Natural History of Brain Function, Quality of Life, and Seizure Control in Patients With Brain Tumor Who Have Undergone Surgery

Radiation Therapy Oncology Group

Status: Completed

Conditions: Seizure; Adult Oligodendroglioma; Adult Diffuse Astrocytoma; Psychosocial Effects of Cancer and Its Treatment; Neurotoxicity; Cognitive/Functional Effects; Adult Mixed Glioma

Treatments: Other: laboratory biomarker analysis; Other: questionnaire administration; Procedure: cognitive assessment; Procedure: quality-of-life assessment; Procedure: magnetic resonance imaging

Study type: Observational

Funder types: Other; NETWORK; NIH

Identifiers

NCT01417507

U10CA037422 (U.S. NIH Grant/Contract)

CDR0000708271

NCI-2011-02982 (Registry Identifier)

RTOG 0925

Details and patient eligibility

About

This trial studies the natural history of brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery. Learning about brain function, quality of life, and seizure control in patients with brain tumor who have undergone surgery may help doctors learn more about the disease and find better methods of treatment and on-going care.

Full description

PRIMARY OBJECTIVES:

I. To determine if there is difference in the average changes of neurocognitive function (NCF) scores from baseline to the time of radiologic tumor progression or up to 5 years (whichever occurs first), between radiologically progressed and non-progressed patients.

SECONDARY OBJECTIVES:

I. To determine if there is difference in the time to neurocognitive decline, as defined by the Reliable Change Index - Within subjects Standard Deviation (RCI-WSD), between radiologically progressed and non-progressed patients.

II. To evaluate NCF during the postoperative observational period of progression-free survival (PFS) and after radiological progression for a total time on study of 5 years.

III. To determine if the changes in cognitive functioning are an early warning biomarker for radiological progression.

IV. To explore the effect of salvage therapy on cognitive outcomes in patients who progress during the study period for up to 5 years.

V. To evaluate quality-of-life (QOL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL-30 and QOL brain module (BCN20) and health utilities as measured by the European Quality of Life-5 Dimensions (EQ-5D), for a total time on study of 5 years.

VI. To evaluate seizure control for a total time on study of 5 years. VII. To evaluate molecular correlates of QOL, NCF, seizure control, and PFS. VIII. To characterize aberrant molecular pathways in low-grade gliomas (LGGs) and test the hypothesis that activation of signaling pathways will predict worse PFS and overall survival (OS).

IX. To explore the relationship between change in cognitive function and symptomatic progression (defined as worsening seizures or new or progressive neurologic deficits) or clinical progression (defined as initiation of treatment interventions such as radiotherapy, chemotherapy, or additional surgery).

OUTLINE:

Patients undergo neurocognitive assessment using the CogState Test battery (the Detection Test (DET), the Identification Test (IDN), the One Card Learning Test (OCLT), and the Groton Maze Learning Test (GMLT)) at baseline* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC Quality of Life Questionnaire-Core 30 (QOL-30), the Brain Cancer Module-20 (BCM20), and the European Quality of Life-5 Dimensions (EQ-5D) questionnaires at baseline*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study.

Patients undergo MRI scans at baseline*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.

NOTE: * 12 weeks after surgery.

Enrollment: 82 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Central pathology confirmed diagnosis of supratentorial grade II oligodendroglioma, astrocytoma, or mixed oligoastrocytoma prior to step 2 registration

• No multifocal disease, based upon the following minimum diagnostic work-up:

  • History/physical examination, including neurologic examination, within 84 days prior to step 2 registration
  • Brain MRI with and without contrast within 84 days prior to Step 2 registration (Note: MRI 70 days after surgery is preferred and highly encouraged)

• The patient must be within one of the following categories:

  • Maximal safe resection with minimal residual disease defined as follows:

    • Removal of T2/fluid-attenuated inversion recovery (FLAIR) abnormalities thought to be primarily tumor, with a residual ≤ 2 cm maximal tumor diameter/T2 FLAIR abnormality on MRI to be done within 84 days post-operatively

    • If there is > 2 cm post-operative residual T2/FLAIR abnormality and the neurosurgeon believes this represents edema and not primarily tumor, the neurosurgeon is encouraged to repeat imaging within the allowed study period (up to 84 days post-operatively) to confirm resolution of edema

      • MRI at the time of enrollment must document a ≤ 2 cm residual maximal tumor diameter/T2 FLAIR abnormality

    • Patients who required a second surgery to obtain a maximal safe resection will be eligible if the second surgery is performed within 84 days of the initial diagnostic procedure

  • Age < 40 (any extent of resection)

  • Age < 50 and preoperative tumor diameter < 4 cm (any extent of resection)

• Karnofsky performance status ≥ 80%

• No prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

• Must be able to undergo MRI of the brain with gadolinium

• No plans for adjuvant radiotherapy or chemotherapy after surgery

• No more than 84 days (12 weeks) since prior surgery

• No brain tumor recurrence

• No prior brain tumor surgery, radiation therapy and/or chemotherapy

Trial design

82 participants in 1 patient group

Supportive care (neurocognitive assessment and MRI)

Description:

Patients undergo neurocognitive assessment using the CogState Test battery (the DET, the IDN, the OCLT, and the GMLT) at baseline\* and at 12, 24, 36, 42, 48, 54, and 60 months. Patients also complete the EORTC QOL-30, the BCM20, and the EQ-5D questionnaires at baseline\*, at 12, 24, 36, 48, and 60 months afterwards, and before undergoing any further treatment. Patients are instructed to complete a seizure and medication diary during study. Patients undergo MRI scans at baseline\*, at 12, 24, 36, 48, and 60 months, and at the time of radiological, clinical, or neurological failure.

Treatment:

Procedure: quality-of-life assessment

Procedure: magnetic resonance imaging

Procedure: cognitive assessment

Other: laboratory biomarker analysis

Other: questionnaire administration