A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma.

BACKGROUND: Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564). METHODS: Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. RESULTS: Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6). CONCLUSION: In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016).

Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies.

BACKGROUND: Yttrium (Y)90 liver radioembolization (TARE) induces both tumor downsizing and contralateral liver hypertrophy. In this study, we report the preliminary results of a sequential strategy combining Y90 radioembolization and portal vein embolization (PVE) before major right liver resections. METHODS: We retrospectively reviewed clinical, radiological, and biological data of 5 consecutive patients undergoing Y90 TARE-PVE before major right liver resections. Comparison was made with patients undergoing PVE alone or liver venous deprivation (LVD) during the same period. RESULTS: Between January 2019 and September 2022, five patients underwent sequential TARE-PVE. Type of resection included the following: right hepatectomy (n = 1), right hepatectomy + 1 (n = 2), and right hepatectomy + 1 + 4 (n = 2) with no postoperative mortality. Volumetric data showed a mean hypertrophy ratio of 30.4% after TARE and an additional 37.4% after sequential PVE. Patients undergoing sequential TARE-PVE had higher hypertrophy ratio (p = 0.02; p = 0.004), hypertrophy degree (p = 0.02; p < 0.0001), shorter time to normalize bilirubin (p = 0.04), and prothrombin time (p = 0.003; p < 0.0001) compared with patients receiving LVD or PVE. Time from diagnosis to surgery was statistically significant longer in patients undergoing sequential TARE-PVE compared with LVD or PVE (293.4 ± 169.1 vs 54.18 ±18.26 vs 58.62±13.15; p = 0.0008; p = <0.0001). CONCLUSIONS: This preliminary report suggests that sequential PVE and TARE can represent a safe and an alternative strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. When compared with PVE and LVD, sequential TARE/PVE takes longer times but achieves some advantages which warrant further evaluation in a larger setting.

Using Deep Learning to Predict Treatment Response in Patients with Hepatocellular Carcinoma Treated with Y90 Radiation Segmentectomy.

Treatment of hepatocellular carcinoma (HCC) with Y90 radioembolization segmentectomy (Y90-RE) demonstrates a tumor dose-response threshold, where dose estimates are highly dependent on accurate SPECT/CT acquisition, registration, and reconstruction. Any error can result in distorted absorbed dose distributions and inaccurate estimates of treatment success. This study improves upon the voxel-based dosimetry model, one of the most accurate methods available clinically, by using a deep convolutional network ensemble to account for the spatially variable uptake of Y90 within a treated lesion. A retrospective analysis was conducted in patients with HCC who received Y90-RE at a single institution. Seventy-seven patients with 103 lesions met the inclusion criteria: three or fewer tumors, pre- and post treatment MRI, and no prior Y90-RE. Lesions were labeled as complete (n = 57) or incomplete response (n = 46) based on 3-month post treatment MRI and divided by medical record number into a 20% hold-out test set and 80% training set with 5-fold cross-validation. Slice-wise predictions were made from an average ensemble of models and thresholds from the highest accuracy epochs across all five folds. Lesion predictions were made by thresholding all slice predictions through the lesion. When compared to the voxel-based dosimetry model, our model had a higher F1-score (0.72 vs. 0.2), higher accuracy (0.65 vs. 0.60), and higher sensitivity (1.0 vs. 0.11) at predicting complete treatment response. This algorithm has the potential to identify patients with treatment failure who may benefit from earlier follow-up or additional treatment.

Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma.

OBJECTIVES: Yttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response. DESIGN: Time-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE. RESULTS: TILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8+ T cells, CD56+ NK cells and CD8+ CD56+ NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB+CD8+ T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8+ and CD4+ T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1+/Tim-3+CD8+ T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs. CONCLUSION: High-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment.

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

PURPOSE: To assess safety/efficacy of yttrium-90 radioembolization (Y90) in patients with recurrent hepatocellular carcinoma (HCC) following curative surgical resection. METHODS: With 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. RESULTS: Forty-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 17 months (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 (P = 0.20). No post-Y90 infectious complications were identified. Median TTP and OS were 11.3 (CI: 6.5-15.5) and 22.1 months (CI: 10.3-31.3), respectively. CONCLUSIONS: Radioembolization is a safe and effective method for treating recurrent HCC following surgical resection, with prolonged TTP and promising survival outcomes.

