To evaluate the diagnostic performance of shear wave elastography (SWE) imaging for differentiating normal liver from tumor and characterizing tumor heterogeneity in the rabbit liver VX2 cancer model. Nine rabbits were implanted with VX2 tumor in liver and imaged with conventional US and SWE 2-3 weeks after tumor implantation. Depending on tumor size, up to 12 ROI were placed in tumor and up to 8 ROI in normal liver. The mean, standard deviation and ratio of SWS values (m/s) and elastic modulus (SWEM, KPa) on SWE were recorded. Additionally, 2D elastic images were classified into four color patterns (red, blue, green and yellow). The area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the diagnostic performance of SWE in differentiating tumor versus normal liver. There were statistically significant differences between tumor rim and tumor core (mean tumor rim SWEM = 32.69, SD = 18.64 KPa, mean tumor core SWEM = 13.21, SD = 2.73 KPa, p = 0.001), total tumor and liver (mean liver = 7.96, SD = 1.28 KPa, p<0.0001), tumor core and liver (p<0.001). Compared with other quantitative SWE parameters, mean values expressed in KPa had the highest AUROC value (AUROC = 0.90), with corresponding cut-off value of 17.8 KPa for differentiating tumor from liver, sensitivity of 85.1%, specificity of 96.6%, accuracy of 94.2%, PPV of 86.9%, and NPV of 96.2%. SWE with elastic modulus values can successfully differentiate tumor rim vs. tumor core vs. normal liver in the rabbit model of liver cancer.

To validate the accuracy of wide-array CT to measure differences in regional liver and tumor perfusion in a rabbit model of liver cancer, during first-pass, contrast-enhanced wide-array CT. 7 NZW male liver VX2 bearing rabbits rabbits were anesthetized and IA injected with gold microspheres (15μm, 2 x 106 spheres, BioPal, Worcester, MA) in 30 sec, into the left ventricle under fluoroscopic guidance. while withdrawing the reference sample at 1 ml/min for 2 min, from the femoral artery. Rabbits were scanned in a wide-array 320-detector row volumetric CT scanner (Acquilion One, Toshiba, Japan) 2 hours before IA injection. Scanning parameters were: FOV = 22 cm, kV = 80, mA = 100, slice thickness = 0.5 mm, scan delay = 6 sec, intermittent scanning for 74 sec (arterial phase every 2 sec, portal venous phase every 3 sec). Rabbits were injected with 1.5 ml/kg of isoosmolar CM at 1 ml/sec, followed by a saline flush. CT data were analyzed using the Toshiba CT body perfusion software and calculated tumor and hepatic perfusion values of arterial flow (AF) portal flow (PF) and perfusion index (PI). All rabbits were euthanized after microsphere injection. Samples were weighed and subsequently analyzed together with the respective reference samples using neutron activation quantification. Regional blood flow for each tissue sample was calculated according to: RBF = Fref_(Asmp/Wsmp)/Aref, where Fref is reference flow ( = withdrawal rate), Asmp is activity sample, Wsmp is weight of sample and Aref is activity of reference. Pearson's correlation was used for correlating stable microsphere and CT perfusion flow values. Mean RBF for tumor was 1.15 (SD = 0.74), left liver 0.48 (0.35) and right liver 0.5 (SD = 0.45) ml/min/g. Mean tumor AF was 0.87 (SD = 0.28), left liver AF 0.56 (SD = 0.24), right liver AF 0.55 (SD = 0.21) ml/min/g. CT perfusion AF values were weakly (r = 0.6), but statistically significantly correlated (p = 0.04) to RBF values measured with stable microspheres. Wide-array CT perfusion AF values provide semiquantitative measurements of tumor regional blood flow in the rabbit model of liver cancer.

The aim of this study was to identify the most significant time-varying prognostic factors of overall survival in hepatocellular carcinoma (HCC) patients treated with chemoembolization (TACE), taking into account baseline imaging and clinical metrics, as well as their values over the entire course of treatment. The analysis of time-varying effects may provide insights on valuable biological information that could be missed otherwise. We performed a complete case analysis (CCA) of longitudinally and prospectively collected clinical and imaging metrics on an IRB-approved, HIPAA-compliant cohort of 119 HCC patients treated with TACE between 2001 and 2008. Baseline and longitudinal data included age, gender, ethnicity, cause of cirrhosis and Eastern European Cooperative Group (ECOG) performance status, Child-Turcotte-Pugh (CTP) score, tumor burden, largest tumor diameter, portal vein thrombosis, tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 and modified RECIST. Data were collected at the time of baseline clinical visit, 1st and 2nd clinical follow-up visit and study exit. Overall survival estimates were calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to assess time-varying predictors of overall survival. Mean overall survival of this cohort was 18.85 months (median 14, range: 1-148). The analysis of variables with time-varying Cox models revealed that an ECOG status of 1 or 2 (adjusted HR=1.83, 95% CI=1.11-3.03, p=0.02) and a CTP score of B (adjusted HR=1.50, 95% CI=1.07-2.12, p=0.02), were statistically significant time-dependent predictors of decreased overall survival. Utilizing time-varying Cox regression analysis, patients with unresectable HCC treated with TACE were observed to have a lower adjusted hazard of death if they have either an ECOG status of 0 or a CTP score of A, compared to other patients. The results of this statistical analysis of longitudinally collected data across the treatment course highlight the prognostic value of these markers and should help clinicians assess HCC patient prognosis using longitudinally collected metrics.

