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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TTField at Recurrence |
| ||
| TTField at New Diagnosis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tumor samples from patients treated with TTFields at initial diagnosis. | Other | 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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Newly Diagnosed Glioblastoma Patients undergoing standard of care treatment consisting of surgery followed by chemo-radiation therapy will have the addition of Optune TTField therapy together with adjuvant chemotherapy. OR Recurrent Glioblastoma Patients with glioblastoma tumor recurrence defined by either imaging criteria, or deteriorating neurological function will be offered Optune TTField treatment at the discretion of the neurooncologist.
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| Name | Affiliation | Role |
|---|---|---|
| Peter LaViolette, PhD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Froedtert & the Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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Samples are obtained from regions suspicious for tumor at autopsy.
| Tumor samples from patients treated with TTFields at tumor recurrence. | Device | 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. |
|
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |