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  • 1
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    EPID-06. Transfusion related iron overload in pediatric patients with CNS tumors
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i47-i48
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i47-i48
    Abstract: BACKGROUND: Patients receiving chemotherapy or autologous hematopoietic stem cell transplant (autoHSCT) routinely receive red cell transfusions as supportive care. Each unit of transfused red cells contains approximately 150mg of iron which the body has no natural mechanism for excreting. Transfusion-related iron overload (TRIO) is an under-recognized complication of therapy which left untreated may result in long-term damage to the liver, heart, or endocrine organs. We sought to identify the prevalence of TRIO in patients with pediatric CNS tumors and evaluate specific risk factors. METHODS: A retrospective record review of pediatric CNS tumor patients treated at Children’s Hospital Colorado was conducted including patients who completing therapy between 1/1/2014 – 12/1/2021. Patients at high risk for TRIO were defined as having a cumulative transfused blood volume of more than 150mL/kg or 4000mL total. The diagnosis of TRIO was confirmed if patients had a serum ferritin greater than 1000ng/mL or elevated liver iron content of 7mg/g dry weight or greater by MRI. RESULTS: There were 173 evaluable patients (40% embryonal tumors, 15% germ cell tumors, 10% ependymomas, 26% low grade gliomas, 5% high grade gliomas, and 3% other tumors). The mean age at completion of therapy was 8 years (range: 0.67 – 25 years). Patients receiving autoHSCT (24% of cohort) were at higher risk for TRIO based on transfused volumes (p & lt;0.0001) than patients not treated with autoHSCT (72% vs 6%, RR 12.0) The prevalence of TRIO in autoHSCT patients was 7.5% (3/40) vs 0.8% (1/121) in patients not undergoing autoHSCT (RR 9.37). For autoHSCT patients at high risk by transfused volume the prevalence of TRIO was 10.3% (3/29). CONCLUSIONS: Pediatric CNS tumor patients who have received an autoHSCT are at higher risk for TRIO than those who have not. Routine screening for TRIO should be offered to patients receiving autoHSCT.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.174
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
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    DDEL-06. DRUG INTERACTION BETWEEN EVEROLIMUS AND CANNABIDIOL IN PEDIATRIC PATIENTS WITH SUBEPENDYMAL GIANT CELL ASTROCYTOMAS: A SINGLE INSTITUTION EXPERIENCE
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii284-iii284
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii284-iii284
    Abstract: Tuberous sclerosis complex (TSC) is an autosomal recessive genetic disorder associated with clinical manifestations including subependymal giant cell astrocytomas (SEGA) and seizures. The combination of everolimus and Epidiolex, a purified form of cannabidiol, has become an increasingly common treatment regimen in this population. Everolimus is primarily metabolized via CYP3A4, which may be inhibited by cannabidiol. We seek to describe our institution’s experience with this drug interaction. METHODS: Investigators conducted a retrospective review of neuro-oncology patients with TSC and SEGA who were treated concurrently with everolimus and cannabidiol. Data collected included demographics, body surface area, everolimus dose, everolimus troughs, date of cannabidiol initiation, documented symptoms, liver and renal function tests, and reason for discontinuing therapy. RESULTS: Three patients (ages 11–17 years) met inclusion criteria. All patients were stable on everolimus doses ranging from 6.5 to 9.5 mg/m2/day and achieving trough goals of 5–10 ng/mL. Two to four weeks after initiating cannabidiol, everolimus trough concentrations rose 200–860% above goal. One patient reported new-onset involuntary movements, but no other toxicities were noted. Cannabidiol was discontinued in all cases due to caregiver concerns regarding drug interactions. All patients were able to achieve goal trough concentrations on previously stable doses of everolimus after discontinuing cannabidiol. CONCLUSIONS: Cannabidiol appears to modulate everolimus metabolism leading to significantly elevated serum concentrations. Additional research is required to determine the need for empiric dose adjustments upon cannabidiol initiation. Patient counseling, frequent trough monitoring, and surveillance for adverse effects are crucial for optimizing outcomes in patients prescribed this regimen.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.041
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 3
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    SWK-10. Survivorship: Education, Clinical Guidelines, and Transition to Adult Care
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i182-i183
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i182-i183
