Risk-based management: Current concepts of treating malignant solid tumorsof childhood

Background: Improved survival with pediatric malignancies has been positive ly influenced by multidisciplinary cooperative studies using surgery, chemo therapy, and radiation therapy, but one-third of all children with cancer s uccumb to their condition. The identification of biologic and genetic chara cteristics as risk factors for the various tumors has led to changes in tre atment using risk-based management as the template for care. Study Design: The purpose of this report is fourfold: (1) to review surviva l 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 ris k-based management, which individualizes treatment in an attempt to maximiz e 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 a nd chemotherapy, but 10% have poor prognostic variables, including unfavora ble (anaplastic) histology, chromosomal loss on Ip and 16q, and diploidy. I nstances 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 depe ndent on the tumor site and pretreatment clinical group. Orbit, paratesticu lar, vulvar, and vaginal tumors have a good prognosis, but other genitourin ary tumors, extremity and trunk lesions, and parameningeal head and neck tu mors 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 i s an embryonal tumor with bizarre behavior and can regress, mature, or rapi dly progress. Most patients have advanced disease at diagnosis. Neuroblasto ma is associated with loss of heterozygosity on chromosome 1p36 and occasio nally deletions on 14q and 17q. Survival is affected by age and stage (at l ess than 1 year, stages I [95% to 100%], II [85% to 90%], and IV-S [more th an 80%] do better) and other risk factors. Patients with advanced disease ( older than 1 year, stage III [70%], and stage IV [12%]) often have amplific ation 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 cur rently categorized into low-, intermediate-, and high-risk groups. Newer pr otocols individualize treatment using risk factors as predictors of outcome s. Risk-based management allows the clinician to weigh the risks and benefi ts of treatment for each patient to maximize survival, minimize longterm mo rbidity, and improve the quality of life. (J Am Coil Surg 1999;189:407-425, (C) 1999 by the American College of Surgeons).