Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma.

INTRODUCTION: Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT). METHODS: rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009-2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards. RESULTS: Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm3 and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients. CONCLUSIONS: SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.

Metastatic Neoplasm Volume Kinetics Following 2-Stage Stereotactic Radiosurgery.

BACKGROUND: Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs. METHODS: Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test. RESULTS: The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14-18 Gy) and 15 Gy (12-16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm3 (1.5-28.5 cm3), 3.3 cm3 (0.8-26.1 cm3), and 2.2 cm3 (0.2-10.1 cm3), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months. CONCLUSIONS: Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.

Gamma Knife Stereotactic Radiosurgery in Combination with Bevacizumab for Recurrent Glioblastoma.

BACKGROUND: Prior retrospective and prospective studies suggest improved survival with the use of stereotactic radiosurgery (SRS) and bevacizumab in the treatment of limited-volume glioblastoma (GBM) recurrences. METHODS: We retrospectively reviewed our experience with gamma knife SRS in combination with bevacizumab for the treatment of focal GBM recurrence during 2009-2015. Outcomes include overall survival, progression free survival (PFS), and radiation-related adverse events. Kaplan-Meier methods and multivariable Cox proportional hazards models were performed for survival analysis. RESULTS: Within a median of 13.7 months after diagnosis, a total of 45 patients with GBM underwent gamma knife SRS and bevacizumab treatment. Median age was 57 years (range: 20-78 years) and 63.3% were women. The median Karnofsky Performance Score (KPS) at recurrence was 80 (range: 40-100). Sixty-four percent of patients had single radiosurgery target (range: 1-4) and median target volume and margin dose were 2.2 cm3 (range: 0.1-25.2 cm3) and 17.0 gray (Gy) (range: 13-24 Gy), respectively. Median PFS and overall survival were 9.3, 31.0 months following diagnosis, and 5.2, 13.3 months after SRS, respectively. Factors associated with poor outcomes were KPS ≤70, SRS dose <18 Gy, and use of <2 chemotherapy agents prior to SRS. No radiation-related adverse events occurred. CONCLUSIONS: SRS in combination with bevacizumab can be safely used to treat focal GBM recurrence. KPS, radiation dose, and multi-agent chemotherapy usage prior to SRS demonstrated significant impact on PFS. Bevacizumab may provide clinically relevant radioprotection.

Planned Gamma Knife Boost After Chemoradiotherapy for Selected Sinonasal and Nasopharyngeal Cancers.

OBJECTIVE: To determine the feasibility of a Gamma Knife boost after intensity-modulated radiation therapy in combination with multimodal therapy in patients with nasopharyngeal carcinoma and sinonasal malignancies with skull base or cavernous sinus involvement. METHODS: Nine patients were treated with intensity-modulated radiation therapy followed by a Gamma Knife boost. In one case Gamma Knife was given as salvage treatment after resection. Five patients had sinonasal malignancies and 4 had nasopharyngeal carcinoma. The mean radiation therapy dose was 64.3 Gy (range, 54-70 Gy) at 2 Gy per fraction. The median interval from completion of radiation therapy to Gamma Knife boost was 2.2 months (range, 1-4 months). The most common indication for Gamma Knife boost was involvement of the cavernous sinus, which was identified in 7 patients. The median margin Gamma Knife dose delivered was 13 Gy (range, 12-20 Gy), with median prescription isodose of 50%. RESULTS: All patients tolerated the procedure well, with minimal toxicity. Local control rates were achieved in all patients and no acute grade 3-5 toxicity was observed. One patient experienced late grade 4 toxicity, which was potentially attributable to treatment. Distant failure occurred in 3 patients (1 patient with nasopharyngeal carcinoma and 2 patients with sinonasal malignancies). CONCLUSIONS: Planned Gamma Knife boost followed intensity-modulated radiation therapy is feasible, safe, and provides excellent local control in patients with sinonasal malignancies and nasopharyngeal carcinoma, particularly in cases with cavernous sinus involvement. Further follow-up will be necessary to determine the long-term effectiveness and complication profile.