Biopsy Versus Resection in Elderly Glioblastoma Patients. A Prospective Cohort Study.

Study Overview
=================
Brief Summary
-----------------
This trial is set up as a prospective observational cohort study to identify if either biopsy or resection should be the surgical modality of choice in elderly glioblastoma patients with a newly diagnosed tumor. Patients who are considered eligible for GBM resection or biopsy will be included. Through shared-decision making patients and their treating physicians will decide upon resection or biopsy. Written informed consent will be obtained. Participants will be followed for 1 year postoperative to assess potential differences in health-related quality of life and overall survival. Follow-up will consist of health-related quality of life questionaires and neurological assessment at 6 weeks, 3 months, 6 months and 12 months postoperative. Additionally Cognitive and neuro-linguistic tests will be done at 3 months postoperative. These will be compared to results pre-operative. After surgery, patients will receive standard adjuvant treatment with concomitant Temozolomide and radiation therapy, and standard follow-up. Patients in whom the diagnosis GBM is not confirmed in histological analyses will be excluded from the study. Total study duration will be 4 years, of which 3 years will comprise patient inclusion, with a follow-up duration of 1 year.

Official Title
-----------------
Biopsy Versus Resection in Elderly Glioblastoma Patients. A Prospective Cohort Study.

Conditions
-----------------
Glioblastoma

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥70 years Tumor diagnosed as glioblastoma on MRI with distinct ring-like pattern of contrast enhancement with thick irregular walls and a core area reduced signal suggestive of tumor necrosis as assessed by the surgeon. Karnofsky Performance Score (KPS) ≥70 Written Informed consent Exclusion Criteria: Tumors of the cerebellum, brain stem or midline Multifocal contrast enhancing lesions Substantial non-contrast enhancing tumor areas suggesting low grade gliomas with malignant transformation Medical reasons precluding MRI (e.g. pacemaker) Inability to give consent as assessed by neurosurgeon (e.g. language barrier) Severe aphasia prohibiting neurolinguistic testing and comprehension of informed consent Previous brain tumor surgery Previous low-grade glioma Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin.

Ages Eligible for Study
-----------------
Minimum Age: 70 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Biopsy<br>Newly diagnosed elderly (>70 years of age) glioblastoma patients who undergo biopsy | |
| Resection<br>Newly diagnosed elderly (>70 years of age) glioblastoma patients who undergo resection | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined as the time from diagnosis to the death of the patient from any cause | 12 months | 
| The difference in mean change score of physical functioning, as measured with the EORTC QLQ-C30 physical functioning scale, between the two groups at 6 weeks and 3 months after surgery compared to mean score on baseline | Measured with the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30), a higher scores means a worse outcome. We assume a minimally important difference of 7 between the 2 groups. | 6 weeks and 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS), defined as the time from diagnosis to disease progression | Increase in residual tumor volume of more than 25%, or occurrence of a new tumor lesion with a volume greater than 0.175cm3), or death. As according to the RANO criteria. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months after surgery | 
| The difference in mean change score of physical functioning, as measured with the EORTC QLQ-C30 physical functioning scale, between the two groups at 6 months and 12 months after surgery compared to mean score on baseline. | Measured with the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30), a higher scores means a worse outcome. | at 6 months and 12 months after surgery | 
| The proportion of patients with deterioration, improvement or stable physical functioning, as measured with the EORTC QLQ-C30 physical functioning scale at 6 weeks and 3 months compared to baseline. | Measured with the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30), a higher scores means a worse outcome. | 6 weeks and 3 months after surgery | 
| Descriptive reporting of changes in the mean scores on the other health-related quality of life (HRQoL) scales at 6 weeks and 3 months after surgery. | HRQoL will be measured using the Measured with the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30), EORTC , EORTC brain cancer module (QLQ-BN20) and EuroQol 5 Dimensions (EQ-5D) questionnaires. A higher scores means a worse outcome. | at 6 weeks and 3 months postoperative | 
| Proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration, improvement or stability at 6 weeks and 3 months after surgery | In which deterioration is defined as an increase of at least one point and improvement as a decrease of at least one point on the total NIHSS score compared to this score at baseline. | at 6 weeks and 3 months postoperative | 
| Descriptive reporting of differences between the groups in cognitive and neuro-linguistic screening at 3 months compared to baseline. | as measured by the Aphasia Bedside Check (ABC), Shortened Token Test, verbal fluency (category and letter), Montreal Cognitive Assessment (MOCA) and optionally CAT-NL Picture Description and Object Naming. | 3 months postoperative | 
| Comparison of the (S)AEs in both groups. |  | 6 weeks postoperative | 
| Cost-effectiveness between the two treatments. | Measured as total intramural medical costs, for a 1 year time horizon | 12 months postoperative | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glioblastoma, High grade glioma, Surgical management, Biopsy, Resection