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To evaluate the effect and mechanism of radiotherapy (RT)-sorafenib pharmacokinetics (PK) in different regimens with conventional or high dose irradiation. Between February 2012 and December 2018, 43 patients with portal vein tumor thrombosis treated with sorafenib plus conventional RT (58%) or stereotactic body radiation therapy (SBRT, 42%) were retrospectively reviewed. In vivo and in vitro studies of concurrent and sequential RT with sorafenib were designed. SBRT resulted in a 3-fold increase in complete recanalization compared to conventional RT group (28% vs. 8%, p = 0.014). Compared to the control group, the area under the concentration vs. time curve (AUC) of sorafenib was increased in the concurrent RT 2Gy and RT 9Gy groups and the sequential RT 9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT 2Gy group (p = 0.036). Sequential RT 2Gy and RT 9Gy increased CYP3A4 activity by 82% (p = 0.028) and 203% (p = 0.0004), respectively, compared to that with the corresponding concurrent regimen. SBRT produced better recanalization than conventional RT with sorafenib. The AUC of sorafenib was modulated by RT. P-gp expression was not influenced by RT. The sequential RT regimen increased CYP3A4 activity that may increase the RT-sorafenib synergy effect and overall sorafenib activity. The biodistribution of sorafenib was modulated by local RT with the different regimens.

Background/aim: The significance of the anatomical variations of proximal jejunal vein [the so-called 1st jejunal vein (J1v)] has been reported from a technical standpoint. The aim of this study was to retrospectively investigate the prognostic impact of the anatomical variations of J1v in the surgical treatment of resectable pancreatic cancer (PC)., Patients and Methods: A total of 49 patients with resectable PC located in the uncinate process were included in this study. The J1v converging pattern was divided into 2 groups in terms of its relation to the SMA (i.e., the J1v status): i) group D: the J1v travels posterior to the SMA; ii) group V: the J1v travels anterior to the SMA. The associations between the J1v status and surgical outcome were assessed., Results: The 5-year survival rate after resection in group V (35%) was significantly lower than that in group D (70%) (p=0.029), and the J1v status of group V was the only independent negative prognostic factor (HR=5.49; 95% CI=1.69-19.3; p=0.005)., Conclusion: The J1v converging pattern is a significant prognostic variable in patients with PC located in the uncinate process: the J1v status of group V was significantly associated with impaired survival., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the dosimetry of 125 I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT)., Methods: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125 I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent., Results: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%., Conclusions: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To investigate the image quality, diagnostic accuracy, and dose reduction potential of a split-bolus protocol(SBP) compared with a multiphasic protocol(MPP) in the detection of recurrent or progressive pancreatic ductal adenocarcinoma(PDAC) or cholangiocarcinoma(CC) using contrast- enhanced computed tomography(CECT)., Materials and Methods: This prospective study included 56 patients who underwent CECT, 28 with our institutional standard MPP(100 ml contrast bolus) and 28 with a novel SBP(110 ml). Radiation exposure was determined in terms of total dose- length product(DLP) and computed tomography dose index(CTDI). Image quality was measured objectively by analysis of attenuation in Hounsfield units(HU) in regions of interest(ROIs) and subjectively by two blinded readers using a Likert scale. Diagnostic accuracy and interreader variability were tested., Results: The total DLP of the SBP group(498.1 ± 43.7 mGy*cm) was significantly lower than in the MPP group(1,092.5 ± 106.9 mGy*cm; p < 0.001). The SBP showed higher contrast enhancement of all critical anatomical structures including portal vein, liver, and pancreas compared with the MPP, except for the aorta(SBP: 326.9 ± 15.7 HU vs. MPP: 246.7 ± 12.2 HU; p < 0.001). Subjective analysis revealed poorer image quality ratings for important landmarks with the MPP (resection surface: p = 0.624, portal vein: p = 0.395, liver p = 0.361). The two blinded readers correlated significantly. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and overall interreader variabilities correlated significantly. Furthermore, significantly fewer slices per exam were required for the SBP(1,823 vs. 3,235; p < 0.001)., Conclusion: The SBP provides the same image quality and diagnostic accuracy as an MPP while significantly lowering radiation exposure in CT follow-up of PDAC or CC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Portal vein thrombosis (PVT) is generally recognized as a prognostic factor in HCC. Our purpose is to assess and compare the survival of patients with PVT and without PVT, after Y-90 Trans-Arterial Radio-Embolization (TARE) of unresectable HCC, unresponsive to other loco-regional treatments., Materials and Methods: Between November 2005 and November 2012, Y-90 resin-based TARE was performed in an IRB-approved prospective protocol, on 89 patients with unresectable HCC. 33/89 patients had PVT, the remaining 56 were resistant-to-cTACE or underwent TARE as a downstaging therapy. All patients were studied with Multi-Detector Computed Tomography (MDCT), angiography, 99mTc-MAA-scintigraphy and liver biopsy. Gastro-duodenal artery was embolized in most cases. Proton-Pump Inhibitors were administered to prevent gastritis and ulcers. χ2 test with Yates correction and log rank test were used to compare the two proportions and Kaplan-Meier survival curves, respectively., Results: The average activity administered was 1.7 ± 0.4 GBq. After the treatment, CTCAE grade 2 adverse events occurred in 46% (41/89) patients: in particular, fever and abdominal pain were found in 25 and 16 patients, respectively. No major side-effect was observed. According to mRECIST criteria, partial response or complete response was found in 70% of patient three months after the treatment, and in 90.5% nine months after the treatment. No significant difference was found in survival of patients with PVT compared to those without PVT (p-value = 0.672). A complete regression of PVT was observed in almost half patients (13/27, 48.1%)., Conclusions: Portal vein invasion does not affect survival in advanced stage HCC-patients undergoing TARE using Y-90 resin-based microspheres. Y90 procedure is associated with regression of portal vein tumor thrombus., Competing Interests: The authors have declared that no competing interests exist.

