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Driver mutations in the CTNNB1 gene (encoding β-catenin) are a hallmark of sporadic hepatoblastoma (HBL). Our results show that CTNNB1 circulating tumour DNA (ctDNA) is readily detected in patients diagnosed with localised HBL, with serial sampling along the course of therapy and follow up providing a sensitive mechanism to monitor tumour dynamics and response to treatment. This exciting potential for CTNNB1 ctDNA to serve as a biomarker for treatment response in HBL holds clinical value, and requires assessment in a larger cohort of mixed tumour stages and recurrent disease., (© 2020 Wiley Periodicals LLC.)

Background: Reporting ototoxicity is frequently complicated by use of various ototoxicity criteria. The International Society of Pediatric Oncology (SIOP) ototoxicity grading scale was recently proposed for standardized use in reporting hearing loss outcomes across institutions. The aim of this study was to evaluate the concordance between the Chang and SIOP ototoxicity grading scales. Differences between the two scales were identified and the implications these differences may have in the clinical setting were discussed., Procedures: Audiological evaluations were reviewed for 379 patients with newly diagnosed medulloblastoma (ages 3-21 years). Each patient was enrolled on one of two St. Jude clinical protocols that included craniospinal radiation therapy and four courses of 75 mg/m(2) cisplatin chemotherapy. The latest audiogram conducted 5.5-24.5 months post-protocol treatment initiation was graded using the Chang and SIOP ototoxicity criteria. Clinically significant hearing loss was defined as Chang grade ≥2a and SIOP ≥2. Hearing loss was considered serious (requiring a hearing aid) at the level of Chang grade ≥2b and SIOP ≥3., Results: A strong concordance was observed between the Chang and SIOP ototoxicity scales (Stuart's tau-c statistic = 0.89, 95% CI: 0.86, 0.91). Among those patients diagnosed with serious hearing loss, the two scales were in good agreement. However, the scales deviated from one another in classifying patients with less serious or no hearing loss., Conclusions: Although discrepancies between the Chang and SIOP ototoxicity scales exist primarily for patients with no or minimal hearing loss, the scales share a strong concordance overall., (© 2013 Wiley Periodicals, Inc.)

Background: To determine the toxicity and efficacy of rapamycin and erlotinib for the treatment of recurrent pediatric low-grade gliomas (LGGs)., Methods: Patients <21 years of age with recurrent LGGs who had failed conventional treatment were eligible, including those with NF1. The treatment consisted of two phases, a feasibility portion which assessed the toxicity of erlotinib at 65 mg/m(2) /day once daily and rapamycin at 0.8 mg/m(2) /dose twice daily for 28 consecutive days., Results: Nineteen (19) patients, median age of 8 years, with recurrent LGGs received the two-drug regimen. Eight (8) of the patients had NF1. The combination of erlotinib and rapamycin was well tolerated and no patient was removed from study due to toxicity. All 19 patients were evaluable for response and one child, with NF1, had a partial response to treatment. Six (6) patients received the planned 12 courses of treatment. The reasons for stoppage of therapy before 1 year of treatment were poor compliance (1), parental desire for withdrawal (1), persistent vomiting which pre-dated initiation of therapy (1), and radiographic progression (10). In those patients with stabilization of disease for 12 months or greater, 3 stayed on therapy and ultimately developed progressive disease, and one patient stopped therapy at 12 months and progressed. Two (2) patients, both with NF1, have had >1 year disease control., Conclusions: The combination of rapamycin and erlotinib is well tolerated in children with LGGs. Objective responses were infrequent, although there was prolonged disease stabilization in some patients with LGGs, especially in two children with NF1., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Central nervous system (CNS) atypical teratoid rhabdoid tumors (AT/RT) are rare tumors of childhood with a dismal prognosis. Historically, surgery and standard dose chemotherapy have resulted in a median survival of 8.5 months from diagnosis., Methods: Thirteen children newly diagnosed with CNS AT/RT were treated with either the "Head Start I" (HS I) or "Head Start II" (HS II) regimens. Therapy included resection followed by five cycles of cisplatin, vincristine, cyclophosphamide, and etoposide. High dose methotrexate was added to each of the five induction courses in HS II. Consolidation for both regimens included carboplatin, thiotepa, and etoposide with autologous hematopoietic progenitor cell rescue (AHPCR)., Results: Six children, median age of 36 months, were treated on HS I between 1992 and 1997. Seven children, median age of 28 months, were treated on HS II between 1997 and 2002. One patient received craniospinal irradiation following AHPCR but prior to recurrence. There are presently three event-free survivors 42+, 54+, and 67+ months following diagnosis; none received RT. All three survivors were enrolled on HS II. Eight patients died of disease (six on HS I); one patient died from infection; one patient died from secondary malignancy following treatment for recurrent AT/RT., Conclusion: Three of seven children with CNS AT/RT treated on HS II have experienced long term remissions. Long term survival can be achieved in a subset of young children with CNS AT/RT following resection with the use of multi-drug chemotherapy including high dose methotrexate and myeloablative chemotherapy without radiation therapy (RT).