Safety and efficacy of repeat Y90 radioembolization to the same hepatic arterial territory.

OBJECTIVE: To study the efficacy and safety of repeat transarterial radioembolization (TARE) to similar hepatic arterial territories. METHODS: Between 3/2011 and 4/2019, 26 patients (25 males and 1 Female, Mean Age: 65 yo, SD: 11.7 yo, Range: 18-83.0 yo) received TARE with Y90 glass microspheres to treat recurrent or residual primary disease in similar hepatic arterial lobe or segments. Tumor response was evaluated by imaging using the modified-RECIST criteria. Incidence of RILD and adverse events were categorized by a standardized scale using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: Mean cumulative activity after the first treatment was 2.50 GBq (SD:1.04 GBq, Range:0.61-4.93 GBq) and second treatment was 2.27 GBq (SD:1.01 GBq, Range:0.92-5.46 GBq). Mean interval time between initial and repeat treatments was 9.6 months (Range: 1-53 months). Tumor responses were complete, partial, or progression in 73% (n = 19/26), 23% (n = 6/26), and 4% (n = 1/26) in repeat treatment patients, respectively. The incidence of RILD was 0%. Toxicity after first and second treatment was seen in 19% (n = 5/26) & 23% (n = 6/26) patients, respectively, and were all of CTCAE Grade 2. No significant predictors of treatment toxicity for repeat treatment were identified except increased MELD score (p = 0.04). Kaplan-Meier survival analysis in patients with repeat treatment showed a median survival of 15.0 months (95% CI 8.8-21.1 months) and 19.0 months (95% CI 8.1-29.9 months) in patients who only received one treatment with a p value of 0.485. CONCLUSION: Repeat TARE with glass microspheres was an effective and safe treatment strategy for disease management in patients with residual or recurrent disease to the similar hepatic arterial territories without any major treatment related toxicity. ADVANCES IN KNOWLEDGE: Although safety and efficacy of repeat radioembolism has been studied, no study has focused on repeat treatment to similar hepatic arterial territories. The current study shows that repeat treatment to the same hepatic arterial territory is as safe as single treatment to the same territory.

Periportal fields cause stronger cooling effects than veins in hepatic microwave ablation: an in vivo porcine study.

BACKGROUND: Vascular cooling effects are a well-known source for tumor recurrence in thermal in situ ablation techniques for hepatic malignancies. Microwave ablation (MWA) is an ablation technique to be considered in the treatment of malignant liver tumors. The impact of vascular cooling in MWA is still controversial. PURPOSE: To evaluate the influence of different intrahepatic vessel types, vessel sizes, and vessel-to-antenna-distances on MWA geometry in vivo. MATERIAL AND METHODS: Five MWAs (902-928 MHz) were performed with an energy input of 24.0 kJ in three porcine livers in vivo. MWA lesions were cut into 2-mm slices. The minimum and maximum radius of the ablation area was measured for each slice. Distances were measured from ablation center toward all adjacent hepatic vessels with a diameter of ≥1 mm and within a perimeter of 20 mm around the antenna. The respective vascular cooling effect relative to the maximum ablation radius was calculated. RESULTS: In total, 707 vessels (489 veins, 218 portal fields) were detected; 370 (76%) hepatic veins and 185 (85%) portal fields caused a cooling effect. Portal fields resulted in higher cooling effects (37%) than hepatic veins (26%, P < 0.01). No cooling effect could be observed in close proximity of vessels within the central ablation zone. CONCLUSION: Hepatic vessels influenced MWA zones and caused a distinct cooling effect. Portal fields resulted in more pronounced cooling effect than hepatic veins. No cooling effect was observed around vessels situated within the central white zone.

[Tolerance of hypofractionated stereotactic radiotherapy for hepatic tumours]. / Tolérance de l'irradiation stéréotaxique hypofractionnée des tumeurs hépatiques.

