Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma.

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States.

BACKGROUND: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown. METHODS: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively. RESULTS: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS. CONCLUSIONS: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA.

Development and validation of a biomarker index for HCC treatment response.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927. CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.

Effect of scheduling inferior vena cava filter removal during the placement encounter on filter removal rate.

OBJECTIVE: In the present study, we sought to determine whether early pre-emptive scheduling of inferior vena cava filter (IVCF) removal during the preoperative IVCF placement visit would affect the IVCF removal rate. METHODS: All electronically documented IVCF placements at a single institution were reviewed from April 2015 to July 2019. The baseline characteristics included age, the clinical indications for IVCF placement, inpatient/outpatient status, and type of IVCF placed. Statistical analysis was performed using the χ2 for discrete variables and the two-tailed paired t test for continuous variables. RESULTS: A total of 599 patients (mean age, 68 years; 273 women and 326 men) had undergone technically successful IVCF placement. During the preoperative consent process for placement, 232 patients had been scheduled for IVCF removal within 3 months after placement. However, 367 patients had not been scheduled for removal at the preoperative consent process. The indications for placement included failure of anticoagulation, a contraindication to anticoagulation (eg, bleeding), preoperative prophylaxis, and others. Of the 232 patients scheduled for IVCF removal during preoperative consent for IVCF placement, 103 (44%) had undergone successful IVCF removal (mean interval from placement, 107 ± 100 days). Of the 367 nonscheduled patients, 89 (24%) had undergone successful IVCF removal (mean time, 184 ± 215 days). We found a significant improvement in the IVCF removal rate between the scheduled and nonscheduled patients (P < .0001). Three patients (all from the scheduled group) had a clot burden within the IVCF, which meant they were inappropriate for removal. These patients were rescheduled and had eventually undergone uncomplicated removal. CONCLUSIONS: Scheduling IVCF removal during the placement encounter significantly increased the IVCF removal rate. This approach could be a viable option for institutions where clinic time and/or resources are limited or unavailable and for patients who have difficulty traveling for clinical evaluations.

Transarterial radioembolization versus systemic treatment for hepatocellular carcinoma with macrovascular invasion: Analysis of the US National Cancer Database.

Background and Aims: Systemic therapy remains the recommended first-line treatment for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). Transarterial radioembolization (TARE) is a promising alternative treatment given superior quality of life. The aims of this study were to 1) characterize trends and correlates for TARE as first-line treatment of HCC patients with MVI in the US and 2) compare survival after TARE versus systemic therapy. Methods: We used the US National Cancer Database to identify patients with T3BN0M0 HCC during 2010-2017. We performed multivariable logistic regression to identify factors associated with use of TARE vs. systemic therapy and Cox proportional hazards regression to identify factors associated with overall survival. Results: Of 11,259 patients with T3BN0M0 HCC, 1454 (12.9%) and 3915 (34.7%) patients were treated with TARE and systemic therapy, respectively. The proportion of patients who received TARE increased from 13.0% in 2010 to 37.0% in 2017. Older age, White race, and receiving care at an academic cancer program were associated with receipt of TARE, while lack of insurance, higher MELD score, Charlson comorbidity Index ≥3, and Northeast region were associated with receipt of systemic therapy. TARE was associated with reduced mortality compared to systemic therapy (adjusted hazard ratio: 0.74, 95%CI: 0.68-0.80), with consistent results observed in propensity weighted analysis and across all examined subgroups. Conclusion: Use of TARE as first-line therapy for HCC with MVI has increased in the US. Patient characteristics, region, and medical center type affected the use of TARE. TARE was associated with reduced mortality compared to systemic therapy for HCC patients with MVI.

Pancreatic neuroendocrine tumors: presentation, management, and outcomes.

