NEUROBLASTOMA

Neuroblastoma is the most common childhood solid tumor arising outside of the brain. This cancer arises from widely diverse locations and demonstrates an usually broad pattern of clinical presentations. This enigmatic disease is responsible for 8% of all childhood cancers and the incidence is approximately 1 in 10,000 live births leading to 550 new cases in the United States each year. The average age approaches 2 years and it is slightly more common in boys. Limited therapy is curative in localized disease. However, patients with advanced neuroblastoma have shown only marginal improvement despite aggressive therapy and of all childhood cancer deaths more than 15% are due to neuroblastoma.

Most children present with a mass in the head and neck, chest, abdomen or pelvis. When the tumor is in the abdomen it may cause generalized discomfort, abdominal distention, and back pain as well as neurologic symptoms. With more widespread disease fatigue, weight loss, fever, and anemia (low blood count) are common. The first successful removal of a neuroblastoma was reported in 1916. However, it has become increasingly clear that intensive multi-modality treatment is necessary for favorable outcomes in the advanced forms of the disease, which generally affect about half the children. Since accurate disease staging is essential for planning appropriate treatment a multinational multidisciplinary forum developed the International Neuroblastoma Staging System in 1993. Surgical expertise was important in implementing this system from the standpoint of initial diagnosis, operative therapy, assessment of response, and detection of recurrent disease.

Most recently, more prognostic factors in neuroblastoma have become evident and the traditional staging system has incorporated these aspects of "biologic" staging to define patient risk group assignment. Children with low risk disease and many with intermediate risk situations may be cured with surgery and local tumor control techniques alone. However, patients with aggressive disease types may require very high dose therapies, which necessitate bone marrow "rescue" with stem cell or bone marrow transplantation. Nevertheless, children may develop resistant or recurrent disease and require innovative therapeutic approaches such as intraoperative radiation therapy or radioactive targeted treatment for local tumor control combined with new systemic biologic therapies such as cytokines, immunotherapy, differentiating agents, and viral therapies.

Surgery plays a key role in the management of neuroblastoma. Initial complete tumor resection may cure localized disease with minimal complications in experienced hands. In children with regional tumors, more than 75% can achieve a long-term survival if the primary tumor is excised. Often preoperative chemotherapy may shrink the tumor and simplify its excision. Surgical planning and execution become far more critical in those patients with advanced metastatic disease, which has resisted initial treatment or has recurred. The crucial issues of timing of operation, extent of resection, relationship to chemotherapy and utilization of innovative operative techniques are carefully assessed and undertaken in surgeons experienced in treating this tumor. With the most favorable interplay of all treatment modalities perhaps one-third to one-half of these high-risk children can be saved.

SELECTED ARTICLES

  1. Haase-Kogan DA, Swift PS, Selch M, Haase GM, Seeger RC, Gerbing RB, Stram DO, Matthay KK: Impact of Radiotherapy for High-Risk Neuroblastoma: A Children's Cancer Group Study. Int J Rad Oncol Biol Phys (in press) 2003.
  2. Haase GM, LaQuaglia MP. Neuroblastoma. Chapter in Operative Pediatric Surgery. Edited by Ziegler MM, Azizkhan RG,  Weber TR, McGraw-Hill, New York, NY 2003.
  3. Perez CA, Matthay KK, Atkinson JB, Seeger RC, Shimada H, Haase GM, Stram DO, Gerbing RB, Lukens JN: Biologic Variables in the Outcome of Stages I and II Neuroblastoma Treated with Surgery as Primary Therapy: A Children's Cancer Group Study. J Clin Oncol 18: 18-26, 2000. 
  4. Black CT, Haase GM. Neuroblastoma and other adrenal tumors. Chapter in The Surgery of Childhood Tumors. Edited by Carachi R, Azmy AF, Grosfeld JL, Arnold Press, London, England, 1999.
  5. Haase GM, Perez C, Atkinson JB. Current aspects of biology, risk assessment and treatment of neuroblastoma. Semin Surg Oncol 16:91-104, 1999.
  6. Matthay KK, Perez C, Seeger RC, Brodeur GM, Shimada H, Atkinson JB, Black CT, Gerbing R, Haase GM, Stram DO, Swift P, Lukens JN. Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children’s Cancer Group Study. J Clin Oncol 16:1256-1264, 1998.