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

Towards a patient-specific hepatic arterial modeling for microspheres distribution optimization in SIRT protocol.

Selective internal radiation therapy (SIRT) using Yttrium-90 loaded glass microspheres injected in the hepatic artery is an emerging, minimally invasive therapy of liver cancer. A personalized intervention can lead to high concentration dose in the tumor, while sparing the surrounding parenchyma. We propose a computational model for patient-specific simulation of entire hepatic arterial tree, based on liver, tumors, and arteries segmentation on patient's tomography. Segmentation of hepatic arteries down to a diameter of 0.5 mm is semi-automatically performed on 3D cone-beam CT angiography. The liver and tumors are extracted from CT-scan at portal phase by an active surface method. Once the images are registered through an automatic multimodal registration, extracted data are used to initialize a numerical model simulating liver vascular network. The model creates successive bifurcations from given principal vessels, observing Poiseuille's and matter conservation laws. Simulations provide a coherent reconstruction of global hepatic arterial tree until vessel diameter of 0.05 mm. Microspheres distribution under simple hypotheses is also quantified, depending on injection site. The patient-specific character of this model may allow a personalized numerical approximation of microspheres final distribution, opening the way to clinical optimization of catheter placement for tumor targeting.

Hepatic arterial phase and portal venous phase computed tomography for dose calculation of stereotactic body radiation therapy plans in liver cancer: a dosimetric comparison study.

PURPOSE: To investigate the effect of computed tomography (CT) using hepatic arterial phase (HAP) and portal venous phase (PVP) contrast on dose calculation of stereotactic body radiation therapy (SBRT) for liver cancer. METHODS: Twenty-one patients with liver cancer were studied. HAP, PVP and non-enhanced CTs were performed on subjects scanned in identical positions under active breathing control (ABC). SBRT plans were generated using seven-field three-dimensional conformal radiotherapy (7 F-3D-CRT), seven-field intensity-modulated radiotherapy (7 F-IMRT) and single-arc volumetric modulated arc therapy (VMAT) based on the PVP CT. Plans were copied to the HAP and non-enhanced CTs. Radiation doses calculated from the three phases of CTs were compared with respect to the planning target volume (PTV) and the organs at risk (OAR) using the Friedman test and the Wilcoxon signed ranks test. RESULTS: SBRT plans calculated from either PVP or HAP CT, including 3D-CRT, IMRT and VMAT plans, demonstrated significantly lower (p <0.05) minimum absorbed doses covering 98%, 95%, 50% and 2% of PTV (D98%, D95%, D50% and D2%) than those calculated from non-enhanced CT. The mean differences between PVP or HAP CT and non-enhanced CT were less than 2% and 1% respectively. All mean dose differences between the three phases of CTs for OARs were less than 2%. CONCLUSIONS: Our data indicate that though the differences in dose calculation between contrast phases are not clinically relevant, dose underestimation (IE, delivery of higher-than-intended doses) resulting from CT using PVP contrast is larger than that resulting from CT using HAP contrast when compared against doses based upon non-contrast CT in SBRT treatment of liver cancer using VMAT, IMRT or 3D-CRT.

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate.

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.

Radioembolization of hepatic tumors: flow redistribution after the occlusion of intrahepatic arteries.

