Glioblastoma (GBM) patients have an estimated survival of ~15 months with treatment, and the standard of care only modestly enhances patient survival. Identifying biomarkers representing vulnerabilities may allow for the selection of efficacious chemotherapy options to address personalized variations in GBM tumors. Irinotecan targets topoisomerase I (TOP1) by forming a ternary DNA–TOP1 cleavage complex (TOP1cc), inducing apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that may reduce the effectiveness of irinotecan. We treated GBM cell lines with increasing concentrations of irinotecan and compared the IC₅₀ values. We found that the TDP1/TOP1 activity ratio had the strongest correlation (Pearson correlation coefficient R = 0.972, based on the average from three sets of experiments) with IC₅₀ values following irinotecan treatment. Increasing the TDP1/TOP1 activity ratio by the ectopic expression of wild-type TDP1 increased in irinotecan IC₅₀, while the expression of the TDP1 catalytic-null mutant did not alter the susceptibility to irinotecan. The TDP1/TOP1 activity ratio may be a new predictive indicator for GBM vulnerability to irinotecan, allowing for the selection of individual patients for irinotecan treatment based on risk–benefit. Moreover, TDP1 inhibitors may be a novel combination treatment with irinotecan to improve GBM patient responsiveness to genotoxic chemotherapies.

Background: Gamma Knife Radiosurgery (GKRS), a specific type of Stereotactic Radiosurgery (SRS), has developed as a significant modality in the treatment of glioblastoma, particularly in conjunction with standard chemotherapy. The goal of this study is to evaluate the efficacy of combining GKRS with surgical resection and chemotherapy in enhancing therapeutic effects for glioblastoma patients aged 55 years and older. Methods: This prospective clinical study, conducted in accordance with the STROBE guidelines, involved 49 glioblastoma patients aged 55 years and older, treated between January 2013 and January 2023. Data were collected prospectively, and strict adherence to the STUPP protocol was maintained. Only patients who conformed to the STUPP protocol were included in the analysis. Due to concerns regarding the cognitive impairment associated with conventional radiotherapy, and at the patients’ request, a radiosurgery plan was offered. Radiosurgery was administered for 4–8 weeks following surgical resection. Any patients who had not received previous radiotherapy received open surgical tumor removal, followed by GKRS along with adjuvant chemotherapy. Results: In this prospective clinical study of 49 glioblastoma patients aged 55 years and older, the average lifespan post-histopathological diagnosis was established at 22.3 months (95% CI: 12.0–28.0 months). The median time before disease progression was 14.3 months (95% CI: 13.0–29.7 months). The median duration until the first recurrence after treatment was 15.2 months, with documented cases varying between 4 and 33 months. The Gamma Knife Radiosurgery (GKRS) treatment involved a median marginal recommended dose of 12.5 Gy, targeting an average volume of 5.7 cm³ (range: 1.6–39 cm³). Local recurrence occurred in 21 patients, while distant recurrence was identified in 8 patients. Within the cohort, 34 patients were subjected to further therapeutic approaches, including reoperation, a second GKRS session, the administration of bevacizumab and irinotecan, and PCV chemotherapy. A cognitive function assessment revealed that the patients treated with GKRS experienced significantly less cognitive decline compared to the historical controls, who were treated with conventional radiotherapy. The median MMSE scores declined by 1.9 points over 12 months, and the median MoCA scores declined by 2.9 points. Conclusion: This study demonstrates that Gamma Knife Radiosurgery (GKRS), when integrated with surgical resection and adjuvant chemotherapy, offers a substantial benefit for glioblastoma patients aged 55 years and older. The data reveal that GKRS not only prolongs overall survival and progression-free survival but also significantly reduces cognitive decline compared to conventional radiotherapy. These findings underscore the efficacy and safety of GKRS, advocating for its incorporation into standard treatment protocols for older glioblastoma patients. The potential of GKRS to improve patient outcomes while preserving cognitive function is compelling and warrants further research to optimize and confirm its role in glioblastoma management.

Glomus jugulare tumors are rare slow-growing hypervascular tumors that arise from the paraganglia of the chemoreceptor system within the jugulare foramen of the temporal lobe. The historical standard treatment has been surgical resection, but because of their high vascularity and involvement with cranial nerves (CNs), Gamma Knife radiosurgery (GKRS) has been advocated as an alternative. The goal of this study is to update and report long-term results of GKRS to achieve local control and symptomatic improvement and to reduce morbidity and mortality when treating glomus jugulare tumors. This study retrospectively collected and reviewed clinical and radiographic data of 32 patients with glomus jugulare tumors treated with GKRS at the Miami Neuroscience Center, South Miami, FL, from 1995 to 2019. For the 32 patients, the mean volume treated was 13.9 cc (0.23 to 40.0 cc), with an average of 8.6 isocenters. The median prescription dose was 12.84 Gy ± 2.07 Gy (range: 10-20 Gy). Follow-up data were available for 29 out of 32 patients, with a median clinical follow-up time of 37.3 months (range: 4.3-169.1 months). At follow-up, patients were evaluated for neurological signs and symptoms and radiographic evidence of progression of disease. The median age of the cohort treated with GKRS was 60 years (range: 14-83 years). There were three males and 27 females. Presenting symptomatology was available for 30 out of 32 patients. The most common presenting symptom was hearing loss (21/30) and the most common CN deficit was in CN VIII (19/30). Out of 29 of the patients followed up, 28 patients had improvement (20/29) or resolution (8/29) of symptoms. At the most recent evaluation or contact, patients were without symptomatic progression of CN deficits. Radiographic tumor control was achieved in 28 out of 29 patients. One patient had a recurrence seven years after GKRS, which was treated with surgery. There were no complications, radionecrosis, or mortality reported from GKRS. These data confirm that GKRS is a reasonable upfront treatment option for glomus jugulare tumors. GKRS should be considered more frequently given its excellent long-term local control with low morbidity and risk of complications.

