The trial effect in patients with glioblastoma: effect of clinical trial enrollment on overall survival.

PURPOSE: To determine whether participation in a clinical trial was associated with improved survival in patients with glioblastoma (GBM). METHODS: Following IRB approval, patients were identified using CPT and ICD codes. Data was collected using retrospective review of electronic medical records. When necessary, death data was obtained from online obituaries. Inverse propensity score matching was utilized to transform the two cohorts to comparable sets. Survival was compared using Kaplan-Meyer curves and Wilcoxon Rank Sum Test. RESULTS: In this cohort of 365 patients, 89 were enrolled in a clinical trial and 276 were not. Patients enrolled in clinical trials had a significantly higher mean baseline KPS score, higher proportion of surgical resections, and were more likely to receive temozolomide treatment than patients not enrolled in a clinical trial. After inverse propensity score matching, patients enrolled in a clinical trial lived significantly longer than those not enrolled (28.8 vs 22.2 months, p = 0.005). A potential confounder of this study is that patients not in a clinical trial had significantly fewer visits with neuro-oncologists than patients enrolled in a clinical trial (7 ± 8 vs 12 ± 9, p < 0. 0001). CONCLUSIONS: Clinical trials enroll patients with the most favorable prognostic features. Even when correcting for this bias, clinical trial enrollment is an independent predictor of increased survival regardless of treatment arm.

In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas.

INTRODUCTION: Laser interstitial thermal therapy (LITT) remains a promising advance in the treatment of primary central nervous system malignancies. As indications for its use continue to expand, there has been growing interest in its ability to induce prolonged blood brain barrier (BBB) permeability through hyperthermia, potentially increasing the effectiveness of current therapeutics including BBB-impermeant agents and immunotherapy platforms. METHODS: In this review, we highlight the mechanism of hyperthermic BBB disruption and LITT-induced immunogenic cell death in preclinical models and humans. Additionally, we summarize ongoing clinical trials evaluating a combination approach of LITT and immunotherapy, which will likely serve as the basis for future neuro-oncologic treatment paradigms. RESULTS: There is evidence to suggest a highly immunogenic response to laser interstitial thermal therapy through activation of both the innate and adaptive immune response. These mechanisms have been shown to potentiate standard methods of oncologic care. There are only a limited number of clinical trials are ongoing to evaluate the utility of LITT in combination with immunotherapy. CONCLUSION: LITT continues to be studied as a possible technique to bridge the gap between exciting preclinical results and the limited successes seen in the field of neuro-oncology. Preliminary data suggests a substantial benefit for use of LITT as a combination therapy in several clinical trials. Further investigation is required to determine whether or not this treatment paradigm can translate into long-term durable results for primary intracranial malignancies.

Off-Label Utilization of Syphontrak Catheter for Mechanical Thrombectomy in Acute Stroke.

BACKGROUND: It is not known whether aspiration-specific catheters are necessary for successful mechanical thrombectomy, but if not, off-label use of more versatile catheters could offer significant cost savings over specialized aspiration catheters. The Syphontrak (Depuy Synthes, Raynham, MA, USA) support catheter is designed for introduction of devices into distal neurovasculature but is not specifically indicated for use in mechanical thrombectomy. We sought to compare our experience using this catheter to historical controls to show the non-inferiority of aspiration achieved. METHODS: Data were collected retrospectively on patients who underwent mechanical thrombectomy using the Syphontrak catheter for aspiration at our institution. Patient demographics, procedure characteristics, and outcome information was recorded. Results were compared to five landmark studies on mechanical thrombectomy: MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND-IA. RESULTS: There were 63 patients who underwent mechanical thrombectomy for anterior circulation ischemic stroke. Despite significantly older patients and greater time from symptom onset to groin puncture, Thrombolysis in Cerebral Infarction grade 2B or 3 reperfusion was achieved in significantly more patients than in MR CLEAN, ESCAPE, and REVASCAT. Development of symptomatic intracranial hemorrhage occurred in 6.4% of patients, which was not significantly different from MR CLEAN, ESCAPE, REVASCAT, and EXTEND-IA. Mortality was 19.1%, which was not significantly different from any of the trials. CONCLUSIONS: These data support the off-label use of distal intracranial support catheters for this mechanical thrombectomy, which may result in significant cost savings over aspiration-specific catheters, especially in low-volume centers.