NovoTTF Treatment Signatures in Glioblastoma Patients at Autopsy

Study Overview
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Brief Summary
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This study will assess whole brain samples from glioblastoma patients at autopsy to determine the underlying pathological signatures of tumor treatment fields at autopsy.

Detailed Description
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RATIONALE: Optune therapy with tumor treatment fields (TTFields) has recently been FDA approved for the treatment of newly diagnosed glioblastoma due to a recent clinical trial that showed improvement in progression free survival and overall survival compared to standard therapy. (1) TTFields also have a role in the recurrent glioblastoma treatment where it has demonstrated equal efficacy to second-line chemotherapy also has been shown to tumor progression and improve overall survival.(2) Though preclinical studies are ongoing, glioblastoma patients who have undergone TTField therapy have not yet been assessed at autopsy to determine both the pathological signature of TTField treatment, and the pattern of failure. This study will determine how the underlying pathological signatures of tumors treated with TTFields differ from those naïve to TTFields by comparing tumor tissue at autopsy. STUDY: All patients undergoing TTField therapy for newly diagnosed and recurrent glioblastoma will be considered for inclusion for this study. The investigators expect to enroll five patients per year for four years, totaling 10 patients treated upfront and 10 patients treated at tumor recurrence. An objective of this study is to determine differences in the pathological pattern of failure when patients are treated with TTFields at initial diagnosis (up-front) compared to those treated at tumor recurrence.

Official Title
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NovoTTF Treatment Signatures in Glioblastoma Patients at Autopsy

Conditions
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Glioblastoma

Intervention / Treatment
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* Other: Tumor samples from patients treated with TTFields at initial diagnosis.
* Device: Tumor samples from patients treated with TTFields at tumor recurrence.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed glioblastoma, World Health Organization (WHO) grade IV, patients undergoing TTField therapy. Recurrent glioblastoma WHO grade IV, patients undergoing TTField therapy. Exclusion Criteria: TTField compliance < 75%. Any contraindication to Optune TTField treatment. Initial brain tumor diagnosis < WHO grade IV. Duration of TTField therapy < 3 months.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| TTField at Recurrence<br> | Device: Tumor samples from patients treated with TTFields at tumor recurrence.<br>* Pathological assessment of tumor cellularity, apoptosis, and quantitative histo-morphometry of residual tumor cells will be performed. Each metric will be statistically compared between groups.<br>|
| TTField at New Diagnosis<br> | Other: Tumor samples from patients treated with TTFields at initial diagnosis.<br>* Pathological assessment of tumor cellularity, apoptosis, and quantitative histo-morphometry of residual tumor cells will be performed. Each metric will be statistically compared between groups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of mitotically active cells | Tissue samples will be obtained at autopsy and stained for KI-67. Slides will then be digitized, and the number of active cells will be counted computationally. | At baseline | 
| Number of mitotically inactive cells | Tissue samples will be obtained at autopsy and stained for KI-67. Slides will then be digitized, and the number of not active cells will be counted computationally. | At baseline | 
| Mitotic Ratio | Number of mitotically active cells divided by the number of not mitotically active cells per patient will be calculated. | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioblastoma, brain tumor autopsy, autopsy, Optune therapy, tumor treatment fields, TTFields, Recurrent glioblastoma, grade IV, brain tumor, newly diagnosed glioblastoma