Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients.

Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity. Clinicians should closely monitor bone health and have a low index of suspicion for serious orthopedic complications including slipped capital femoral epiphyses and inform patients of related risks as part of consent when treating with FGFR TKIs.

Treatment and revaccination of children with paraneoplastic opsoclonus-myoclonus-ataxia syndrome and neuroblastoma: The Memorial Sloan Kettering experience.

OBJECTIVE: To review the treatment and revaccination of neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome (OMAS) patients at Memorial Sloan Kettering Cancer Center (MSK). PROCEDURE: Institutional Review Board approval was obtained for this retrospective study of patients with neuroblastoma-associated OMAS followed at MSK from 2000 to 2016. RESULTS: Fourteen patients (nine female) were 9-21 (median 17) months old at diagnosis of neuroblastoma and OMAS syndrome. They had stage 1 (n = 12), stage 2B, or intermediate-risk stage 4. Tumor histology was favorable in 11 patients, unfavorable in two, and unknown in one patient. No patient had amplified MYCN. All patients underwent tumor resection at diagnosis. Anti-neuroblastoma treatment was limited to chemotherapy in one patient. Overall survival is 100% at 3-16 (median 10) years. For OMAS, 13 patients received intravenous immune globulin (IVIg), adrenocorticotropic hormone (ACTH), and rituximab, and one received ACTH and IVIg. Seven patients experienced OMAS relapse. For these relapses, five patients received low-dose cyclophosphamide and two received rituximab. The mean total OMAS treatment was 20-96 (median 48) months. Seven patients started rituximab ≤3 months from diagnosis and did not relapse. The other six experienced OMAS relapse. To date, six patients have been revaccinated at a minimum of 2 years after completion of OMAS therapy without OMAS recurrence. CONCLUSIONS: Patients with neuroblastoma-associated OMAS had excellent overall survival. Early initiation of rituximab, IVIg, and ACTH may reduce risks of OMAS relapse. Revaccination can be resumed without exacerbation of OMAS. Further investigation with a larger cohort of patients is needed.

Impact of Sub-Retinal Fluid on the Long-Term Incidence of Macular Atrophy in Neovascular Age-related Macular Degeneration under Treat & Extend Anti-Vascular Endothelial Growth Factor Inhibitors.

Sub-retinal fluid (SRF) has been discussed as a protective factor against macular atrophy in eyes with neovascular age-related macular degeneration (nAMD).To gauge the impact of SRF on macular atrophy, a database of 310 nAMD eyes was screened for eyes manifesting an SRF-only phenotype under treat & extend anti-VEGF treatment, defined as nAMD expressing CNV exudation beyond the three monthly anti-VEGF loading doses by SRF only without any signs of exudative intra-retinal fluid (IRF) for ≥3 years. Incidence of macular atrophy and treatment responses were evaluated on multimodal imaging, including optical coherence tomography (OCT), blue autofluorescence (BAF) and near-infrared (NIR) confocal scanning laser ophthalmoscopy and fluorescence and indocyanine green angiography (FAG/ICGA). In total, 27 eyes (8.7%) of 26 patients with a mean follow-up of 4.2 ± 0.9 (3-5) years met the inclusion criteria. Mean age was 72 ± 6 (range: 61-86) years. The SRF only phenotype was seen from baseline in 14 eyes (52%), and in 13 eyes (48%) after a mean 1.0 ± 1.3 (1-3) injections. In years 1 to 5, mean 7.5, 5.9, 6.1, 6.1 and 7.0 anti-VEGF injections were given (p = 0.33). Cumulative macular atrophy incidence was 11.5% at year 1, 15.4% throughout years 2 to 4, and 22.4% at year 5. In conclusion, eyes manifesting activity by SRF only in treat & extend anti-VEGF regimen for nAMD seem to exhibit rather low rates of macular atrophy during long-term follow-up. SRF might be an indicator of a more benign form of nAMD.

Rapid autopsy of a patient with recurrent anaplastic ependymoma.