Concurrent chemoradiation therapy (CRT) is a standard option for locally advanced pancreatic cancer (LAPC) but has significant toxicity. Localized hyperthermia produced by magnetic iron oxide nanoparticles may enhance efficacy enabling reduced dosing of CRT to minimize toxicity. Local control is inversely related to tumor size for radiation therapy whereas larger tumors can be ideal candidates for magnetic nanoparticle hyperthermia (MNPH). Human pancreas cancer MiaPaCa-02 cells were cultured for both in-vitro screening and development of subcutaneous tumor models in mice. In-vitro screening of toxicity from combinations of MIONs (0.2 mg/mL, 4 hour incubation), 43°C in water bath for 30 min, and radiation (4 Gy) were performed to guide experimental design of in-vivo experiments. MiaPaCa-02 xenografts were obtained by injecting 5×106 cells suspended in gel matrix on the right thigh of 4-6 week old female nude mice. Mice were anesthetized and MIONs (5.5 mgFe/cc of tumor) or PBS was directly injected into the tumors once they reached a prerequisite volume. To assess radiation therapy enhancement with MNPH mice bearing small (0.15 ± 0.03 cm3) and large (0.3 ± 0.06 cm3) tumors were randomly assigned to control (MION-no AMF or PBS-AMF), AMF (18 kA/m, 160 ± 5 kHz, for 20 min), radiation (5 Gy), and combination (AMF-18 kA/m + 5 Gy) groups. Motivated by the intent to provide image-guided delivery of MIONs to LAPC, MIONS were added to ethiodized oil (CT contrast agent) to yield a stable formulation. MiaPaCa-02 cells treated at 43°C for 30 minutes showed a slightly reduced viability (91 ± 1%) compared to controls. MION, 4 Gy, MION + 4 Gy at 43°C produced significantly reduced viabilities compared to ones at 37°C (25 ± 6, 8 ± 3, and 1 ± 1 vs 97 ± 1, 71 ± 5, and 48 ± 14). In-vivo, large tumors treated with AMF-18 kA/m showed better tumor control compared to smaller tumors (16 ± 3 vs 10 ± 2 days to 2 x initial volume). For small tumors, 5 Gy group showed significant tumor growth delay (25 ± 2 days to 4 x) while AMF-18 kA/m group was modest (17 ± 4 days to 4 x) compared to control (12 ± 1 days to 4 x). Combination treatment showed significant tumor control (52 ± 11 days to 4 x) than 5 Gy or AMF-18 kA/m alone. Radiosensitization studies for large tumors are ongoing. The MION-ethiodized oil formulation retained heating and imaging abilities. Preliminary results are promising and suggest that MNPH enhances therapeutic effects of radiation therapy both in-vitro and in-vivo. Large tumors have better therapeutic response compared to small tumors when treated with tumor volume-normalized iron dose and fixed AMF amplitude. The tested MION-ethiodized oil formulation can be a potential theranostic agent.

Magnetic nanoparticle (NP) hyperthermia after intratumoral NP injection and heating with alternating magnetic fields (AMF) offers potential therapeutic options for intractable cancer. To obtain consistent NP distribution within the tumor we explore the development of a NP-ethiodized oil emulsion (NLE). We present in vitro characterization and preliminary in vivo data of the NLE properties. NLE comprises lipiodol (50% w/v), polysorbate 20 (0.2% w/v) and biocompatible Fe3O4 nanoparticles (BNF, 49.8% w/v). Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were performed to characterize particle size of NP alone and in NLE. MR imaging of the NLE was performed with a 3T clinical scanner, using a 12-well plate with graded concentrations of NLE, NP, and lipiodol, suspended in agarose gel. T1-weighted (W), T2-W and T2*-W imaging sequences were acquired for MR relaxation time measurements. MRI data were compared with NP iron concentration to correlate MRI signal intensity with iron content in samples. TEM imaging was performed in HepG2 cell cultures at 18 hours after NLE infusion. In vivo experiments included intratumoral injections of a) NLE (n = 20), b) BNF (n = 12), c) PBS (n = 14) in Foxnu1 mice bearing flank xenograft HepG2 tumors with and without AMF hyperthermia exposure (15-min, 300-700 Gauss, 150 kHz, 18 hours post-injection). Core and intratumoral temperature measurements were acquired at 1-s intervals. Animals were either euthanized at 1-7 days or observed for tumor growth delay. Pathologic analysis included semiquantitative evaluation of tumor necrosis and iron distribution. In vitro MR reverse relaxation time measurements showed a linear increase along the iron gradient for NLE and NP (r = 0.94 and 0.98, respectively). Measured specific heating rate of NLE was higher than NP, 0.08°C/(s × mg Fe), compared with 0.06°C/(s × mg Fe). Mean particle diameter measured with PCS was 120 nm for NP alone and 276 nm for the NLE. Average maximum temperature increase measured at the tumor surface for NLE group (n = 8) was 7.4 ± 0.5°C while the NP alone group (n = 5) was 5.4 ± 0.3°C. At 24 days, there was a 4-fold difference in tumor growth delay between PBS and NLE-AMF heated tumors. Increased tumor necrosis was observed at 7 days in the NLE group. Semi-quantitative intratumoral iron distribution of NLE samples showed a characteristic distribution of NLE along the vascular tumor pathways at the tumor rim. Histological analysis confirmed intratumoral iron deposition and cellular damage consistent with cytotoxic thermal exposure. Intratumor iron distribution for NLE suggests that lipiodol influences NP distribution. Initial results are encouraging and motivate further in vivo evaluation.

