Specialty Section: Pediatric Surgery

Risk-Based Management: Current Concepts of Treating Malignant Solid Tumors of Childhood

Jay L Grosfeld, MD, FACS

Background: Improved survival with pediatric malignancies has been positively influenced by multidisciplinary cooperative studies using surgery, chemotherapy, and radiation therapy, but one-third of all children with cancer succumb to their condition. The identification of biologic and genetic characteristics as risk factors for the various tumors has led to changes in treatment using risk-based management as the template for care.

Study Design: The purpose of this report is fourfold: (1) to review survival data concerning three solid malignant tumors of childhood (Wilms' tumor, rhabdomyosarcoma, and neuroblastoma), (2) to describe important prognostic genetic and biologic risk factors for each tumor, (3) to update changes in staging criteria, and (4) to familiarize the reader with the concept of risk-based management, which individualizes treatment in an attempt to maximize survival and minimize longterm morbidity.

Results: The overall survival rates for Wilms' tumor, rhabdomyosarcoma, and neuroblastoma are currently 90%, 70%, and 40%, respectively. Most patients with Wilms' tumor have favorable histology and survive after nephrectomy and chemotherapy, but 10% have poor prognostic variables, including unfavorable (anaplastic) histology, chromosomal loss on 1p and 16q, and diploidy. Instances of lung or liver metastases, major tumor spillage during resection, remote lymph node involvement, and bilateral tumors have worse outcomes. Rhabdomyosarcoma is associated with chromosomal translocation of t(2:13) in alveolar types, the p53 tumor suppressor gene, and 11p15. Survival is dependent on the tumor site and pretreatment clinical group. Orbit, paratesticular, vulvar, and vaginal tumors have a good prognosis, but other genitourinary tumors, extremity and trunk lesions, and parameningeal head and neck tumors have a worse prognosis. Survival rates by clinical group are stage I, 93%; II, 81%; III, 73%; and IV, 30%. Resectability, lymph node involvement, DNA ploidy, and pretreatment TNM staging affect outcomes. Neuroblastoma is an embryonal tumor with bizarre behavior and can regress, mature, or rapidly progress. Most patients have advanced disease at diagnosis. Neuroblastoma is associated with loss of heterozygosity on chromosome 1p36 and occasionally deletions on 14q and 17q. Survival is affected by age and stage (at less than 1 year, stages I [95% to 100%], II [85% to 90%], and IV-S [more than 80%] do better) and other risk factors. Patients with advanced disease (older than 1 year, stage III [70%], and stage IV [12%]) often have amplification of the N-myc oncogene, diploid tumors, 1p36 deletion, and unfavorable histology and fare worse.

Conclusions: On the basis of these data, children with solid tumors are currently categorized into low-, intermediate-, and high-risk groups. Newer protocols individualize treatment using risk factors as predictors of outcomes. Risk-based management allows the clinician to weigh the risks and benefits of treatment for each patient to maximize survival, minimize longterm morbidity, and improve the quality of life.