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

BACKGROUND: In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. METHODS: We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. RESULTS: Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001). CONCLUSION: Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

Assessment of Y-90 Radioembolization Treatment Response for Hepatocellular Carcinoma Cases Using MRI Radiomics.

Objectives: This study aimed to investigate the ability of radiomics features extracted from magnetic resonance imaging (MRI) images to differentiate between responders and non-responders for hepatocellular carcinoma (HCC) cases who received Y-90 transarterial radioembolization treatment. Methods: Thirty-six cases of HCC who underwent MRI scans after Y-90 radioembolization were included in this study. Tumors were segmented from MRI T2 images, and then 87 radiomic features were extracted through the LIFEx package software. Treatment response was determined 9 months after treatment through the modified response evaluation criteria in solid tumours (mRECIST). Results: According to mRECIST, 28 cases were responders and 8 cases were non-responders. Two radiomics features, "Grey Level Size Zone Matrix (GLSZM)-Small Zone Emphasis" and "GLSZM-Normalized Zone Size Non-Uniformity", were the radiomics features that could predict treatment response with the area under curve (AUC)= 0.71, sensitivity= 0.93, and specificity= 0.62 for both features. Whereas the other 4 features (kurtosis, intensity histogram root mean square, neighbourhood gray-tone difference matrix strength, and GLSZM normalized grey level non-uniformity) have a relatively lower but acceptable discrimination ability range from AUC= 0.6 to 0.66. Conclusion: MRI radiomics analysis could be used to assess the treatment response for HCC cases treated with Y-90 radioembolization.

Update on Locoregional Therapies for Liver Cancer: Radiation Segmentectomy.

Over 900,000 people worldwide were diagnosed with liver cancer in 2022 alone, with hepatocellular carcinoma (HCC) accounting for 75-85% of cases. Treatment for HCC includes some combination of systemic therapies, surgery, liver transplantation, ablation, and intra-arterial therapies with transarterial chemoembolization (TACE) or transarterial radioembolization (TARE). Currently, the Barcelona Clinic Liver Cancer (BCLC) guidelines have acknowledged liver transplantation, surgical resection, and thermal ablation as curative therapies in very early to early stage HCC (BCLC-0 and BCLC-A). While these modalities are the preferred curative treatments for a very early to early stage disease, there are challenges associated with these options, such as organ availability and patient eligibility. Current data shows the role of radiation segmentectomy as a curative therapeutic option for very early to early stage HCC that is unresectable and not amenable to ablation. As future data continues to elucidate the ability for radiation segmentectomy to achieve complete pathologic necrosis, the goal is for the BCLC staging model to acknowledge its role as a curative treatment in this patient population and incorporate it into the ever-evolving guidelines.

Safety and Efficacy of Concurrent Atezolizumab/Bevacizumab or Nivolumab Combination Therapy with Yttrium-90 Radioembolization of Advanced Unresectable Hepatocellular Carcinoma.

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.

Advances in Radiation Therapy for Primary Liver Cancer.

During the past 30 years, several advances have been made allowing for safer and more effective treatment of patients with liver cancer. This report reviews recent advances in radiation therapy for primary liver cancers including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. First, studies focusing on liver stereotactic body radiation therapy (SBRT) are reviewed focusing on lessons learned and knowledge gained from early pioneering trials. Then, new technologies to enhance SBRT treatments are explored including adaptive therapy and MRI-guided and biology-guided radiation therapy. Finally, treatment with Y-90 transarterial radioembolization is reviewed with a focus on novel approaches focused on personalized therapy.

Determination of Tumor Dose Response Thresholds in Patients with Chemorefractory Intrahepatic Cholangiocarcinoma Treated with Resin and Glass-based Y90 Radioembolization.

PURPOSE: To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). METHODS: Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors' dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3 months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. RESULTS: Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9 Gy; Glass: 254.7 Gy), maximum TD (Resin: 162.9 Gy; Glass: 591 Gy), minimum TD (Resin: 53.7 Gy; Glass: 149.1 Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75 Gy or maximum TD ≥ 150 Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150 Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). CONCLUSION: TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. LEVEL OF EVIDENCE: Level 3, Retrospective Study.

