Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma.

PURPOSE: Despite intensive treatment with surgery, radiation therapy, temozolomide (TMZ) chemotherapy, and tumor-treating fields, mortality of newly diagnosed glioblastoma (nGBM) remains very high. SurVaxM is a peptide vaccine conjugate that has been shown to activate the immune system against its target molecule survivin, which is highly expressed by glioblastoma cells. We conducted a phase IIa, open-label, multicenter trial evaluating the safety, immunologic effects, and survival of patients with nGBM receiving SurVaxM plus adjuvant TMZ following surgery and chemoradiation (ClinicalTrials.gov identifier: NCT02455557). METHODS: Sixty-four patients with resected nGBM were enrolled including 38 men and 26 women, in the age range of 20-82 years. Following craniotomy and fractionated radiation therapy with concurrent TMZ, patients received four doses of SurVaxM (500 µg once every 2 weeks) in Montanide ISA-51 plus sargramostim (granulocyte macrophage colony-stimulating factor) subcutaneously. Patients subsequently received adjuvant TMZ and maintenance SurVaxM concurrently until progression. Progression-free survival (PFS) and overall survival (OS) were reported. Immunologic responses to SurVaxM were assessed. RESULTS: SurVaxM plus TMZ was well tolerated with no serious adverse events attributable to SurVaxM. Of the 63 patients who were evaluable for outcome, 60 (95.2%) remained progression-free 6 months after diagnosis (prespecified primary end point). Median PFS was 11.4 months and median OS was 25.9 months measured from first dose of SurVaxM. SurVaxM produced survivin-specific CD8+ T cells and antibody/immunoglobulin G titers. Apparent clinical benefit of SurVaxM was observed in both methylated and unmethylated patients. CONCLUSION: SurVaxM appeared to be safe and well tolerated. The combination represents a promising therapy for nGBM. For patients with nGBM treated in this manner, PFS may be an acceptable surrogate for OS. A large randomized clinical trial of SurVaxM for nGBM is in progress.

Sellar and Parasellar Pain Syndromes.

PURPOSE OF REVIEW: Sellar and parasellar lesions are numerous and varying in terms of their patholphysiology and physical and radiographic characteristics but often incite pain syndromes that are similar in semiology. The goal of this review was to familiarize the reader with a variety of sellar and parasellar lesions grouped together based on common clinical symptomatology, with a focus on important imaging characteristics that are often distinguishing features diagnostically. RECENT FINDINGS: In most cases, tissue acquisition via surgical resection or stereotactic biopsy are the mainstay for definitive diagnosis of sellar and parasellar lesions. With advances in MRI technology in particular in terms of resolution and the inclusion of new techniques including dynamic imaging with delayed contrast, imaging studies of lesions in the sellar and parasellar regions have become increasingly important for diagnostic purposes, with pituitary adenomas and schwannomas as prime examples. In the case of chordoid gliomas, molecular features of the tumor also help distinguish it from other disease processes similar in presentation, which have dramatic impacts on management. Advances in surgical approaches and radiation techniques offer more precise and targeted therapy to lesions in an area with increased risk of clinical morbidity given the high concentration of critically important structures that must be spared during treatment. Sellar and parasellar lesions have the potential to cause significant morbidity and mortality, highlighting the importance of clinical recognition of warning signs/symptoms, obtaining high-quality imaging studies in various modalities for diagnostic purposes, and prompt management which often involves a multimodal approach that includes surgical resection, radiation, and/or medical therapy. Future advanced imaging techniques will only improve presurgical diagnostic accuracy and lead to more prompt and efficient management.