    Abstract: As the cure rates of patients with pediatric brain tumors increases, the long term care needs of the survivors increase as well. Survivorship includes several facets of multidisciplinary care including education, clinical care guidelines, and transition to adult medical care. The neuro-oncology program at a large tertiary care hospital has developed a team to address survivorship needs. The Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers was utilized as a backbone that was then customized for neuro-oncology patient education including disease type and treatment. The education was compiled into patient handouts as well as electronic medical record (EMR) statements that can easily be added to a clinic note or letter to referring providers. In addition, a diagnosis and treatment summary was placed both in the EMR as well as given to patients at various time points to ensure long term knowledge. Next, follow-up guidelines and roadmaps were developed and customized to tumor type and treatment received (surgery, radiation, chemotherapy). The roadmaps ensure patients are receiving high-quality comprehensive follow-up and screening from a large multidisciplinary team. Finally, patients will transition to adult care. With a large seven state catchment area, the adult care providers vary on local provider availability, knowledge, and medical complexity of the survivor. Each patient is evaluated based on their needs, availability of care locally, and ability to travel. The team developed relationships with the clinical team at the academic center adjacent to the pediatric hospital to support a smooth transition to adult care. The adult neuro-oncology care team can also serve as a consulting service for local adult providers. The survivorship team will continue to address the complex needs of brain tumor survivors and provide education for a smooth transition to adult care.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.682
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 4
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    OTHR-16. CONCURRENT USE OF APREPITANT AND IFOSFAMIDE IN PEDIATRIC CANCER PATIENTS
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii424-iii424
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii424-iii424
    Abstract: Aprepitant, a selective neurokinin-1 receptor antagonist, is commonly used for prevention of chemotherapy-induced nausea and vomiting. Its use with ifosfamide is controversial due to the putative risk of potentiating neurotoxicity via inhibition of cytochrome P450 3A4 (CYP3A4). The current literature examining this interaction is inconclusive, and little data exists in pediatrics. We seek to describe a single-institution experience with concurrent aprepitant and ifosfamide administration. METHODS A retrospective review of patients treated with ifosfamide and aprepitant from 2009–2018 was conducted. Data collected included demographics, tumor type, number of days of concurrent therapy, dosing, and documented of neurotoxicity. RESULTS Twenty patients aged 7–21 years (median 17 years) were identified. Diagnoses included thirteen sarcomas and seven CNS tumors (6 germ cell tumors; 1 intracranial sarcoma). Five patients received high dose ifosfamide ( & gt;2,000mg/m2/day). The number of concurrent ifosfamide and aprepitant doses ranged from 2–18 (median, 8.5). Only one patient (5%) developed ifosfamide-induced neurotoxicity: a 7-year-old female with a nongerminomatous germ cell tumor who presented with seizures and somnolence. She received methylene blue and returned to her neurologic baseline. She completed her ifosfamide course without incident. She was the only patient to require weight-based aprepitant dosing and to receive the liquid formulation. CONCLUSIONS Aprepitant should be used with caution when administered concurrently with ifosfamide due to the risk of neurotoxicity. However, the incidence of neurotoxicity in this retrospective pediatric cohort was low. This interaction may be more significant in younger patients due to age-related differences in hepatic metabolism, but further study is required.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.637
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
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    MODL-01. SAFETY IN CONCOMITANT USE OF MEK AND BRAF INHIBITORS WITH BEVACIZUMAB
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii411-iii412
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii411-iii412
    Abstract: MEK and BRAF inhibitors are increasingly common treatments for pediatric nervous system tumors. While effective in blocking Ras/Raf/MEK/ERK pathway activation driving tumor progression, the side effect profile differs from traditional cytotoxic chemotherapies. Little data exists on overlapping toxicities with other targeted agents like bevacizumab despite their potential combined therapeutic benefit. METHODS A retrospective review of patients treated with MEK +/- BRAF inhibitors and bevacizumab from 2015–2019 was conducted. Data collected included demographics, tumor type, neurofibromatosis status, treatment duration, reason for concurrent treatment, and toxicities. RESULTS Fifteen patients aged 3–24 years old (median age 14 years) were identified. Diagnoses