Improved Tumor Response in Patients on Metformin Undergoing Yttrium-90 Radioembolization Segmentectomy for Hepatocellular Carcinoma.

PURPOSE: Metformin is associated with improved outcomes after external radiation and chemotherapy but has not been studied for Y-90 radiation segmentectomy (RS). This study evaluates the effect of metformin on tumor response after Y-90 RS in patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: A retrospective analysis of patients with HCC who underwent Y-90 RS between 2014-2018 was performed. Comparisons were made between all patients taking and not taking metformin, and diabetic patients taking and not taking metformin. Tumor response was analyzed with logistic regression to compare absolute and percent change in total tumor diameter (TTD) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was evaluated using Kaplan-Meier estimation and log-rank analysis. RESULTS: A total of 106 patients underwent 112 Y-90 RS, of which 40 were diabetic (38.8%) and 19 (18.4%) were on metformin. At baseline, the two groups of patients on metformin and not on metformin had no significant difference in age, Child-Pugh score, MELD score, ALBI grade, total tumor diameter, and size of dominant tumor. The only significant baseline difference was ECOG status. Uni- and multivariate analysis demonstrated a larger reduction in TTD and objective response by mRECIST criteria for patients undergoing Y-90 RS on metformin compared to those not on metformin. OS was similar between patients taking and not taking metformin (p = 0.912). CONCLUSION: Metformin may be associated with increased tumor response after Y-90 RS in patients with HCC. LEVEL OF EVIDENCE: III, Retrospective Study.

Technical Aspects and Practical Approach Toward Same-Day Y90 Radioembolization in the Management of Hepatocellular Carcinoma.

Radioembolization with Yttrium-90 (Y90) has been proven safe and effective for the treatment of primary and secondary hepatic malignancies. Standard protocols have necessitated planning angiography with Technetium-99m macroaggregated albumin (Tc99m MAA) administration/scan typically 1-2 weeks prior to the radioembolization therapy. The intent of this practice is to ensure appropriate patient selection and treatment candidacy while also confirming best dosimetry approaches. At our center, we started performing "same-day Y90" in 2008; in a subset of international patients with travel hardship, we performed the planning and treatment procedures consecutively on the same day. In this article, we reveal our practical approach to treating patients on the same day as planning angiography. With more than 160 same-day procedures completed between 2008 and 2017, the safety and efficacy of such a paradigm has been established at our center. This approach is appealing to patients, their families, and referring physicians. Appropriate patient selection and proper preprocedure planning based on baseline imaging are key elements in successful same-day radioembolization treatments.

Tc-99m sulfur colloid SPECT-CT and assessment of functional liver reserve after Y90 radioembolization: A case report.

INTRODUCTION: Quantitative assessment is an essential tool in determining the proportion of liver to be reserved before lobectomy. Technetium-99 m sulfur colloid single-photon emission computed tomography (Tc-99 m SC SPECT-CT) can help in the quantitative assessment of functioning liver tissues and percentage of liver reserve before segmentectomy and lobectomy Matesan et al. (2017), Bowen et al. (2016) and Lam et al. (2013). PRESENTATION OF CASE: A 64-year-old man with alcoholic cirrhosis was admitted to our hospital with a 15 × 10 x 13 cm bilobar HCC. Y90 radioembolization was utilized to downstage the liver tumor. On follow-up CT scan of the liver after radiotherapy, the HCC was much reduced to 6.5 cm in size but still viable with elevated alpha fetoprotein ([AFP] from 225 to 381 to 959 ng/mL). Resection was considered. Constitutional indocyanine green retention at 15 min (ICG-R-15) was 22%. We introduced the Tc-99 m SC SPECT-CT scan in order to assess the percentage liver function of each lobe. It showed minimal uptake in the remaining functioning right lobe with a hypertrophic left lobe to whole liver uptake ratio of 87.1%. This finding gave us confidence to perform right hepatectomy. DISCUSSION: We used Tc-99 m SC SPECT-CT to estimate the normal functional liver reserve after Y90 radioembolization of a hepatocellular carcinoma (HCC). To our understanding, it is the first case report using Tc-99 m SC to predict the percentage of functional liver reserve after yttrium-90 (Y90) radioembolization. CONCLUSION: Tc-99 m SC SPECT-CT is a novel helper used to assess the differential liver function after Y90 radioembolization of HCC and before segmentectomy and lobectomy of the liver.

