Patterns of cervical lymph node metastasis in supraglottic laryngeal cancer and therapeutic implications of surgical staging of the neck.

PURPOSE: Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail. RESULTS: On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients. CONCLUSION: Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.

Comparative Effectiveness of Thermal Ablation, Surgical Resection, and Active Surveillance for T1a Renal Cell Carcinoma: A Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked Population Study.

Purpose To compare adverse events and survival outcomes, including cancer-specific survival and overall survival (OS), in patients with T1aN0M0 renal cell carcinoma (RCC) who are undergoing partial nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), or active surveillance (AS). Materials and Methods Through use of the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 to 2011 with at least 1 year of consecutive follow-up, a HIPAA-compliant retrospective propensity score-matched study of patients with T1aN0M0 RCC who underwent PN, RN, TA, or AS was performed. Medicare beneficiaries (n = 10 218) with T1aN0M0 RCC as first primary cancer diagnosis were included. Survival and adverse health outcomes were compared across treatment groups. Results Overall, cancer-specific survival significantly differed in the PN versus RN (P < .001), AS versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4% versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively. With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-specific survival and OS for all AS comparisons were significantly lower. In addition, compared with the patients undergoing TA, those in the PN and RN groups had increased rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the procedure (P < .05 for all comparisons). Conclusion For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with surgical management, with significantly fewer adverse outcomes at 1 year after the procedure and similar rates of secondary cancer events compared with surgery.

Survival Rates after Thermal Ablation versus Stereotactic Radiation Therapy for Stage 1 Non-Small Cell Lung Cancer: A National Cancer Database Study.

Purpose To compare survival rates of thermal ablation and stereotactic radiation therapy (SRT) for stage 1 non-small cell lung cancer (NSCLC). Materials and Methods In this retrospective study, patients with stage 1 NSCLC treated by thermal ablation (TA) or SRT were identified in the 2004-2013 National Cancer Database. Patients who underwent TA and SRT were one-to-one propensity matched to undergo thermal ablation. Outcomes were overall survival and unplanned hospital readmission within 30 days after treatment. Results This study included 28 834 patients (TA, 1102 patients; SRT, 27 732 patients). Patients treated with TA had more comorbidities (Charlson comorbidity index of 1 vs ≥2, 32.8% [362 of 1102] vs 19.7% [217 of 1102], respectively) compared with SRT (Charlson comorbidity index of 1 vs ≥2, 26.9% [7448 of 27 732] vs 15.3% [4251 of 27 732], respectively; P , .001) and smaller tumor size (mean tumor size, TA vs SRT: 19 mm vs 22 mm, respectively; P , .001). In the propensity score-matched cohort with balanced distribution of potential confounders, there was no significant difference in overall survival between TA and SRT at a mean follow-up of 52.4 months (survival difference, P = .69). Overall survival rates were comparable between TA and SRT (1 year, 85.4% vs 86.3%, respectively, P = .76; 2 years, 65.2% vs 64.5%, respectively, P = .43; 3 years, 47.8% vs 45.9%, respectively, P = .32; 5 years, 24.6% vs 26.1%, respectively, P = .81). Unplanned hospital readmission rates were higher for patients who underwent TA versus those who underwent SRT (3.7% [40 of 1070] vs 0.2% [two of 1070], respectively; P , .001). Conclusion Regarding overall survival, thermal ablation was noninferior to stereotactic radiation therapy for primary treatment of stage 1 non-small cell lung cancer. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Shyn in this issue.

Racial Disparities and Sociodemographic Differences in Incidence and Survival Among Pediatric Patients in the United States With Primary Liver Cancer: A Surveillance, Epidemiology, and End Results (SEER) Population Study.