Romaric Loffroy, MD, PhD MingDe Lin, PhD Gayane Yenokyan, PhD Pramod P. Rao, MD Nikhil Bhagat, MD Niels Noordhoek, PhD Alessandro Radaelli, PhD Järl Blijd, MSc Eleni Liapi, MD Jean-François Geschwind, MD Purpose: To investigate whether C-arm dual-phase cone-beam computed tomography (CT) performed during transcatheter arterial chemoembolization (TACE) with doxorubicin-eluting beads can help predict tumor response at 1-month follow-up in patients with hepatocellular carcinoma (HCC).

C-arm based tomographic 3D imaging is applied in an increasing number of minimal invasive procedures. Due to the limited acquisition speed for a complete projection data set required for tomographic reconstruction, breathing motion is a potential source of artifacts. This is the case for patients who cannot comply breathing commands (e.g. due to anesthesia). Intra-scan motion estimation and compensation is required. Here, a scheme for projection based local breathing motion estimation is combined with an anatomy adapted interpolation strategy and subsequent motion compensated filtered back projection. The breathing motion vector is measured as a displacement vector on the projections of a tomographic short scan acquisition using the diaphragm as a landmark. Scaling of the displacement to the acquisition iso-center and anatomy adapted volumetric motion vector field interpolation delivers a 3D motion vector per voxel. Motion compensated filtered back projection incorporates this motion vector field in the image reconstruction process. This approach is applied in animal experiments on a flat panel C-arm system delivering improved image quality (lower artifact levels, improved tumor delineation) in 3D liver tumor imaging.

To evaluate the effect of 70-150 μm doxorubicin drug-eluting beads (DEB) on plasma and tissue pharmacokinetics, liver function tests and tumor necrosis of the rabbit hepatic VX2 tumor model.

PurposeTo prospectively evaluate whether dynamic first-pass area-detector CT imaging can depict perfusion changes following intra-arterial therapy in the liver VX2 model.Materials and Methods17 liver VX2 bearing rabbits were scanned in a 320-detector row CT scanner (Acquilion One, Toshiba, Japan) before and at 7 days following intra-arterial therapy (DEB-embolization or bland embolization). The volumetric scanning parameters were: FOV=22 cm, kV=120, mA=80, slice thickness=0.5 mm, scan delay=6 sec, intermittent scanning for 67 sec (arterial phase q 2 sec, portal venous phase q 3 sec). Rabbits were injected with 1.5 ml/kg of isoosmolar CM at 1 ml/sec, followed by a saline flush. CT data were analyzed using the Toshiba CT body perfusion software and calculated tumor, ipsilateral and contralateral to tumor hepatic perfusion using the maximum slope model. Blood samples for liver function tests (LFTs) were obtained at baseline and before euthanasia. All rabbits were euthanized after the final CT scan and tumor and liver samples were evaluated for percentage of tumor necrosis, presence of peritumoral fibrous capsule and microsphere count per tumor slide.ResultsFollowing treatment, arterial flow (AF) of the tumor was significantly reduced (AF pre=130.03, AF post=78.15, p=0.0009), while tumor portal flow (PF) and perfusion index (PI) remained unchanged (p=0.49 and 0.31, respectively). AF to the ipsilateral liver lobe was significantly reduced after treatment (AF pre=132.412, AF post=74.09, p=0.04). PF of the ipsilateral liver lobe was also slightly reduced after treatment (p=0.07). AF, PF and PI to the contralateral liver lobe remained unchanged after treatment (p=0.87, 0.41 and 0.41, respectively). No statistically significant difference was observed between baseline and final LFTs. On pathology, all tumors were successfully embolized, with an average of 7 beads/tumor slide. Tumors had a fibrous capsule with a mean tumor necrosis of 67.7%. No correlation was found between the percentage of tumor necrosis and changes in the tumor AF.ConclusionDynamic first-pass area-detector CT imaging can successfully depict changes in liver and tumor perfusion at 7 days following intra-arterial therapy in the liver VX2 model. PurposeTo prospectively evaluate whether dynamic first-pass area-detector CT imaging can depict perfusion changes following intra-arterial therapy in the liver VX2 model. To prospectively evaluate whether dynamic first-pass area-detector CT imaging can depict perfusion changes following intra-arterial therapy in the liver VX2 model. Materials and Methods17 liver VX2 bearing rabbits were scanned in a 320-detector row CT scanner (Acquilion One, Toshiba, Japan) before and at 7 days following intra-arterial therapy (DEB-embolization or bland embolization). The volumetric scanning parameters were: FOV=22 cm, kV=120, mA=80, slice thickness=0.5 mm, scan delay=6 sec, intermittent scanning for 67 sec (arterial phase q 2 sec, portal venous phase q 3 sec). Rabbits were injected with 1.5 ml/kg of isoosmolar CM at 1 ml/sec, followed by a saline flush. CT data were analyzed using the Toshiba CT body perfusion software and calculated tumor, ipsilateral and contralateral to tumor hepatic perfusion using the maximum slope model. Blood samples for liver function tests (LFTs) were obtained at baseline and before euthanasia. All rabbits were euthanized after the final CT scan and tumor and liver samples were evaluated for percentage of tumor necrosis, presence of peritumoral fibrous capsule and microsphere count per tumor slide. 17 liver VX2 bearing rabbits were scanned in a 320-detector row CT scanner (Acquilion One, Toshiba, Japan) before and at 7 days following intra-arterial therapy (DEB-embolization or bland embolization). The volumetric scanning parameters were: FOV=22 cm, kV=120, mA=80, slice thickness=0.5 mm, scan delay=6 sec, intermittent scanning for 67 sec (arterial phase q 2 sec, portal venous phase q 3 sec). Rabbits were injected with 1.5 ml/kg of isoosmolar CM at 1 ml/sec, followed by a saline flush. CT data were analyzed using the Toshiba CT body perfusion software and calculated tumor, ipsilateral and contralateral to tumor hepatic perfusion using the maximum slope model. Blood samples for liver function tests (LFTs) were obtained at baseline and before euthanasia. All rabbits were euthanized after the final CT scan and tumor and liver samples were evaluated for percentage of tumor necrosis, presence of peritumoral fibrous capsule and microsphere count per tumor slide. ResultsFollowing treatment, arterial flow (AF) of the tumor was significantly reduced (AF pre=130.03, AF post=78.15, p=0.0009), while tumor portal flow (PF) and perfusion index (PI) remained unchanged (p=0.49 and 0.31, respectively). AF to the ipsilateral liver lobe was significantly reduced after treatment (AF pre=132.412, AF post=74.09, p=0.04). PF of the ipsilateral liver lobe was also slightly reduced after treatment (p=0.07). AF, PF and PI to the contralateral liver lobe remained unchanged after treatment (p=0.87, 0.41 and 0.41, respectively). No statistically significant difference was observed between baseline and final LFTs. On pathology, all tumors were successfully embolized, with an average of 7 beads/tumor slide. Tumors had a fibrous capsule with a mean tumor necrosis of 67.7%. No correlation was found between the percentage of tumor necrosis and changes in the tumor AF. Following treatment, arterial flow (AF) of the tumor was significantly reduced (AF pre=130.03, AF post=78.15, p=0.0009), while tumor portal flow (PF) and perfusion index (PI) remained unchanged (p=0.49 and 0.31, respectively). AF to the ipsilateral liver lobe was significantly reduced after treatment (AF pre=132.412, AF post=74.09, p=0.04). PF of the ipsilateral liver lobe was also slightly reduced after treatment (p=0.07). AF, PF and PI to the contralateral liver lobe remained unchanged after treatment (p=0.87, 0.41 and 0.41, respectively). No statistically significant difference was observed between baseline and final LFTs. On pathology, all tumors were successfully embolized, with an average of 7 beads/tumor slide. Tumors had a fibrous capsule with a mean tumor necrosis of 67.7%. No correlation was found between the percentage of tumor necrosis and changes in the tumor AF. ConclusionDynamic first-pass area-detector CT imaging can successfully depict changes in liver and tumor perfusion at 7 days following intra-arterial therapy in the liver VX2 model. Dynamic first-pass area-detector CT imaging can successfully depict changes in liver and tumor perfusion at 7 days following intra-arterial therapy in the liver VX2 model.

