Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors

Study Overview
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Brief Summary
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This clinical trial studies cancer survivors to identify those who are at increased risk of developing late-occurring complications after undergoing treatment for childhood cancer. A patient's genes may affect the risk of developing complications, such as congestive heart failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer treatment. Genetic studies may help doctors identify survivors of childhood cancer who are more likely to develop late complications.

Detailed Description
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PRIMARY OBJECTIVES: I. To identify key adverse events developing in patients (cases) with a primary cancer diagnosed at age 21 or younger. II. To characterize the key adverse events with respect to the nature of the primary malignancy (pathology, stage) and coded details of the therapeutic protocol. III. To identify treatment-related and demographic risk factors through a direct comparison of the case-group and controls identified from the remaining patients with the same primary diagnosis. IV. To compare the frequency of mutations or polymorphisms in specific candidate genes in cases and controls, using constitutional deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from the cases and controls. V. To explore the role and nature of gene-environment interaction in the development of key adverse events. OUTLINE: DNA and RNA from peripheral blood or saliva sample of patients is analyzed for the presence of polymorphisms in genes associated with an increased risk of late-occurring complications.

Official Title
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Key Adverse Events After Childhood Cancer

Conditions
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Childhood Malignant Neoplasm

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ELIGIBILITY CRITERIA - CASES Diagnosis of primary cancer at age 21 or younger, irrespective of current age No prior history of allogeneic (non-autologous) hematopoietic cell transplant Development of one of the following key adverse events at any time following initiation of cancer therapy: Cardiac dysfunction; please note: case enrollment has been closed due to achievement of target accrual Ischemic stroke (IS) Subsequent malignant neoplasm (SMN) Avascular necrosis (AVN); please note: case enrollment has been closed due to achievement of target accrual Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center at the University of Alabama at Birmingham as per the requirements; please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's white blood cell (WBC) is > 2,000 Written informed consent from the patient and/or the patient's legally authorized guardian In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required ELIGIBILITY CRITERIA - CONTROLS CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell transplant CONTROLS: No clinical evidence of any of the following key adverse events: Cardiac dysfunction (CD); please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's WBC is > 2,000 Ischemic stroke (IS) Avascular necrosis (AVN) Subsequent malignant neoplasm (SMN) CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center Laboratory at the University of Alabama at Birmingham as per the requirements CONTROLS: Written informed consent from the patient and/or the patient's legally authorized guardian CONTROLS: In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required

Ages Eligible for Study
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Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (genetic analysis)<br>DNA from peripheral blood or saliva sample of patients is analyzed for the presence of polymorphisms in genes associated with an increased risk of late-occurring complications. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse events (cardiac dysfunction, AVN, ischemic stroke, and SMN using a matched case-control) | Epidemiological, clinical and laboratory variables will be tested for their association with key adverse events. McNemar's test for paired data will be used to compare the unmatched general characteristics of cases and controls. | Up to 1 year | 
| Frequency of mutations or polymorphisms in specific candidate genes in cases and controls | Allele frequencies will be estimated by the gene counting method, and the chi-square test will be used to check for departures from Hardy-Weinberg equilibrium. | Up to 1 year | 
| Crude disease-exposure | The crude disease-exposure association will be determined by estimating the OR and its 95% confidence interval (CI). This will be done by univariate conditional logistic regression, to account for the matched design. The significance of the OR will be assessed by the Wald test. Backward stepwise regression procedures will be used to develop the final multivariate model and possible interactions will be examined. The fit of the model will be assessed by the logistic regression diagnostics procedure. | Up to 1 year |