Aim: Prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) is extremely poor. However, proper therapeutic strategies have not been established yet. The purpose of this study is to identify the effects of external beam radiation therapy (EBRT) for MVI of HCC., Methods: We have analyzed and evaluated 80 consecutive patients with HCC with MVI who underwent EBRT, and factors associated with enhanced survival in EBRT were evaluated by univariate and multivariate analysis., Results: The local response rate of radiotherapy for the irradiated MVI was 66.2%. The time to progression of the irradiated MVI was 5.8 months. Univariate and multivariate analyses showed that the higher irradiation dose (over 45 Gy) and the irradiation location (hepatic vein tumor thrombus - HVTT) were significant factors associated with survival benefits of EBRT. The response of EBRT for HVTT was significantly superior to that for portal vein or bile duct tumor thrombus., Conclusion: We conclude that a multidisciplinary therapeutic strategy based on EBRT should be proactively selected in the treatment of advanced HCC with MVI., (© 2019 S. Karger AG, Basel.)

Purpose: To evaluate the safety and efficacy of iodine-125 ( 125 I) seed strand implantation in combination with transarterial chemoembolization for the treatment of hepatitis B-related unresectable hepatocellular carcinoma (HCC) with portal vein invasion., Materials and Methods: From January 2013 to June 2016, 76 HCC patients with type II tumor thrombus were included in this single-center retrospective study. Twenty patients underwent 125 I seed strand implantation combined with transarterial chemoembolization (group A; n = 20), while 56 patients underwent transarterial chemoembolization alone (group B; n = 56). The procedure-related and radiation complications were assessed. Overall survivals were compared by propensity-score analysis., Results: The technique was successfully performed in all patients. The mean intended dose (r = 10 mm; z = 0; 240 days) was 62.6 ± 1.8 Gy. No grade 3 or 4 adverse events related to the procedure occurred in either group. After propensity-score-matching analysis, 19 patients were selected into each group, respectively. In the propensity-matching cohort, the median overall survival time was significantly longer in group A than in the group B (19 pairs; 28.0 ± 2.4 vs 8.7 ± 0.4 mo; P = .001). Treatment strategy, arterioportal shunt, and number of transarterial chemoembolization sessions were significant predictors of favorable overall survival time., Conclusions: 125 I seed strand implantation combined with transarterial chemoembolization is a safe and effective treatment for HCC patients with portal vein invasion., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Background: To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT)., Methods: Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test., Results: Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values., Conclusion: Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP., Trial Registration: ClinicalTrials.gov identifier NCT01556282 , registered March 16, 2012.