To report the outcome patients with HCC and history of either hepatitis B (Hep B) or C (Hep C) infection or alcohol-induced cirrhosis (AIC) treated with TACE with a focus on disease outcomes [tumor size change according to RECIST, Child-Pugh (CP) score and survival]. 178 patients with history of either Hep B or C or AIC were selected from a comprehensive database of 347 patients with unresectable HCC that were treated in our institution between 1996 and 2007. Patients with combined history of alcohol abuse and viral hepatitis infection or combined co-infection were excluded from this study. Tumor response was assessed according to the RECIST criteria. T-tests, chi-square and Wilcoxon signed rank tests were used to assess differences in disease characteristics. Overall survival (OS) rates were calculated with the Kaplan-Meyer test and comparison of survival differences with the Log rank test. 51 patients were diagnosed with hep B, 91 with hepatitis C and 36 patients with AIC. There was no significant difference in the baseline distribution of CP scores among the 3 groups. Mean baseline tumor size was 8.3 cm for hep B, 5.9 cm for hep C and 5.7 cm for AIC patients (p>0.05).There was no significant difference in tumor response among the 3 groups. AIC patients had a slightly higher percentage of partial response and a slightly higher OS rate compared to hep C patients (p=0.07 and 0.06, respectively). All other survival time comparisons were not statistically significant different. Mean OS for hep B patients was 38.57 months (median 18.9, SE: 12.745). Mean OS for hep C patients was 25.36 months (median 19.5, SE: 2.57). Mean OS for AIC patients was 34.67 months (median 26.3, SE: 4.33). In this selected cohort of patients with unresectable HCC treated with TACE, no statistically significant differences were noted between OS and tumor response rates between patients with alcohol-induced cirrhosis and history of hepatitis B or C infection. Patients with alcohol-related cirrhosis showed slightly better survival and a marginally higher percentage of partial response than patients with hepatitis C infection following treatment with conventional chemoembolization.