Pancreatic neuroendocrine tumors (pNETs) are an uncommon pancreatic neoplasm. We reviewed the presentation, management, and outcome of patients with pNETs treated at a single center by a multidisciplinary approach between 2004 and 2008. Over this time period, 154 patients with carcinoid and neuroendocrine tumors were treated, which included 46 patients (30% of total) with pNETs. The most common presentations included abdominal pain (20 of 46 [43%]), systemic symptoms such as hypoglycemia (15 of 46 [33%]), and incidental mass (7 of 46 [15%]). Fourteen patients had functional tumors. At the time of diagnosis, 22 patients (48%) presented without metastases and 24 (52%) had metastatic disease. Median follow up for the entire group was 42 months. All patients with nonmetastatic pNET underwent pancreatic resection with 95 per cent postoperative survival. Overall survival in this group at 3 years was 86 per cent and disease-free survival was 81 per cent. In patients presenting with metastatic pNET, multiple treatment modalities were used, including liver resection or ablation (n = 15), hepatic chemoembolization (n = 17), pancreatic resection (n = 12), and systemic treatments (n = 7). Three-year survival was 70 per cent. Pancreatic resection results in greater than 80 per cent 3-year survival in nonmetastatic pNET. In patients presenting with metastatic pNET, excellent survival rates are also achievable using a multidisciplinary multimodal approach.

Complications and retrieval characteristics of Celect Platinum inferior vena cava filters.

BACKGROUND: The purpose of this study was to retrospectively assess the retrieval characteristics and rate of filter-related complications associated with use of the Celect Platinum (Cook Medical, Bloomington, Ind) inferior vena cava filter (IVCF). METHODS: A single-center, retrospective review was conducted to identify patients who received a Celect Platinum IVCF between June 2013 and February 2016. The patients' charts and imaging records (computed tomography [CT] and cavography) associated with filter placement, follow-up, and filter retrieval procedures were assessed for attempted and successful retrieval rates and filter-related complications. RESULTS: During the review period, 562 Celect Platinum filters were placed in 556 patients. Outcome and evaluable imaging data (CT and cavography) were available from 335 patients, with median CT follow-up time of 45 days (average, 126 days) and median cavography follow-up time of 90 days (average, 102 days). IVCF leg perforation of the inferior vena cava wall >3 mm was identified in 65 cases (19.4%) on follow-up imaging (64 cases). In addition, filter tilt >15 degrees was identified in 4 filters (1.2%), filter migration >2 cm in 1 filter (0.3%), and occlusive filter or inferior vena cava or iliac vein thrombus in 11 filters; no filter fracture was observed. One case of breakthrough pulmonary embolism and two additional indeterminate cases were identified on follow-up CT pulmonary angiography (2.6%-7.7%). Retrieval was successful in 155 of 155 patients (median indwell time, 90 days; range, 1-445 days); an advanced retrieval technique was used in 11 retrievals. CONCLUSIONS: The outcomes for the Celect Platinum filter were comparable to those previously reported for the first-generation Celect filter in all categories assessed.

The Clinicopathological Aspects of Primary Presacral Neuroendocrine Neoplasms: One Center Experience.

OBJECTIVES: Presacral neuroendocrine neoplasms (NENs) are rare entities that are found at the presacral space. We report our experience in the diagnosis, management, and outcomes of primary presacral NENs. METHODS: This was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of NENs at Cedars-Sinai Medical Center between January 2000 and April 2016. RESULTS: Ten patients were identified. The median age at presentation was 38 years (range, 20-77 years), and 8 were women. One patient presented with carcinoid-like symptoms, 2 were diagnosed incidentally, and 7 presented with symptoms related to mass effect. The median size of the tumor was 7.0 cm (range, 3-12 cm). On pathologic review, 3 of 10 were low-grade and well-differentiated, 5 of 10 were intermediate-grade and well-differentiated, 2 of 10 were grade 3 and classified as high-grade and poorly differentiated neuroendocrine tumors. Seven cases were metastatic on presentation with lymph node, liver, lung, or skeletal metastasis. Seven of 8 cases were detectable using Octreoscan. Eight patients were treated with a somatostatin analog and 5 patients were treated surgically. CONCLUSIONS: Presacral NENs are clinically similar to gastroenteropancreatic tumors. Octreoscan imaging and somatostatin analog therapies were frequently applied. Further biologic characterization of this rare subtype is needed.