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

Purpose: To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. Methods: This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Results: Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. Conclusions: During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

A Lesion-Based Response Prediction Model Using Pretherapy PET/CT Image Features for Y90 Radioembolization to Hepatic Malignancies.

We present a probabilistic approach to identify patients with primary and secondary hepatic malignancies as responders or nonresponders to yttrium-90 radioembolization therapy. Recent advances in computer-aided detection have decreased false-negative and false-positive rates of perceived abnormalities; however, there is limited research in using similar concepts to predict treatment response. Our approach is driven by the goal of precision medicine to determine pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging parameters to facilitate the identification of patients who would benefit most from yttrium-90 radioembolization therapy, while avoiding complex and costly procedures for those who would not. Our algorithm seeks to predict a patient's response by discovering common co-occurring image patterns in the lesions of baseline fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scans by extracting invariant shape and texture features. The extracted imaging features were represented as a distribution of each subject based on the bag-of-feature paradigm. The distribution was applied in a multinomial naive Bayes classifier to predict whether a patient would be a responder or nonresponder to yttrium-90 radioembolization therapy based on the imaging features of a pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography scan. Comprehensive published criteria were used to determine lesion-based clinical treatment response based on fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography imaging findings. Our results show that the model is able to predict a patient with liver cancer as a responder or nonresponder to yttrium-90 radioembolization therapy with a sensitivity of 0.791 using extracted invariant imaging features from the pretherapy fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography test. The sensitivity increased to 0.821 when combining extracted invariant image features with variable features of tumor volume.

Process improvement for the safe delivery of multidisciplinary-executed treatments-A case in Y-90 microspheres therapy.

PURPOSE: To develop a safe and robust workflow for yttrium-90 (Y-90) radioembolization procedures in a multidisciplinary team environment. METHODS AND MATERIALS: A generalized Define-Measure-Analyze-Improve-Control (DMAIC)-based approach to process improvement was applied to a Y-90 radioembolization workflow. In the first DMAIC cycle, events with the Y-90 workflow were defined and analyzed. To improve the workflow, a web-based interactive electronic white board (EWB) system was adopted as the central communication platform and information processing hub. The EWB-based Y-90 workflow then underwent a second DMAIC cycle. Out of 245 treatments, three misses that went undetected until treatment initiation were recorded over a period of 21 months, and root-cause-analysis was performed to determine causes of each incident and opportunities for improvement. The EWB-based Y-90 process was further improved via new rules to define reliable sources of information as inputs into the planning process, as well as new check points to ensure this information was communicated correctly throughout the process flow. RESULTS: After implementation of the revised EWB-based Y-90 workflow, after two DMAIC-like cycles, there were zero misses out of 153 patient treatments in 1 year. CONCLUSIONS: The DMAIC-based approach adopted here allowed the iterative development of a robust workflow to achieve an adaptable, event-minimizing planning process despite a complex setting which requires the participation of multiple teams for Y-90 microspheres therapy. Implementation of such a workflow using the EWB or similar platform with a DMAIC-based process improvement approach could be expanded to other treatment procedures, especially those requiring multidisciplinary management.

Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one of the deadliest. Patients with chronic liver disease are at the highest risk for developing this tumor. This link provides an opportunity for developing preventive strategies and surveillance that aims at early detection of this tumor and possibly improving outcomes. In this review, we will discuss the latest developments in surveillance strategies, diagnosis, and treatment of this tumor. HCC is the sixth most common cancer in the world, with 782,000 new cases occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of HCC, which varies geographically, is related to the prevalence of hepatotropic virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It is estimated that the incidence of HCC in Europe and United States will peak at 2020-there will be 78,000 new HCC cases in Europe and 27,000 in the United States-and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already plateaued and started to slowly fall.4 Cirrhosis is the most important risk factor for HCC regardless of etiology and may be caused by chronic viral hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease, Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in 90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is important to discuss surveillance for this tumor.