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Brain Cancer Health Center

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Neuroblastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment of Low-Risk Neuroblastoma

Table 6. Children's Oncology Group (COG) Neuroblastoma Low-Risk Group Assignment Schema Used for COG Studiesa continued...

Treatment options for low-risk neuroblastoma include the following:

  1. Surgery followed by observation.
  2. Chemotherapy with or without surgery (for symptomatic disease or unresectable progressive disease after surgery).
  3. Observation without biopsy (for perinatal neuroblastoma with small adrenal tumors). Not considered standard treatment.

Surgery followed by observation

Treatment for patients categorized as low risk (refer to Table 6) may be surgery alone, which is curative for most patients with low-risk neuroblastoma. Patients need not undergo complete resection of disease to be cured by surgery alone.[2]

There is controversy about the need to attempt resection, whether at the time of diagnosis or later, in asymptomatic infants aged 12 months or younger with apparent stage 2B and 3 MYCN-nonamplified and favorable biology disease. In a German clinical trial, some of these patients were observed after biopsy or partial resection without chemotherapy or radiation, and many did not progress locally and never received additional resection.[3]

Chemotherapy with or without surgery (for symptomatic disease or unresectable progressive disease after surgery)

Results from the COG-P9641 study showed that surgery alone, even without complete resection, can cure nearly all patients with stage 1 neuroblastoma, and the vast majority of patients with asymptomatic, favorable biology, INSS stage 2A and 2B disease.[2] The use of chemotherapy may be restricted to specific situations (e.g., children with MYCN-amplified stage 1 and 2 neuroblastoma and children with MYCN-nonamplified stage 2B neuroblastoma who are older than 18 months or who have unfavorable histology or diploid disease). These children have a less favorable outcome than other low-risk patients.[2,4]

Chemotherapy is also reserved for low-risk patients who are symptomatic, such as from spinal cord compression or, in stage 4S, respiratory compromise secondary to hepatic infiltration. The chemotherapy consists of carboplatin, cyclophosphamide, doxorubicin, and etoposide. The cumulative chemotherapy dose of each agent is kept low to minimize permanent injury (COG-P9641).[2]

Evidence (chemotherapy):

  1. The COG-P9641 study was one of the first COG studies to test risk stratification based on consensus-derived factors. In this phase III nonrandomized trial, 915 patients underwent an initial operation to obtain tissue for diagnosis and biology studies and for maximal safe primary tumor resection. Chemotherapy was reserved for patients with, or at risk of, symptomatic disease, with less than 50% tumor resection at diagnosis or with unresectable progressive disease after surgery alone.[2]
    • Stage 1: Patients with stage 1 disease achieved 5-year EFS of 93% and 5-year OS of 99%.
    • Stage 2A and 2B: Asymptomatic patients with stage 2A and 2B disease (n = 306) who were observed after initial operation had a 5-year EFS of 87% and OS rate of 96%. EFS was significantly better for patients with stage 2A than for patients with 2B neuroblastoma (92% vs. 85%; P = .0321), but OS did not differ significantly (98% and 96%; P = .2867). The primary study objective (to achieve a 3-year OS of 95% for asymptomatic patients with stage 2A and 2B disease) was met. Patients with stage 2B disease had a lower EFS and OS for those with unfavorable histology (EFS, 72%; OS, 86%) or diploid tumors (EFS, 75%; OS, 84%) or for patients older than 18 months. Outcome for patients with stage 2B, diploid tumors, and unfavorable histology was particularly poor (EFS, 54%; OS, 70%), with no survivors in the few patients with additional 1p loss of heterozygosity and all deaths occurring in children older than 18 months.
    • Asymptomatic patients at diagnosis who were observed after initial operation: Of the initial 915 patients, 800 were asymptomatic at diagnosis and observed after their initial operations. Within this group, 11% experienced recurrent or progressive disease. Of the 115 patients who received immediate chemotherapy (median, four cycles; range, one to eight), 81% of the patients had a very good partial response or better. After chemotherapy, 10% of the patients had disease recurrence or progression. For patients treated with surgery alone, the 5-year EFS rate was 89% and the overall survival estimate was 97% and for patients treated with surgery and immediate chemotherapy, the 5-year EFS rate was 91% and the overall survival estimate was 98%.
    • MYCN amplification: The impact of MYCN-amplified tumors was analyzed in stage I disease. For patients with MYCN-nonamplified tumors the 5-year EFS was 93% and the OS was 99% and for MYCN-amplified tumors the 5-year EFS was 70% (P = .0042) and OS was 80% (P < .001).
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