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Evaluating Surgical Resection Extent and Adjuvant ...
Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma
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Video Transcription
Before we get started, I would like to thank the American Association of Neurological Surgeons for giving me the opportunity to present our work examining surgical resection extent and adjuvant therapy and the management of glial sarcoma. Glial sarcoma is a distinct histopathologic variant of glial blastoma that accounts for about 2% of all glial blastoma cases. Commonly referred to as a glial blastoma with sarcomatous components, recent iterations of the World Health Organization classification scheme have renamed glial sarcoma as a separate subset of classical glial blastoma. The diagnosis of glial sarcoma is made based off a biphasic tissue pattern consisting of two distinct malignant cell populations. One component being GFAP positive and fulfilling the criteria for a glial blastoma. The second population has malignant mesenchymal differentiation with positive reticulum staining and fulfilling the criteria of a sarcoma. The pathogenesis of glial sarcomas have been debated. Glial sarcoma was previously regarded as a polyclonal or collision tumor where the two major components developed from different cells of origin. However, recent molecular studies have suggested a monoclonal origin instead. Currently, the reigning theory is that neoplastic cells acquire phenotypic properties of a sarcoma during tumor progression. These findings are made based off the presence of shared somatic alterations, including that of tumor suppressors TP53 and P10, as well as shared chromosomal imbalances. Compared to IDH wild-type glial blastoma, glial sarcomas have been suggested to be more aggressive with porous survival. However, not all studies have been able to reproduce this finding. Glial sarcomas are also more likely to metastasize extracranially, with metastases being reported in up to 11% of cases. Compared to glial blastomas, which have an alteration frequency of up to 50%, these alterations are only reported to occur in about 48% of glial sarcomas. The goals of this project are to characterize the presenting characteristics of glial sarcoma, specifically with differences between primary and secondary disease. In addition, while the management of glial sarcoma is similar to that of glial blastoma, it is unclear how the biphasic histology, specifically the coexistence of the glial and sarcomatous components, impacts outcomes following resection and adjuvant therapy. Therefore, we sought to elucidate the impact of temozolomide and resection extent on glial sarcoma outcomes. To address this, we developed our historical series of histologically confirmed glial sarcoma cases and evaluated the importance of total macroscopic tumor resection and post-surgical temozolomide in extending progression-free and overall survival. Given the rare nature of glial sarcoma, most existing studies to date group together patients that are often treated together in a very heterogeneous manner. Therefore, we additionally sought to evaluate glial sarcoma in the context of modern therapies as defined by the STOOP protocol. A total of 71 patients were included in the analysis. The most common tumor location was the temporal lobe. Primary glial sarcoma patients defined as glial sarcomas arose de novo, made up the majority of the cohort. A minority of patients presented as secondary glial sarcoma, defined as the recurrence of a prior glial tumor with glial sarcoma features. The majority transformed from a prior glial blastoma with a median transformation time of nine months. Median overall survival in our cohort was 15 months. When landmarking from the time of initial diagnosis, primary glial sarcomas were associated with extended progression-free survival, with a median progression-free survival of six and a half compared to five months in a secondary setting. Overall survival was also longer among primary disease, with a median overall survival of 25 versus 10 months. However, secondary glial sarcoma can be viewed as a recurrent blastoma. Therefore, when comparing secondary glial sarcoma landmarked at diagnosis to progressive primary glial sarcoma landmarked at the time of progression, there were no differences in overall survival. Among primary glial sarcoma patients treated with concurrent chemoradiation and adjuvant hemotimozolomide, we examined the effect of resection extent. Patients with near-total and subtotal resection were classified as less than glial-total resection, as both reflect residual macroscopic disease. In this case, glial-total resection was associated with improved overall survival and progression-free survival. Any resection extent less than total macroscopic removal of tumor were associated with poorer outcomes. After adjusting for factors that are significant on univariate analysis, such as MGMT status, a multivariable Cox analysis found that both glial-total resection and temozolomide were independently associated with prolonged progression-free survival. Treatment with temozolomide was additionally associated with improvements in overall survival in the adjusted analysis. In the case that illustrates the metastatic potential of glial sarcoma, we present a 59-year-old male who presented to our clinic with mental status changes over the past few weeks. An MRI showed a large contrast-enhancing lesion in the right temporal lobe, after which the patient underwent a near-total resection. A chest workup at the time of a central line placement was unremarkable. After resection, the patient was treated with concurrent chemoradiation and adjuvant temozolomide per the STOOP protocol. Ten months after initial diagnosis, this patient presented with worsening neurologic function secondary to disease progression and was taken in for a resection. The pathology of the brain specimen was consistent with recurrent glial sarcoma. A second chest workup at the time to confirm another central line placement revealed multiple previously unrecognized lung masses. At the time, a spinal MRI also showed multiple drop metastases. A large right lower lung mass is biopsied, showing components that was negative for GFAP. This biopsy was consistent with metastatic disease of the sarcomatous areas of the primary glial sarcoma. Given the continued rapid progression of brain disease, this patient was ultimately transferred to hospice care. In conclusion, glial sarcoma is a distinct histologic subtype of glial blastoma that is responsive to alkylating DNA damage caused by temozolomide when administered concurrent with an adjuvant to radiotherapy. Despite the retrospective nature of this study and the limited cohort size, our results indicate that glial total resection may be important for achieving best outcomes, even in the context of extensive postoperative management through systemic and radiotherapeutic measures. Our findings suggest that any discernible macroscopic residual disease, either following subtotal or near-total resections, is associated with worse overall and progression-free survival. While additional prospective studies are warranted to further establish the best practices for the clinical management of glial sarcoma, our findings support the notion of treating glial sarcoma akin to classic IDH wild-type glial blastoma, which is maximal safe resection and adjuvant chemoradiation with temozolomide. I would like to thank all the authors who worked on this project, especially Michael Jin, Dr. Seema Nagpal, and Dr. Gordon Lee. Lastly, I would like to extend my sincerest gratitude to all the patients without whom this research would not have been possible. Thank you.
Video Summary
In this video presentation, the speaker discusses the characteristics and management of glial sarcoma, a type of brain tumor. Glial sarcoma is a distinct variant of glial blastoma, with a biphasic tissue pattern consisting of malignant cell populations. The pathogenesis of glial sarcomas is still debated but recent studies suggest a monoclonal origin. Glial sarcomas are more aggressive than glial blastomas and have a higher tendency to metastasize extracranially. The speaker presents a historical series of 71 glial sarcoma cases and evaluates the impact of surgical resection extent and post-surgical temozolomide on outcomes. The study suggests that total macroscopic tumor resection and temozolomide improve progression-free and overall survival. However, more prospective studies are needed for confirmation.
Asset Subtitle
Elisa Liu
Keywords
glial sarcoma
brain tumor
management
surgical resection
temozolomide
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