Study of Late-Occurring Complications in Childhood Cancer Survivors

RATIONALE: A patient's genes may affect the risk of developing complications, such as congestive heart failure, heart attack, 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.

PURPOSE: This clinical trial is studying cancer survivors to identify those who are at increased risk of developing late-occurring complications after undergoing treatment for childhood cancer.

OBJECTIVES:

• Identify key late-occurring complications, specifically, cardiac dysfunction (closed to accrual as of 4/17/09), myocardial infarction (closed to accrual as of 6/5/06), ischemic stroke, avascular necrosis (closed to accrual as of 11/26/08), and subsequent malignant neoplasm, in childhood cancer survivors.
• Correlate key late-occurring complications with pathology and staging of the primary malignancy and therapeutic treatment protocol details in these patients.
• Identify treatment-related and demographic risk factors by comparing patients who develop late-occurring complications (case group) vs those with the same primary malignancy who do not develop late-occurring complications (control group).
• Compare the frequency of mutations or polymorphisms in specific candidate genes in both the case and control groups using constitutional DNA and RNA from both groups.
• Explore the role and nature of gene-environment interaction in the development of late-occurring complications in these patients.

OUTLINE: This is a multicenter study.

DNA from peripheral blood or buccal sample of patients is analyzed for the presence of polymorphisms in candidate genes associated with an increased risk of late-occurring complications, such as cardiac dysfunction (closed to accrual as of 4/17/09), myocardial infarction (closed to accrual as of 6/5/06), ischemic stroke, avascular necrosis (closed to accrual as of 11/26/08), and subsequent malignant neoplasms.

Patients also complete a questionnaire detailing family history and health history.

PROJECTED ACCRUAL: A total of 6,900 patients (1,725 with late-occurring complications [case group] and 5,175 without late-occurring complications [control group] [myocardial infarction patients closed to accrual as of 6/5/06, avascular necrosis patients closed to accrual as of 11/26/08, cardiac dysfunction patients closed to accrual as of 4/17/09]) will be accrued for this study.

• Genetic: cytogenetic analysis
• Genetic: mutation analysis
• Genetic: polymorphism analysis
• Other: questionnaire administration

DISEASE CHARACTERISTICS:

• Diagnosis of primary cancer at age 21 or younger

• In active follow-up by a Children's Oncology Group (COG) institution

  • Date of last visit or contact by a COG institution within the past 24 months

• Case group

  • Development of one of the following key adverse events after initiation of prior cancer therapy:

    • Cardiac dysfunction, meeting 1 of the following criteria (closed to accrual as of 4/17/09):

      • Symptomatic cardiac dysfunction, including current or previous diagnosis of congestive heart failure based on any of the following clinical criteria:

        • Pulmonary and/or peripheral edema
        • Dyspnea
        • Orthopnea
        • Fatigue
        • Hepatomegaly

      • Asymptomatic cardiac dysfunction

        • Ejection fraction < 40% on echocardiogram OR MUGA and/or fractional shortening < 28% on echocardiogram without clinical symptoms

    • Myocardial infarction, meeting 1 of the following criteria (closed to accrual as of 6/5/06):

      • Definite ECG changes
      • Typical, atypical, or inadequately described symptoms AND probable ECG, AND abnormal enzymes, including creatine kinase MB
      • Typical symptoms AND abnormal enzymes, including creatine kinase MB, AND ischemic ECG, non-codable ECG, or ECG not available

    • Ischemic stroke, meeting the following criteria:

      • Fixed neurological deficit lasting more than 24 hours
      • Confirmed by CT scan or MRI within 7 days of onset of symptoms
      • No subarachnoid or intracerebral hemorrhage, transient ischemic attacks, or amaurosis fugax

    • Avascular necrosis, meeting the following criteria (closed to accrual as of 11/26/08):

      • Clinical symptoms of joint pain, joint stiffness, or decreased range of motion
      • Confirmed by plain radiographs, CT scan, MRI, or bone scan

    • Subsequent malignant neoplasm, meeting the following criteria:

      • Histologically distinct neoplasm developing in patients treated for a primary cancer
      • Confirmed by an institutional pathology report

• Control group

  • No clinical evidence of any of the following:

    • Cardiac dysfunction (closed to accrual as of 4/17/09)
    • Myocardial infarction (closed to accrual as of 6/5/06)
    • Ischemic stroke
    • Avascular necrosis (closed to accrual as of 11/26/08)
    • Subsequent malignant neoplasm

PATIENT CHARACTERISTICS:

Age

• 21 and under at diagnosis, any age at study entry

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior allogeneic (non-autologous) hematopoietic cell transplant