Gamma knife radiosurgery (GKRS), a form of stereotactic radiosurgery (SRS), has gained importance in treating glioblastoma alongside conventional chemotherapy. This study aims to assess the efficacy of combining GKRS with surgery and chemotherapy to enhance treatment outcomes for glioblastoma patients. This prospective clinical study, adhering to STROBE guidelines, assessed 121 glioblastoma patients from June 2008 to December 2022. All patients who had not undergone prior radiotherapy underwent open surgical tumor resection, GKRS, and adjuvant chemotherapy. In the analyzed cohort, the median survival post-diagnosis was 21.2 months (95% CI: 11.4–26.7) and the median progression-free survival was 13.6 months (95% CI: 12.5–28.3). The median time to first recurrence post-treatment was 14.5 months (range: 4–33 months). The median prescribed dose for GKRS was 12 Gy (range: 10–17 Gy), with a median target volume of 6.0 cm³ (range: 1.6–68 cm³). Post GKRS, 92 patients experienced local recurrence, 21 experienced distant recurrence, and 87 received additional treatment, indicating diverse responses and treatment engagement. This study evaluates the use of GKRS for glioblastomas, emphasizing its efficacy and complications in a single-center trial. It suggests integrating GKRS into initial treatment and for recurrences, highlighting the comparable survival rates but underscoring the need for further research.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) has been well established and considered a safe alternative for primary central nervous system lymphomas (PCNSLs). However, in HIV-related PCNSL, the use of SRS remains controversial. The purpose of this study was to evaluate the efficacy and safety of SRS in HIV-related PCNSL. METHODS: Forty-two adult patients with confirmed PCNSL and no previous radiotherapy or chemotherapy were selected, with 16 receiving Gamma Knife Radiosurgery (GKRS) alone and 26 receiving Highly Active Antiretroviral Therapy (HAART) before GKRS. Follow-up evaluations were conducted at 3, 6, 12, and 24 months post-treatment using clinical and imaging techniques. Statistical analyses were performed using SPSS v22, assessing for new lesions, changes in lesion size, progression-free survival, and overall survival. RESULTS: HAART/GKRS showed a significantly higher rate of complete response compared with the GKRS group, with 53.8% vs 18.8% (P = .048). The mean progression-free survival for the HAART/GKRS group and the GKRS group was 39.7 months and 31.2 months, respectively (P = .0051). Patients with a delayed HAART initiation (>6 months) exhibited an increased burden of T2 white matter lesions and a higher number of large lesions (odds ratio = 1.9, 95% CI = 1.44-2.42, P = .001). However, no significant difference was observed between the two groups regarding radionecrosis. CONCLUSION: The study highlights the potential benefits of adding HAART to GKRS for patients with PCNSL, leading to improved survival outcomes. An early initiation of HAART was associated with less tumor progression, underscoring the importance of timely administration of HAART in patients with AIDS-related PCNSL.

Gamma Knife® radiosurgery (GKRS) has been demonstrated to be a well-known approach for treating patients with medical refractory trigeminal neuralgia (TN). Herein, the authors review the outcomes of pain among a large cohort of patients who had undergone a second GKRS delivered at a significantly reduced dose. The authors conducted a prospective analysis of patients who have undergone two GKRS procedures between the years 2012 to 2021 at one institution. Baseline characteristics, radiosurgical dosimetry and technique, pain outcomes, and adverse effects were reviewed. Pain outcomes were measured with the Barrow Neurological Institute (BNI) pain intensity scale, which included the best BNI attained after the last treatment and recurrence. A total of 202 patients were identified, including 55 males and 147 females. Pain recurrence was reported in all patients prior to the second GKRS treatment (median = 4 months). Pain recurrence in the preceding Japan Neuroscience Society (JNS) 2021 study was also reported in all patients after each GKRS with a median value of 20 months between the second and third procedures. Complete to partial pain relief (BNI ≤ III) was achieved in 80% of patients after the second treatment. Over a median of 12 months of follow-up, 60% of patients maintained complete to partial pain relief compared to 77% of patients over the course of three treatments. In the present study, one patient developed facial spasms while 10 patients experienced persistent facial tingling. Subjective mild numbness was also found to be present in 16% of patients, with only 2% being bothersome, as compared to the JNS study, where subjective mild numbness was found to be present in 14%, with only 14.3% being bothersome. Among the 202 patients, 74 (37%) patients had undergone subsequent additional procedures such as a third GKRS, microvascular decompression (MVD), or other percutaneous procedures. The authors describe the largest study to date of patients undergoing a second GKRS treatment for type 1 medical refractory trigeminal neuralgia. A reduced dose of radiation for a second treatment may produce outcomes similar to those of three consecutive treatments in regard to limiting recurrence and adverse effects.