Hepatic Radioembolization: A Multistep Theragnostic Procedure.

This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed.

Image-guided percutaneous strategies to improve the resectability of HCC: Portal vein embolization, liver venous deprivation, or radiation lobectomy?

Despite considerable advances in surgical technique, many patients with hepatic malignancies are not operative candidates due to projected inadequate hepatic function following resection. Consequently, the size of the future liver remnant (FLR) is an essential consideration when predicting a patient's likelihood of liver insufficiency following hepatectomy. Since its initial description 30 years ago, portal vein embolization has become the standard of care for augmenting the size and function of the FLR preoperatively. However, new minimally invasive techniques have been developed to improve surgical candidacy, chief among them liver venous deprivation and radiation lobectomy. The purpose of this review is to discuss the status of preoperative liver augmentation prior to resection of hepatocellular carcinoma with a focus on these three techniques, highlighting the distinctions between them and suggesting directions for future investigation.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Experimental validation of the accuracy of robotic-assisted radioactive seed implantation for tumor treatment.

An experimental validation of a robotic system for radioactive iodine-125 seed implantation (RISI) in tumor treatment was conducted using customized phantom models and animal models simulating liver and lung lesions. The robotic system, consisting of planning, navigation, and implantation modules, was employed to implant dummy radioactive seeds into the models. Fiducial markers were used for target localization. In phantom experiments across 40 cases, the mean errors between planned and actual seed positions were 0.98 ± 1.05 mm, 1.14 ± 0.62 mm, and 0.90 ± 1.05 mm in the x, y, and z directions, respectively. The x, y, and z directions correspond to the left-right, anterior-posterior, and superior-inferior anatomical planes. Silicone phantoms exhibiting significantly smaller x-axis errors compared to liver and lung phantoms (p < 0.05). Template assistance significantly reduced errors in all axes (p < 0.05). No significant dosimetric deviations were observed in parameters such as D90, V100, and V150 between plans and post-implant doses (p > 0.05). In animal experiments across 23 liver and lung cases, the mean implantation errors were 1.28 ± 0.77 mm, 1.66 ± 0.69 mm, and 1.86 ± 0.93 mm in the x, y, and z directions, slightly higher than in phantoms (p < 0.05), with no significant differences between liver and lung models. The dosimetric results closely matched planned values, confirming the accuracy of the robotic system for RISI, offering new possibilities in clinical tumor treatment.

[Stereotactic radiation therapy for liver tumours]. / Radiothérapie stéréotaxique hépatique.

Liver lesions are common in oncology, and various focal treatments can be used, such as surgery, chemoembolization, radiofrequency, and systemic treatment. However, these treatments are often not feasible for a number of reasons, including the patient's general health or the characteristics of the lesion itself. Additionally, localized relapses may occur after focal treatments. In the past, liver radiotherapy was limited by the toxicities it caused and was mainly used in palliative situations or specific pre-transplant management. However, advancements in high-precision radiotherapy, like hypofractionated radiotherapy in stereotactic conditions, have allowed to treat the lesions with minimal margins, delivering higher doses while reducing the healthy liver's exposure. Increasingly, retrospective and prospective studies have demonstrated the effectiveness and safety of hypofractionation for both primary and secondary liver lesions. This review discusses the indications, results, and techniques of this type of treatment.

Les lésions hépatiques primitives ou secondaires sont une situation fréquente en oncologie. Plusieurs types de traitements focaux peuvent être appliqués : chirurgie, chimio-embolisation, radio-fréquence, traitement systémique. Néanmoins, les traitements focaux sont régulièrement contre-indiqués, soit par l'état général et les antécédents du patient, soit par la lésion en elle-même (volume, situation). De plus, il peut y avoir des patients qui présentent des rechutes localisées après ce type de prise en charge. Le foie est un organe très radiosensible, et la radiothérapie hépatique a longtemps été limitée par les toxicités qu'elle engendrait. La radiothérapie est le plus souvent utilisée dans les situations très palliatives (irradiation hépatique en totalité) ou dans certains schémas de prise en charge avant greffe. Pourtant, l'avènement de la radiothérapie de haute précision, telle que la radiothérapie hypofractionnée en condition stéréotaxique, permet de traiter les lésions avec des marges minimes et donc, d'augmenter la dose délivrée en diminuant le volume de foie sain irradié. On retrouve aujourd'hui un nombre de plus en plus important de séries rétrospectives et prospectives qui décrivent son efficacité et sa tolérance tant pour les lésions primitives que secondaires. Nous faisons ici un point sur les indications, les résultats et les modalités de ce type de traitement.

Dosimetric Effect of Target Position Accuracy on Single-Isocenter Multiple Liver Metastases SBRT.

Purpose: To evaluate the dosimetric effects of intrafraction baseline shifts combined with rotational errors on Four-dimensional computed tomography-guided stereotactic body radiotherapy for multiple liver metastases (MLMs). Methods: A total of 10 patients with MLM (2 or 3 lesions) were selected for this retrospective study. Baseline shift errors of 0.5, 1.0, and 2.0 mm; and rotational errors of 0.5°, 1°, and 1.5°, were simulated about all axes. All of the baseline shifts and rotation errors were simulated around the planned isocenter using a matrix transformation of 6° of freedom. The coverage degradation of baseline shifts and rotational errors were analyzed according to the dose to 95% of the planning target volume (D95) and the volume covered by 95% of the prescribed dose (V95), and related changes in gross tumor volume were also analyzed. Results: At the rotation error of 0.5° and the baseline offset of less than 0.5 mm, the D95 and V95 values of all targets were >95%. For rotational errors of 1.0° (combined with all baseline shift errors), 36.3% of targets had D95 and V95 values of <95%. Coverage worsened substantially when the baseline shift errors were increased to 1.0 mm. D95 and V95 values were >95% for about 77.3% of the targets. Only 11.4% of the D95 and V95 values were >95% when the baseline shift errors were increased to 2.0 mm. When the rotational error was increased to 1.5° and baseline shift errors increased to 1.0 mm, the D95 and V95 values were >95% in only 3 cases. Conclusions: The multivariate regression model analysis in this study showed that the coverage of the target decreased further with reduced target volume, increasing the baseline drift, the rotation error, and the distance to the target.

Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.

Effect of cytokines on advanced hepatocellular carcinoma prognosis receiving radiotherapy and tislelizumab plus anlotinib: a single-center phase II clinical trial.

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.

Selective internal radiation therapy segmentectomy: A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy (SIRT) has emerged as a minimally invasive approach for the treatment of tumors. This percutaneous technique involves the local, intra-arterial delivery of radioactive microspheres directly into the tumor. Historically employed as a palliative measure for liver malignancies, SIRT has gained traction over the past decade as a potential curative option, mirroring the increasing role of radiation segmentectomy. The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods, particularly well-suited for patients where surgical resection or ablation is not feasible. Radiation segmentectomy is a more selective approach, aiming to deliver high-dose radiation to one to three specific hepatic segments, while minimizing damage to surrounding healthy tissue. Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model.

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

Comparison between Volumetric Modulated arc Therapy based Coplanar and Noncoplanar Planning for Stereotactic Body Radiation Therapy of Liver

BACKGROUND: The study aims to investigate potential dosimetric benefits between non-coplanar and coplanar beam arrangements of Volumetric-Modulated Arc Therapy (VMAT) plans for liver stereotactic body radiotherapy (SBRT). METHODS: Thirteen patients who had undergone liver SBRT treatment in our department were chosen retrospectively for the study. Two sets of SBRT-VMAT plans namely, non-coplanar (NC-VMAT) and Coplanar (C-VMAT) were generated in Monaco(v5.11) planning system for Elekta Versa HD Linac using unflatten 6MV photon. The NC-VMAT plans were created by two/three non-coplanar partial arcs with couch rotation of ±150 and had an arc span of 1300 to 1600 whereas the C-VMAT plans consisted of a full arc. Both plans were compared by statistically analyzing various dosimetric and technical parameters. RESULTS: There is no statistically significant difference observed between the C-VMAT and NC-VMAT plans for planning target volume (PTV) coverage. However, the spine dose (D1cc) was much less in the NC-VMAT plan compared to the C-VMAT plan, with mean values of 6.127 ± 3.08Gy and 9.058 ± 4.76Gy, respectively (p-value=0.002). The low dose spillage to the healthy tissue was compared by the volume receiving 5Gy (V5Gy) and 10Gy (V10Gy). V5Gy of the NC-VMAT plan was 2399.23±1870.76cc while that of C-VMAT plans was 2835.36±1930.20cc with the p-value <0.001. Moreover, the monitor units(MU) were less with NC-VMAT than with C-VMAT SBRT plans (p=0.015). CONCLUSION: The plan quality of NC-VMAT plans was favorable compared to C-VMAT plans for liver SBRT especially in reducing spine dose, low dose spillage to healthy tissue, and MU.

Ablative Radioembolization (SIRT) of a Large Inoperable Renal Cell Carcinoma Invading the Liver That Resulted in Hematuria Control and Complete Necrosis by mRECIST Criteria.

ABSTRACT: We report the successful application of radioembolization (SIRT) in a 77-year-old man with end-stage renal disease on hemodialysis and repeated episodes of macroscopic hematuria due to a large renal cell carcinoma of the right kidney extending to liver segment VI. A compassionate SIRT therapy was performed with resin microspheres through the upper pole renal artery and the feeding segmental artery of liver segment VI. Hematuria was resolved after treatment, and 4 months later, a follow-up CT scan revealed tumor size reduction and complete tumor necrosis (Response Evaluation Criteria in Solid Tumors criteria). Ablative SIRT therapy could be a safe and efficient option in a large inoperable RCC.

Radionuclide Therapy With 177 Lu-PSMA in a Patient With Hepatocellular Carcinoma.

ABSTRACT: A 69-year-old man diagnosed with progressive bone metastatic castration-resistant prostate adenocarcinoma and concurrent alcoholic cirrhosis with multiple hepatocellular carcinoma (HCC) nodules was referred to our nuclear medicine service for 177 Lu-PSMA-617 therapy. The patient's pretreatment screening using 68 Ga-PSMA-11 PET/CT revealed high prostate-specific membrane antigen expression in both prostatic and HCC lesions. The patient underwent 2 doses of 177 Lu-PSMA-617. Subsequent imaging assessments with 68 Ga-PSMA-11 PET/CT and hepatic MRI indicated progressive HCC nodules, while showing a partial response in prostatic bone metastases. Positive clinical and biological responses were observed only in prostatic disease, but not in HCC nodules.

Markerless liver online adaptive stereotactic radiotherapy: feasibility analysisCervantes.

Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in thisin-silicostudy the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context.Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagatedand the GTVConventional, the vector lengths between their centres of mass (lCoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction.Main results.The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding tolCoM(mean: 4.3 +/- 2.1 mm), HD95 (mean 4.8 +/- 3.2 mm) and volume preservation between GTVPropagatedand GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints ('priority 1 constraints', 4.2 versus 0.9%, respectively;p< 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive).Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.

Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.