To assess relevant parameters for the minimally invasive treatment of liver tumors by employing mild hyperthermia and exposure of tumors to an alternating magnetic field. The specific absorption rate (SAR) of different samples of a formulation that can be delivered intratumorally into liver cancer was determined by assessing rates of temperature change over time. Temperature elevations based on iron mass and magnetic field amplitude (300-700 Gauss; frequency, 150 kHz) were investigated by using a formulation containing lipiodol (50% w/v), EDTA (0.2% w/v) and biodegradable bioferrite nanoparticles (1.35 -13.5 mg/ml iron). Parameter combinations (intra-tumoral iron concentration, 900-second magnetic field exposure, 300-700 Gauss, 150 Khz) were tested in Foxnu1 mice bearing flank xenograft human hepatocellular carcinomas (HepG2 cells). Histologic sections of heated tumor tissue were analyzed. SAR data of different formulations ranged from 3 to 211 W/g. Temperature elevation as a function of the iron mass increased linearly up to 13.5 mg. Similarly, intra-tumoral temperature elevation as a function of iron concentration injected increased in a linear fashion using the same AMF power settings. For a given iron concentration, intra-tumoral temperature elevation as a function of power settings also increased linearly. Typical macroscopic findings included visible intratumoral iron deposition. Histologically, intratumoral iron deposition was confirmed and nuclear degenerations were observed in heated malignant cells. Alternating magnetic thermotherapy with intratumoral injection of a formulation containing lipiodol and bioferrite nanoparticles of liver tumors shows potential as a novel locoregional therapy for liver cancer.

To report the outcome of the care of 144 patients with hepatocellular carcinoma (HCC) and history of hepatitis B or C infection treated with transcatheter arterial chemomembolization (TACE) with a focus on disease outcomes [tumor size change according to Response Evaluation Criteria in Solid Tumors (RECIST), Child-Pugh (CP)score and survival]. 144 patients with history of either hepatitis B or C infection were selected from a comprehensive database of 347 patients with unresectable HCC that were treated in our institution between 1996 and 2007. Patients with combined history of alcohol abuse and viral hepatitis infection or combined co-infection were excluded from this study. Disease status was evaluated before and at the end of the treatment period with tumor size measurements according to the RECIST criteria. T-tests, chi-square and Wilcoxon signed rank tests were employed to assess differences in tumor and liver background characteristics. The Kaplan-Meyer test was used to generate survival data and the Log rank test was utilized to assess patient survival differences. Fifty-three patients (47 male, 6 female) were diagnosed with hepatitis B, and 91 patients (80 male, 11 female) with hepatitis C. There was no significant difference in the baseline distribution of CP score (arithmetic) between the two groups (p=0.9). There was no difference in mean tumor size at presentation (6.5 cm for hepatitis B and 7.3 for hepatitis C patients). Regarding tumor response, no significant difference between the two groups was noted at the end of the treatment period (p =0.93). No significant differences were noted between the 2 groups in terms of overall survival (logrank test, p=0.62). Mean survival time for hepatitis B patients was 35.69 months (median 23.06, SD: 8.00). Mean survival time for hepatitis C patients was 25.60 months (median 18.33, SD: 2.18). In this selected cohort, patients with history of hepatitis B or C infection and unresectable HCC, showed similar survival and tumor response rates following treatment with conventional chemoembolization.

To compare the clinical and radiological (anatomic and functional) outcome of patients treated with transarterial chemoembolization (CE) versus yttrium-90 (Y-90) glass microspheres radioembolization (RE) for unresectable liver metastases originating from a variety of neuroendocrine tumors. 38 patients with neuroendocrine hepatic metastases that underwent CE Y-90 RE (26 and 12 patients wespectively)in a single institution,were included in this retrospective study. These patients were matched for age, sex, tumor burden and other prior treatments. All patients underwent radiological, biochemical, and clinical evaluation before and 6 months after treatment. The Response Evaluation Criteria for Solid Tumors v1.1 was utilized to assess anatomic tumor response. Diffusion-weighted imaging apparent co-efficients for all targeted tumors were used to assess radiologic functional tumor response. All patients were followed until death or censored at the time other therapy was given after CE or RE. Kaplan Meier curves and the log-rank test were employed to compare differences in survival and progression. A total of 96 targeted lesions was evaluated (66 targeted with CE and 30 with RE). There were no major complications in any of the two groups. Mean tumor size was 5.6 cm for the CE group and 3.8 cm for the RE group before treatment and was significantly reduced in both groups after treatment (p<0.0001). Partial response was achieved in 23% of CE patients and 25% of RE patients, while the rest remained stable. The tumor ADC increased from 1.51 x 10-3 mm2/s before treatment to 1.79 x 10-3 mm2/s after treatment (p < 0.0001) for the CE group, and from 1.55 x 10-3 to 1.84 x 10-3 mm2/s after treatment for the RE group (p=0.0004). Mean survival times were 69 months for CE patients and 57 months for RE patients (p = 0.56). Delay between metastatic diagnosis and first RE or CE predicted earlier demise following palliative therapy (p = 0.015). Patients with unresectable neuroendocrine hepatic metastases may undergo palliative treatment with CE or RE with similar anatomic and functional radiological and clinical outcome. Early intervention may lead to improved survival.

e15522 Background: To report the outcome of the care of patients with hepatocellular carcinoma (HCC) treated with standardized transcatheter arterial chemomembolization (TACE), with a focus on tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST), progression of underlying cirrhosis [Child-Pugh (CP) score], time to progression (TTP) and survival from 1996 to 2008. Methods: TACE was performed on 365 patients in 1,035 sessions. According to a standardized protocol, all patients received imaging (MRI and/or CT) at baseline and at 4–6 weeks after each session and were clinically, biochemically and radiologically evaluated before each session. Liver disease status was evaluated before and at the end of the treatment period with the CP class system and tumor size measurements according to the RECIST. The Barcelona Clinic Liver Cancer (BCLC) classification was employed to stage patients. Three chemotherapeutic agents and lipiodol, followed by non-occlusive embolization were utilized during TACE. Complete vessel occlusion was avoided at all times. Overall survival and TTP were calculated according to the Kaplan-Meier method. The log-rank test was used to calculate differences between groups in the subgroup analysis. Results: All patients (78% male, mean age: 63.5 years) received an average of 3 TACE sessions (range: 1–10 and average interval between sessions: 75 days). Sixty six percent of patients had 3 or more tumors, with a mean tumor size at presentation of 6.9 cm. Partial response was achieved in 32 % of patients, while 65% remained stable over the course of 3 TACEs. CP class remained unchanged for 75% of patients over the above course of treatment. Median survival for the entire cohort was 20 months and TTP was 14 months. Interestingly, advanced BCLC patients achieved similar tumor response (PR:33%), TTP of 13.4 months and median survival of 13.7 months. Conclusions: Patients with HCC treated with the aforementioned standardized TACE and follow-up protocol showed durable survival, stable liver disease and effective tumor control. [Table: see text]

