Insurance (FNHI) perspective. METHODS: The ADERADHTA study was a prospective pilot study aiming to evaluate both safety and efficacy of the novel use of adrenal RFA on the patients with PA. This study conducted on two French sites and enrolled adult patients, between 2016 and 2018, presenting hypertension and underwent the RFA procedure. Direct medical (inpatient and outpatient) and non-medical (transportation, daily allowance) costs were calculated over a 6-month follow-up period. Moreover, the procedure costs for the RFA were calculated from the hospital perspective. Descriptive statistics were implemented. RESULTS: Analysis was done on 21 patients in RFA groups and 27 patients in the surgery group. The difference in hospital costs between the RFA and surgery groups was €3774 (RFA: €1923; Surgery: €5697 p < 0.001) in favour of RFA. Inpatient and outpatient costs over the 6-month follow-up period were estimated at €3,48 for patients who underwent RFA. The production cost of implementing the RFA procedure was estimated at €1539 from the hospital perspective. CONCLUSION: Our study was the first to show that RFA is 2 to 3 times less costly than surgery. The trial is registered at ClinicalTrials.gov under the number NCT02756754.

Comparison of MRI-based response criteria and radiomics for the prediction of early response to transarterial radioembolization in patients with hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the capabilities of radiomics using magnetic resonance imaging (MRI) data in the assessment of treatment response to 90yttrium transarterial radioembolization (TARE) in patients with locally advanced hepatocellular carcinoma (HCC) by comparison with predictions based on European Association for the Study of the Liver (EASL) criteria. PATIENTS AND METHODS: Twenty-two patients with HCC (19 men, 3 women; mean age: 66.7 ± 9.8 [SD]; age range: 37-82 years) who underwent contrast-enhanced MRI 4 ± 1 weeks before and 4 ± 4 weeks after TARE, were enrolled in this retrospective study. Regions of interest were placed manually along the contours of the treated tumor on each axial slice of arterial and portal phase images using the ITK-SNAP post-processing software. For each MRI, the Pyradiomics Python package was used to extract 107 radiomics features on both arterial and portal phases, and resulting delta-features were computed. The Mann-Whitney U test with Bonferroni correction was used to select statistically different features between responders and non-responders (i.e., those with progressive or stable disease) at 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Finally, for each selected feature, univariable logistic regression with leave-one-out cross validation procedure was used to perform receiver operating characteristic (ROC) curve analysis and compare radiomics parameters with MRI variables. RESULTS: According to mRECIST, 14 patients (14/22; 64%) were non-responders and 8 (8/22; 36%) were responders. Four radiomics parameters (long run emphasis, minor axis length, surface area, and gray level non-uniformity on arterial phase images) were the only predictors of early response. ROC curve analysis showed that long run emphasis was the best parameter for predicting early response, with 100% sensitivity (95% CI: 68-100) and 100% specificity (95% CI: 78-100). EASL morphologic criteria yielded 75% sensitivity (95% CI: 41-96%) and 93% specificity (95% CI: 69-100%). CONCLUSION: Radiomics allows identify marked differences between responders and non-responders, and could aid in the prediction of early treatment response following TARE in patients with HCC.

Key Role of Personalized Dosimetry in Dose Adjustment for Selective Internal Radiotherapy: Retrospective Study of Patients Treated With 90Y Resin Microspheres.

PURPOSE: Selective internal radiotherapy with 90Y microspheres is widely used for the treatment of patients with liver cancer. A dosimetric analysis using the dosimetry software Simplicit90y (Boston Scientific, Natick, MA) was conducted to define doses to the tumor and healthy liver, and to determine a threshold tumor dose that could predict progression-free survival. METHODS: Patients experiencing hepatocellular carcinoma and treated with 90Y-labeled resin microspheres were included in a retrospective study. The time-to-progression of the target lesions (TTPLs) and overall survival (OS) were evaluated using Kaplan-Meier tests, and this comparison was based on a log-rank test. RESULTS: Twenty-four procedures for patients with portal vein thrombosis were realized. Median follow-up was 16 months. A threshold tumor dose of 125 Gy was determined with a sensitivity of 89% and a specificity of 100%. For patients with a tumor dose of less than 125 Gy, the median OS was 7.5 months (95% confidence interval [CI], 5-14 months) and the TTPL was 3 months (95% CI, 2-6 months) versus 33 months (95% CI, 22-39 months) and 23 months (95% CI, 7-38 months), respectively, for those with a tumor dose of 125 Gy or more (P = 0.002 and P = 0.0004). CONCLUSIONS: Personalized dosimetry based on 99mTc-MAA SPECT/CT is predictive of TTPL and OS in patients with hepatocellular carcinoma. Customized dosimetry software is essential to optimize treatment planning.

