Accurate histologic characterization of pediatric tumors is necessary for the enrolment of patients in the clinical trials of the Pediatric Oncology Branch (POB) at the NCI. The diagnosis of the solid pediatric tumors is often difficult and requires a combination of diagnostic techniques. Most pediatric solid tumors are characterized by consistent chromosomal translocations which result in the fusion of genes and subsequent formation of novel chimeric genes. These molecular markers can be detected by RT-PCR or fluorescence in situ hybridization (FISH) and can be used not only to establish the diagnosis in difficult cases, but also to understand the pathogenesis of these tumors. The pediatric tumor service at the NCI is complex and the staff is involved in 24-hour coverage of all aspects of the service, including on site-consultation with clinicians and prompt evaluation of pathology material upon its receipt, frozen section consultation, tissue procurement, histologic evaluation of tumor tissue for sarcoma translocation studies and final sign-out of surgical and molecular pathology reports on all pediatric tumors submitted through POB. Teaching of residents and fellows occurs during sign-out of pediatric tumor cases and in structured lectures (departmental conferences).
Our pediatric tumor material is dictated by the following POB protocols and consists of small round cell tumors of childhood (Ewing sarcoma family tumors, rhabdomyosarcoma and neuroblastoma), osteosarcoma and various soft tissue sarcomas, including nerve sheath tumors in neurofibromatosis (NF) patients.
1.NCI-99-C-0125: Osteosarcoma: Outcome of Therapy Based on Histologic Response: A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma
2. NCI-00-C-0092: Phase II Randomized Trial of filgastrim-SD/01 vs. filgastrim(G-CSF) with concurrent chemotherapy in patients with newly diagnosed sarcoma
3. NCI-01-C-0222: Phase II Randomized, Cross-Over, Double-Blinded, Placebo-Controlled Trial of the Farnesyltransferase Inhibitor R115777 in Pediatric Patients With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
4. NCI-02-C-0259: Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas
5. NCI-04-C-0001: Phase II Study of Sequential Gemcitabine and Docetaxel in Patients with Recurrent Osteosarcoma or Ewings Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma
6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development
7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1
8. NCI-01-C-0091: Phase I Trial and Pharmacokinetic Study of Tariquidar (XR9576), a P-Glycoprotein Inhibitor, in Combination With Doxorubicin, Vinorelbine or Docetaxel in Pediatric Patients With Refractory Solid Tumors Including Brain Tumors
9. NCI-02-C-0141: Phase I Study of 7-Day or 21-Day ABT-751 in Children with Refractory Solid Tumors
10. NCI-04-C-0080: Phase II trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
11. NCI-05-C-0235: Phase I Study of Valproic Acid in Young Patients with Recurrent or Refractory Solid Tumors or CNS Tumors
12. NCI-05-C-0239: Phase I study of Talabostat in Combination with Temozolomide or Carboplatin in Pediatric Patients with Relapsed or Refractory Solid Tumors, Including Brain Tumors
13. NCI-06-C-0043: Phase II Trial of Neoadjuvant Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Unresectable Malignant Peripheral Nerve Sheath Tumors
14. NCI-06-C-0146: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors
15. NCI-06-C-0233: A Phase I Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor BAY 43-9006 (Sorafenib) in Children with Refractory Solid Tumors or Refractory Leukemias
On-going collaborative projects with the POB include:
1. the development of childhood cancer and plexiform neurofibroma tissue microarray for molecular target screening and childhood drug development (Neurofibromatosis Consortium Development Site Award)- We will contribute pediatric tumor tissues and interpret immunohistochemical staining along with a group of other pathologists using an on line system for array viewing and scoring.
2. immunohistochemical evaluation of 50 osteosarcoma tissues for P-glycoprotein (Pgp) expression in order to obtain preliminary data regarding relative frequency of Pgp positivity in osteosarcoma. The data will help initiate a clinical study which will address the feasibility of the Pgp inhibitor tariquidar as a therapeutic regimen in patients with osteosarcoma
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