Children's Oncology Group Neuroblastoma Risk Grouping
In North America, the COG investigated a risk-based neuroblastoma treatment plan that assigned all patients to a low-, intermediate-, or high-risk group based on age, INSS stage, and tumor biology. The relevant biological attributes of the tumor included MYCN status, International Neuroblastoma Pathologic Classification (INPC) histopathology classification, and tumor DNA index. The low-risk group was observed without further treatment unless the patient had life- or organ-threatening tumors. The intermediate-risk group received limited chemotherapy, additional surgery in some instances, and avoided radiation therapy. This study involved an overall reduction in treatment compared to prior treatment plans. The high-risk group was treated with aggressive chemotherapy, second-look surgery, high-dose chemotherapy with stem cell rescue, radiation therapy, and cis -retinoic acid. The outcome for the low- and intermediate-risk groups combined was an event-free survival and overall 3-year survival of 88% and 96%, respectively. There was no unexpected toxicity. These studies (COG-P9641 and COG-A3961) have established a new standard of care for children in North America with neuroblastoma.
Some controversies exist regarding the treatment of several small subsets of patients and the INSS staging system;[10,11,12] risk group assignment and recommended treatment are expected to mature as additional outcome data are analyzed. For example, the risk group for INSS stage 4, including patients aged 12 to 18 months was changed for patients with MYCN-nonamplified status in 2005.[13,14,15] Table 1 describes the risk group assignment criteria used to assign treatment in these studies.
Table 1. Children's Oncology Group (COG) Neuroblastoma Low-, Intermediate-, and High-Risk Group Assignment Schema Used for COG-9641 and COG-A3961 Studiesa
INPC = International Neuroblastoma Pathologic Classification; INSS = International Neuroblastoma Staging System.
a The COG-9641 and COG-A3961 trials established the current standard of care for neuroblastoma patients in terms of risk group assignment and treatment strategies.
b DNA Ploidy: DNA Index (DI) > 1 is favorable, = 1 is unfavorable; hypodiploid tumors (with DI < 1) will be treated as a tumor with a DI > 1 (DI < 1 [hypodiploid] to be considered favorable ploidy).
c INSS stage 2A/2B symptomatic patients with spinal cord compression, neurologic deficits, or other symptoms should be treated with immediate chemotherapy for four cycles.
d INSS stage 3 or stage 4 patients with clinical symptoms as listed above should receive immediate chemotherapy.
e INSS stage 4S infants with favorable biology and clinical symptoms should be treated with immediate chemotherapy until asymptomatic (2-4 cycles). Clinical symptoms include: respiratory distress with or without hepatomegaly or cord compression and neurologic deficit or inferior vena cava compression and renal ischemia; or genitourinary obstruction; or gastrointestinal obstruction and vomiting; or coagulopathy with significant clinical hemorrhage unresponsive to replacement therapy.
|INSS Stage ||Age ||MYCN Status || INPC Classification ||DNA Ploidyb||Risk Group|
|1||0-21 y ||Any||Any||Any||Low|
|2A/2Bc||<365 d ||Any ||Any||Any||Low|
|?365 d-21 y ||Nonamplified||Any||-||Low|
|?365 d-21 y||Amplified||Favorable||-||Low|
| ?365 d-21 y ||Amplified ||Unfavorable||-||High|
|3d||<365 d||Nonamplified ||Any||Any||Intermediate|
|?365 d-21 y ||Nonamplified ||Favorable||-||Intermediate|
|?365 d-21 y ||Nonamplified ||Unfavorable||-||High|
|?365 d-21 y ||Amplified||Any||-||High|
|4d||<548 d [13,14,15]||Nonamplified||Any||Any||Intermediate|
|?548 d-21 y||Any||Any||-||High|
|�||<365 d||Amplified||Any||Any ||High|
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- Navarro S, Amann G, Beiske K, et al.: Prognostic value of International Neuroblastoma Pathology Classification in localized resectable peripheral neuroblastic tumors: a histopathologic study of localized neuroblastoma European Study Group 94.01 Trial and Protocol. J Clin Oncol 24 (4): 695-9, 2006.
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- George RE, London WB, Cohn SL, et al.: Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 23 (27): 6466-73, 2005.