PURPOSE: Radioembolization using 90yttrium is an emerging therapy option for unresectable liver malignancies. In order to reduce the number of yttrium injections, endovascular occlusion of a segmental hepatic artery has been proposed. The aim of this study was to assess whether sufficient vascular redistribution of the occluded liver segments through intrahepatic collaterals can be observed. MATERIALS AND METHODS: 27 patients with hepatocellular carcinoma (n = 16) or hepatic metastases (n = 11) were studied. Hepatic angiography was performed on average 16 days prior to radioembolization. The segment II/III artery (n = 9) or the segment IV artery (n = 18) was occluded using coils. Technectium-99m-labeled macroaggregated albumin (99mTc-MAA) was injected into the right and the remaining part of the left hepatic artery in order to identify any hepatic volume not included in the perfused area. Patients underwent a SPECT/CT on average 1 h after the 99mTc-MAA injection. Two radiologists evaluated the SPECT/CT scans regarding the presence of non-perfused hepatic segments. Furthermore, hepatic perfusion was assessed by digital subtraction angiography (DSA) on the day of radioembolization. RESULTS: In 16/27 patients (59%) a perfusion of the occluded liver segment was visible on the SPECT/CT scan. In 8/11 patients without flow redistribution at the time of the SPECT/CT, perfusion of the occluded segment through hepatic collaterals was observed during angiography prior to radioembolization. Hence, flow redistribution was eventually found in 24/27 patients (89%). CONCLUSION: Flow redistribution after the occlusion of intrahepatic arteries prior to radioembolization can be successfully induced in the majority of patients with anatomical variants of the hepatic arteries.

Is prophylactic embolization of the hepatic falciform artery needed before radioembolization in patients with 99mTc-MAA accumulation in the anterior abdominal wall?

PURPOSE: While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of (99m)Tc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours. METHODS: A total of 224 diagnostic hepatic angiograms combined with (99m)Tc-MAA SPECT/CT were acquired in 192 patients with different types of cancer, of whom 142 were treated with a total of 214 radioembolization procedures. All patients received a whole-body scan, and planar and SPECT/CT scans of the abdomen. Only patients with extrahepatic (99m)Tc-MAA accumulation in the anterior abdominal wall were included in this study. Posttreatment bremsstrahlung SPECT/CT and follow-up results for at least 3 months served as reference standards. RESULTS: Tracer accumulation in the anterior abdominal wall was present in pretreatment (99m)Tc-MAA SPECT/CT images of 18 patients (9.3%). The HFA was found and embolized by radiologists before treatment in one patient. In the remaining patients radioembolization was performed without any modification in the treatment plan despite the previously mentioned extrahepatic accumulation. Only one patient experienced abdominal muscle pain above the navel, which started 24 h after treatment and lasted for 48 h without any skin changes. The remaining patients did not experience any relevant side effects during the follow-up period. CONCLUSION: Side effects after radioembolization in patients with tracer accumulation in the anterior abdominal wall on (99m)Tc-MAA scans indicating a patent HFA are neither common nor severe. Thus, there is no absolute need for prophylactic embolization of the HFA or modification of the treatment plan if the HFA is not detectable on angiography.

Modeling bimodal vessel effects on radio and microwave frequency ablation zones.

A bench liver model is presented that separates the thermal and electrical effects of large blood vessels within radio and microwave frequency ablation boundaries. The model includes a cylindrical tissue environment with a 5 mm vessel placed parallel to and 15 mm way from either a Covidien Energy-based Devices Evident MW Ablation Percutaneous Antenna or a CoolTip RF Ablation Single Electrode Kit. An array of fiber optic thermal probes is used to monitor radial temperature profile on the vessel and non-vessel sides of the ablation zone. Circulating blood exhibits higher electrical conductivity than surrounding liver tissue and provides a significant means for transport of thermal energy. Data from the thermal probes indicate key performance differentiators between MW and RF ablation modalities when they are used next to large blood vessels clarifying the difference between thermal and electrical energy sink. The results suggest RFA is susceptible to both the thermal and electrical energy sink effects of large vasculature while MWA is only susceptible to thermal sink. Ablation zone boundaries were distorted on both the vessel and non-vessel sides with RFA whereas with MWA only the vessel side is affected.

Ultrasound monitoring of a novel microwave ablation (MWA) device in porcine liver: lessons learned and phenomena observed on ablative effects near major intrahepatic vessels.

