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PURPOSE NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. METHODS IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. RESULTS Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. CONCLUSION This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

BackgroundGrade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. MethodsWe included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy...

Study Design This is a retrospective review of a prospectively maintained database of anterior cervical discectomy and fusion with plating (ACDFP) cases. Objective The aim of this study is to evaluate within a clinical practice evidence-based results of short-term morbidity with multilevel ACDFP. Methods Clinical morbidity, length of hospital stay, visual analog scale (VAS) and Odom scores, Neck Disability Index (NDI), hardware failure, and return-to-work (RTW) status were prospectively collected in an electronic database for 678 patients who underwent 1-, 2-, 3-, or 4-level ACDFP during an 8-year period. A total of 519 patients met the study criteria and were retrospectively analyzed. Results The majority of all patients noted “Excellent” or “Good” status for 1 month (91%), 2 months (92%), and 3 months (96%). Patients with 1-, 2-, and 3-level ACDFP returned to work sooner, 60% at 1 month, 70% at 2 months, and 68% at 3 months. For 4-level patients, the majority did not RTW until 3 months (71%). The only significant increase in morbidity with increasing levels was hospital stay for 3- and 4-level ACDFP and RTW for 4-level ACDFP. Conclusion Multilevel ACDFP can be performed with low initial morbidity. An individual practice can review results to allow for ongoing evidence-based care. Final class of evidence - treatment Yes Study design RCT Cohort • Case control Case series Methods Concealed allocation (RCT) Intention to treat (RCT) Blinded/independent evaluation of primary outcome • F/U ≥ 85% Adequate sample size • Control for confounding Overall class of evidence III

This multicenter clinical study was performed to assess the safety and effectiveness of Trinity Evolution® (TE), a viable cellular bone allograft, in combination with a PEEK interbody spacer and supplemental anterior fixation in patients undergoing anterior cervical discectomy and fusion (ACDF). In a prospective, multi-center study, 31 patients that presented with symptomatic cervical degeneration at one vertebral level underwent ACDF with a PEEK interbody spacer (Orthofix, Inc., Lewisville, TX, USA) and supplemental anterior fixation. In addition all patients had the bone graft substitute, Trinity Evolution (Musculoskeletal Transplant Foundation, Edison, NJ, USA), placed within the interbody spacer. At 6 and 12 months, radiographic fusion was evaluated as determined by independent radiographic review of angular motion (≤4°) from flexion/extension X-rays combined with presence of bridging bone across the adjacent endplates on thin cut CT scans. In addition other metrics were measured including function as assessed by the Neck Disability Index (NDI), and neck and arm pain as assessed by individual Visual Analog Scales (VAS). The fusion rate for patients using a PEEK interbody spacer in combination with TE was 78.6 % at 6 months and 93.5 % at 12 months. When considering high risk factors, 6-month fusion rates for patients that were current or former smokers, diabetic, overweight or obese/extremely obese were 70 % (7/10), 100 % (1/1), 70 % (7/10), and 82 % (9/11), respectively. At 12 months, the fusion rates were 100 % (12/12), 100 % (2/2), 100 % (11/11) and 85 % (11/13), respectively. Neck function, and neck/arm pain were found to significantly improve at both time points. No serious allograft related adverse events occurred and none of the 31 patients had subsequent additional cervical surgeries. Patients undergoing single-level ACDF with TE in combination with a PEEK interbody spacer and supplemental anterior fixation had a high rate of fusion success without serious allograft-related adverse events.

BACKGROUND: Recent results of R9802 (Buckner et al; J Clin Oncol 32:5s, 2014 (suppl; abstr 2000)) demonstrated that PCV given with RT at the time of initial diagnosis prolongs both progression-free survival (PFS) and overall survival (OS) for all patients enrolled in the trial. Herein, we report the impact of treatment on PFS and OS based upon specific histologic type. METHODS: Eligibility criteria included age 40 with any extent of resection, and supratentorial grade ll oligodendroglioma (O), oligo-astrocytoma (OA), or astrocytoma (A). Patients were stratified by age, histology, Karnofsky Performance Status, and presence versus absence of contrast enhancement on the preoperative imaging study and randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. In an exploratory analysis, we used the log rank test to compare survival and progression free survival (PFS) distributions for each histologic type. RESULTS: 251 eligible patients were accrued from 1998 to 2002: 107 had O, 79 had OA, and 65 had A. In total, 67% have progressed and 55% have died. Median PFS (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 4.0 vs 10.4 (p < 0.001); 6.0 vs not reached (NR) (p < 0.001); 3.0 vs 8.9 (p = 0.01); and 1.8 vs 3.7 (p = 0.06) years. Median survival times (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 7.8 vs 13.3 (p = 0.002); 10.8 vs NR (p = 0.008); 5.9 vs 11.4 (p = 0.05); and 4.4 vs 7.7 (p = 0.31) years. CONCLUSIONS: For grade 2 glioma patients with less than gross total tumor resection or >40 years of age, PCV + RT prolongs both OS and PFS compared with RT alone. The observed benefit is most definitive for O and OA patients.

Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear. In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms. The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively. Based on computer-generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality.

Eighteen patients underwent CT guided stereotactic biopsies using either a Riechert-Mundinger stereotactic frame modified for use in the CT scanner or the CT-based intracranial landmark technique of Gildenberg and a Todd-Wells frame. In seven patients undergoing biopsy with the modified frame technique, representative tissue samples were obtained in all cases. Eleven patients had biopsies using the Gildenberg technique and representative tissue samples were obtained in 10 of the 11. No major postoperative complications occurred in either group. Both techniques allowed samples of intracranial tissue to be obtained safely and efficiently. The modified frame technique provided a higher degree of accuracy while the Gildenberg technique required significantly less CT time and provided a satisfactory degree of accuracy. In seven patients with ring enhancing lesions, biopsies of the enhancing rim provided diagnostic tissue while biopsy of the central low density center of the lesion in three patients provided necrotic material which was useful in histologically grading the tumour.

A preliminary study utilizing viable HLA mismatched cultured glioma cells as adjuvant therapy for patients with malignant gliomas