2019 Background: To date, the first line chemotherapy treatment in the majority of countries for children with NF-1 and OPG is vincristine + carboplatin. Toxicity of this regimen consists mostly in neuropathy, allergic reactions, and hearing loss. Vinblastine has shown promising activity in a phase II study in children with recurrent/refractory low grade glioma (LGG). The aim of this study was to assess the activity of vinblastine in chemotherapy naïve children, and to assess the toxicity profile. Methods: Patients < 18 years old with unresectable or progressive LGG were eligible if they had not received any previous treatment with chemotherapy or radiation. Vinblastine was administered weekly at a dose of 6 mg/m2 over a period of 70 weeks. Patients who showed progression on 2 consecutive imaging studies or evidence of clinical progression were removed from treatment. Results: Overall, the study enrolled 54 patients with LGG. A total of 13 patients (24.1%) had NF-1. Patients with NF-1were younger at diagnosis: median age 3.84 y (range, 1.74-16.36 y) vs. 7 years in non-NF-1. Tumor location in all NF-1 patients was the optic pathway. Treatment was very well tolerated, however, 5 patients (38%) needed dose reductions. Most common toxicity was hematological: only 1 patient who experienced grade 3+ neutropenia (vs. 10 patients non-NF1). There were only 2 episodes of febrile neutropenia, no RBC transfusions and no toxic death. Best response to chemotherapy was assessed centrally by an independent radiologist: 2 PR, 1 MR, 8 SD, and 2 PD, for a response rate of 23.1%. At a median follow-up of 5.37 years (3.45 – 6.57 years): Only two NF-1patients had progression. Five year progression free survival (PFS) was 85.1± 9.7% (vs. 42±7,9% for all non-NF1, p = 0.01; and 41.7±14% for non-NF1 with OPG, p = 0.01). None of the NF1 patients received radiation (0 vs. 6 patients non-NF1). No patients died of progression (0 vs. 3 patients non-NF1). Conclusions: Weekly vinblastine is well tolerated and can be used in NF-1 children with OPG as first line chemotherapy with good results. The toxicity profile is lower than with other chemotherapies, offering a better quality of life to these patients. Clinical trial information: NCT00575796.
Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m 2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome. Results Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome. Conclusion Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.
The authors present a patient with diastematomyelia and a spinal intramedullary teratoma, remote from the split cord malformation. A split cord malformation at the L<sub>2</sub>–L<sub>3</sub> level was initially discovered during investigations for thoracic congenital scoliosis, and this was treated surgically. The teratoma, which was at the level of the scoliosis, went undiagnosed until neurological deterioration occurred many years later. Surgical removal of the teratoma resulted in return to normal function. The potential for coexisting congenital anomalies at separate levels of the spinal cord must be considered in radiological investigations of a developmental spinal lesion.
10029 Background: Vinblastine has shown promising activity in a phase II study in children with recurrent/refractory LGG. The aim of this study was to assess the activity of vinblastine in chemotherapy naïve children. Methods: Patients < 18 years old with unresectable or progressive LGG were eligible if they had not received any previous treatment with chemotherapy or radiation. Vinblastine was administered weekly at a dose of 6 mg/m 2 over a period of 70 weeks. Patients who showed progression on 2 consecutive imaging studies or evidence of clinical progression were removed from treatment. Results: 54 patients (23 female) were enrolled between 2007 and 2010. Median age at inclusion was 7 years, 13 patients were < 3 years. 32 had chiasmatic/hypothalamic tumours, 6 had evidence of dissemination. 13 had neurofibromatosis type 1. Histology was pilocytic astrocytoma (25), pilomyxoid astrocytoma (4), low grade astrocytoma variant (8); 17 patients had no histological diagnosis. Treatment was well tolerated; however, only 14 patients received full dose for the duration of the study. Most common toxicity was haematological: 40 patients who experienced grade 3+ neutropenia. There were only 6 episodes of febrile neutropenia, 3 RBC transfusions and no toxic death. Best response to chemotherapy was assessed centrally by an independent radiologist: 1 CR, 10 PR, 3 MR, 28 SD, 12 PD, for a response rate of 24.5%. With a median follow-up of 2 years (9-48 months), progression-free survival at 2 years was 72.1% (95%CI: 58.1-82.2). One patient died of progression. Conclusions: Weekly vinblastine is well tolerated in paediatric LGG patients. Although the response rate appears inferior to other common LGG regimens, progression free survival at 2 years favourably compares to most currently used regimens. Supported by a grant from the Ontario Institute Cancer Research. Clinical trial information: 1000011227.
The evaluation of treatments such as embolization, stereotactic radiation, and even surgery would be enhanced by an objective method of measuring flow in feeding arteries or draining veins. We developed a non-invasive method of measuring vascular flow using cardiac gated phase contrast MR angiography (MR Q flow). The purpose of this work was to employ the same technique in a series of patients with vascular malformations of the head and neck. We selected a series of vascular malformations with simple arterial and venous architecture and significantly smaller vessel diameters than that encountered with Vein of Calen Malformations. Our aim was to determine the reproducibility of the derived flow values by using multiple velocity encoded sequences (VENC) and compare the values derived from the arterial feeders to the venous outflow data. There are inherent technical difficulties with assessing flow through multiple arterial feeders or draining veins, so the technique is most easily applied to AVMs with simple, easily defined feeding arteries or draining veins. Nonetheless, this technique is relatively straightforward to learn, rapid, cost-effective and may provide an objective means to assess therapeutic maneuvers when applied to head and neck vascular malformations.
Childhood cerebral X-linked adrenoleukodystrophy (ALD) remains one of the most devastating neurological diseases of childhood. Cardinal features are inflammatory cerebral demyelination that coincides with an advancing zone of gadolinium enhancement on brain MRI. Therapeutic options, including the role of antiinflammatory therapy, are limited and poorly understood. We report the failure of repeated cyclophosphamide pulse therapy to halt the clinical progression or alter the gadolinium accumulation in two cases of childhood cerebral ALD.