OTHER PUBLICATIONS OF INTEREST

  1. Schmidt ML, Lukens JN, Seeger RC, Brodeur GM, Shimada H, Gerbing RB, Stram DO, Perez C, Haase GM, Matthay KK: Biologic factors determine prognosis in infants with stage IV neuroblastoma: a prospective Children's Cancer Group study. J Clin Oncol 18: 1260-1268, 2000.
  2. DuBois SG, Kalika Y, Lukens JN, Brodeur GM, Seeger RC, Atkinson JB, Haase GM, Black CT, Perez C, Shimada H, Gerbing R, Stram DO, Matthay KK: Metastatic sites in stage IV and IV-S neuroblastoma correlate with age, tumor biology and survival. J Pediatr Hematol Oncol 21:181-189, 1999.
  3. Castleberry RP, Pritchard J, Ambros P, Berthold F, Brodeur GM, Castel V, Cohn SL, DeBernardi B, Dicks-Mireaux C, Frappaz D, Haase GM, Haber M, Jones DR, Joshi W, Kaneko M, Kemshead JT, Kogner P, Lee REJ, Matthay KK, Michon JM, Monclair R, Roald BR, Seeger RC, Shaw PJ, Shimada H, Shuster JJ. The international neuroblastoma risk groups (INRG): a preliminary report. Eur J Cancer 33:2113-2116, 1997.
  4. Black CT, Haase GM, Azizkhan RG, Stram DO, Matthay KK. Optimal timing of primary resection in high risk neuroblastoma. Med Pediatr Oncol 27:220, 1996.
  5. Haase GM, O’Leary MC, Stram DO, Seeger RC, Shimada H, Lukens J, Matthay KK: Pelvic neuroblastoma: implications for a new favorable sub-group. A Children’s Cancer Group experience. Ann Surg Oncol 2:516-523, 1995.
  6. Matthay KK, O’Leary MC, Ramsay NK, Villablanca J, Reynolds CP, Atkinson JB, Haase GM, Stram DO, Seeger RC: Role of myeloablative therapy in improved outcome for high risk neuroblastoma: review of recent Childrens Cancer Group results. Eur J Cancer 31A:572-575, 1995.
  7. Haase GM, Atkinson JB, Stram DO, Lukens JN, Matthay KK: Surgical management and outcome of loco-regional neuroblastoma: comparison of the Childrens Caner Group and the international staging systems. J Pediatr Surg 30:312-316, 1995.
  8. Haase GM: Metastatic neuroblastoma: does combining several "magic bullets" make a difference? Ann Surg Oncol 2:91-92, 1995.
  9. Matthay KK, Seeger RC, Reynolds CP, Stram DO, O’Leary M, Harris RE, Selch M, Atkinson JB, Haase GM, Hammond DG, Ramsay NK: Comparison of autologous and allogeneic bone marrow transplantation for neuroblastoma. Prog Clin Biol Res 385:301-307, 1994.
  10. Haase GM: Head and neck neuroblastoma. Semin Pediatr Surg 3:1-10, 1994.
  11. Azizkhan RG, Haase GM, Current biologic and therapeutic implications in the surgery of neuroblastoma, Semin Surg Oncol 9:493-501, 1993.
  12. Martinez DA, King DR, Ginn-Pease ME, Haase GM, Wiener ES: Resection of the primary tumor is appropriate for children with stage IV-S neuroblastoma, an analysis of 37 patients. J. Pediatr Surg 27:1016-1021, 1992. 
  13. Haase GM, O’Leary MC, Ramsay NKC, Romansky SG, Stram DO, Seeger RC, Hammond GD: Aggressive surgery combined with intensive chemotherapy improves survival in poor risk neuroblastoma. J Pediatr Surg 26 (9):1119-24, 1991.
  14. Haase GM: Staging systems for neuroblastoma: A look at the old and the new. Pediatr Surg Int 6:14-18, 1991.
  15. Smith EL, Haase GM, Seeger RC, Brodeur GM: A surgical perspective on the current staging in neuroblastoma-the international neuroblastoma staging system proposal. J Pediatr Surg 24(4):386-390, 1989. 
  16. Matthay KK, Sather HN, Seeger RC, Haase GM, Hammond GD: Excellent outcome of stage ll neuroblastoma is independent of residual disease and radiation therapy. J Clin Oncol 7(2):236-244, 1989. 
  17. Haase GM, Wong KY, deLorimier AA, Sather HN, Hammond GD: Improvement in survival after excision of primary tumor in stage lll neuroblastoma. J Pediatr Surg 24(2):194-200, 1989.

 

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