Preoperative Stereotactic Radiosurgery for Glioblastoma

Lehrer, Eric J.; Ruiz‐Garcia, Henry; Nehlsen, Anthony D.; Sindhu, Kunal K.; Sarabia-Estrada, Rachel; Borst, Gerben R.; Sheehan, Jason P.; Quiñones‐Hinojosa, Alfredo; Trifiletti, Daniel M.

doi:10.3390/biology11020194

Cited by 15 publications

(12 citation statements)

References 114 publications

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“…An important factor is also better oxygenation of the area irradiated before surgery, which, by increasing the chance of causing damage to the DNA double helix, may contribute to greater effectiveness of radiotherapy [ 160 ]. It should also be noted that in preclinical models, SRS used before surgery has been shown to increase the immune response against neoplasticity by increasing the concentration of circulating cytotoxic T lymphocytes [ 161 ]. The above premises contributed to the design of the currently conducted phase I/IIA clinical trial, the so-called NeoGlioma study (NCT05030298), in which, for the standard treatment regimen according to Stupp in one group of patients 14 days before the planned surgery, radiosurgery with a dose of 10 Gy is used.…”

Section: Development Prospects Of Radiotherapy In Glioblastomasmentioning

confidence: 99%

New Directions in the Therapy of Glioblastoma

Szklener

Mazurek²,

Wieteska³

et al. 2022

Cancers

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Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% of all cases. Despite the standard management based on surgical resection and radiotherapy, it is related to poor outcome, with a 5-year relative survival rate below 6.9%. In order to improve the overall outcome for patients, the new therapeutic strategies are needed. Herein, we describe the current state of knowledge on novel targeted therapies in glioblastoma. Based on recent studies, we compared treatment efficacy measured by overall survival and progression-free survival in patients treated with selected potential antitumor drugs. The results of the application of the analyzed inhibitors are highly variable despite the encouraging conclusions of previous preclinical studies. This paper focused on drugs that target major glioblastoma kinases. As far, the results of some BRAF inhibitors are favorable. Vemurafenib demonstrated a long-term efficacy in clinical trials while the combination of dabrafenib and trametinib improves PFS compared with both vemurafenib and dabrafenib alone. There is no evidence that any MEK inhibitor is effective in monotherapy. According to the current state of knowledge, BRAF and MEK inhibition are more advantageous than BRAF inhibitor monotherapy. Moreover, mTOR inhibitors (especially paxalisib) may be considered a particularly important group. Everolimus demonstrated a partial response in a significant proportion of patients when combined with bevacizumab, however its actual role in the treatment is unclear. Neither nintedanib nor pemigatinib were efficient in treatment of GBM. Among the anti-VEGF drugs, bevacizumab monotherapy was a well-tolerated option, significantly associated with anti-GBM activity in patients with recurrent GBM. The efficacy of aflibercept and pazopanib in monotherapy has not been demonstrated. Apatinib has been proven to be effective and tolerable by a single clinical trial, but more research is needed. Lenvatinib is under trial. Finally, promising results from a study with regorafenib may be confirmed by the ongoing randomized AGILE trial. The studies conducted so far have provided a relatively wide range of drugs, which are at least well tolerated and demonstrated some efficacy in the randomized clinical trials. The comprehensive understanding of the molecular biology of gliomas promises to further improve the treatment outcomes of patients.

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Section: Development Prospects Of Radiotherapy In Glioblastomasmentioning

confidence: 99%

New Directions in the Therapy of Glioblastoma

Szklener

Mazurek²,

Wieteska³

et al. 2022

Cancers

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“…The addition of SRS to ICIs has been used synergistically for other primary and metastatic CNS tumors [ 4 , 5 , 6 , 7 , 8 , 9 , 12 , 24 ]. Preclinical data suggest that radiation-induced immunogenic cell death increases antigen presentation and activation of immune cells and, in combination with ICIs, subverts the immunosuppressive tumor microenvironment [ 61 , 62 ].…”

Section: Meningioma Treatmentmentioning

confidence: 99%

“…Glioblastoma is the most common primary malignant brain tumor, and is associated with a very poor prognosis, with a median OS of 15–21 months despite optimal therapy [ 13 ]. While SRS has been explored in the adjuvant setting and yielded disappointing results [ 23 ], there has been recent interest in incorporating preoperative SRS as a dose-escalation strategy [ 24 ]. Furthermore, preclinical studies and case reports have suggested that ICI therapy may enhance anti-tumor immune responses against glioblastoma, which can potentially lead to improved outcomes [ 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors

et al. 2022

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Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.

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“…Due to patterns of failure on glioblastoma, there has long been an interest in dose intensification; however, studies have yielded disappointing results ( 11 , 110 ). BN001 is a randomized controlled trial that is comparing standard of care chemoradiotherapy to dose-escalated RT in the management of glioblastoma.…”

Section: High Grade Glioma and Glioblastomamentioning

confidence: 99%

“…Preoperative therapy has become widely adopted in multiple malignancies, such as cancers of the esophagus and rectum ( 54 – 57 ). While most studies exploring the role of preoperative radiosurgery have focused on brain metastases, there has been recent growing interest in applying this treatment paradigm to high grade glioma and glioblastoma ( 11 ). While the use of postoperative SRS in the management of glioblastoma yielded disappointing results ( 58 – 60 ); however, its use in the preoperative setting shares many of the potential advantages observed with brain metastases and further might also be used as a strategy to enhance anti-tumor immunity ( 61 , 62 ).…”

Section: Introductionmentioning

confidence: 99%

Preoperative stereotactic radiosurgery in the management of brain metastases and gliomas

Lehrer

Kowalchuk²,

Ruiz‐Garcia³

et al. 2022

Front. Surg.

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Stereotactic radiosurgery (SRS) is the delivery of a high dose ionizing radiation in a highly conformal manner, which allows for significant sparing of nearby healthy tissues. It is typically delivered in 1–5 sessions and has demonstrated safety and efficacy across multiple intracranial neoplasms and functional disorders. In the setting of brain metastases, postoperative and definitive SRS has demonstrated favorable rates of tumor control and improved cognitive preservation compared to conventional whole brain radiation therapy. However, the risk of local failure and treatment-related complications (e.g. radiation necrosis) markedly increases with larger postoperative treatment volumes. Additionally, the risk of leptomeningeal disease is significantly higher in patients treated with postoperative SRS. In the setting of high grade glioma, preclinical reports have suggested that preoperative SRS may enhance anti-tumor immunity as compared to postoperative radiotherapy. In addition to potentially permitting smaller target volumes, tissue analysis may permit characterization of DNA repair pathways and tumor microenvironment changes in response to SRS, which may be used to further tailor therapy and identify novel therapeutic targets. Building on the work from preoperative SRS for brain metastases and preclinical work for high grade gliomas, further exploration of this treatment paradigm in the latter is warranted. Presently, there are prospective early phase clinical trials underway investigating the role of preoperative SRS in the management of high grade gliomas. In the forthcoming sections, we review the biologic rationale for preoperative SRS, as well as pertinent preclinical and clinical data, including ongoing and planned prospective clinical trials.

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Preoperative Stereotactic Radiosurgery for Glioblastoma

Cited by 15 publications

References 114 publications

New Directions in the Therapy of Glioblastoma

New Directions in the Therapy of Glioblastoma

A Review of the Role of Stereotactic Radiosurgery and Immunotherapy in the Management of Primary Central Nervous System Tumors

Preoperative stereotactic radiosurgery in the management of brain metastases and gliomas

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