Objective: Determination of the peculiarities of ultrastructural changes and metabolism of reactive forms of oxy gen and nitrogen in the tissues of the myocardium, aorta and portal vein of the radiosensitive BALB/c mice due long term exposure to the complex of radionuclides of Chоrnobyl fallout (ejection) and low intensity low dose γ irradiation., Materials and Methods: Experimental studies were performed on 60 mice female radiosensitive lines BALB/c with a body weight of 20-22 g, which were divided into 3 groups: I group (control) animals age 6-9 months which were born and lived their lives in Kyiv vivarium under conditions natural radioactive background; ІІ - animals age 6 months, which were born and lived in the Chornobyl exclusion zone throughout their lives; ІІІ - animals, which from 3 months of age for 6 months were constantly located in cages with flat ionizing radiation sources and exposed to external γ irradiation in a total dose of 0.43 Sv. Animals of II and III groups were kept in the vivarium of the Institute for Safety Problems of Nuclear Power Plants of the National Academy of Sciences of Ukraine (Chornobyl). Mice of the BALB/c lines are sensitive to radiation: for males LD 50/30 < 5.7 Gy, for females - 5.85 Gy., Results and Conclusions: The peculiarities of structural and functional changes in the organs of the cardiovascular system (CVS) and mechanisms of the development of oxidative and nitrosatitative stress due long term exposure to the complex of radionuclides of the Chornobyl fallout (ejection) and low intensity low dose γ radiation based on the study of ultrastructural organization and metabolism of reactive oxygen species (ROS) and nitrogen (NRS) of the atri al cardiomyocytes (CMC), the aortic endothelium and portal vein of the BALB/c mice. Found that the permanent expo sure to low doses of radiation changes occur, including the dominant mechanism is to run a CMC apoptosis and endothelial cells of the aorta and portal vein. It is shown that the development of oxidative stress accompanied by increased activity of ROS metabolism that occurs due to activation of nucleotide and lipid superoxide generators. Found that under these conditions the development of nitrosative stress is due to the activation of inducible NO syn thesis enzyme iNOS and inhibit its synthesis constitutive eNOS enzyme. High levels of simultaneous generation of superoxide and NO, bindting, lead to the formation of toxic peroxynitrite, which initiates the process of apoptosis., (I. V. Horot, M. M. Tkachenko.)

Sorafenib has improved the median overall survival of unresectable or otherwise untreatable hepatocellular carcinoma (HCC) of ∼3 months, compared to supportive cares. Complete response, although rare, has been reported. The authors reported herein a case of complete biochemical and radiological remission of advanced unresectable HCC with lymph node metastasis and tumoral portal vein thrombosis treated by 5 months therapy with sorafenib followed by adjuvant Yttrium-90 radioembolization. At 12 months follow-up, there is no evidence of HCC recurrence.

The purpose of this study was a comparison of the X-ray density in certain organs and anatomical structures and the determination of the radiation exposure during venous-arterial MSCT scanning and classical two-phase CT of organs of the abdominal cavity. It has been established that the technique of venous-arterial MSCT scanning provided a significant reduction of radiation dose during CT of organs of the abdominal cavity and could be used as an alternative to two-phase examination in the process of dynamic monitoring of cancer patients.

The aim of the study is to evaluate the practicability and therapeutic efficacy of (125)iodine seeds implantation percutaneously for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Nineteen patients with HCC accompanied with PVTT received ultrasound-guided implantation of 8-30 (125)iodine seeds, 8 mm apart within the portal vein tumor thrombi. The patients were followed up postoperatively for a period of 3-22 months. The successful rates of the procedure, postoperative changes of liver and renal function, hemogram, complications and therapeutic response were monitored. (125)I seeds were successfully implanted in the portal veins in all patients without serious complications. During the follow-up period, the portal vein tumor thrombi all shrunk obviously. Percutaneous implantation of (125)iodine seeds into the portal vein is an effective and safe treatment for PVTT accompanying HCC.

