Karen Marshall

Radiographic Response to Locoregional Therapy in Hepatocellular Carcinoma Predicts Patient Survival Times

BACKGROUND & AIMS It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs) (chemoembolization and radioembolization). METHODS Patients received LRTs over a 9-year period (n = 463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh B7 or lower were analyzed. Response (based on European Association for the Study of the Liver [EASL] and World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared with those of patients with stable disease and progressive disease. RESULTS Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P = .002 and .0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P = .0463 and .707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P < .0001 and .004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P = .0132 and .010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P < .0001; P = .596 with WHO criteria). In the subanalysis, responders lived longer than patients with stable disease or progressive disease. CONCLUSIONS Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease.

Internal Pair Production of 90Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Radioembolization with 90Y microspheres represents a novel transarterial radiation treatment for liver tumors. The purpose of this pilot study was to evaluate the findings of postimplantation PET/CT of 90Y glass microspheres. Methods: Three patients with hepatocellular carcinoma and 2 patients with liver metastases (1 neuroendocrine, 1 colorectal) underwent PET/CT after radioembolization. Four patients underwent imaging at 1 mo to assess response and confirm PET/CT findings; 1 patient underwent PET/CT at 4 d after 90Y implantation. Patients were followed for adverse events. Results: Standard PET/CT enabled the localization of 90Y glass microspheres for all patients. None of the patients experienced adverse events related to nontarget deposition. Conclusion: Standard PET/CT may be used to assess the localization of 90Y glass microspheres. This approach provides a simple, rapid, and universally applicable method of confirming microsphere deposition. With further validation, this technique may potentially become the standard of care for confirming microsphere distribution.

Outpatient Single-Session Yttrium-90 Glass Microsphere Radioembolization

PURPOSE To investigate the feasibility of yttrium-90 ((90)Y) glass microsphere radioembolization (including angiography, lung shunt assessment, and treatment) as a single-session, outpatient procedure. MATERIALS AND METHODS Between January 2008 and June 2013, 14 patients underwent outpatient, single-session radioembolization with (90)Y glass microspheres. As part of the routine diagnostic work-up, all patients underwent either computed tomography (CT) or magnetic resonance imaging of the liver with three-dimensional analysis and had laboratory results forwarded to our center for confirmation of candidacy before treatment. On treatment day, all patients underwent planning mesenteric angiography with flat panel cone-beam CT imaging. Patients were administered 33-85 MBq of technetium-99m macroaggregated albumin ((99m)Tc-MAA) via a microcatheter positioned in a hepatic artery supplying the tumor of interest. Planar scintigraphy was initiated within 2 hours after the administration of (99m)Tc-MAA and lung shunt fraction was determined. Final dosimetry calculations were performed while the patient was being transferred back from nuclear medicine to interventional radiology. RESULTS All patients successfully underwent planning angiography with administration of (99m)Tc-MAA and (90)Y radioembolization as a single-session treatment. There were no reportable or recordable medical events; treatment was carried out to the desired dose in all cases. The mean total procedure time was 2.70 hours ± 0.72 (range, 1.63-3.97 h). CONCLUSIONS This study reports a novel proof of concept for performing radioembolization in a single-session setting. By using the described method, time between initial clinical assessments and radioembolization treatment is decreased, and costs are minimized.

