This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.
I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and genomic features) while maintaining an OS of 99%.
III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
IV. To achieve a 3-year event free survival (EFS) of > 70% for non-high-risk infants < 12 months of age with INRG stage M neuroblastoma and unfavorable biology (histologic and/or genomic features) through the addition of isotretinoin therapy.
I. To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation.
II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease.
III. To define the genomic profile of tumors from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
IV. To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
V. To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection.
VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy.
VIII. To describe bone abnormalities on bilateral tibial radiographs obtained before and after isotretinoin therapy.
IX. To determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels and/or genetic variations correlate with EFS or systemic toxicity.
OUTLINE: Patients are assigned to 1 of 4 treatment groups.
GROUP A: Patients undergo clinical observation for 96 weeks.
GROUP B: Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin intravenously (IV) over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a partial response (PR) or better is achieved, patients undergo clinical observation for 3 years.
GROUP C: Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years.
GROUP D: Patients receive first-line chemotherapy as in Group B. Patients who achieve a complete response (CR) or very good partial response (VGPR) following first-line chemotherapy receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years. Patients who achieve a PR or stable disease (SD) following first-line chemotherapy receive salvage chemotherapy comprising cyclophosphamide IV over 30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment with salvage chemotherapy repeats every 21 days for 2-6 courses. Patients then receive isotretinoin PO BID on days 1-14. Treatment with isotretinoin repeats every 28 days for 6 courses. Patients then undergo clinical observation for 3 years.
After completion of study treatment, patients are followed up annually for 5 years.