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CLIN-PEDIATRICS CLINICAL RESEARCH

ABSTRACT: BACKGROUND: PTC299 is a novel, orally bioavailable small molecule that selectively inhibits vascular endothelial growth factor receptor protein synthesis at the post-transcriptional level. METHODS: A phase I and pharmacokinetic study was performed in children between aged 3-21 years, inclusive, with recurrent brain tumors. PTC299 was given 2-3 times per day every day based on body weight. Six patients were enrolled at each dose level. Four dose levels were planned, beginning at 1.2 mg/kg/dose BID up to 2.0 mg/kg/dose TID; escalation was based on tolerability and mandatory pharmacokinetic data. RESULTS: A total of 28 patients (median age 11.6 years [range 5.5-21.1]) were enrolled, with a wide variety of tumors including 8 low-grade gliomas, 9 high-grade gliomas, and 4 brainstem gliomas; 21 patients were evaluable for toxicity. One dose-limiting toxicity (DLT) possibly related to treatment (hyponatremia) was identified during the first course of treatment. Possibly related grade 3 toxic effects of hypernatremia (1), hypertension (1), and lethargy (1) were noted with prolonged use. Pharmacokinetic analysis in cycle 1 demonstrated the expected rise in drug concentrations with increasing doses. Concentrations at dose level three were similar to adult phase II levels. With prolonged use, some patients had drug accumulations without associated toxicity. Objective radiographic responses were not seen, but prolonged (greater than 6 months) stable disease was seen in 5 of 8 patients with low-grade gliomas, 2 of whom maintained disease control for more than 1 year. Four evaluable patients were entered at dose level 4, but the study was suspended pending evaluation of toxicity seen in the adult trials. CONCLUSIONS: PTC299 was well tolerated and prolonged disease control was seen in children with low-grade gliomas. Further study, possibly in combination with other agents, is reasonable, although the pharmacokinetic profile may be challenging, and the adult toxicity profile must be taken into account.

SUBMITTER: Packer R

PROVIDER: S-EPMC3488788 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Project description:Supratentorial primitive neuroectodermal tumors while histologically similar to medulloblastoma is less curable. Gross total resection and therefore early recognition is crucial to a favorable outcome. We report our experience with a 4 year old girl whose clinical course and radiology were atypical. The patient was referred to our center for management of a seizure disorder manifesting as episodic choking, spitting, drooling and vomiting. MRI showed cortical thickening (right perisylvian fissure; right frontal operculum; insula) patchy/gyriform enhancement of the right sylvian fissure resembling angiomatous dysplasia and clusters of dysplastic meningeal vessels. There was no mass effect, midline shift, ventriculomegaly and MRV/MRA were normal. The radiological differential diagnoses offered were polymicrogyria, focal cortical dysplasia, neuronal migrational disorders, neurofibromatosis and Sturge-Webber syndrome. She had no neurological deficits and seizures were controlled with Topiramate/Levetiracetam. Brain CT 3 months later showed focal dystrophic calcification in the right perisylvian region superimposed on the cortical dysplasia again suggestive of a phakomatosis. ASA was commenced to reduce risk of stroke. MRI performed two months later showed progression of leptomeningeal enhancement involving the suprasellar cistern/perimesencephalic cistern, left sylvian fissure, ventral brainstem and cerebellar vermis. There was tumefactive material in the right pre-pontine cistern and right ventricular effacement. Spinal cord MRI done at this time showed diffuse subarachnoid spread. Throughout this period apart from episodic facial pain the patient had no neurological, speech, ocular, cerebellar or major cognitive deficits. A biopsy was performed and histopathology was consistent with supratentorial PNET. CSF was negative for malignant cells. Due to the extent /inoperability of the tumor, minimal possibility of cure/high likelihood of severe treatment related side-effects parents opted for supportive care rather than curative treatment. The patient passed away a few months later. A high index of suspicion and low threshold to biopsy is recommended for early diagnosis of these tumors.

Project description:Although most children treated for acute lymphoblastic leukemia (ALL) survive, the noncognitive neurologic sequelae of ALL treatment are inadequately described, and most reported studies utilize self-administered questionnaires. We undertook a prospective, IRB-approved, cross-sectional study to define neurologic morbidity in ALL survivors who were more than 5 years from diagnosis. An investigator administered the questionnaire and disability scales, and a board-certified neurologist performed a quantitative neurologic examination. The PedMIDAS tool was completed to determine headache-related disability. The International Headache Society criteria were applied to classify headache type. Of 375 long-term survivors available, 162 consented and participated in the study. There were no significant differences in clinical or biological features between participants and non-participants. Headache was reported by 76 (47%) of the 162 patients: 34 of 70 (49%) girls and 42 of the 92 boys (46%). Median time from onset of the first headache episode was 5.7 years (0.1-18 years), and median age at headache onset was 9.5 years (3.1-27 years). Migraine was diagnosed in 46 survivors (61%), and 25 experienced one or more aura. Episodic tension-type headache was present in 39 (51%) patients, and 17 patients (22%) experienced both migraine and tension-type headaches. Chronic daily headaches were present in 12 survivors (8 with migraine and 4 with tension-type headache). Among survivors with headache, 13 (17%) reported a frequent need to interrupt activities, 36 (47%) occasionally restricted activity, and 27 (36%) did not restrict activity during a headache episode. More than two-thirds (67%) had never seen a physician for headache, and only 8% had visited the hospital emergency room over the last year. PedMIDAS scores revealed no headache-related disability in 42 (55%) patients, mild disability in 22 (29%) patients, and moderate disability in 12 (16%) patients. In conclusion, migraine and tension-type headaches are common in ALL survivors, affect both sexes equally, and in general cause relatively little morbidity.

