This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.
Patients must be ≥ 3 years and < 30 years at the time of study enrollment
Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required
Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) AND hCGbeta ≤ 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. No histologic confirmation required
Patients with hCGbeta 51-100 mIU/mL in serum and/or CSF and institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists) in both serum and CSF. Histologic confirmation of germinoma IS required
Endodermal sinus (yolk sac)
Embryonal carcinoma, choriocarcinoma
Malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some germinoma)
Patients with only mature teratoma upon tumor sampling at diagnosis and negative tumor markers are not eligible
Parallel
3-Dimensional Conformal Proton Radiation Therapy
RadiationUndergo 3D-CPRT
3-Dimensional Conformal Radiation Therapy
RadiationUndergo 3D-CRT
Biospecimen Collection
Procedure/SurgeryUndergo blood and CSF sample collection
Carboplatin
DrugGiven IV
Etoposide
DrugGiven IV
Intensity-Modulated Proton Therapy
Procedure/SurgeryUndergo IMPT
Intensity-Modulated Radiation Therapy
RadiationUndergo IMRT
Lumbar Puncture
Procedure/SurgeryUndergo LP
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Questionnaire Administration
Other interventionAncillary studies
Surgical Procedure
Procedure/SurgeryUndergo second-look surgery
7
Treatment groupsSee each treatment group below.
Event-free survival (EFS) (Stratum I)
Will be estimated for eligible and evaluable patients assigned to Stratum 1 using Kaplan-Meier (KM) EFS estimates at 2 and 3 years with respective 80% two-sided confidence intervals. Time from initiation of radiation to the first occurrence of any of the following events: biochemical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
EFS (Stratum II)
Will be estimated for eligible and evaluable patients assigned to Stratum 2 using KM methods at 2 and 3 years with respective 80% two-sided confidence intervals. Time from initiation of radiation to the first occurrence of any of the following events: biochemical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
EFS (Stratum III)
Will be estimated for eligible and evaluable patients assigned to Stratum 3 using KM methods at 2 and 3 years with respective 80% two-sided confidence intervals. Time from initiation of radiation to the first occurrence of any of the following events: biochemical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
Radiographic response rate
Will report the response rates using the respective sample proportions and exact binomial two-sided 95% confidence intervals.
Marker tumor response rate
Will report the response rates using the respective sample proportions and exact binomial two-sided 95% confidence intervals.
EFS (Stratum IV and Stratum V)
Will be estimated separately for eligible and evaluable patients assigned to Stratum 4 and 5 using KM methods at 2 and 3 years with respective 80% two-sided confidence intervals. Time from initiation of radiation to the first occurrence of any of the following events: biochemical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
EFS (Stratum VI and Stratum VII)
Will be estimated separately for eligible and evaluable patients assigned to Stratum 6 and 7 using KM methods at 2 and 3 years with respective 80% two-sided confidence intervals. Time from initiation of radiation to the first occurrence of any of the following events: biochemical or radiographic disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
Incidence of cerebral vascular events (stroke or transient ischemic attacks)
Will be reported as the number of cerebral vascular events.
Working memory
Will be assessed by Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) or Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span subtest depending on age. Mean scores over time will be computed for each stratum.
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