TPS10070 Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor with poor prognosis. Sonodynamic therapy (SDT) with ALA is a non-invasive strategy that sensitizes target tissues with a non-toxic chemical agent followed by exposure to low intensity MR-guided focused ultrasound (MRgFUS). Preclinical studies have shown that ALA is preferentially taken up by glioma cells and metabolized to protoporphyrin IX (PpIX). SDT activates protoporphyrin IX and induces tumor cell death via photodynamic effect (lipoperoxidation, apoptosis). Suheiro et al and Wu et al demonstrated that SDT killed tumors via apoptosis and lipoperoxidation in rodent glioma models with minimal damage to surrounding normal brain.1,2 ALA SDT was well-tolerated in an ongoing first-in-human trial in adults with recurrent high-grade gliomas and demonstrated biomarker evidence of the photodynamic effect3. Methods: A Phase 1/2, multicenter, open label study (NCT05123534) is enrolling patients at Children’s National Hospital. The study employs the Bayesian optimal interval (BOIN) algorithm to evaluate safety and tolerability of treatment with SDT in newly diagnosed DIPG subjects to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of MRgFUS energy in combination with ALA. The study will evaluate 3 ALA doses and 3 acoustic energy doses. ALA is administered IV six to nine hours prior to MRgFUS with the Exablate type-2 device. The first cohort, B1C1, evaluates the lowest drug-device dose combination and if no dose-limiting toxicity (DLT) is encountered after 3 patients, ascending dose-escalation will proceed to the second cohort, B2C1, treated with lowest dose of ALA with the second level of MRgFUS energy. Again, if no DLT is experienced, the next cohort will receive a higher dose combination. The initial patient in each cohort is treated in 2 sessions 21 to 28 days apart, each covering one-half of the pons. Subsequent patients are treated in 1 session to the whole pons. The primary objective is to evaluate the safety and tolerability of SDT in DIPG subjects. Secondary outcomes include preliminary efficacy assessments, pharmacokinetics of ALA and PpIX, mechanical performance of the Exablate Type-2 device, and radiographic evidence of tumor physiological changes associated with SDT. All patients at least 5 years of age with newly diagnosed, radiographically typical DIPG between 4-24 weeks after completion of standard radiotherapy are eligible for the trial. Patients with evidence of disease progression, diagnosis of porphyria, or prior or concurrent therapy with any other anticancer or investigational intervention will be excluded. Cohort 1 has been completed without DLT. References: 1. Suheiro et al. J Neurosurg 2018;129:1416-1428. 2. Wu et al. Sci Rep 2019;9:10465. 3. Sanai et al. NeuroOnco 2022;24(&):vii72-vii73. Clinical trial information: NCT05123534 .

OBJECTIVE Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 gene. CNS tumors are the fourth most common tumor type in LFS, and recent screening guidelines demonstrate that early tumor detection is associated with improved long-term survival. However, there is a paucity of data regarding surgical intervention when lesions are identified in asymptomatic patients on surveillance imaging. The authors investigated this through their cohort and literature review. METHODS The cohort consisted of children seen in the Pediatric Cancer Genetics Program at Children’s National Hospital between August 2012 and August 2021. The authors also include a PubMed (MEDLINE) literature search of articles from 2006 to 2021 related to surveillance and CNS tumors in patients with LFS. Studies in which CNS tumors were not identified or detailed patient information was not provided were excluded. Patients from the selected articles and the authors’ cohort were added for further analysis. RESULTS Between August 2012 and August 2021, 10 children with LFS and CNS tumors were assessed at Children’s National Hospital: 4 who were known carriers of the TP53 mutation had CNS lesions found on surveillance imaging, whereas 6 presented with symptomatic CNS lesions and were either known or subsequently found to have germline TP53 mutations. The literature search identified 148 articles, 7 of which were included in this review. Patients from the literature and the present cohort were added for a total of 56 CNS lesions. A majority of the low-grade CNS lesions (22/24, 92%) were found on surveillance protocols in asymptomatic patients, whereas the majority of the high-grade lesions (22/26, 85%) presented in symptomatic patients who were not undergoing routine surveillance or as the initial diagnosis of LFS. The authors noted a significant survival advantage in pediatric patients with low-grade lesions, with an overall survival of 100% at 30 months. Minor limitations of the study include patient sample size and limitations in the patient cohort due to this being a retrospective rather than a prospective study. CONCLUSIONS Data presented in this study support surveillance protocols in LFS and demonstrate the importance of dedicated CNS imaging and early surgical intervention when lesions are identified. Systematic review registration no.: CRD42022372610 (www.crd.york.ac.uk/prospero)

INTRODUCTION Transcranial magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has demonstrated efficacy in the treatment of adult essential tremor through targeted thermoablation visualized in real-time with MR thermography. The minimally invasive nature of MRgHIFU and lack of ionizing radiation makes it an appealing treatment modality for pediatric patients. There is limited data describing MRgHIFU for pediatric brain tumors. This case report describes the use of MRgHIFU to treat a low grade glioma in a pediatric patient. METHODS A prospective, non-randomized, single-arm study enrolled patients 8-22 years old with benign intracranial tumors requiring intervention to be treated with the ExAblate 4000 System. Clinical and radiographic examinations were performed at the following intervals after treatment: 1 day, 14 days, 3 months, 6 months, and 1 year. RESULTS One patient was treated with MRgHIFU in 2022. A 12 year-old female with headaches and Neurofibromatosis Type 1 (NF1) without prior medical or surgical treatment presented with a progressive enhancing lesion in the right parieto-occipital region. Stereotactic biopsy confirmed pathological diagnosis of a low-grade glioma. MRgHIFU was used to treat the lesion with 5 sonications ranging 600-800 watts resulting in immediate T2 and FLAIR changes. There were no complications or adverse events. MRI demonstrated slight volume reduction after one year. The patient scored herself a 7 on the Patient Global Impression of Change scale for considerable improvement. Her headaches improved and she participates actively in school and sports. CONCLUSION MRgHIFU is an attractive alternative to open craniotomy and/or radiation for pediatric patients with benign brain tumors. In our experience with one patient, the use of MRgHIFU for treatment of a low-grade glioma demonstrated safety in addition to radiographic disease control at 1 year with favorable patient impression scores. Additional patient enrollment and extended follow-up time will be necessary to determine generalizability and therapeutic longevity.

OBJECTIVE Patients requiring intrathecal baclofen (ITB) therapy are at high risk for surgical site infections (SSIs) given their poor functional status. After years of a nominal infection rate, there was an inexplicable increase in ITB pump infections at the authors’ institution and multiple investigations offered no solution. Use of intraoperative topical antibiotics is well-documented in the orthopedic literature and was considered for ITB pump insertion. In this study, the authors investigated whether intraoperative vancomycin and tobramycin powder at the ITB pump site could reduce SSIs. METHODS Operative and infection data were collected and analyzed retrospectively to determine the efficacy of this change. Patients were stratified into three cohorts (1998–2009, 2010–2012, and 2013–2021) to better understand the trends before and after implementation of intraoperative topical antibiotics. Each cohort had similar demographics. RESULTS One hundred fifty-four patients underwent 272 ITB pump procedures between 1998 and 2021 (131 in 1998–2009, 49 in 2010–2012, and 92 in 2013–2021) for cerebral palsy (69.5%), spastic quadriparesis due to traumatic brain injury (7.1%), anoxic brain injury (6.5%), and other causes (16.9%). Infection rates were reduced from a high of 32% in 2010–2011 to 3.8% over the last 2.5 years (p = 0.0094). There were no adverse effects from the use of topical antibiotics. CONCLUSIONS In the setting of an intractable rise in ITB pump infections, the addition of intraoperative topical antibiotics significantly reduced postoperative infections in a high-risk population. One could appreciate a significant drop each year in the rate of infections after the institution of intraoperative topical antibiotics. The reduction in SSIs significantly improved the long-term outcomes for these patients.