ABSTRACTObjective:Our aim was to outline a procedure for obtaining a rapid autopsy in order to collect high-quality postmortem tissue for genomic analysis. METHODS: This report details a bi-institutional collaborative effort to coordinate a rapid autopsy for a pediatric patient who had died at home. We discuss the scientific rationale for offering a rapid autopsy to caregivers of pediatric patients as well as parental perspectives on broaching the subject of autopsy. We then review the logistics and coordination involved with planning a rapid autopsy and the sequence of events needed to maximize tissue quality. RESULTS: We report the successful coordination of a rapid autopsy for a patient who died in a hospice setting at her out-of-state home. The time interval from death to the start of the rapid autopsy procedure was 4.5 hours, despite the logistical considerations demanded by the location of the patient. Tumor aliquots and nonneoplastic tissues were successfully snap frozen for downstream genomic studies. SIGNIFICANCE OF RESULTS: Physicians should consider trialing a rapid autopsy program at their institution that could be offered to caregivers of pediatric patients. This case report offers a framework to help clinicians develop their own rapid autopsy programs as well as guidelines to help streamline this process for appropriate candidates going forward.

The Effect of Ophthalmic Artery Chemosurgery on Immune Function in Retinoblastoma Patients: A Single Institution Retrospective Analysis.

BACKGROUND: Ophthalmic artery chemosurgery (OAC) is associated with grade 3 and 4 neutropenia, however the effect on T-cell number and function is unknown. The purpose of this retrospective review was to confirm that patients treated with OAC do not develop immunosuppression warranting Pneumocystis pneumonia prophylaxis. PROCEDURE: IRB approval was obtained for a single center retrospective review of immune function tests in retinoblastoma patients who received OAC. RESULTS: Twenty-three patients received ≥3 cycles of OAC and had immune function testing (absolute CD4 count) performed at a median of 34 days postcompletion of therapy (range, 15 to 63 d). Only 1 patient had a low absolute CD4 count of 189 cells/µL (normal, 359 to 1570 cells/µL) 2 and a half months after IV carboplatin and 28 days after their third dose of OAC. This patient was found to have coexisting hypogammaglobulinemia. Repeat immune function testing normalized through continued OAC treatment. CONCLUSIONS: Clinically significant immune suppression appears rare following OAC alone, but patients previously treated with IV chemotherapy may be immunosuppressed and may benefit from pneumocystis pneumonia prophylaxis until the CD4 count recovers.

Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors.

Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Pediatric central nervous system tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from pediatric central nervous system tumors is disproportionately high compared to other childhood malignancies. Management of children with central nervous system tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life.

Extraneural ependymoma: distant bone, lung, liver, and lymph node metastases following bevacizumab.

Extraneural metastases of ependymoma are rare, and have been reported in the lungs, lymph nodes, pleura, mediastinum, liver, diaphragmatic muscle, and bone. We report a case of anaplastic ependymoma with distant metastases to the vertebral bones, lungs, liver, and lymph nodes following treatment with bevacizumab. Recent research has hypothesized that angiogenic tumors may develop means of resistance to antiangiogenic therapies, and some evidence suggests potential for antiangiogenic therapies to promote additional means for cancer spread. Nevertheless, antiangiogenic therapies continue to demonstrate potential as potent therapies for the treatment of many cancers, and should continue to be researched for future uses.

Establishing successful cerebrospinal fluid flow for radioimmunotherapy.

Successful delivery of intraventricular radioimmunotherapy is contingent on adequate CSF flow. The authors present a patient with medulloblastoma in whom obstructed CSF flow was causing hydrocephalus, which was initially corrected by implantation of a programmable shunting device. While managing the hydrocephalus, an endoscopic third ventriculostomy (ETV) needed to be performed in a collapsed ventricular system to ensure adequate radioimmunotherapy distribution. This 18-month-old patient with medulloblastoma involving leptomeningeal dissemination presented for intraventricular radioimmunotherapy. A CSF (111)In-DTPA scintigraphy study obtained through the existing programmable ventriculoperitoneal shunt demonstrated activity in the lateral and third ventricles, but no activity over the cerebral convexities or spinal canal, consistent with obstruction at the level of the cerebral aqueduct. By maximization of ventricular size in a controlled setting, the patient was able to undergo a trial of ETV through very small ventricles. A postoperative CINE MR imaging study confirmed patent ETV. The pressure settings on the shunt were kept at the highest opening pressure (200 mm H(2)O) to maximize flow through the stoma and improve the distribution of CSF throughout the subarachnoid space. The CSF flow scintigraphy study was again performed, this time with tracer activity demonstrated down the thecal sac at 3 hours, and symmetrically over the cerebral convexities at 24 hours. The patient began weekly intraventricular administration of (131)I-3F8 therapy. Successful rerouting of CSF flow for the purpose of therapeutic radioisotope administration is possible. Endoscopic third ventriculostomy can be considered in patients with programmable shunting devices; normal or slit ventricles do not preclude successful ETV.