Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.

Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; however, few have assessed long-term hepatic function. This study aimed to evaluate a clinical real-world experience of Y90 effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with Child-Pugh (CP) class A or B who received Y90 for primary HCC between 2008 and 2016. Model for end-stage liver disease (MELD) and CP scores were calculated on the day of treatment and 1, 3, 6, 12, and 24 months post-procedure. Results: Of the 134 patients included, the mean age was 60 years old and median overall survival (OS) from date of diagnosis was 28 months [95% confidence interval (CI): 22.21-38.05]. Patients with CP class A (85%) had a median progression-free survival (PFS) of 3 months (95% CI: 2.99-5.55) and median OS of 17 months (95% CI: 9.59-23.10) from date of Y90 treatment compared to a median PFS of 4 months (95% CI: 2.07-8.28) and OS of 8 months (95% CI: 4.60-15.64) for patients with CP class B. MELD scores were significantly higher post-treatment than pre-treatment, with significant recovery at 24 months. No significant differences were seen between cancer stage and OS, while PFS and cancer stage did show difference between cancer stage 1 and 3 with longer median PFS seen in stage 1. Conclusions: While our study supports the literature for OS in Y90-treated patients, we found a shorter PFS in this population. This may reflect the differences between the utilization of RECIST in clinical trials and clinical radiology practice in determining progression. Significant factors associated with OS were age, MELD, CP scores and portal vein thrombosis (PVT). For PFS, CP score and stage at diagnosis were significant. Increasing MELD scores over time likely reflected a combination of radioembolization-induced liver disease, liver decompensation or progression of HCC. The downtrend at 24 months is likely due to long term survivors with significant benefit from therapy with no long-term complications from Y90.

Induction Therapy in Localized Pancreatic Cancer.

OBJECTIVES: Pancreatic cancer (PDAC) with localized stage includes resectable (RPC), borderline resectable (BRPC), or locally advanced unresectable (LAPC). Standard of care for RPC is adjuvant chemotherapy. There are no prospective randomized trials for best treatment of BRPC and LAPC. We evaluate the impact of induction chemotherapy on localized PDAC. METHODS: Charts of PDAC patients treated at Emory University between 2009 and 2016 were reviewed. The primary end point was overall survival (OS). RESULTS: A total of 409 localized PDACs were identified. Resectability was prospectively determined at a multidisciplinary tumor conference. Median age was 67 years (range, 30-92 years), 49% were male, 66% were white, 171 had RPC, 131 had BRPC, and 107 had LAPC. Median OSs for RPC, BRPC, and LAPC were 19.5, 16.1, and 12.7 months, respectively. Type of chemotherapy and age were predictors of OS. Induction chemotherapy was used in 106 with BRPC (81%) and 74 with RPC (56.5%); patients with BRPC who received combination chemotherapy and resection had a median OS of 31.5 compared with 19.5 months in patients with RPC (P = 0.0049). Patients with LAPC had a median OS of 12.7 months. CONCLUSIONS: In patients with BRPC who undergo resection after induction treatment, the OS was significantly better than in patients with RPC. Neoadjuvant treatment should be considered for all localized PDACs.

Randomized study of doxorubicin-based chemotherapy regimens, with and without sildenafil, with analysis of intermediate cardiac markers.

BACKGROUND: Doxorubicin chemotherapy is used across a range of adult and pediatric malignancies. Cardiac toxicity is common, and dysfunction develops over time in many patients. Biomarkers used for predicting late cardiac dysfunction following doxorubicin exposure have shown promise. Preclinical studies have demonstrated potential cardioprotective effects of sildenafil. METHODS: We sought to confirm the safety of adding sildenafil to doxorubicin-based chemotherapy and assess N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) and high sensitivity cardiac troponin I (hsTnI) as early markers of anthracycline-induced cardiotoxicity. We randomized 27 patients (ages 31-77, 92.3% female) receiving doxorubicin chemotherapy using a blocked randomization scheme with randomly permuted block sizes to receive standard chemotherapy alone or with the addition of sildenafil. The study was not blinded. Sildenafil was dosed at 100 mg by mouth daily during therapy; patients took sildenafil three times daily on the day of doxorubicin. Doxorubicin dosing and schedule were dependent on the treatment regimen. Echocardiography was obtained prior to initiation of treatment and routinely thereafter up to 4 years. NT-proBNP and hsTnI were obtained with each cycle before, 1-3 h after, and 24 h after doxorubicin. RESULTS: Fourteen patients were randomized to receive standard doxorubicin chemotherapy alone (14 treated and analyzed), while 13 patients were randomized to the experimental doxorubicin and sildenafil arm (10 treated and analyzed). No toxicity signal was seen with the addition of sildenafil to doxorubicin-based regimens. There was no statistical difference between the treatment arms in relation to the change of mean left ventricular ejection fraction (LVEF) between the first and last evaluation. In both arms, hsTnI levels increased over time; however, elevated hsTnI was not associated with declines in LVEF. CONCLUSION: Adding sildenafil was safe, but did not offer cardioprotection following doxorubicin treatment. Increases in hsTnI levels were observed over time, but elevations during therapy did not correlate with subsequent decreases in LVEF. TRIAL REGISTRATION: This clinical trial (NCT01375699) was registered at www.clinicaltrials.gov on June 17, 2011.