BACKGROUND: Primary liver cancer, including Hepatoblastoma (HB) and hepatocellular carcinoma (HCC), in pediatric populations is often fatal. The outcomes are poor despite universal health care access in pediatric patients. AIM: We investigated the sociodemographic factors affecting outcomes in pediatric patients with primary liver cancer. MATERIALS AND METHODS: This is a large population database study of Surveillance, Epidemiology, and End Results cancer registry data from 1973 to 2011. HB and HCC were analyzed regarding age, sex, race, geographic area, and treatment-related information including survival. RESULTS: In total, 998 patients, the median age at time of diagnosis was 1 year for HB [0-19; 95% confidence interval (CI), 1.5-1.9] and 14 years for HCC (0-19; 95% CI, 12.1-13.3) (P<0.001). Overall Survival (OS) in HB was 374 months (25% failures 19) versus HCC 21 months (25% failures 5; P<0.0001). In HCC, the fibrolamellar subgroup OS was 41 months (32-.) versus 16 months (11-21) in all others [hazard ratio (HR) 2.0; P=0.005]. Diagnosis between 2000 and 2011 (HB: 25% failures not reached; HCC: 38) versus diagnosis 1973 to 1999 (HB: 374; HCC: 12) had different survival (P=0.01; HR 1.9). For HB, OS in patients with age of diagnosis under 2, 25% failures was not reached versus 374 months over the age of 2 (HR 1.7; P<0.0007). African American children with HB had OS of 67 (17-.) versus all others (25% failures 21) and 48% of African American children were diagnosed after the age of 2 versus 34% of whites (HR 1.9; P=0.01). CONCLUSIONS: Later diagnosis and decreased survival in African American children with HB warrants further research.

Targeted Yttrium 89-Doxorubicin Drug-Eluting Bead-A Safety and Feasibility Pilot Study in a Rabbit Liver Cancer Model.

The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemoembolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive surrogate for therapeutic (yttrium-90, lutetium-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100 µL; 100-300 µm), and administered intra-arterially in six rabbits at increasing doses (0.2-1.0 mg/kg). As controls, two rabbits each received either doxorubicin IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and histopathological evaluation after sacrifice were performed. One-Way ANOVA incl. Bonferroni Post-Hoc test was performed to compare groups. Targeted compound synthesis, loading onto DEB, and intra-arterial administration were feasible and successful in all cases. Serum liver enzyme levels increased in a dose dependent manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be euthanized after 3/24 h due to worsening general condition. Histopathological necrosis increased over time in a dose depended manner with 95-100% tumor necrosis 3-7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be formulated and safely administered at a concentration of 0.6 mg/kg. Loading with radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is feasible.

Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma.

OBJECTIVE: To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 (90Y)-radioembolization for hepatocellular carcinoma (HCC). METHODS: Studies comparing conventional (c)TACE versus 90Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. RESULTS: Fourteen studies comparing DEB-TACE or 90Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. CONCLUSION: DEB-TACE and 90Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90Y-radioembolization but direct comparison is warranted for further evaluation. KEY POINTS: • This meta-analysis shows greater 1-year survival benefit for DEB-TACE over 90 Y-radioembolization. • DEB-TACE has a favourable 2- & 3-year survival benefit trend over 90 Y-radioembolization. • No significant difference for tumour response was detected. • Direct comparison of these methods for a more robust evaluation is warranted.

Percutaneous Management of Benign Biliary Strictures with Large-Bore Catheters: Comparison between Patients with and without Orthotopic Liver Transplantation.

PURPOSE: To prospectively evaluate stricture resolution and patency rates of benign biliary strictures treated with percutaneous large-bore catheter "stenting" in patients with and without previous orthotopic liver transplantation (OLT) and to compare treatment outcomes between these two groups. MATERIALS AND METHODS: Forty-six consecutive patients (25 with OLT) underwent percutaneous catheter placement in extrahepatic and single-site biliary stricture for 6-8 months, with progressive catheter upsizing to 18-20 F. Primary patency rate was defined as the proportion of patients without recurrent bile duct stricture during the follow-up period after successful stricture resolution. Secondary patency rate was defined as the proportion of patients with a patent bile duct at the end of follow-up after stricture resolution, including patients with stricture recurrence and successful repeat percutaneous biliary catheter treatment. RESULTS: Eleven patients terminated the protocol early, 6 as a result of treatment-related reasons in the orthotopic liver transplantation (OLT) group. Sixty-four percent of the OLT group and 86.4% of control patients successfully completed the protocol, with resolved biliary strictures (P = .1) after a median treatment time of 7 months for both groups (P = .96). During mean follow-up times of 20.3 months ± 11.8 (standard deviation) and 13.1 months ± 11.73 for OLT and non-OLT patients (P = .08), respectively, the primary/secondary patency rates were comparable between groups, at 81.25%/87.5% for OLT patients and 89.5%/100% for non-OLT patients (P = .64/P = .2). The mean time to recurrent stricture was 11.2 months ± 11.88. CONCLUSIONS: Percutaneous large-bore catheter treatment of benign, single-site biliary strictures showed a promising rate of stricture resolution, with comparable high primary and secondary patency rates in patients with and without previous OLT.

