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Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling ("liquid biopsy") via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices. Methods: A single institution retrospective review of DMG patients ≤21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed. Results: At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n = 3, EVD n = 8, unspecified n = 2), and 80.6% permanent CSF access (ETV + reservoir n = 13, shunt n = 41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22 to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications. Conclusions: Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.

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INTRODUCTION Diffuse midline gliomas (DMG) are the number one cause of cancer death in children. H3K27M mutations occur in 80% of DMG, with distinct tumor biology and poorer response to treatment. H3K27M is detectable in cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA), depending on CSF tumor proximity, and correlates with tumor volume and treatment response. Ventricular access devices (VAD) for serial CSF sampling (liquid biopsy) could therefore play a significant role in DMG management. Here, we set to characterize VAD placement practices in pediatric DMG. METHODS A retrospective review of patients <21 yr treated for DMG at our institution was performed (1984-2019). A MEDLINE search was conducted to identify reports of VAD placement in DMG. Full-text English reports of patients = 21 yr with VAD outcomes were analyzed. RESULTS A total of 106 DMG patients at our institution were identified. In total 49% had brainstem disease (n = 52). A total of 46.23% (n = 49) had VADs: 32.65% transient (ETV n = 5, EVD n = 11), 67.35% permanent (reservoir n = 7, shunt n = 26). A total of 17 had ETV at biopsy, 7 with concurrent reservoir placement. Of 10 ETV patients without initial reservoir, 5 ultimately underwent permanent VAD placement (reservoir n = 1, shunt n = 4). A total of 9 patients received EVDs at tumor surgery, 8 required EVD for acute hydrocephalus (HCP), with 6 converted to shunts. A total of 15 shunts were placed at tumor diagnosis: 4 required revision (27%). A total of 14 articles describing 240 DMG patients cited HCP in 22%-100%, with VAD placement in 22%-63%, and shunt-induced extraneural metastases in 7. Ventricular chemotherapy via indwelling reservoirs (481 patients) was associated with 29 infectious and 50 noninfectious complications. Standardized reservoir access procedures decreased infection rates. CONCLUSION VAD placement is clinically indicated in a significant proportion of pediatric DMG patients, with low morbidity. Ventricular CSF is superior to lumbar for ctDNA sequencing and quantification. VAD placement should therefore be considered to facilitate liquid biopsy in DMG.

Purpose Postoperative pediatric cerebellar mutism syndrome (CMS) is a known complication following surgical resection of posterior fossa tumors. However, minimal information exists describing the progression of the syndrome and how to best support these patients. At Ann & Robert H. Lure Children's Hospital of Chicago, the brain tumor team has been fortunate enough to work together for years. Throughout the time that this particular team has been collaborating, a typical protocol has been developed for children at most risk for postoperative pediatric CMS, refined with each patient experience, to the current model. Much of what has been written about postoperative pediatric CMS (and varying terminology) has focused on potential risk factors, surgical approach, and causes, as well as definitively defining the syndrome. We would like to focus on the impact the mutism has on this constellation of symptoms. We would like to focus on the patient and family and how we as caregivers can prepare, educate, and support the family throughout this difficult diagnosis and early management of mutism. Conclusions There is much work to be done in describing and quantifying postoperative pediatric CMS. In the care of children with pediatric brain tumors in the preoperative and immediately postoperative phase, a team approach is paramount. When discussing expectations following surgery, consistent message and communication of hope are essential.