To report the outcome of the care of 359 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemomembolization (TACE) with a focus on tumor size change [Response Evaluation Criteria in Solid Tumors (RECIST) criteria], Child-Pugh (CP) class change over time and survival from 1996 to 2008. TACE was performed on 359 patients in 1015 sessions. According to a standardized protocol, all patients received imaging (MRI and/or CT) at baseline and at 4-6 weeks after each session and were clinically, biochemically and radiologically evaluated before each session. Disease status was evaluated before and at the end of the treatment period with the CP class system (nominal and categorical) and tumor size measurements according to the RECIST criteria. Three chemotherapeutic agents and lipiodol, followed by non-occlusive embolization were utilized during TACE. Complete vessel occlusion was avoided at all times. Kaplan-Meier estimates of overall survival and time to progression were computed. All patients (78% male, mean age: 63.5 years) received an average of 3 TACE sessions (range: 1-10 and average interval between sessions: 75 days). Sixty six percent of patients had 3 or more tumors, with a mean tumor size at presentation of 6.9 cm. There was a 36 % mean overall response, corresponding to partial response according to RECIST. Most patients had a CP class B (66%, score of 6) at presentation, which did not significantly change over time (p=0.1). Median survival for the entire cohort was 20 months and TTP was 14 months. Patients treated with the aforementioned standardized TACE and follow-up protocol showed durable survival, stable liver disease and effective tumor control.

PurposeTo evaluate and compare the cell preparation methods favorable to subsequent experimental study when implanting Vx-2 carcinoma into rabbit liver.Materials and MethodsForty adult NZ white rabbits underwent Vx-2 carcinoma implantation into the left lateral lobe of the liver by open laparotomy method. Based on the cell preparation method, twenty rabbits underwent implantation with using minced cells (Group I), and the other twenty rabbits underwent implantation with using a chunk (3 mm3) of tumor (Group II). In Group I, minced tumor cells were contained in a 16-G angiocath needle, punctured the liver, and then 0.035-inch guide wire pushed the minced cells into the liver. In Group II, a chunk of tumor was prepared in size of 3 mm3, liver capsule was lacerated, and then the chunk of tumor was inserted directly through the lacerated capsule and tract. The tumor growth and size, location, vascularity and peritoneal seeding were evaluated by MR imaging, angiography and autopsy two weeks after the implantation.ResultsTumor implantation and tumor growing was successful in all rabbits. Tumor size and vascularity were not significantly different. Mean tumor size in both Group I and II were 1.6 and 1.8 cm, respectively (p > 0.05). All tumors showed hypervascular tumor staining with hypertrophic feeder suitable for intervention. In Group I, all tumors were confined near the center of the liver apart from the capsule. In Group II, however, 15 of 20 (75%) tumors were located just beneath the capsule of liver which might affect higher peritoneal seeding in Group II (10/20, 50%) than Group I (2/20, 10%) (p < 0.05).ConclusionBoth implantation methods achieved successful tumor growth, sufficient size and vascularity. However, in terms of tumor location inside the liver, peritoneal seeding and a possible tumor cell contamination during implantation, minced cell preparation within angiocath is favorable to experimental study. PurposeTo evaluate and compare the cell preparation methods favorable to subsequent experimental study when implanting Vx-2 carcinoma into rabbit liver. To evaluate and compare the cell preparation methods favorable to subsequent experimental study when implanting Vx-2 carcinoma into rabbit liver. Materials and MethodsForty adult NZ white rabbits underwent Vx-2 carcinoma implantation into the left lateral lobe of the liver by open laparotomy method. Based on the cell preparation method, twenty rabbits underwent implantation with using minced cells (Group I), and the other twenty rabbits underwent implantation with using a chunk (3 mm3) of tumor (Group II). In Group I, minced tumor cells were contained in a 16-G angiocath needle, punctured the liver, and then 0.035-inch guide wire pushed the minced cells into the liver. In Group II, a chunk of tumor was prepared in size of 3 mm3, liver capsule was lacerated, and then the chunk of tumor was inserted directly through the lacerated capsule and tract. The tumor growth and size, location, vascularity and peritoneal seeding were evaluated by MR imaging, angiography and autopsy two weeks after the implantation. Forty adult NZ white rabbits underwent Vx-2 carcinoma implantation into the left lateral lobe of the liver by open laparotomy method. Based on the cell preparation method, twenty rabbits underwent implantation with using minced cells (Group I), and the other twenty rabbits underwent implantation with using a chunk (3 mm3) of tumor (Group II). In Group I, minced tumor cells were contained in a 16-G angiocath needle, punctured the liver, and then 0.035-inch guide wire pushed the minced cells into the liver. In Group II, a chunk of tumor was prepared in size of 3 mm3, liver capsule was lacerated, and then the chunk of tumor was inserted directly through the lacerated capsule and tract. The tumor growth and size, location, vascularity and peritoneal seeding were evaluated by MR imaging, angiography and autopsy two weeks after the implantation. ResultsTumor implantation and tumor growing was successful in all rabbits. Tumor size and vascularity were not significantly different. Mean tumor size in both Group I and II were 1.6 and 1.8 cm, respectively (p > 0.05). All tumors showed hypervascular tumor staining with hypertrophic feeder suitable for intervention. In Group I, all tumors were confined near the center of the liver apart from the capsule. In Group II, however, 15 of 20 (75%) tumors were located just beneath the capsule of liver which might affect higher peritoneal seeding in Group II (10/20, 50%) than Group I (2/20, 10%) (p < 0.05). Tumor implantation and tumor growing was successful in all rabbits. Tumor size and vascularity were not significantly different. Mean tumor size in both Group I and II were 1.6 and 1.8 cm, respectively (p > 0.05). All tumors showed hypervascular tumor staining with hypertrophic feeder suitable for intervention. In Group I, all tumors were confined near the center of the liver apart from the capsule. In Group II, however, 15 of 20 (75%) tumors were located just beneath the capsule of liver which might affect higher peritoneal seeding in Group II (10/20, 50%) than Group I (2/20, 10%) (p < 0.05). ConclusionBoth implantation methods achieved successful tumor growth, sufficient size and vascularity. However, in terms of tumor location inside the liver, peritoneal seeding and a possible tumor cell contamination during implantation, minced cell preparation within angiocath is favorable to experimental study. Both implantation methods achieved successful tumor growth, sufficient size and vascularity. However, in terms of tumor location inside the liver, peritoneal seeding and a possible tumor cell contamination during implantation, minced cell preparation within angiocath is favorable to experimental study.