The aim of this study was to evaluate the role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVT) and to determine the prognostic factors for overall survival. Altogether, 106 patients with HCC and PVT referred for radiotherapy between 2004 and 2009 were retrospectively reviewed. A total of 60 Gy in 30 daily fractions was delivered with intensity-modulated radiotherapy techniques. Patient-related and treatment-related factors were analyzed to evaluate their prognostic significance for the overall survival rate. Complete response was noted in 10 patients and partial response in 55 patients. The liver lesions had become resectable after the completion of radiotherapy in 12 patients, and surgery was subsequently performed. One or two courses of transarterial chemoembolization (TACE) were administered to 19 patients following radiotherapy. The 1-year and 2-year overall survival rates were 34.7% and 11%, respectively, and the median survival was 7 months for the entire cohort of patients. Post-radiotherapy treatment modality, response to radiotherapy and JIS score were demonstrated as independent prognostic factors for overall survival (P = 0.003, P < 0.001, P < 0.001, respectively). For patients who received surgical intervention after radiotherapy, the median survival was 30 months and the 2-year overall survival rate was 67%. Radiotherapy achieved a 61.5% objective response rate and prolonged survival in patients with PVT. The liver tumors had become resectable after radiotherapy in 11% of patients. Our results suggested that radiotherapy could offer survival benefits and should be considered as a treatment option for patients with PVT. Radiotherapy could also be considered as a preoperative treatment modality in patients with HCC and PVT., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: To assess by means of computer simulations whether the heat sink effect inside a large vessel (portal vein) could protect the vessel wall from thermal damage close to an internally cooled electrode during radiofrequency (RF)-assisted resection., Methods: First,in vivo experiments were conducted to validate the computational model by comparing the experimental and computational thermal lesion shapes created around the vessels. Computer simulations were then carried out to study the effect of different factors such as device-tissue contact, vessel position, and vessel-device distance on temperature distributions and thermal lesion shapes near a large vessel, specifically the portal vein., Results: The geometries of thermal lesions around the vessels in the in vivo experiments were in agreement with the computer results. The thermal lesion shape created around the portal vein was significantly modified by the heat sink effect in all the cases considered. Thermal damage to the portal vein wall was inversely related to the vessel-device distance. It was also more pronounced when the device-tissue contact surface was reduced or when the vessel was parallel to the device or perpendicular to its distal end (blade zone), the vessel wall being damaged at distances less than 4.25 mm., Conclusions: The computational findings suggest that the heat sink effect could protect the portal vein wall for distances equal to or greater than 5 mm, regardless of its position and distance with respect to the RF-based device.

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.

Purpose: To compare positron emission tomography/computed tomography (PET/CT) imaging with bremsstrahlung single photon emission computed tomography (SPECT) in patients after yttrium-90 ((90)Y) microsphere radioembolization to assess particle uptake., Materials and Methods: This prospective study comprised patients with large (> 5 cm) hepatocellular carcinoma (HCC) or tumor-associated portal vein thrombus (PVT), or both. After radioembolization for HCC, patients underwent bremsstrahlung SPECT/CT and time-of-flight PET/CT imaging of (90)Y without additional tracer administration. Follow-up imaging and toxicity was analyzed. Imaging analyses of PET/CT and bremsstrahlung SPECT/CT were independently performed., Results: There were 13 patients enrolled in the study, including 7 with PVT. Median tumor diameter was 7 cm. PET/CT demonstrated precise localization of (90)Y particles in the liver, with specific patterns of uptake in large tumors. In cases of PVT, PET/CT showed activity within the PVT. When correlated to short-term follow-up imaging, areas of necrosis correlated with regions of uptake seen on PET/CT. Compared with bremsstrahlung imaging, PET/CT demonstrated at least comparable spatial resolution with less scatter. Quantitative uptake in nontreated regions of interest showed significantly reduced scatter with PET/CT versus SPECT/CT (1% vs 14%, P < .001)., Conclusions: Evaluation of (90)Y particle uptake with PET/CT potentially demonstrates high spatial resolution and low scatter compared with bremsstrahlung SPECT/CT. Confirmation of particles within PVT on PET/CT correlates with response on follow-up imaging and may account for the efficacy of radioembolization in patients with PVT., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning., Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model., Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT., Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which could aid in individualizing therapy, particularly for patients at risk for liver injury after RT., (Copyright © 2013. Published by Elsevier Inc.)

Background and Purpose: To compare the efficacy and toxicity of short-course carbon ion radiotherapy (C-ion RT) for patients with hepatocellular carcinoma (HCC) in terms of tumor location: adjacent to the porta hepatis or not., Materials and Methods: The study consisted of 64 patients undergoing C-ion RT of 52.8 GyE in four fractions between April 2000 and March 2003. Of these patients, 18 had HCC located within 2 cm of the main portal vein (porta hepatis group) and 46 patients had HCC far from the porta hepatis (non-porta hepatis group). We compared local control, survival, and adverse events between the two groups., Results: The 5-year overall survival and local control rates were 22.2% and 87.8% in the porta hepatis group and 34.8% and 95.7% in the non-porta hepatis group, respectively. There were no significant differences (P=0.252, P=0.306, respectively). Further, there were no significant differences in toxicities. Biliary stricture associated with C-ion RT did not occur., Conclusions: Excellent local control was obtained independent of tumor location. The short-course C-ion RT of 52.8 GyE in four fractions appears to be an effective and safe treatment modality in the porta hepatis group just as in the non-porta hepatis group., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radiobiologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation., (Copyright (c) 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT)., Methods: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram., Results: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively., Conclusion: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.

