Gregory Joseph Zipfel

BACKGROUND AND OBJECTIVES: Radiation-induced meningiomas (RIMs) are the most common secondary intracranial tumors. Compared with sporadic meningiomas (SMs), RIMs exhibit more aggressive clinical behavior. Surgical resection has traditionally been the primary treatment modality for these tumors; however, previous studies have demonstrated stereotactic radiosurgery (SRS) is an effective treatment for RIMs. The aims of this study were to further characterize these rare tumors and to directly compare the outcomes after SRS vs surgical resection as the primary treatment modality for RIMs. METHODS: A single-institution retrospective analysis of surgically and SRS-treated RIMs was conducted. Patient demographic data, World Health Organization grade, tumor volume, multiplicity, complications, and extent of resection were collected. The primary outcome was local control. RESULTS: Forty-seven patients with one or multiple RIMs comprising 73 tumors were identified and compared with a cohort of 75 patients with SMs (n = 86 tumors). Patients with RIMs more frequently harbored multiple tumors (44.4% vs 16.0%; P = .002). RIMs treated surgically exhibited a significantly worse local control compared with surgically treated SMs (log-rank P = .043). Among RIMs, primary treatment with SRS was associated with a significantly better local control compared with surgery as the primary treatment modality ( P = .011). SRS demonstrated superior 5- and 7-year local control rates even after controlling for size and restricting the analysis to gross totally resected tumors. CONCLUSION: SRS was associated with better local control compared with surgical resection for the primary treatment of RIMs. Frequent multifocal presentation and high rates of treatment failure support the notion that RIMs represent a distinct biological entity. Given the long latency and ongoing risk of tumor development after cranial irradiation, these findings underscore the importance of long-term surveillance in this patient population.

Was not provided for this article.

BACKGROUND: Hemorrhagic risk in dural arteriovenous fistulas (dAVFs) is largely determined by venous anatomy, but the contribution of systemic cardiovascular factors and their medical therapy remains poorly defined. This study examined associations between cardiovascular risk factors and antithrombotic use and hemorrhagic presentation, angiographic obliteration, and early functional outcomes after treatment. METHODS: We analyzed 1350 adults with intracranial dAVFs from the international Consortium for Dural Arteriovenous Fistula Outcomes Research registry, which retrospectively accrued cases across 14 centers in 4 countries between 1990 and 2017. Demographics, cardiovascular comorbidities, antithrombotic use, angioarchitectural features, treatment strategies, and follow-up outcomes were collected from prospectively maintained databases. Primary end points were hemorrhagic presentation, angiographic obliteration, and 90-day functional status after treatment. Univariable and multivariable logistic regressions were performed with model-specific adjustments. RESULTS: Hemorrhage occurred in 375 patients (27.8%) and was most strongly associated with high-grade dAVF classification and male sex; antithrombotic therapy was associated with lower odds of hemorrhagic presentation. Other cardiovascular risk factors showed no independent relationship with bleeding. Angiographic obliteration was achieved in 621 of 845 patients (73.5%). Hemorrhagic onset, high dAVF grade, and surgical treatment were independently associated with angiographic obliteration, whereas smoking and embolization demonstrated only nonsignificant trends after adjustment. At 90 days, 934 patients (88.9%) were functionally independent. Baseline modified Rankin Scale score was the strongest factor associated with 90-day functional outcome, while neither cardiovascular comorbidities nor treatment modality independently influenced functional status. CONCLUSIONS: In this large multicenter dAVF cohort, hemorrhagic presentation was most strongly associated with venous angioarchitecture. Male sex and antithrombotic therapy were also independently associated with hemorrhagic presentation. Angiographic obliteration was common, particularly among surgically treated lesions, and 90-day functional outcome was most strongly associated with baseline functional status.

PVAC-Seq predicted neoantigens for each subject and each tumor region from whole exome sequencing data

ImmunoSEQ resolved TCR sequences for each subject PBMCs pre- and post-NeoVax

Bar graph displaying number of validated variants for each subject

CDR3beta sequences ranked by ratio

Mutect2 called and validated variants for each subject and each tumor region from whole exome sequencing data

CIBERSORTx relative percents of deconvoluted immunocytes

Representativeness of study participants