PurposeTransarterial chemoembolization (TACE) is the standard treatment in patients with unresectable HCC. The purpose of this study was to test the feasibility of a new TACE drug delivery system (drug eluting beads) which was designed to increase efficacy and reduce toxicities of TACE.Materials and MethodsFrom 11/1/05- 10/1/07, 17 patients with unresectable HCC were enrolled based on protocol selection criteria. Criteria allowed Childs A-B and ECOG PS ≤ 2. The drug eluting beads are polyvinyl beads modified to allow the sequestration of chemotherapy drugs (in this case doxorubicin) in vitro. Delivered intra-arterially into the tumor bed, the beads release the drug in a controlled manner over two weeks. Primary endpoints were tumor response assessed by imaging (EASL and RECIST criteria) and safety. Safety was assessed by serious adverse event reporting and toxicities with CTCAE V 3.0.ResultsAside from serious adverse events (SAEs), all toxicities were < grade 3, other than a single grade 3 (hypoalbuminemia). SAEs included pancreatitis and cholecystitits (recovered), gastric enteritis (recovered) and hydrothorax (recovered). Five patients died of disease progression (not related to study device).ConclusionTabled 1Imaging Response following TACE with Doxorubicin Eluting BeadsF/U intervalNEASL Partial or complete responseEASL Stable diseaseEASL Progressive diseaseRECIST Partial responseRECIST Stable diseaseRECIST Progressive disease<30days from tx31-3 mths⁎n=1 bridged to surgery, included.1211/12 (91%)1/124/126/122/125-7 mths⁎⁎n=1 bridged to surgery, not included65/5 (100%)1/54/513-14 mths⁎⁎n=1 bridged to surgery, not included42/3 (66%)1/31/31/31/3 n=1 bridged to surgery, included. n=1 bridged to surgery, not included Open table in a new tab PurposeTransarterial chemoembolization (TACE) is the standard treatment in patients with unresectable HCC. The purpose of this study was to test the feasibility of a new TACE drug delivery system (drug eluting beads) which was designed to increase efficacy and reduce toxicities of TACE. Transarterial chemoembolization (TACE) is the standard treatment in patients with unresectable HCC. The purpose of this study was to test the feasibility of a new TACE drug delivery system (drug eluting beads) which was designed to increase efficacy and reduce toxicities of TACE. Materials and MethodsFrom 11/1/05- 10/1/07, 17 patients with unresectable HCC were enrolled based on protocol selection criteria. Criteria allowed Childs A-B and ECOG PS ≤ 2. The drug eluting beads are polyvinyl beads modified to allow the sequestration of chemotherapy drugs (in this case doxorubicin) in vitro. Delivered intra-arterially into the tumor bed, the beads release the drug in a controlled manner over two weeks. Primary endpoints were tumor response assessed by imaging (EASL and RECIST criteria) and safety. Safety was assessed by serious adverse event reporting and toxicities with CTCAE V 3.0. From 11/1/05- 10/1/07, 17 patients with unresectable HCC were enrolled based on protocol selection criteria. Criteria allowed Childs A-B and ECOG PS ≤ 2. The drug eluting beads are polyvinyl beads modified to allow the sequestration of chemotherapy drugs (in this case doxorubicin) in vitro. Delivered intra-arterially into the tumor bed, the beads release the drug in a controlled manner over two weeks. Primary endpoints were tumor response assessed by imaging (EASL and RECIST criteria) and safety. Safety was assessed by serious adverse event reporting and toxicities with CTCAE V 3.0. ResultsAside from serious adverse events (SAEs), all toxicities were < grade 3, other than a single grade 3 (hypoalbuminemia). SAEs included pancreatitis and cholecystitits (recovered), gastric enteritis (recovered) and hydrothorax (recovered). Five patients died of disease progression (not related to study device). Aside from serious adverse events (SAEs), all toxicities were < grade 3, other than a single grade 3 (hypoalbuminemia). SAEs included pancreatitis and cholecystitits (recovered), gastric enteritis (recovered) and hydrothorax (recovered). Five patients died of disease progression (not related to study device). ConclusionTabled 1Imaging Response following TACE with Doxorubicin Eluting BeadsF/U intervalNEASL Partial or complete responseEASL Stable diseaseEASL Progressive diseaseRECIST Partial responseRECIST Stable diseaseRECIST Progressive disease<30days from tx31-3 mths⁎n=1 bridged to surgery, included.1211/12 (91%)1/124/126/122/125-7 mths⁎⁎n=1 bridged to surgery, not included65/5 (100%)1/54/513-14 mths⁎⁎n=1 bridged to surgery, not included42/3 (66%)1/31/31/31/3 n=1 bridged to surgery, included. n=1 bridged to surgery, not included Open table in a new tab