18F-choline PET-computed tomography for the prediction of early treatment responses to transarterial radioembolization in patients with hepatocellular carcinoma.

BACKGROUND: Transarterial radioembolization (TARE) is widely used for the treatment of hepatocellular carcinoma (HCC), but early treatment response can be very difficult to assess. The aim was to evaluate 18F-fluorocholine PET/computed tomography (CT) to assess the treatment response in patients with intermediate or locally advanced HCC. METHODS: Between March 2019 and July 2020, nine HCC patients treated with TARE, who underwent PET/CT at baseline and 1 month after treatment, were enrolled. The maximum, mean (SUVmean), and peak (SUVpeak) standardized uptake value (SUV), SUV normalized by lean body mass (SUL), and total lesion glycolysis (TLG) were measured. Statistical analysis used the Mann-Whitney test to evaluate the differences in parameters between responders (partial and complete response) and nonresponders (stable or progressive disease) at the 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS: Three patients were nonresponders (progressive disease and stable disease) and six were responders. Delta SUVmean, delta SUL, and delta TLG could predict an early response (P = 0.02, P = 0.04, and P = 0.02, respectively). None of the pre-therapeutic parameters were correlated with the response. Post-therapeutic SUL, SUVmean, TLG, and SUVpeak were also predictive of the response. CONCLUSIONS: Our preliminary results showed that changes in certain metabolic parameters (from baseline PET to 1-month PET) are predictive of the response to TARE in HCC (Delta SUVmean, delta TLG, and delta SUL). The absence of post-treatment inflammation could lead to a better prediction than MRI evaluation. This study suggests that 1-month 18F-choline PET/CT could modify the clinical management predicting responders.Video Abstract: http://links.lww.com/NMC/A193.

Radiofrequency ablation for adenoma in patients with primary aldosteronism and hypertension: ADERADHTA, a pilot study.

OBJECTIVE: To evaluate the efficacy and the feasibility of radiofrequency ablation to treat aldosterone-producing adenomas. METHODS: In an open prospective bicentric pilot study, patients with hypertension on ambulatory blood pressure measurement, a primary aldosteronism, an adenoma measuring less than 4 cm, and confirmation of lateralization by adrenal venous sampling were recruited. The primary endpoint, based on ABPM performed at 6 months after the radiofrequency ablation, was a daytime SBP/DBP less than 135/85 mmHg without any antihypertensive drugs or a reduction of at least 20 mmHg for SBP or 10 mmHg for DBP. RESULTS: Thirty patients have been included (mean age = 51 ±â€Š11 years; 50% women). Mean baseline daytime SBP and DBP were 144 ±â€Š19 / 95 ±â€Š15 mmHg and 80% received at least two antihypertensive drugs. At 6 months: 47% (95% CI 28-66) of patients reached the primary endpoint, mean daytime SBP and DBP were 131 ±â€Š14 (101-154)/87 ±â€Š10 (71-107) mmHg; 43% of them did not take any antihypertensive drug and 70% of them did not take potassium supplements. Few complications were recorded: four cases of back pain at day 1 postablation; three limited pneumothoraxes, which resolved spontaneously; one lesion of a polar renal artery. CONCLUSION: Radiofrequency ablation for hypertensive patients with aldosterone-producing adenomas seems to be an emerging promising alternative to surgery. Its efficacy and its feasibility have to be confirmed in a larger sample of patients.

Radiological Simultaneous Portohepatic Vein Embolization (RASPE) Before Major Hepatectomy: A Better Way to Optimize Liver Hypertrophy Compared to Portal Vein Embolization.

OBJECTIVE: The aim of this retrospective study was to compare portal vein embolization (PVE) and radiologica simultaneous portohepatic vein embolization (RASPE) for future liver remnant (FLR) growth in terms of feasibility, safety, and efficacy. SUMMARY OF BACKGROUND DATA: After portal vein embolization (PVE), 15% of patients remain ineligible for hepatic resection due to insufficient hypertrophy of the FLR. RASPE has been proposed to induce FLR growth. MATERIALS AND METHODS: Between 2016 and 2018, 73 patients were included in the study. RASPE was proposed for patients with a ratio of FLR to total liver volume (FLR/TLV) of <25% (RASPE group). This group was compared to patients who underwent PVE for a FLR/TLV <30% (PVE group). Patients in the 2 groups were matched for age, sex, type of tumor, and number of chemotherapy treatments. FLR was assessed by computed tomography before and 4 weeks after the procedure. RESULTS: The technical success rate in both groups was 100%. Morbidity post-embolization, and the time between embolization and surgery were similar between the groups. In the PVE group, the FLR/TLV ratio before embolization was 31.03% (range: 18.33%-38.95%) versus 22.91% (range: 16.55-32.15) in the RASPE group (P < 0.0001). Four weeks after the procedure, the liver volume increased by 28.98% (range: 9.31%-61.23%) in the PVE group and by 61.18% (range: 23.18%-201.56%) in the RASPE group (P < 0.0001). Seven patients in the PVE group, but none in the RASPE group, had postoperative liver failure (P = 0.012). CONCLUSIONS: RASPE can be considered as "radiological associating liver partition and portal vein ligation for staged hepatectomy." RASPE induced safe and profound growth of the FLR and was more efficient than PVE. RASPE also allowed for extended hepatectomy with less risk of post-operative liver failure.

