Brain tumors are the leading cause of cancer-related deaths among children. Despite considerable efforts to refine the treatment of these tumors, the overall prognosis of affected patients has improved minimally during the last decade. To improve outcome, coordinated efforts are required to evaluate new treatment approaches in parallel with correlative studies of tumor biology to identify novel therapeutic strategies. Our proposal for inclusion in the Pediatric Brain Tumor Clinical Trials Consortium (PBTCTC) reflects our institutional commitment to contribute to such studies. To accomplish the goal of developing more effective therapies for children with brain tumors, we propose to: 1) share institutional expertise with clinicians and researchers at other consortium centers; 2) design and conduct innovative pilot, phase I, and phase II clinical trials for children with brain tumors, and provide adequate patient populations for their timely completion; and 3) share brain tumor specimens and other data that will be useful in the conduct of clinical, pharmacological, and correlative laboratory and imaging studies. This proposal describes the extensive neuro-oncology activities at the Children s Hospital of Pittsburgh (CHP) and the University of Pittsburgh Medical Center (UPMC). Our group has been at the forefront of applying stereotactic radiosurgical approaches to the treatment of brain tumors and in translating novel preclinical therapeutic strategies to the clinical arena. The broad-based biological and molecular therapeutics efforts for brain tumors reflect the depth of institutional resources within the University of Pittsburgh Cancer Institute (UPCI). Promising approaches that are currently being translated to clinical studies that could be adopted by the Consortium include cytokine-based glioma vaccines and novel signal transduction inhibitors. Innovative imaging modalities for evaluating disease response are provided by institutional PET and MR Research Centers. Our group is also leading multi-institutional molecular marker studies on childhood high-grade gliomas, which could potentially be incorporated in PBTCTC studies. CHP, UPMC, and UPCI will provide essential support for consortium-related clinical trials through such facilities as the General Clinical Research Center, the Tumor Tissue Bank, the Pediatric Brain Tumor Registry, the Center for Image-Guided Neurosurgery, and the Imaging Core facilities. In addition to the above, our institution is a regional and national referral center for childhood brain tumors, with approximately 80 new or recurrent brain tumor patients per year, and 20 to 25 children who are entered on institutional pilot or cooperative phase I or phase II studies. With these clinical and scientific resources, our institution is well poised to collaborate with other members of the PBTCTC to rapidly evaluate new treatments by enrolling patients in studies of the Consortium and to develop promising new therapeutic strategies through translational laboratory studies.
| Witham, Timothy F; Erff, Melanie L; Okada, Hideho et al. (2002) 7-Hydroxystaurosporine-induced apoptosis in 9L glioma cells provides an effective antigen source for dendritic cells and yields a potent vaccine strategy in an intracranial glioma model. Neurosurgery 50:1327-34; discussion 1334-5 |
