J.F. Geschwind

Transcatheter Therapy for Hepatic Malignancy: Standardization of Terminology and Reporting Criteria

The field of interventional oncology includes tumor ablation as well as the use of transcatheter therapies such as embolization, chemoembolization, and radioembolization. Terminology and reporting standards for tumor ablation have been developed. The development of standardization of terminology and reporting criteria for transcatheter therapies should provide a similar framework to facilitate the clearest communication among investigators and provide the greatest flexibility in comparing established and emerging technologies. An appropriate vehicle for reporting the various aspects of catheter directed therapy is outlined, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings. Methods for standardizing the reporting of outcomes toxicities, complications, and other important aspects that require attention when reporting clinical results are addressed. It is the intention of the group that adherence to the recommendations will facilitate achievement of the groups main objective: improved precision and communication for reporting the various aspects of transcatheter management of hepatic malignancy that will translate to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes.

Weight-based rt-PA Thrombolysis Protocol for Acute Native Arterial and Bypass Graft Occlusions

PURPOSE To determine technical success and complications with weight-adjusted dosing of recombinant tissue plasminogen activator (rt-PA) for arterial and bypass graft occlusions. MATERIALS AND METHODS During an 8-month period, prospective data were collected on patients undergoing catheter-directed thrombolysis. Retrospective review of all medical charts and blood bank data were performed for confirmation. All patients underwent a standard weight-adjusted protocol for catheter-directed thrombolysis. Thrombolytic therapy with rt-PA (0.2 mg/mL) was defined as low-dose when 0.02 mg/kg/h rt-PA was used and high-dose when 0.04 mg/kg/h of rt-PA was used. Low-dose heparin therapy was used. Total infusion time, total dose, and hourly rate of dose were calculated. Technical success, defined as complete removal of all clot without surgical intervention, complications, and frequency of transfusions were tabulated. RESULTS A total of 35 patients underwent catheter-directed thrombolysis with rt-PA, including a total of 21 bypass grafts (60%) and 14 native arteries (40%). Mean age was 57 years (+/- 22.5; range, 3 mo to 83 y). Average rate of heparin infusion was 472.8 U/h (+/- 227). Success rates for graft thrombolysis were 90% (18 of 21). Success rates for native vessels were 79% (11 of 14). In patients who underwent only a low-dose protocol, the transfusion rate was 15% and major complications were 10%. In patients with a combined low-dose/high-dose administration, the transfusion rate was 46% and major complications were 13%. Overall success rate and major complication rates were 86% (30 of 35) and 11% (four of 35), respectively. Frequency of transfusions was 37% (13 of 35; mean, 2.8 U). CONCLUSION Although weight-adjusted dosing for rt-PA provides a high efficacy of relieving ischemia, the rate of complications, especially bleeding, seems excessive in comparison to historical experience with urokinase. Administration of short-term high doses of rt-PA did not appear to have any beneficial effect. Further investigation with lower dosing and concentration should be considered.

Islet Cell Liver Metastases: Assessment of Volumetric Early Response with Functional MR Imaging after Transarterial Chemoembolization

PURPOSE To assess early response to transarterial chemoembolization by using volumetric functional magnetic resonance (MR) imaging in patients with islet cell liver metastases (ICLMs). MATERIALS AND METHODS This retrospective institutional review board-approved HIPAA-compliant study included 215 ICLMs in 26 patients (15 men, 11 women; mean age, 59.7 years; age range, 37-79 years). Volumetric measurements were performed by an experienced radiologist on diffusion-weighted and contrast material-enhanced MR images at baseline and 1-month follow-up. Measurements included mean change (three-dimensional [3D] mean apparent diffusion coefficient [ADC], 3D mean enhancement) and percentage of tumor with change above a predetermined threshold (3D threshold ADC, 3D threshold enhancement). Response by volumetric measurements at 1-month follow-up was compared with Response Evaluation Criteria in Solid Tumors (RECIST) at 6-month follow-up. Lesions that had complete or partial response were considered responders, while those with stable or progressive disease were considered nonresponders. Statistical analysis included the t test, receiver operating characteristic (ROC) curve analysis, and logistic regression analysis. RESULTS RECIST criteria at 6-month follow-up indicated 78 (36.3%) lesions responded, while 137 (63.7%) did not. The increase in 3D mean ADC was significantly higher in responders than in nonresponders (median, 26.2% vs 10.9%; P<.001). The 3D threshold ADC was 71.1% in responders and 47.6% in nonresponders (P<.001). Decrease in 3D mean arterial enhancement (AE) was significantly higher in responders than in nonresponders (median, 40.5% vs 18.0%; P<.001). Decrease in 3D mean venous enhancement (VE) was significantly higher in responders than in nonresponders (median, 28.0% vs 10.0%; P<.001). The 3D threshold VE and 3D threshold AE did not differ between responders and nonresponders. In unadjusted logistic regression analyses, 3D mean ADC and 3D threshold ADC had the highest odds ratio (1.02 and 1.03, respectively) and the largest area under the ROC curve (0.698 and 0.695, respectively). CONCLUSION Volumetric functional MR imaging could be used to predict early response of hepatic ICLMs to therapy and to distinguish between responders and nonresponders.

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.