Late Effects After Treatment in Patients With Previously Diagnosed High-Risk Neuroblastoma

PRIMARY OBJECTIVES:

I. To estimate the prevalence of organ dysfunction, subsequent malignant neoplasm (SMN),
growth impairment, abnormal pubertal development, and neurobehavioral dysfunction in a large
cohort of representative 5-year survivors of high-risk neuroblastoma treated with modern
therapy.

II. To identify the demographic, clinical and treatment-related risk factors associated with
increased risk of organ dysfunction, SMN, growth impairment, abnormal pubertal development
and neurobehavioral dysfunction in long-term survivors of high-risk neuroblastoma.

III. To explore the impact of new biologic therapies and diagnostics including immunotherapy,
immunocytokines, isotretinoin (cis-retinoic acid) and iobenguane I-131 (131 I-MIBG) on the
risk of late effects.

IV. To determine the impact of impaired organ function, physical growth, pubertal
development, and neurobehavioral function on health-related quality of life (HRQOL) in
long-term survivors of high-risk neuroblastoma.

SECONDARY OBJECTIVES:

I. To establish a cohort of high-risk neuroblastoma survivors, with stored peripheral blood
samples, who were treated with multi-modal therapies since the year 2000 as a resource for
future investigation.

OUTLINE:

Patients undergo collection of blood and urine samples on day 1. Patients also undergo
clinical assessments, laboratory, radiographic, and other ancillary studies on day 1.

Inclusion Criteria:

- Patients must have been enrolled on COG neuroblastoma biology study ANBL00B1

- Patient must have been diagnosed with high-risk neuroblastoma per ANBL00B1 definition

- Patient must have been diagnosed on or after January 1, 2000

- At least 5 years must have elapsed since diagnosis

- Patients must have been treated for high-risk neuroblastoma

- Note: patients may have had any therapy for high-risk neuroblastoma, including
second line or non-established therapies (for example in the setting of less than
optimal initial response or concerns for high risk of relapse); patients may have
received therapy for refractory or relapsed neuroblastoma, or treatment for an
SMN; however all cytotoxic anti-neuroblastoma therapy should have been
administered >= 2 years of the enrollment date; SMN therapy may be completed or
ongoing at the time of enrollment

Exclusion Criteria:

- Patients must not be currently receiving active anti-neuroblastoma cytotoxic
chemotherapy

- Patients must not have received anti-neuroblastoma cytotoxic chemotherapy within the
last two years

- Note: cytotoxic therapies include (but are not limited to) chemotherapy (platinum
agents, alkylators, anthracyclines, topoisomerases, vinca alkaloids, other
cytotoxic chemotherapy), any kind of transplant, MIBG therapy, and/or radiation
therapy

- Non-cytotoxic (biologic/targeted/differentiating/other) therapies are permitted
at the time of enrollment; for example, patients receiving oral differentiating
agents, antiangiogenic therapy, immune modulators, holistic therapies,
difluoromethylornithine (DMFO), other minimal residual disease (MRD)
therapies/relapse-prevention therapies are eligible

- Patients with current active neuroblastoma relapse are ineligible