Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters.

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 RT2Gy and RT9Gy groups and the sequential RT9Gy group by 132% (p = 0.046), 163% (p = 0.038) and 102% (p = 0.018), respectively; and was decreased by 59% in the sequential RT2Gy group (p = 0.036). Sequential RT2Gy and RT9Gy 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.

The Anatomical Pattern of the Proximal Jejunal Vein as a Prognostic Factor in Patients With Pancreatic Head Cancer Treated With Preoperative Chemoradiation Therapy.

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.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I 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 125I 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.

Split-bolus vs. multiphasic contrast bolus protocol in patients with pancreatic cancer or cholangiocarcinoma.

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.

Yttrium-90 trans-arterial radioembolization in advanced-stage HCC: The impact of portal vein thrombosis on survival.

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.

Dose and Location of Irradiation Determine Survival for Patients with Hepatocellular Carcinoma with Macrovascular Invasion in External Beam Radiation Therapy.

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.

Treatment of Hepatocellular Carcinoma with Tumor Thrombus with the Use of Iodine-125 Seed Strand Implantation and Transarterial Chemoembolization: A Propensity-Score Analysis.

PURPOSE: To evaluate the safety and efficacy of iodine-125 (125I) 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 125I 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: 125I seed strand implantation combined with transarterial chemoembolization is a safe and effective treatment for HCC patients with portal vein invasion.

Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization.

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.

Peculiarities of ultrastructural organization and metabolism of reactive forms of oxygen and nitrogen in a cardiovascular system for permanent effects of ionizing radiation in low doses. / OSOBLYVOSTI UL'TRASTRUKTURNOÏ ORGANIZATsIÏ I METABOLIZMU REAKTYVNYKh FORM KYSNIu TA AZOTU V SERTsEVO SUDYNNIY̆ SYSTEMI ZA POSTIY̆NOÏ DIÏ IONIZUIuChOGO VYPROMINIuVANNIa U NYZ'KYKh DOZAKh.

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.

Complete Remission of Unresectable Hepatocellular Carcinoma After Combined Sorafenib and Adjuvant Yttrium-90 Radioembolization.

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.

Features of contrast enhancement in different methods of multislice computed tomography.

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.

Percutaneous implantation of (125)iodine seeds for treatment of portal vein tumor thrombosis in hepatocellular carcinoma.

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 role of radiotherapy in the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

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.

Could the heat sink effect of blood flow inside large vessels protect the vessel wall from thermal damage during RF-assisted surgical resection?

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.

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.

Comparison of positron emission tomography and bremsstrahlung imaging to detect particle distribution in patients undergoing yttrium-90 radioembolization for large hepatocellular carcinomas or associated portal vein thrombosis.

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.

Prediction of liver function by using magnetic resonance-based portal venous perfusion imaging.

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.