Magnetic resonance texture parameters are associated with ablation efficiency in MR-guided high-intensity focussed ultrasound treatment of uterine fibroids.

OBJECTIVES: The objective of this study is to assess the association between texture parameter analysis derived from T2-weighted images and efficiency of magnetic resonance-guided focussed ultrasound (MRgFUS) ablation for the treatment of uterine fibroids. MATERIALS AND METHODS: Fifty-five women treated by MRgFUS were included in this retrospective analysis. Texture parameters were calculated using three 2D regions of interest placed on three consecutive slices on the same sagittal 3D T2-weighted images obtained at the beginning of MRgFUS ablation. Using uni- and multi-variate linear regression, texture parameters, fibroids/muscular T2W ratio (T2Wr), Funaki type, and fibroid depth were correlated with ablation efficiency, defined as the ratio of non-perfused volume (NPV) on post-treatment contrast-enhanced MRI by total volume of treatment-cell sizes used. Inter-rater reproducibility for texture analysis was assessed using variation coefficients. RESULTS: The mean total treatment cell volume was 49.5 (±30) ml, corresponding to a mean NPV of 57.2 (±57) ml (28%). The mean ablation efficiency was 1.14 (±0.7), with a range of 0.03-3.6. In addition to fibroid/muscular T2Wr, seven of the 14 texture parameters were significantly correlated with ablation efficiency: mean signal intensity (p = .047); Skewness (p = .03); Kurtosis (p = .015); mean uniformity (p = .052); mean sum of square (p = .045); mean sum entropy (p = .021) and mean entropy (p = .051). In multivariate linear regression, fibroid/muscular T2Wr and sum of entropy were associated with ablation efficiency. The inter-rater coefficient of variation for sum entropy was 2.6%. CONCLUSIONS: Uterine fibroid texture parameters provide complementary information to T2Wr, and are associated with MRgFUS efficiency. Key points Mean sum entropy is negatively correlated with MRgFUS efficiency (ρ = -0.307, p = .021). Fibroids/muscular T2-weighted ratio and entropy are associated with MRgFUS efficiency. Texture parameters are better predictors of MRgFUS efficiency than Funaki type. Fibroid MR texture analysis can improve patient selection for MRgFUS.

Three-Dimensional Measurement of Hepatocellular Carcinoma Ablation Zones and Margins for Predicting Local Tumor Progression.

PURPOSE: To propose a postprocessing technique that measures tumor surface with insufficient ablative margins (≤ 5 mm) on magnetic resonance (MR) imaging to predict local tumor progression (LTP) following radiofrequency (RF) ablation. MATERIALS AND METHODS: A diagnostic method is proposed based on measurement of tumor surface with a margin ≤ 5 mm on MR imaging. The postprocessing technique includes fully automatic registration of pre- and post-RF ablation MR imaging, a semiautomatic segmentation of pre-RF ablation tumor and post-RF ablation volume, and a subsequent calculation of the three-dimensional exposed tumor surface area. The ability to use this surface margin ≤ 5 mm to predict local recurrence at 2 years was then tested on 16 patients with cirrhosis who were treated by RF ablation with a margin ≤ 5 mm in 2012: eight with LTP matched according to tumor size and number and α-fetoprotein level versus eight without local recurrence. RESULTS: The error of estimated tumor surface with a margin ≤ 5 mm was less than 12%. Results of a log-rank test showed that patients with a tumor surface area > 425 mm(2) had a 2-year LTP rate of 77.5%, compared with 25% for patients with a tumor surface area ≤ 425 mm(2) (P = .018). CONCLUSIONS: This proof-of-concept study proposes an accurate and reliable postprocessing technique to estimate tumor surface with insufficient ablative margins, and underscores the potential usefulness of tumor surface with a margin ≤ 5 mm to stratify patients with HCC treated by RF ablation according to their risk of LTP.