Project description:Skull base tumors are challenging lesions for neurosurgeons, but these cannot always be removed via surgical resection. Helical tomotherapy (HT) delivers small beamlets of photons in continuous rotational treatment arcs and has an advantage of soft-tissue verification using computed tomography. We present our experience with HT for skull base tumors when the tumors were not accessible via surgery or recurred after surgery. From December 2005 to October 2010, 60 patients underwent HT for brain tumors. Among them, 13 patients had skull base tumors; four patients had petroclival meningiomas; two patients had cerebellopontine angle (CPA) meningiomas; two patients had acoustic schwannomas; one patient had foramen magnum meningioma; one patient had sphenoid meningioma; one patient had cavernous meningioma; one patient had jugular foramen meningioma; and one patient had clival meninigioma. Eight patients (62%) underwent surgery before HT. The target size ranged from 0.55 to 141.86 cm3 (median 3.85 cm3), and the target dose ranged from 9 to 57 Gy in 1-31 fractions (median 25 Gy in 5 fractions). The median follow-up period was 11 months. The results of HT for skull base tumors are described in Table 1. Twelve patients (92%) had favorable radiologic response. Six patients (46%) had partial response, and another six patients (46%) had stable disease after HT. One patient with CPA meningioma (case 11) had disease progression and underwent a second surgery. One patient with acoustic schwannoma (case 8) had transient radiation-induced changes on the cerebellum, but other patients did not have radiation-induced complications. HT is a useful treatment modality for skull base tumors when surgical access is not possible, and HT is well tolerated by patients with skull base tumors. PURPOSE: A breast cancer-specific graded prognostic assessment (GPA) was developed to better estimate prognosis for breast cancer patients with brain metastases. This GPA was further refined by adding genetic subtype on the basis of a retrospective, multi-institutional analysis. We sought to externally validate this breast-cancer GPA via an independent, large, multi-institutional data set. MATERIALS AND METHODS: Between 1993 and 2012, 275 women from two institutions who had breast cancer metastases to the brain and complete information available to assign breast-GPA (age, Karnofsky Performance Score, and genetic subtype of luminal A or B, HER2, or basal) were evaluated. Median overall survival (OS) with 95% confidence interval (95% CI) was calculated for each breast-GPA group. Differences between groups were tested using the log-rank test. RESULTS: Of the 275 women, 208 (76%) are deceased. The median OS was 11.5 months (95% CI 8.4, 12.9). The median OS by GPA scores of 0-1.0, 1.5-2.0, 2.5-3.0, 3.5-4.0 were 3.9 (n = 46), 8.0 (n = 88), 13.8 (n = 95), and 17.6 (n = 46) months, respectively (p < 0.0001). These results compared favorably with those of Sperduto et al.: median OS of 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively. Genetic subtype was associated with OS, with luminal A and B, HER2, and basal subtypes having a median OS of 12.5 (n = 81), 16.2 (n = 66), 14.9 (n = 34), and 5.8 months (n = 94), respectively (p < 0.0001). CONCLUSIONS: In this cohort of women, the breast-GPA incorporating genetic subtype demonstrated wide variation in prognosis according to GPA score and tumor subtype, in a manner similar to the original report. This analysis validates the prognostic value of including genetic subtype in the breast-GPA, which has been shown to have superior predictive power compared with tumor subtype alone.

Project description:BackgroundCOVID-19 pandemic has significantly impacted the field of medical training, necessitating innovative approaches to education and practice. During this period, the use of novel technologies like virtual reality (VR), augmented reality (AR), and mixed reality (MR) has become increasingly vital. These technologies offer the advantage of transcending the limitations of time and space, thus enabling medical professionals to access various personalized programs for both education and service delivery. This shift is particularly relevant in the realm of pediatric medicine, where traditional training and clinical methods face unique challenges.PurposeThe primary aim of this study is to explore the application of VR, AR, and MR technologies in pediatric medical settings, with a focus on both clinical applications and the training of pediatric medical professionals. We aim to comprehensively search and review studies that have utilized these technologies in the treatment of pediatric patients and the education of healthcare providers in this field.MethodsPeer-reviewed articles published in PubMed, the Cochrane Library, ScienceDirect, Google Scholar, and Scopus from January 1, 2018, to March 1, 2023, were comprehensively searched. The review was conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) guidelines. Among the 89 studies, 63 investigated the clinical applications of VR (n=60) or AR (n=3) in pediatric patients, and 25 investigated the applications of VR (n=19), AR (n=5), or MR (n=1) for training medical professionals.ResultsA total of 36 randomized controlled trials (RCTs) for clinical application (n=31) and medical training (n=5) were retrieved. Among the RCTs, 21 reported significant improvements in clinical applications (n=17) and medical training (n=4).ConclusionDespite a few limitations in conducting research on innovative technology, such research has rapidly expanded, indicating that an increasing number of researchers are involved in pediatric research using these technologies.

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CLIN-PEDIATRICS CLINICAL RESEARCH

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