Baseline and Early MR Apparent Diffusion Coefficient Quantification as a Predictor of Response of Unresectable Hepatocellular Carcinoma to Doxorubicin Drug-Eluting Bead Chemoembolization.

PURPOSE: To investigate baseline and early apparent diffusion coefficients (ADC) derived from diffusion-weighted imaging (DWI) as a predictor of objective response (OR) and survival in unresectable hepatocellular carcinoma (HCC) treated with doxorubicin drug-eluting bead (DEB) transcatheter arterial chemoembolization. MATERIALS AND METHODS: In a prospective study, 57 patients underwent DEB chemoembolization. Dynamic contrast-enhanced magnetic resonance imaging and DWI were performed at baseline and 1 and 3 months after DEB chemoembolization. OR was evaluated per modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) guidelines. Baseline ADCs of tumors that showed OR at 1 and 3 months were compared with nonresponding tumor ADCs by two-sample t test and receiver operating characteristic curves. Additionally, ADC changes at 30 days were correlated with OR. Finally, Kaplan­Meier analysis was used to compare survival between patients with lesions demonstrating more restricted baseline diffusion and others. RESULTS: At 1 month, 33 patients (60%) showed OR (21 complete responses and 12 partial responses). At baseline, tumors with OR at 1 month showed significantly more restricted diffusion (0.731 × 10(−3) mm2/s) compared with others (1.057 × 10(−3) mm2/s; P = .031). No difference between response rates at 1 and 3 months according to mRECIST and EASL was observed. For an area under the curve of 0.965, the sensitivity and specificity of predicting objective tumor response at 1 month using a baseline HCC ADC of 0.83 × 10(−3) mm2/s were 91% and 96%, respectively. In addition, patients with lesions with a baseline ADC < 0.83 × 10(−3) mm2/s showed prolonged survival compared with others (P < .001). CONCLUSIONS: In unresectable HCC, a baseline ADC < 0.83 × 10(−3) mm2/s is a predictor of survival and treatment response at 1 and 3 months after DEB chemoembolization with high sensitivity and specificity.

Bilobar Radioembolization Carries the Risk of Radioembolization-Induced Liver Disease in the Treatment of Advanced Hepatocellular Carcinoma: Safety and Efficacy Comparison to Systemic Therapy with Atezolizumab/Bevacizumab.

Recommended treatment options for advanced-stage hepatocellular carcinoma (HCC) include systemic therapy (ST) and trans-arterial radioembolization (TARE) with Yttrium-90 (Y90). Before the approval of immune-checkpoint inhibitors, a similar safety profile was reported for TARE and ST with tyrosine kinase inhibitors (TKI). However, whole-liver treatment and underlying cirrhosis were identified as risk factors for potentially lethal radioembolization-induced liver disease (REILD). Therefore, the safety and efficacy of TARE and ST with atezolizumab/bevacizumab were compared in patients with advanced HCC involving at least both liver lobes in a retrospective real-world cohort. In total, 74 patients with new or recurrent advanced-stage HCC (BCLC stage B/C) were included if treated with either bilobar TARE (n = 33) or systemic combination therapy with atezolizumab plus bevacizumab (n = 41). Most patients had compensated liver function (90.5% were classified as Child-Pugh Score A, 73% as ALBI Grade 1) at baseline. Although not significant, patients treated with ST showed a more prolonged overall survival than those treated with Y90 TARE (7.1 months vs. 13.0 months, p = 0.07). While a similar disease control rate could be achieved with bilobar TARE and atezolizumab/bevacizumab, in the TARE group, overall survival was curtailed by the occurrence of REILD. In patients with underlying liver cirrhosis, the liver function at baseline was a predictor for REILD.

Radiation Dose Aspects of Hepatic Artery Infusion Chemotherapy in Uveal Melanoma Patients with Liver Metastases.

PURPOSE: In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investigate the radiation exposure of HAIC. MATERIAL AND METHODS: In this retrospective study, dose data from 841 procedures in 140 patients (mean age 65.3 ± 9.9 years, 74 female) who underwent HAIC between 06/2017 and 10/2021 at one of three different angiography systems were analyzed. RESULTS: In the overall population, dose area product (DAP) (median (IQR)) was 1773 cGy·cm2 (884-3688). DAP was significantly higher in the first intervention, where a complete diagnostic workup of the vasculature was performed, than in follow-up interventions: 5765 cGy·cm2 (3160-8804) versus 1502 cGy·cm2 (807-2712) (p < 0.0001). DAP also increased significantly with the number of infusion positions (median, (IQR)): one position 1301 cGy·cm2 (633-2717), two positions 1985 cGy·cm2 (1118-4074), three positions 6407 cGy·cm2 (2616-11590) (p < 0.0001). CONCLUSION: In uveal melanoma patients with liver metastases undergoing HAIC, radiation exposure is significantly higher both at the first intervention compared to follow-up interventions, but also with increasing number of infusion positions.

Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis.

The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment.

Prediction of left lobe hypertrophy after right lobe radioembolization of the liver using a clinical data model with external validation.

In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.

Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience.

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results: The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7-19.3] versus 6.0 months (95% CI: 3.2-8.9; p < 0.001) and mPFS: 8.7 months (95% CI: 5.9-11.5) versus 3.7 months (95% CI: 2.7-4.7; p < 0.001)]. Prior systemic treatment did not significantly affect mOS [hazard ratio (HR): 1.32 (95% CI: 0.78-2.23; p = 0.305)]. mOS according to ALBI grades 1/2/3 were 15.0 months (95% CI: not estimable), 8.6 months (95% CI: 5.4-11.7), and 3.2 months (95% CI: 0.3-6.1), respectively. ALBI grade and ECOG score were identified as independent prognostic factors [ALBI grade 2 versus 1; HR: 2.40 (95% CI: 1.34 - 4.30; p = 0.003), ALBI grade 3 versus 1; HR: 7.28 (95% CI: 3.30-16.08; p < 0.001), and ECOG ⩾2 versus 0; HR: 2.09 (95% CI: 1.03 - 4.23; p = 0.042)], respectively. Sixty-seven patients (45.6%) experienced an adverse event classified as CTCAE grade ⩾3. Patients in the IMbrave-OUT group were at increased risk of hepatic decompensation with encephalopathy (13.7% versus 1.4%, p = 0.004) and/or ascites (39.7% versus 9.5%; p < 0.001). Conclusion: In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.

LiMAx Prior to Radioembolization for Hepatocellular Carcinoma as an Additional Tool for Patient Selection in Patients with Liver Cirrhosis.

BACKGROUND AND AIMS: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. PATIENTS AND METHODS: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. RESULTS: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child-Pugh score B 28 days after RE or with a deterioration in Child-Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child-Pugh score A or with stable Child-Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. CONCLUSION: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child-Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure.

European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden.

To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan-Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3-18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child-Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6-10.3) months. The best response was achieved after a median of 3 (range: 1-6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.

Predictive impact of the inflammation-based indices in uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion.

BACKGROUND: The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. PATIENTS AND METHODS: 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1-11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed. RESULTS: Median OS of the study cohort was 7.7 (6.3-10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5 vs. 5.2; p = 0.0005), low SII (10.8 vs. 5.6; p = 0.0005), low NLR (11.1 vs. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5 vs. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5 vs. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2 vs. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11-0.7; p = 0.005), low SII (HR: 0.19, 0.11-0.7; p = 0.008), and low ALT (HR: 0.13, 0.02-0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001). CONCLUSIONS: Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.

Co-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer.

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor dual checkpoint inhibition significantly affected the tumoral infiltration of lymphocytes. After treatment with dual inhibitors, infiltrating CD8+ T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p < 0.05) and LAG3 (446.2 vs. 694.4 and 707; p < 0.05) along with significantly more expression of TIM3 (12,611 vs. 2961 and 4259; p < 0.05) versus the control and anti-PD-1 groups. These results suggest that dual therapy with anti-CTLA-4 and anti-PD-1 antibodies significantly inhibits growth of microsatellite stable CRC by suppressing immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism and a target for future combination immunotherapies in CRC.

The effect of chronic viral hepatitis on prognostic value of inflammatory biomarkers in hepatocellular carcinoma.

BACKGROUND: Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. METHODS: Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan-Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). RESULTS: A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low-NLR group (

Oligometastatic Disease and Interventional Oncology: Rationale and Research Directions.

Oligometastatic disease (OMD) is generally defined as a stage of clinically or radiographically demonstrated metastatic disease limited in total disease burden and without rapid spread. Interventional oncology performs local therapies for primary and metastatic cancers, including OMD. Interventional oncology treatments can be pursued both as definitive therapy and for palliative purposes. Applied to OMD, these interventions can offer patients a decreasing overall tumor burden, minimizing cancer morbidity, and early evidence suggests a survival benefit. Here, we discuss the range of interventional oncology treatments, including ablation, chemoembolization, radioembolization, and irreversible electroporation. We describe the rationale for their application to OMD and discuss future directions for research.