Background and Purpose: The prognosis of patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor, as effective treatment options are limited. The authors performed a retrospective review to evaluate the efficacy of proton-beam therapy (PBT) for patients presenting with PVTT in the setting of HCC., Patients and Methods: Between February 1991 and September 2005, 35 patients with HCC and tumor thrombi in the main trunk or major branches of the portal vein presented for consideration of PBT. Their tumor sizes ranged from 25 mm to 130 mm (median, 60 mm). A median total dose of 72.6 GyE in 22 fractions was delivered over 31 days to a target volume that encompassed both the primary hepatic lesion and the PVTT., Results: 32 patients were progression-free during a median follow-up period of 21 months (range, 2-88 months) and three patients experienced disease progression. Local progression-free survival rates were 46% at 2 years and 20% at 5 years, and the median local progression-free survival was 21 months. Acute toxicity > or = grade 3 was observed in three patients, and no patient experienced late toxicity > or = grade 3. None of the patients had to discontinue treatment as a result of toxicity., Conclusion: PBT improved local control and significantly prolonged survival in HCC patients with PVTT.

Background/aims: The purpose of this study is to evaluate the effect of radiation therapy (RT) for tumor thrombosis (TT) in the major portal vein (PV) or inferior vena cava (IVC) from unresectable hepatocellular carcinoma., Methodology: Fifteen HCC patients with main PVTT (n = 10) and IVCTT (n 5) were treated with three-dimensional conformal RT between 2001 and 2004. The mean dose was 38.5 Gy (range 28 to 54Gy). The concurrent therapies to intrahepatic tumor included transcatheter arterial chemoembolization (TACE) in 7, TACE + hepatic arterial infusion in 2 and systemic chemotherapy in 1 patient. The therapeutic effect was assessed by tumor regression for TT., Results: An objective response was observed in 3 of 15 patients (20%). There were no patients with progressive disease. The median survival time was 10 months. In 12 cases with stable disease, time to progression (TTP) estimated above 6 months were 42% (5/12 cases). In univariate analysis, therapeutic effect and TTP were affected to survival time. All patients did not have severe deterioration of liver function., Conclusions: In the current study, we concluded that RT was superior treatment in terms of local control capability and was useful to continue further treatment because RT did not make liver function worse.

Context: Radiofrequency ablation of pancreatic tumours carries a risk of injury to important structures such as the bile duct and duodenum. We have recently developed an ex-vivo model of radiofrequency ablation of the porcine pancreas., Objective: This study evaluates the effect of variations in probe temperature, duration of ablation and simulated portal venous flow on radiofrequency-induced injury. SPECIMEN RETRIEVAL: Pancreata of 30 6-month-old healthy pigs undergoing sacrifice in a commercial abattoir were used., Interventions: Radiofrequency energy was applied to a pre-marked area of the pancreatic head. Pancreatic head biopsies were taken after ablation to incorporate duodenum, portal vein and bile duct respectively and frozen in liquid nitrogen. For each experiment a portion of the tail of the pancreas was studied as non-ablated control. Paired slides using haematoxylin and eosin (H&E) and nicotinamide adenine dinucleotide (NADH) stains were prepared., Main Outcome Measures: The effects of variation in target temperature (100 degrees C to 80 degrees C), duration of ablation and of simulated portal perfusion were studied., Results: Optimal thermal kinetic characteristics were produced by a target temperature of 90 degrees C applied for 5 minutes. At this temperature there was ablation of pancreas without injury to adjacent viscera. Higher temperatures resulted in injury to the bile duct and portal vein. Simulated portal circulation had no effect on ablation., Conclusions: In this ex-vivo study radiofrequency produced a temperature and duration dependent ablation with the optimal characteristics being 90 degrees C for 5 minutes.