included five high-grade gliomas, four low-grade gliomas, four benign nerve sheath tumors, and one ependymoma. Nearly half (46.7%) were positive for neurofibromatosis type 1. Three patients were treated with a BRAF + MEK inhibitor and twelve were treated with a MEK inhibitor combined with bevacizumab. Duration of treatment ranged from 16–420 days (median 119 days). Reasons for concomitant therapy included progressive disease with neurologic decline (46.7%), painful benign nerve sheath tumors (26.7%), and visual loss with optic pathway gliomas (26.7%). Toxicities while on concurrent therapy included one episode of grade 1 left ventricular dysfunction, one grade 1 bleeding episode, and one grade 2 wound complication. There were no episodes of hypertension, thrombosis, GI perforations, or cytopenias. CONCLUSIONS Our preliminary experience suggests bevacizumab in combination with MEK and BRAF inhibitors can be used safely across a variety of pediatric nervous tumors. Larger studies are needed to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.578
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 6
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    OTHR-03. Oxaliplatin as a hearing-sparing alternative to carboplatin in tandem autologous stem cell transplants in pediatric CNS malignancy
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i147-i147
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i147-i147
    Abstract: BACKGROUND: Intensive chemotherapy with tandem autologous stem cell transplants (autoSCT) is shown to improve survival for children with CNS malignancy. Platinum-based chemotherapeutic agents in these regimens, mainly cisplatin and carboplatin, have resulted in significant sensorineural hearing loss. Oxaliplatin, a newer platinum-based agent, is considered less ototoxic. Empiric substitution of oxaliplatin for carboplatin in preparative regimens for autoSCT have been tried. However, the survival and ototoxicity outcomes have not been studied. OBJECTIVE: To compare the overall survival and ototoxicity of oxaliplatin versus carboplatin preparatory chemotherapy regimens in children who received tandem autoSCT for treatment of CNS malignancy. METHODS: We performed a retrospective chart review of all pediatric patients with primary CNS tumors who received tandem autoSCT from 2011 to 2018 at Children’s Hospital Colorado. Demographics, clinical outcomes, and medication administration records were extracted from electronic medical records. Hearing evaluations, performed at pre-transplant, after each transplant episode, and at follow-up visits, were reviewed and graded by an audiologist. Comparisons were performed using Fisher’s exact tests and log rank test statistics. RESULTS: 32 pediatric patients with CNS tumors met inclusion criteria. Seven patients received oxaliplatin in place of carboplatin in one or more preparatory regimens. There was no statistically significant difference in overall survival between the two groups (p=0.99). A total of 85 follow-up audiograms were available for assessment, including long-term follow up. Of the 13 audiograms that showed hearing loss, one (8%) had prior oxaliplatin exposure, compared to 18/72 (25%) audiograms without hearing loss had prior oxaliplatin exposure (p=0.28). CONCLUSIONS: Oxaliplatin is effective and well-tolerated when used in lieu of carboplatin in preparatory regimen for autoSCT for pediatric CNS malignancy. This study is limited by its small size. A larger, multi-center study is warranted to confirm oxaliplatin’s safety and effect on survival and ototoxicity in pediatric autoHSCT.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.542
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
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    RARE-32. Phase 0 and feasibility single-institution clinical trial of intravenous tocilizumab for adamantinomatous craniopharyngioma
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i17-i17
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i17-i17
    Abstract: BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control. METHODS: Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado. The phase I stratum involves IV tocilizumab prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥30kg or 12 mg/kg for patients who weigh & lt;30kg. RESULTS: To date, three patients have been enrolled on the Phase 0 component of the trial. These patients demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and/or tumor tissue, compared to undetectable levels in control samples. Two patients (1 male and 1 female; median age 10.5 years) have enrolled on the feasibility stratum; one patient had best response of minor response but met definition of progressive disease at cycle 11. One patient with extensive disease required dose reduction for myelosuppression. CONCLUSION: Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is planned through a CONNECT consortium international Phase II trial.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.057
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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