BACKGROUND: Microwave ablation (MWA) is postulated to have several advantages over other thermoablative modalities in the treatment of hepatic tumors. Herein, we use an in vivo porcine model to determine the effect of hepatic blood flow on a novel MWA applicator. METHODS: Four 100-kg pigs underwent hepatic MWA (2,450 MHz, 100 W, 4 min) using a 5.7-mm diameter applicator (Microsulis Americas, Sulis V) inserted near large intrahepatic blood vessels. Real-time monitoring was performed using 3, 5, and 12 MHz diagnostic ultrasound transducers. The ablated zones were sectioned for gross and histological processing. RESULTS: Ablation zones were uniform in shape and size (3-4 cm) and related to power deliver only. Gross and microscopic examination revealed direct extension of ablation zones to the margin of major hepatic blood vessels and occasionally beyond the intended target. Of note, a momentary acoustic white-out occurred around the probe at 25 +/- -1 s in every ablation. DISCUSSION: The Sulis V MWA applicator produced uniform zones of ablation that remain unaffected by convective heat loss. The applicator induced a reproducible but temporary event as seen by ultrasound. Further study is warranted to define the physics, benefits, limits, and clinical safety of this new MWA technology.

Incidence of radiation pneumonitis after hepatic intra-arterial radiotherapy with yttrium-90 microspheres assuming uniform lung distribution.

OBJECTIVE: To assess the incidence of clinical and imaging radiation pneumonitis (RP) in a cohort of patients treated with >30 Gy cumulative lung dose (CLD) using Y90 microspheres. MATERIALS AND METHODS: Four hundred three patients were treated with Y90 microspheres during a 4-year period. Of these, 58 patients received >30 Gy CLD. Patients were followed for toxicities suggestive of imaging or clinical RP. Toxicities were graded using the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. Patients were also followed for survival from time of first treatment. RESULTS: There were 44 men and 14 women. Forty-three patients had hepatocellular carcinoma (HCC), whereas 15 had liver metastases. Mean and median follow-up were 7.3 and 6.0 months, respectively. Mean lung shunt fraction was slightly greater in the patients with HCC versus metastases (20% vs. 16.7%, P = 0.2308). The lifetime CLD for metastases and HCC groups were not statistically different (54.04 Gy vs. 48.44 Gy, P = 0.4303). Forty-three of 53 patients demonstrated no lung imaging findings suggestive of pneumonitis. Imaging findings in 10 patients included pleural effusions, atelectasis, and ground glass attenuation. There were no cases of clinical or imaging RP. Survival varied depending on stage as well as single and CLD. None of the patient deaths were attributed to respiratory compromise. CONCLUSION: RP was not predicted using the currently used Y90 dosimetry models that assume uniform distribution in the lungs. Further investigation and dose escalation studies are required to more precisely define the radiation tolerance of lung parenchyma using this mode of therapy.

The toxicity of liver directed yttrium-90 microspheres in primary and metastatic liver tumors.

BACKGROUND: Selective Internal Radiation (SIR) therapy with yttrium-90 microspheres has become an alternative approach to treat hepatic tumors. METHODS: A single institution retrospective chart review was performed to assess the safety of SIR microspheres in twenty-one patients with hepatic malignancies. The yttrium-90 radiation dose was dependent upon the percentage of tumor involvement of the liver, with a dose modification (reduction) adjusted for macroaggregated albumin (MAA) shunted to the lung. RESULTS: Twenty-one patients underwent twenty-five treatments with SIR microsphere therapy for primary and metastatic liver tumors. One mortality was secondary to fulminant hepatic failure after developing radiation hepatitis. Morbidities included radiation hepatitis (1) and peptic ulcer disease (6). CONCLUSIONS: The application of SIR microspheres has been utilized for a variety of liver tumors. Although it has been a useful treatment option in selected patients, safety still remains an issue.

Intraoperative radiation therapy in liver tissue in a pig model: monitoring with dual-modality PET/CT.

