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Biomedical subjects

A Byron Young

Publications and source records attributed to A Byron Young.

6 recordsLinked to original sources
PubMed2006

Unilateral intraputaminal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year each of treatment and withdrawal.

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally into the putamen for 6 months was previously shown to improve motor functions and quality of life measures significantly in 10 patients with Parkinson disease (PD) in a Phase I trial. In this study the authors report the safety and efficacy of continuous treatment for 1 year or more. After the trial was halted by the sponsor, the patients were monitored for an additional year to evaluate the effects of drug withdrawal. METHODS: During the extended study, patients received unilateral intraputaminal infusion of 30 mg/day GDNF at a basal infusion rate supplemented with pulsed boluses every 6 hours at a convection-enhanced delivery rate to increase tissue penetration of the protein. When the study was stopped, the delivery system was reprogrammed to deliver sterile saline at the basal infusion rate of 2 ml/hour. The Unified PD Rating Scale (UPDRS) total scores after 1 year of therapy were improved by 42 and 38%, respectively, in the "off" and "on" states. Motor UPDRS scores were also improved: 45 and 39% in the off and on conditions, respectively. Benefits from treatment were lost by 9 to 12 months after GDNF infusion was halted. At that time, the patients had returned to their baseline UPDRS scores and required higher levels of conventional antiparkinsonian drugs to treat symptoms. After 11 months of treatment, the delivery system had to be removed in one patient because of the risk of infection. In seven patients antibodies to GDNF developed, with no evidence of clinical sequelae. There was also no evidence of GDNF-induced cerebellar toxicity, as evaluated using magnetic resonance imaging analysis and clinical testing. CONCLUSIONS: Unilateral administration of GDNF results in significant, sustained bilateral benefits. These improvements are lost within 9 months after drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.

Aged↗
PubMed2004

Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases.

PURPOSE: Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classes I and II for patients with brain metastases is derived from a database made up primarily of patients with unresected and multiple metastases. An analysis of a previously published randomized trial was performed to determine the applicability of these RPA prognostic classes in the setting of resection of single metastases to the brain. PATIENTS AND METHODS: Ninety-five patients with single metastases to the brain that were treated with complete surgical resection entered this study. Patients were randomly assigned to treatment with postoperative whole brain radiotherapy (WBRT) (n = 49 patients) or no further brain treatment (n = 46 patients). All patients entered on this study had a Karnofsky performance status of > or =70. Therefore, although the RTOG RPA has 3 classes, only patients with RPA classes I (n = 26) or II (n = 69) were eligible for this study analysis. RESULTS: For RPA class I, the median survival was 10.9 months versus 9.8 months for class II patients (P = 0.45). Multivariate analysis showed that only postoperative WBRT, independent of RPA class I or II, lessened the risk of brain tumor recurrence (P < 0.0001). CONCLUSION: This analysis of a randomized trial evaluating postoperative WBRT in the treatment of single metastases to the brain showed no difference in survival between RPA class I or II patients. In addition, the use of postoperative WBRT after complete surgical resection of single brain metastases results in substantially better control of disease in the brain independent of RPA classes I or II.

Adult↗
PubMed2003

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer.

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.

Brain Neoplasms↗
PubMed2002

Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications.

PURPOSE: A single-institution experience using primary stereotactic radiosurgery (SRS) alone in the management of newly diagnosed brain metastases was analyzed to identify the risk of symptomatic brain tumor recurrence (BTR) and neurologic deficit associated with such a treatment strategy. METHODS AND MATERIALS: Thirty-six patients were treated for newly diagnosed single/multiple brain metastases using SRS alone followed by planned observation. SRS minimum tumor dose ranged from 8 to 25 Gy (median: 20 Gy). Factors evaluated in analysis of treatment outcome included number of metastases, site of metastasis, primary tumor site, histology, extent of intracranial and extracranial disease, and interval to diagnosis of brain metastasis. RESULTS: Median and 1-year survival for the entire group was 9 months and 36%, respectively. BTR anywhere in the brain occurred in 47% (17/36) of patients. Forty-seven percent of BTR (8/17) recurred at the site of original metastasis; 35% (6/17) recurred at both original [corrected] and distant sites in the brain, and 18% (3/17) recurred at distant only [corrected] brain sites. Seventy-one percent (12/17) of the patients were symptomatic at the time of recurrence, and 59% (10/17) had an associated neurologic deficit. Multivariate analysis found that only the extent of disease was a predictor of BTR. Patients who had disease limited to the brain only had a BTR rate of 80% (8/10) vs. 35% (9/26) who had disease involving the brain, primary site, and/or other extracranial metastatic sites (p = 0.03). CONCLUSIONS: Use of primary SRS alone in this setting is associated with an increasingly significant risk of BTR with increasing survival time. In addition, the majority of such recurrences are symptomatic and associated with a neurologic deficit, a finding not analyzed in recently reported experiences withholding whole brain radiation therapy as part of the primary treatment of brain metastasis.

Adult↗
PubMed2002

Clinical trials in head injury.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Brain Injuries↗