The Center for Pediatric Hematology and Oncology is actively participating in Children's Oncology Group (COG) trials for the treatment of childhood leukemias and solid tumors. COG is an association of more than 250 childhood cancer treatment and research centers located primarily throughout North America that cooperates in clinical and translational research programs related to cancers of infants, children, and young adults.

Members of our group, who have leadership roles in COG, have focused on novel treatments for children with brain tumors, bone sarcomas, and malignant lymphomas. One member of our group serves as the principal investigator for a pilot osteosarcoma trial that is evaluating the toxicity and usefulness of Herceptin, a humanized monoclonal antibody that targets the HER2 receptor, when given concomitantly with chemotherapy to children with previously untreated metastatic osteosarcoma.

Our group has a commitment to develop effective and less toxic treatments for children with malignancies. In collaboration with our colleagues in Pediatric Radiation Oncology at Massachusetts General Hospital Cancer Center and the Massachusetts Eye & Ear Infirmary, we have developed two active trials combining proton beam radiation with chemotherapy for children with medulloblastoma and retinoblastoma. One of the major objectives of these trials is to reduce both the acute and long-term sequelae of therapy by using protons instead of standard radiation techniques (photons or electrons). Compared to other forms of radiation therapy, protons do not have an exit path and, therefore, should spare toxicity to many normal tissues in a growing child. A large multidisciplinary team is involved in these studies, including subspecialists in ophthalmology, pediatric neurosurgery, pediatric oncology, pediatric radiation oncology, pediatric neurology, pediatric endocrinology, speech and language, and neuro-psychology.

During the past 10 years, we have been active members of a Hodgkin's disease consortium. We have completed several trials that successfully reduced therapy and maintained excellent survival for children with favorable stages of Hodgkin's disease. The current Hodgkin's trial is designed to further reduce therapy by omitting involved field irradiation for children who achieve a complete response to up front chemotherapy.

We have also developed a program focusing on quality of life for our young cancer patients. An active trial is testing the feasibility of early discharge from the hospital for children who are admitted with fever and neutropenia. This protocol assesses the medical outcomes, financial implications, and, very importantly, how families cope with this extra burden of home care. Another study in development with our colleagues in pediatric neurology and pediatric radiology is designed to unravel the complexities of the neurotoxicity of methotrexate. We will be utilizing new imaging modalities, coupled with neuropsychologic testing and pharmacogenomics, to elucidate the pathogenesis of the neurotoxicity of methotrexate, a key drug in the treatment of childhood acute lymphoblastic leukemia, Burkitt's lymphoma, and osteosarcoma.

In keeping with the theme of improving quality of life, we have developed a school outreach program for our patients at all levels of education. A team of nurses and social workers visits the schools of our patients and presents relevant information to the faculty and classmates. An ongoing, productive dialogue ensues often with follow-up visits and bi-directional recommendations. This program has been enormously successful in maintaining a sense of normalcy for our patients.

Selected Clinical Research Protocols

Study of craniospinal and posterior fossa irradiation using proton beam radiotherapy for medulloblastoma: Assessment of acute and long term sequelae

Intraocular retinoblastoma: Carboplatin and vincristine combined with proton beam radiation therapy limited to involved retina

A pilot study of early discharge therapy for children with low risk fever and neutropenia

Risk-adapted therapy in pediatric Hodgkin's disease

A groupwide phase II study of trastuzumab (Herceptin) in metastatic osteosarcoma patients with tumors that overexpress HER2

Faculty
Howard J. Weinstein, MD
Clinical Director

Annah Abrams, MD
Peter Barrett, PhD
William Butler, MD
David H. Ebb, MD
Alison M. Friedmann, MD, MSc
Verena Göbel, MD
Eric F. Grabowski, MD, ScD
Mary S. Huang, MD
Robin Jones, MD
David A. Sweetser, MD, PhD
Nancy Tarbell, MD
Torunn Yock, MD

Selected Publications
Smith RS, Chen Q, Hudson MM, Link MP, Kun L, Weinstein H, Billett A, Marcus KJ, Tarbell NJ, Donaldson SS. Prognostic factors for children with Hodgkin's disease treated with combined-modality therapy. J Clin Oncol 2003; 21(10):2026-33.

Borges E, Ferry JA, Friedmann AM. Epstein-Barr virus negative precursor B cell lymphoblastic lymphoma after liver transplantation: A unique form of posttransplant lymphoproliferative disease. Transplantation 2002; 73:541-4.

Kaban LB, Troulis M, Ebb D, August M, Hornicek F, Dodson T. Anti-angiogenic therapy with interferon-alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg 2002; 60(10):1103 11.

Grabowski EF. Retinoblastoma, in Current Pediatric Therapy. Burg FD, Polin RA, Ingelfinger JR, Wald ER, Eds. 2002. Hodgson DC, Goumnerova LC, Loeffler JS, Dutton S, Black PM, Alexander E, Xu R, Kooy H, Silver B, Tarbell NJ. Radiosurgery in the management of pediatric brain tumors. Int J Radiat Oncol Biol Phys 2001; 50:929-35.

Friedmann AM, Hudson MM, Weinstein HJ, Donaldson SS, Kun L, Tarbell NJ, Link MP. Treatment of unfavorable childhood Hodgkin's disease with VEPA and low-dose, involved field radiation. J Clin Oncol 2002; 20:3088-94.

Ebb D, Green DM, Shamberger RB, Tarbell NJ. Solid tumors of childhood. Principles and Practice of Oncology, 6 th Ed. DeVita VT, Hellman S, Rosenberg SA, Eds. Lippincott Williams & Wilkins 2001; 44 (Sect. 2):2169-2214.