Search

Abstract: Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma, and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL., (© 2021 by The American Society of Hematology.)

Chimeric antigen receptor (CAR) T cells targeting CD19 have emerged as a leading engineered T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma. The phase 1/2 clinical trials that led to US Food and Drug Administration approval excluded patients with central nervous system (CNS) involvement, due to strict eligibility criteria. Here, we report on our institutional experience with 8 secondary CNS lymphoma patients treated with commercial tisagenlecleucel. No patient experienced greater than grade 1 neurotoxicity, and no patient required tocilizumab or steroids for CAR T-cell-mediated toxicities. Biomarker analysis suggested CAR T-cell expansion, despite the absence of systemic disease, and early response assessments demonstrated activity of IV infused CAR T cells within the CNS space., (© 2019 by The American Society of Hematology.)

Purpose: Central neurocytomas (CNs) are rare World Health Organization grade II tumors managed with surgery and radiation therapy. We report our experience in managing CN with proton beam therapy (PBT) when radiation therapy was used., Methods and Materials: We identified 61 patients with pathologically diagnosed CN treated at our institution between 1996 and 2016, of which 24 met inclusion criteria. Patient, tumor, and treatment characteristics are reported in context of progression-free survival and treatment-related adverse events., Results: Of 24 patients identified, median age at diagnosis was 21 years (range, 14-60). Median maximal tumor diameter was 4.5 cm (range, 1.4-6.8). Eighteen (75%) patients underwent upfront surgery alone. Sixteen (67%) patients received adjuvant or salvage PBT at a median dose of 54 Gy (relative biological effectiveness). Median follow-up was 56 months. Median progression-free survival (PFS) was 61 months. Eleven patients had disease progression with median time to progression of 22 months. Of the 5 patients with gross total resection, 4 experienced local recurrence and had MIB-1 >4% (range, 4.5-30). There was improved PFS with addition of PBT to definitive surgery (log-rank, P = .06); there was no disease progression to date. In patients who experienced disease recurrence/progression, MIB-1 <4% was associated with improved PFS (log-rank, P = .007). All patients tolerated PBT well with toxicities typical for cranial irradiation and with no grade 3+ toxicities., Conclusion: In our cohort, CN with elevated MIB-1 index were at increased risk for disease progression. However, adjuvant radiation therapy appears to effectively prevent failure. PBT toxicities appear to be comparable to if not less than published photon experiences., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: In treating glioblastoma (GB), surgical and chemotherapeutic treatment guidelines are, for the most part, independent of tumor location. In this work, we compiled imaging data from a large cohort of GB patients to create statistical atlases illustrating the disease spatial frequency as a function of patient demographics as well as tumor characteristics., Materials and Methods: Two-hundred-six patients with pathology-proven glioblastoma were included. Of those, 65 had pathology-proven recurrence and 113 had molecular subtype and genetic information. We used validated software to segment the tumors in all patients and map them from patient space into a common template. We then created statistical maps that described the spatial location of tumors with respect to demographics and tumor characteristics. We applied a chi-square test to determine whether pattern differences were statistically significant., Results: The most frequent location for glioblastoma in our patient population is the right temporal lobe. There are statistically significant differences when comparing patterns using demographic data such as gender (p = 0.0006) and age (p = 0.006). Small and large tumors tend to occur in separate locations (p = 0.0007). The tumors tend to occur in different locations according to their molecular subtypes (p < 10(- 6)). The classical subtype tends to spare the frontal lobes, the neural subtype tend to involve the inferior right frontal lobe. Although the sample size is limited, there was a difference in location according to EGFR VIII genotype (p < 10(- 4)), with a right temporal dominance for EFGR VIII negative tumors, and frontal lobe dominance in EGFR VIII positive tumors., Conclusions: Spatial location of GB is an important factor that correlates with demographic factors and tumor characteristics, which should therefore be considered when evaluating a patient with GB and might assist in personalized treatment.