Y90 Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort

We report survival outcomes for patients with advanced-stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with 90Y radioembolization. Methods: With institutional review board approval, we searched our prospectively acquired database for 90Y patients treated between 2003 and 2017. Inclusion criteria were patients who had HCC with tumor PVT. Patients with metastases were excluded. Laboratory data were collected at baseline and 1 mo after 90Y radioembolization. Toxicity grades were reported according to the Common Terminology Criteria for Adverse Events, version 4.0, and long-term survival outcomes were reported and stratified by Child–Pugh class (CP). Overall survival was calculated using the Kaplan–Meier method. Multivariate analysis was performed using Cox proportional hazards regression. A subanalysis for patients with a high level of α-fetoprotein (AFP) (>100 ng/dL) was conducted. Results: In total, 185 patients with HCC PVT underwent 90Y radioembolization. Seventy-four (40%) were CP-A, 51 (28%) were CP-B7, and 60 (32%) were ≥CP-B8. New albumin, bilirubin, and alkaline phosphatase grade 3/4 toxicities were, respectively, 3%, 10%, and 0% for CP-A; 14%, 12%, and 6% for CP-B7; and 23%, 32%, and 3% for ≥CP-B8. Median overall survival for CP-A patients was 13.3 mo (95% confidence interval [CI], 8.7–15.7 mo). CP-B7 and ≥CP-B8 patients exhibited median overall survival of 6.9 mo (95% CI, 5.3–10.1 mo) and 3.9 mo (95% CI, 2.9–5.0 mo), respectively. Significant overall survival prognosticators on univariate analysis were albumin, bilirubin, ascites, tumor size 5 cm or smaller, focality, distribution, infiltration, Eastern Cooperative Oncology Group status, AFP level, and PVT extent. Multivariate analysis showed the prognosticators of overall survival to be bilirubin, no ascites, tumor size 5 cm or smaller, solitary lesion, baseline AFP level lower than 100 ng/dL, and Eastern Cooperative Oncology Group status. Of 123 patients with a high AFP level (>100 ng/dL), 12 patients achieved restored normal AFP levels (<13 ng/dL) and exhibited median overall survival of 23.9 mo (95% CI, 20.1–124.1 mo). AFP responders at 1 mo had better overall survival than nonresponders, at 8.5 mo versus 4.8 mo (P = 0.018); AFP responders at 3 mo had overall survival of 13.3 mo, versus 6.9 mo for nonresponders (P = 0.021). Conclusion: 90Y radioembolization can serve as a safe and effective treatment for advanced-stage HCC patients with tumor PVT. Overall survival outcomes are affected by baseline liver function, tumor size, and AFP level.

Renal Cell Carcinoma Metastatic to the Liver: Early Response Assessment after Intraarterial Therapy Using 3D Quantitative Tumor Enhancement Analysis

PURPOSE Liver metastases from renal cell carcinoma (RCC) are not uncommon in the course of disease. However, data about tumor response to intraarterial therapy (IAT) are scarce. This study assessed whether changes of enhancing tumor volume using quantitative European Association for the Study of the Liver (qEASL) on magnetic resonance imaging (MRI) and computed tomography (CT) can evaluate tumor response and predict overall survival (OS) early after therapy. METHODS AND MATERIALS Fourteen patients with liver metastatic RCC treated with IAT (transarterial chemoembolization: n= 9 and yttrium-90: n= 5) were retrospectively included. All patients underwent contrast-enhanced imaging (MRI: n= 10 and CT: n= 4) 3 to 4 weeks pre- and posttreatment. Response to treatment was evaluated on the arterial phase using Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization, modified RECIST, EASL, tumor volume, and qEASL. Paired t test was used to compare measurements pre- and post-IAT. Patients were stratified into responders (≥65% decrease in qEASL) and nonresponders (<65% decrease in qEASL). OS was evaluated using Kaplan-Meier curves with log-rank test and the Cox proportional hazard model. RESULTS Mean qEASL (cm3) decreased from 93.5 to 67.2 cm3 (P= .004) and mean qEASL (%) from 63.1% to 35.6% (P= .001). No significant changes were observed using other response criteria. qEASL was the only significant predictor of OS when used to stratify patients into responders and nonresponders with median OS of 31.9 versus 11.1 months (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19-0.97; P= .042) for qEASL (cm3) and 29.9 versus 10.2 months (HR, 0.09; 95% CI, 0.01-0.74; P= .025) for qEASL (%). CONCLUSION Three-dimensional (3D) quantitative tumor analysis is a reliable predictor of OS when assessing treatment response after IAT in patients with RCC metastatic to the liver. qEASL outperforms conventional non-3D methods and can be used as a surrogate marker for OS early after therapy.