Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Assessment of quality of life in pediatric patients with pulmonary hypertension.

The aim of this study is to evaluate quality of life in four domains (physical, emotional, social, and school) in pediatric patients with pulmonary hypertension (PH) using a validated survey (PedsQL). This is a prospective cohort study of pediatric patients aged 2-18 years with PH. Parents of all children and patients aged 8-18 years with appropriate developmental capacity completed the PedsQL survey in the clinic. Results were compared with published norms for pediatric patients, those with congenital heart disease (CHD) and cancer. Thirty-three children were enrolled yielding 32 parent and 18 patient self-reports: seven patients were aged 2-4 years; three were aged 5-7 years; 11 were aged 8-12 years, and 12 were aged 13-18 years. Twenty-one patients were classified as World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH), 11 WHO Group III PH due to lung disease, and one WHO Group V with segmental PH. Thirteen patients were NYHA functional class (FC) 1, 12 were FC 2, eight were FC 3, and none were FC 4. The PH cohort had significantly lower scores than healthy children in all domains on both parent and self-report. The PH cohort also had significantly lower scores than patients with CHD (parent report: total, physical, social, school; patient self-report: total, physical, school) and cancer (parent report: school; patient self-report: physical, school). Close to 50% of participants reported at risk scores in each domain. The quality of life in pediatric PH patients assessed by PedsQL revealed functional impairment in multiple domains. Administration of the PedsQL during outpatient encounters may provide an easy, reproducible method to assess quality of life and direct referral for interventional services.