CNS Oncology最新文献

Aim: Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating tumor DNA (ctDNA) could facilitate genomic interrogation in these patients. Methods: Data from 419 PBT patients tested clinically with a ctDNA NGS panel at a CLIA-certified laboratory were analyzed. Results: A total of 211 patients (50%) had ≥1 somatic alteration detected. Detection was highest in meningioma (59%) and gliobastoma (55%). Single nucleotide variants were detected in 61 genes, with amplifications detected in ERBB2, MET, EGFR and others. Conclusion: Contrary to previous studies with very low yields, we found half of PBT patients had detectable ctDNA with genomically targetable off-label or clinical trial options for almost 50%. For those PBT patients with detectable ctDNA, plasma cfDNA genomic analysis is a clinically viable option for identifying genomically driven therapy options.

Aim: Long-term survivors (LTS) after glioma recurrence while on bevacizumab (Bev) therapy are rarely reported in the current literature. The purpose of this case series is to confirm the existence of and describe a large cohort of recurrent glioma LTS treated with Bev (Bev-LTS). Patients & methods: We identified Bev-LTS as patients with post-Bev initiation survival times of ≥3 years among 1397 Bev treated recurrent glioma patients. Results: Among 962 grade-IV, 221 grade III, and 214 grade II Bev-treated glioma patients, we identified 28 (2.9%), 14 (6.3%) and 8 (3.7%) Bev-LTS patients, respectively. 45 Bev-LTS patients recurred on Bev, with 36 of those patients continuing therapy. Conclusion: Our study shows that a small portion of grade-IV, -III, and -II glioma patients can have long-term survival on Bev therapy even after Bev recurrence.

Aim: To assess the efficacy and safety of alternative fotemustine administration schedule in elderly patients with recurrent glioblastoma. Patients & methods: Patients aged >65 years with recurrent glioblastoma received fotemustine (80 mg/m²; days 1, 15, 30, 45 and 60, and subsequently every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months. Main secondary end point was safety. Results: 58 patients were enrolled at two centers. PFS at 6 months was 47% (27 patients) and overall response rate was 29%. Median PFS and survival were 6 and 7 months, respectively, and longer in responders versus nonresponders. No grade 3-4 hematological toxicities occurred. Conclusion: The alternative fotemustine administration schedule was an effective and safe treatment for recurrent glioblastoma in elderly patients.

Aim: Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. Patients & methods: 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Results: Significantly mutated genes included TP53, EGFR, PIK3R1, PTEN, NF1, RET and STAG2. EGFR mutations noted included EGFRvIII-expression, EGFR-L816Q missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). TP53 mutations were noticed in COSMIC hot-spot driver gene and accompany IDH1 and ATRX mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. Conclusion: This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.

Aim: Evaluation of the Nativis Voyager^® device in patients with recurrent glioblastoma (rGBM).

Materials & methods: Voyager is a noninvasive, nonthermal, nonionizing and portable investigational device which delivers ultra-low radio frequency energy (ulRFE^®) that uses a magnetic field to penetrate tissues to alter specific biologic functions within cells. Patients with rGBM were treated with Voyager alone (V) or Voyager in combination with standard of care (V + SoC). Safety and clinical utility were assessed every 2-4 months.

Results: Data from the first 11 patients treated are reported here. Median progression-free survival was 10 weeks in the V arm and 16 weeks in the V + SoC arm. Median overall survival was 16 months in V arm and 11 months in the V + SoC arm. No serious adverse events associated with the device were reported.

Conclusion: These data suggest that the Voyager is safe and feasible for the treatment of rGBM.