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., (Copyright RSNA, 2004)

Ablative therapies such as radio-frequency (RF) ablation are increasingly used for treatment of tumours in liver and other organs. Often large vessels limit the extent of the thermal lesion, and cancer cells close to the vessel survive resulting in local tumour recurrence. Accurate estimates of the heat convection coefficient h for large vessels will help improve ablation techniques, and are required for estimation of thermal lesion dimensions in simulations. Previous estimates of h did not consider that only part of the vessel is heated, and assumed uniform temperature distribution at the vessel wall. An analytical relationship between the heat convection coefficient, blood velocity and temperature is formulated. The heat convection coefficient evaluated will assist both simulations and design of proper protocols for in vivo measurements. The mathematical model developed in this work describes the exchange of heat between a solid surface and a moving fluid and it is based on energy and motion equations for Navier-Stokes fluids. A particular case of a laminar blood flow in the portal vein is studied when a portion of its surface is heated. The results show that heating a larger portion of the vessels reduces convective heat loss, which may result in more effective ablation strategies.

Irradiation of the rat portal vein's fragments with the He-Ne laser for 3, 5 and 10 minutes reduced the fragments tone by half. Frequency of phasic and tonic contractions did not change, their amplitude, however, increased by neatly 40% as compared with the initial level. The NO synthase blocker N-nitro-L-arginine administered prior to the irradiation had no effect on the above parameters. The data obtained suggest that the decrease of the vessel tone is due to production of the EDRF and cGMP. The increase in the amplitude of phasic and tonic contractions of the vein's smooth muscle cells is associated with an increased Ca++ entry in each contraction cycle.

Purpose: To evaluate the ability of 32phosphorus intraluminal irradiation to reduce pseudointimal hyperplasia in a transjugular intrahepatic portosystemic shunt (TIPS)., Materials and Methods: TIPS were successfully placed in 11 swine with normal portal pressures. Six animals received 15.2 Gy intraluminal irradiation to the hepatic parenchyma and venous outflow tract at the time of TIPS placement with use of a NA32P-filled balloon angioplasty catheter. Five control animals underwent TIPS and balloon angioplasty with saline. All animals were followed up for 28 days, at which time percutaneous portography was performed, the animals were killed, and the tissue around the TIPS stent was processed for histologic analysis. Maximum pseudointimal hyperplasia as a percentage of estimated TIPS diameter was calculated for each animal., Results: At the time of euthanasia, all five control TIPS and all but one irradiated TIPS were occluded. Histologic analysis demonstrated considerable variability in the degree of pseudointimal hyperplasia within each TIPS and between animals. No statistically significant difference was found in the maximum pseudointimal hyperplasia, measured as a percentage of stent radius, between control (80.2%+/-17.4%) and irradiated animals (69.2%+/-25.2%)., Conclusions: Irradiation of TIPS with 15.2 Gy 32P delivered at the time of TIPS placement did not significantly improve TIPS patency or reduce the degree of pseudointimal hyperplasia in swine with normal portal pressures.

We developed a new method that provides a wide retroperitoneal irradiation field for patients with cancer of the pancreas in whom a long invaded portal vein is resected during intraoperative radiotherapy. This method involves the use of a venous bypass with a heparinized catheter that does not require systemic anticoagulation or a pump. Anastomosis is completed after intraoperative radiotherapy. Mean (+/- SD) duration of the venous bypass was 3.0 +/- 1.5 hours (range, 2.0 to 6.6 hours), during which no abnormalities of systemic blood pressure, heart rate, and electrocardiographic activity and no signs of congestion of the intestines were observed. Eleven patients were treated with this method, and no complications ascribed to intraoperative radiotherapy or venous bypass were found. We recommend this method as safe and simple for expanding the irradiation field for intraoperative radiotherapy in patients with pancreatic cancer in whom the portal vein is resected.

Tolerance of surgical portal vein anastomosis to intraoperative radiation therapy (IORT) was studied in dogs after single doses of zero, 10, 20 and 40 Gy (290 kVp x-rays). Portal venography was performed prior to IORT and before sacrificing. The dogs were sacrificed 3 and 12 months respectively after irradiation. Portal venography revealed no radiation induced anastomotic stenosis. Autopsy disclosed macroscopic periportal fibrosis in all dogs, independent of radiation dose and observation periods. Microscopically, the three tunicas of the vein did not show any pathological changes after any dose level.

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.