PURPOSE: To assess, in a pig model, the value of dual-modality positron emission tomography (PET)/computed tomography (CT) for monitoring radiation therapy. MATERIALS AND METHODS: Central bile duct resection followed by creation of a biliodigestive anastomosis was performed in nine pigs. Six of these pigs were also treated with intraoperative radiation therapy (IORT) (20 Gy) in the area of the anastomosis. Two, 4, and 8 weeks postoperatively, contrast material-enhanced fluorine 18 fluorodeoxyglucose (FDG) PET/CT of the liver was performed in all of the animals. The radioactive tracer concentration in the region of the anastomosis was quantified, and the values were compared intraindividually with the values at the liver periphery. Histologic evaluation of the liver was performed 8 weeks postoperatively. The PET/CT images were assessed for changes in liver volume and bile duct diameter over time. RESULTS: In all nine pigs, the region of the anastomosis could be clearly defined on the fused PET/CT images. PET/CT revealed a decreased concentration of FDG in the irradiated field 2 and 4 weeks after IORT. At 8 weeks, however, the distribution of the tracer in the irradiated pigs did not differ from that in the nonirradiated pigs. Homogeneous tracer uptake in all liver regions was observed in the nonirradiated animals. The CT images showed an increase in liver volume in all pigs and bile duct dilatation that increased over time in the irradiated pigs. CONCLUSION: The morphologic and functional changes due to IORT in liver tissue can be accurately monitored with dual-modality PET/CT. By enabling the integration of functional and morphologic data, PET/CT may have an important role in monitoring radiation treatment.

[Premises for intravascular radiological interventions in hepatic hemangiomas]. / Predposylki k vnutrisosudistym rentgenoradiologicheskim vmeshatel'stvam v lechenii hemangiom pecheni.

In the paper anatomic and radiological preconditions are considered for intravascular treatment of hemangiomas of the liver based on the study blood vessels of corrosion preparations of 5 tumors, removed during a resection of a liver; results of 69 angiographies of the liver and 73 hepatic radiographies. The authors offer a 3-marks evaluation of the arterial blood flow in a total blood supply of the hemangiomas. Study of the versions of the arterial blood supply for hemangiomas enabled to validate the different approach in use of intravascular treatment (ligation or embolization of hepatic artery) in patients with hemangiomas of the liversince a surplus arterial flow in the tumors was found in 53.6% of observations.

Tolerance of bile duct to intraoperative irradiation.

In order to determine the effects of intraoperative radiation therapy of the bile duct and surrounding tissues, seven adult dogs were subjected to laparotomy and intraoperative irradiation with 11 MeV electrons. Two animals were treated at each dose level of 2000, 3000, and 4500 rads. A single dog which received a laparotomy and sham irradiation served as a control. The irradiation field consisted of a 5 cm diameter circle encompassing the extrahepatic bile duct, portal vein, hepatic artery, and lateral duodenal wall. The animals were followed clinically for mor than 18 months after treatment, and autopsies were performed on dogs that died to assess radiation-induced complications or tissue damage. All dogs developed fibrosis and mural thickening of the common duct, which appeared by 6 weeks following irradiation and which was dose-related, being mild at low doses and more severe at high doses. Hepatic changes were seen as early as 6 weeks after irradiation, consisting of periportal inflammation and fibrosis. The hepatic changes appeared earliest at the highest doses. Frank biliary cirrhosis eventually developed at all dose levels. Duodenal fibrosis appeared in the irradiation portal, being most severe at the highest doses and in some animals resulting in duodenal obstruction. No changes were observed in irradiated portions of portal vein and hepatic artery at any dose level. It was concluded that intraoperative radiation therapy delivered to the region of the common duct leads to ductal fibrosis, partial biliary obstruction with secondary hepatic changes, and duodenal fibrosis if bowel wall is included in the field. Clinical use of intraoperative radiation therapy to the bile duct in humans may require routine use of biliary and duodenal bypass to prevent obstructive complications.