R. Mora

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience

Yttrium‐90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000‐patient cohort acquired over a 15‐year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child‐Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention‐to‐treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty‐three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty‐eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5‐80.3) months, BCLC B 25.0 (CI, 17.3‐30.5) months, and BCLC C 15.0 (CI, 13.8‐17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21‐30.2) months, BCLC B 15.0 (CI, 12.3‐19.0) months, and BCLC C 8.0 (CI, 6.8‐9.5) months. Forty‐nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. Conclusion: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first‐line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Radioembolization for hepatocellular carcinoma: Statistical confirmation of improved survival in responders by landmark analyses

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child‐Pughu2009>u2009B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child‐Pughu2009≤u2009B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk‐of‐death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3‐month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26‐0.82; Pu2009=u20090.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37‐1.32; Pu2009=u20090.32). At the 6‐month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15‐0.77; Pu2009<u20090.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29‐0.87; Pu2009=u20090.021). At the 12‐month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15‐0.77; Pu2009<u2009 0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27‐0.98; Pu2009=u20090.049). At 6 months, risk of death was lower for responders by EASL (Pu2009<u2009 0.001) and RECIST 1.1 (Pu2009=u20090.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3‐, 6‐, and 12‐month Landmarks on uni/multivariate analyses. Conclusion: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873–883)

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.

Clinical outcomes of Y90 radioembolization for recurrent hepatocellular carcinoma following curative resection

PurposeTo assess safety/efficacy of yttrium-90 radioembolization (Y90) in patients with recurrent hepatocellular carcinoma (HCC) following curative surgical resection.MethodsWith IRB approval, we searched our prospectively acquired database for patients that were treated with Y90 for recurrent disease following resection. Baseline characteristics and bilirubin toxicities following Y90 were evaluated. Intention-to-treat overall survival (OS) and time-to-progression (TTP) from Y90 were assessed.ResultsForty-one patients met study inclusion criteria. Twenty-six (63%) patients had undergone minor (≤3 hepatic segments) resection while 15 (37%) patients underwent major (>3 hepatic segments) resections. Two patients (5%) had biliary-enteric anastomoses created during surgical resection. The median time from HCC resection to the first radioembolization was 17xa0months (95% CI: 13–37). The median number of Y90 treatment sessions was 1 (range: 1–5). Ten patients received (entire remnant) lobar Y90 treatment while 31 patients received selective (≤2 hepatic segments) treatment. Grades 1/2/3/4 bilirubin toxicity were seen in nine (22%), four (10%), four (10%), and zero (0%) patients following Y90. No differences in bilirubin toxicities were identified when comparing lobar with selective approaches (Pxa0=xa00.20). No post-Y90 infectious complications were identified. Median TTP and OS were 11.3 (CI: 6.5–15.5) and 22.1xa0months (CI: 10.3–31.3), respectively.ConclusionsRadioembolization is a safe and effective method for treating recurrent HCC following surgical resection, with prolonged TTP and promising survival outcomes.

Survival Analysis of Advanced HCC Treated with Radioembolization: Comparing Impact of Clinical Performance Status Versus Vascular Invasion/Metastases

PurposeIn this study, we aim to compare the effects of prognostic indicators on survival analysis for Barcelona Clinic Liver Cancer (BCLC) C patients undergoing yttrium-90 radioembolization (Y-90).MethodsA prospectively acquired database (2003–2017) for BCLC C hepatocellular carcinoma (HCC) patients that underwent radioembolization with Y-90 was searched. The criteria for BCLC C status (Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2, metastases, and/or portal vein thrombosis (PVT)) were recorded. Kaplan–Meier survival analyses were performed from the date of the first radioembolization with Y-90, censored to curative treatment, to determine median overall survival (OS). Cox regression hazards model was used for multivariate analyses. Significance was set at Pxa0<xa00.05.Results547 BCLC C patients treated with radioembolization with Y-90 had a median OS of 10.7xa0months (range: 9.5–12.9). 43% (233 of 547) patients classified as BCLC C solely by their ECOG PS had a median OS of 19.4xa0months (14.7–23.7); 57% (314 of 547) patients with PVT/metastases had a median OS of 7.7xa0months (6.7–8.7). On multivariate analysis, ECOG PS was not found to be a statistically significant prognostic indicator of OS in BCLC C whereas metastases and PVT exhibited hazards ratios (95%CI) of 0.51 (0.38–0.69) and 0.49 (0.38–0.63), respectively (Pxa0<xa00.0001).ConclusionPatients classified as BCLC C due to ECOG PS 1 demonstrated longer survival when compared to those presenting with PVT, metastases and/or ECOG PS 2. Hence, ECOG PS 1, as an isolated variable, may not be a true indicator of advanced disease.