Purpose3-bromopyruvate (3-BrPA) is a potent new inhibitor of tumor metabolism, with encouraging results when injected intra-arterially in the hepatic artery of Vx-2 tumor-bearing rabbits. In this study, we sought to determine the survival benefits of using FDG-PET/CT imaging to monitor tumor response.Materials and Methods24 New Zealand white male rabbits with VX2 liver tumors were divided into two groups of 12 each. The first group received a 1 hr intraarterial infusion of 25 cc of 1.75 mM 3-bromopyruvate solution (in PBS) while the second control group received a 1 hr intraarterial infusion of carrier (PBS). The animals were injected with 1 mCi of FDG one day before treatment (baseline), 2 hours, 24 hours and 1 week following treatment for imaging in a clinical PET/CT scanner.ResultsRabbits treated with 1.75 mM intraarterial 3-BrPA survived statistically significantly longer than the animals in the control group that received an intraarterial sham injection of saline. The mean survival time in the control group was 18.6 days, whereas the mean survival time in the treatment group was 50.0 days, showing a statistically significant 269% increase in survival for the rabbits treated intra arterially with 3-BrPA (p-value < 0.001). Intense FDG uptake was demonstrated in the tumor on PET in all baseline studies, whereas low FDG uptake in the tumor was noted in all control studies following treatment.ConclusionIntraarterial injection of 3-BrPA results in successful survival and markedly decreased FDG uptake by PET/CT imaging in an animal model of liver cancer. Purpose3-bromopyruvate (3-BrPA) is a potent new inhibitor of tumor metabolism, with encouraging results when injected intra-arterially in the hepatic artery of Vx-2 tumor-bearing rabbits. In this study, we sought to determine the survival benefits of using FDG-PET/CT imaging to monitor tumor response. 3-bromopyruvate (3-BrPA) is a potent new inhibitor of tumor metabolism, with encouraging results when injected intra-arterially in the hepatic artery of Vx-2 tumor-bearing rabbits. In this study, we sought to determine the survival benefits of using FDG-PET/CT imaging to monitor tumor response. Materials and Methods24 New Zealand white male rabbits with VX2 liver tumors were divided into two groups of 12 each. The first group received a 1 hr intraarterial infusion of 25 cc of 1.75 mM 3-bromopyruvate solution (in PBS) while the second control group received a 1 hr intraarterial infusion of carrier (PBS). The animals were injected with 1 mCi of FDG one day before treatment (baseline), 2 hours, 24 hours and 1 week following treatment for imaging in a clinical PET/CT scanner. 24 New Zealand white male rabbits with VX2 liver tumors were divided into two groups of 12 each. The first group received a 1 hr intraarterial infusion of 25 cc of 1.75 mM 3-bromopyruvate solution (in PBS) while the second control group received a 1 hr intraarterial infusion of carrier (PBS). The animals were injected with 1 mCi of FDG one day before treatment (baseline), 2 hours, 24 hours and 1 week following treatment for imaging in a clinical PET/CT scanner. ResultsRabbits treated with 1.75 mM intraarterial 3-BrPA survived statistically significantly longer than the animals in the control group that received an intraarterial sham injection of saline. The mean survival time in the control group was 18.6 days, whereas the mean survival time in the treatment group was 50.0 days, showing a statistically significant 269% increase in survival for the rabbits treated intra arterially with 3-BrPA (p-value < 0.001). Intense FDG uptake was demonstrated in the tumor on PET in all baseline studies, whereas low FDG uptake in the tumor was noted in all control studies following treatment. Rabbits treated with 1.75 mM intraarterial 3-BrPA survived statistically significantly longer than the animals in the control group that received an intraarterial sham injection of saline. The mean survival time in the control group was 18.6 days, whereas the mean survival time in the treatment group was 50.0 days, showing a statistically significant 269% increase in survival for the rabbits treated intra arterially with 3-BrPA (p-value < 0.001). Intense FDG uptake was demonstrated in the tumor on PET in all baseline studies, whereas low FDG uptake in the tumor was noted in all control studies following treatment. ConclusionIntraarterial injection of 3-BrPA results in successful survival and markedly decreased FDG uptake by PET/CT imaging in an animal model of liver cancer. Intraarterial injection of 3-BrPA results in successful survival and markedly decreased FDG uptake by PET/CT imaging in an animal model of liver cancer.