Treatment outcome and pattern of failure in hepatoblastoma treated with a consensus protocol in Hong Kong.

BACKGROUND AND AIM: We reviewed the results and pattern of failure of the consensus HB/HCC 1996 treatment protocol for pediatric hepatoblastoma (HB) in Hong Kong. The role of SIOPEL and Children's Hepatic tumors International Collaboration (CHIC) risk stratification was evaluated. METHODS: Patients enrolled on the protocol from 1996 to 2014 were included. PRETEXT staging, SIOPEL, and CHIC risk groups were retrospectively assigned. RESULTS: Sixty patients were enrolled with median age at diagnosis of 1.1 years and median follow-up time of 6.8 years. Alpha-fetoprotein (AFP) was raised (>100 ng/mL) in 58 (97%) patients. Five (8%) had metastases at presentation and 7 (12%) experienced tumor rupture prior to or during treatment. Twenty-nine patients (48%) received a first-line cisplatin, 5-fluorouracil, and vincristine regimen only while 23 (38%) also had alternative chemotherapeutic agents. Hepatic resection could be performed in 48 (80%) patients. Three (5%) patients underwent upfront liver transplantation. Five-year event-free survival and overall survival rates were 69.2% ± 6.1% and 77.6% ± 5.5% respectively. Among the 16 patients with relapse/progression, 9 had intrahepatic failure only, 5 had distant failure only, and 2 had combined local and distant failure. Predictors of inferior outcome included advanced Evans staging, disease involving both lobes, rupture, low AFP, and suboptimal response to first-line chemotherapy. Assigned in 44 patients, PRETEXT staging, SIOPEL, and CHIC risk groups significantly predicted EFS and OS. CONCLUSIONS: Although the consensus HB/HCC 1996 protocol led to cure in three-quarters of pediatric HB patients, an upfront risk stratification system is required to identify and improve the outcome of high-risk patients.

Hepatitis B Virus Seropositivity Is a Poor Prognostic Factor of Pediatric Hepatocellular Carcinoma: a Population-Based Study in Hong Kong and Singapore.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. Hepatitis B virus (HBV) infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with national HBV vaccination. METHODS: Review of population-based databases for patients (< 18 years old) diagnosed with HCC from 1993 to 2017 in two Southeast Asian regions with universal HBV vaccination (instituted since 1988 and 1987 in Hong Kong and Singapore, respectively). RESULTS: Thirty-nine patients were identified (Hong Kong, 28; Singapore, 11). Thirty were male; median age at diagnosis was 10.8 years (range, 0.98-16.6). Abdominal pain was the commonest presentation while five patients were diagnosed through surveillance for underlying condition. Alpha-fetoprotein was raised in 36 patients (mean, 500,598 ng/ml). Nineteen had bilobar involvement, among the patients in whom pretreatment extent of disease (PRETEXT) staging could retrospectively be assigned, 3 had stage I, 13 had stage II, 4 had stage III, and 11 had stage IV disease. Seventeen had distant metastasis. HBsAg was positive in 19 of 38 patients. Two patients had fibrolamellar HCC. Upfront management involved tumor resection in 16 (liver transplantation, 2), systemic chemotherapy in 21, interventional procedures in 6 [transarterial chemoembolization (TACE), 5, radiofrequency ablation (RFA), 1], and radiotherapy in 4 (selective internal radiation, 3, external beam radiation, 1). Five-year event-free survival (EFS) and overall survival (OS) were 15.4 ± 6.0 and 26.1 ± 7.2%, respectively. Patient's HBsAg positivity, metastatic disease and inability to undergo definitive resection represent poor prognostic factors in univariate and multivariable analyses. Patients diagnosed by surveillance had significantly better outcome. CONCLUSION: Pediatric HCC has poor outcome. HBV status remains relevant in the era of universal HBV vaccination. HBV carrier has inferior outcome and use of surveillance may mitigate disease course.

Left and Right Ventricular Systolic and Diastolic Functional Reserves Are Impaired in Anthracycline-Treated Long-Term Survivors of Childhood Cancers.

BACKGROUND: The aim of this study was to test the hypothesis that left ventricular (LV) and right ventricular (RV) functional reserves are altered in anthracycline-treated long-term survivors of childhood cancers. METHODS: One hundred three survivors (55% men) aged 25.0 ± 5.8 years at 15.2 ± 5.8 years after chemotherapy and 61 healthy control subjects (52% men) were studied. Tissue Doppler-derived mitral and tricuspid systolic (s) and early diastolic (e) velocities and LV myocardial acceleration during isovolumic contraction (IVA) were determined at rest and during bicycle exercise. The slope of the LV force-frequency relationship was derived from changes in IVA with heart rate during exercise (ΔIVA/Δ[heart rate]). LV and RV functional reserves were further assessed by the systolic functional reserve index (Δs × [1 - 1/s at baseline]) and diastolic functional reserve index (Δe × [1 - 1/e at baseline]). RESULTS: At baseline, mitral annular tissue Doppler indices were similar between survivors and control subjects (P > .05 for all), while tricuspid s and e velocities were significantly lower in survivors (P < .05 for both). The force-frequency relationship slope (P < .001), LV systolic functional reserve index (P < .001), and RV systolic functional reserve index (P = .001) were significantly lower in survivors than control subjects. For diastolic functional reserve, LV but not RV diastolic functional reserve index was significantly lower in survivors (P < .001). Multivariate analysis revealed survivor status (ß = -0.39, P < .001) and baseline LV IVA (ß = 0.15, P < .044) as significant determinants of the LV force-frequency relationship. CONCLUSIONS: LV and RV functional reserves during exercise are impaired in anthracycline-treated long-term survivors of childhood cancer.