Radiation Segmentectomy: Potential Curative Therapy for Early Hepatocellular Carcinoma

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function.

Pictorial essay: imaging findings following Y90 radiation segmentectomy for hepatocellular carcinoma

Transarterial radioembolization is a novel therapy that has gained rapid clinical acceptance for the treatment of hepatocellular carcinoma (HCC). Segmental radioembolization [also termed radiation segmentectomy (RS)] is a technique that can deliver high doses (>xa0190xa0Gy) of radiation selectively to the hepatic segment(s) containing the tumor. The aim of this comprehensive review is to provide an illustrative summary of the most relevant imaging findings encountered after radiation segmentectomy. A 62-patient cohort of Child–Pugh A patients with solitary HCCxa0<xa05xa0cm in size was identified. A comprehensive retrospective imaging review was done by interventional radiology staff at our institution. Important imaging findings were reported and illustrated in a descriptive account. For the purposes of completeness, specific patients outside our initial cohort with unique educational imaging features that also underwent segmentectomy were included in this pictorial essay. This review shows that response assessment after RS requires a learning curve with common drawbacks that can lead to false-positive interpretations and secondary unnecessary treatments. It is important to recognize that treatment responses and pathological changes both are time dependent. Findings such as benign geographical enhancement and initial benign pathological enhancement can easily be misinterpreted. Capsular retraction and segmental atrophy are some other examples of unique post-RS response that are not seen in any other treatment.

MR imaging findings of the prostate gland following prostate artery embolization: results from a prospective phase 2 study

PurposeTo assess changes in imaging and volume characteristics of the prostate gland by magnetic resonance (MR) following prostatic artery embolization (PAE) for benign prostate hyperplasia.MethodsWith IRB approval, we analyzed prospectively acquired MR data of PAE patients at baseline and 6-month following treatment from 2015 to 2017. We reviewed prostate MRs looking for sequelae of embolization [changes in signal intensity and/or enhancement, infection/inflammation, infarction, edema, and change in intravesical prostatic protrusion (IPP)]. We calculated the total volume (TV) and central gland volumes (CGV) using DynaCAD® and measured change in volumes. Analyses were performed using SPSS with pu2009<u20090.05 considered significant.ResultsForty-three patients (nu2009=u200943) met our inclusion criteria. 93% (30/43) and 100% (43/43) showed a decrease in TV and CGV at 6-months respectively. At baseline, median TV was 86xa0cc (range 29.4–232) and median CGV was 54.4xa0cc (range 12.9–165.5). Median decrease in TV was 18.2% (CI 13.3–27.2) (pu2009=u20090.0001) and median decrease in CGV was 26.7% (CI 20.4–35.9) (pu2009=u20090.0001). Thirty-seven percent (16/43) of patients had IPP at baseline; 100% showed a decrease in size of median lobe at follow-up. At 6-month follow-up, 33% (14/43) showed imaging features of infarction, 79% (34/43) had decrease in T2-signal intensity, and 51% (22/43) showed a decrease in enhancement. None had edema, peri-prostatic fat changes or infection/inflammation.ConclusionPAE causes a statistically significant reduction in the TV and CGV. There is also a reduction of the degree of IPP. Non-specific findings of infarction, decrease in T2-signal, and enhancement were also seen.