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Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients.

ABSTRACT: The purpose of this pilot study was to determine whether blood-borne microvesicles from newly diagnosed glioblastoma patients could be used as biomarkers. We collected 2.8 mL blood from 16 post-operative patients at the time that they were being simulated for chemoradiation therapy (radiation with concurrent temozolomide). Two additional samples were collected during chemoradiation therapy and a final sample was collected at the end of chemoradiation therapy. Patients continued with the therapy suggested by their physicians, based on tumor conference consensus and were followed for recurrence and overall survival. Microvesicles were isolated using serial centrifugation and stained for surface markers (Annexin V for phosphotidyl serine, CD41 for platelets, anti-EGFR for tumor cells, and CD235 for red blood cells). Flow cytometry analysis was performed. Our findings provide initial evidence that increases in Annexin V positive microvesicle levels during chemoradiation therapy are associated with earlier recurrence and shorter overall survival in newly diagnosed glioblastoma patients. The effect is dramatic, with over a four-fold increase in the hazard ratio for an individual at the 75th versus the 25th percentile. Moreover the pattern of Annexin V positive microvesicles remain significant after adjustment for confounding clinical variables that have previously been shown to be prognostic for recurrence and survival. Inclusion of neutrophil levels at the start of chemoradiation therapy in the model yielded the largest attenuation of the observed association. Further studies will be needed to verify and further investigate the association between these two entities.

SUBMITTER: Evans SM

PROVIDER: S-EPMC4783260 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients.

Evans Sydney M SM Putt Mary M Yang Xiang-Yang XY Lustig Robert A RA Martinez-Lage Maria M Williams Dewight D Desai Arati A Wolf Ronald R Brem Steven S Koch Cameron J CJ

Journal of neuro-oncology 20160108 2

The purpose of this pilot study was to determine whether blood-borne microvesicles from newly diagnosed glioblastoma patients could be used as biomarkers. We collected 2.8 mL blood from 16 post-operative patients at the time that they were being simulated for chemoradiation therapy (radiation with concurrent temozolomide). Two additional samples were collected during chemoradiation therapy and a final sample was collected at the end of chemoradiation therapy. Patients continued with the therapy ...[more]

PMID: 26746692

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Project description:BackgroundThe impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS).Patients and methodsIn this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded.ResultsClinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46).ConclusionOur data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.

Project description:Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV).VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use.The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

Dataset Information

Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients.

Publications

Initial evidence that blood-borne microvesicles are biomarkers for recurrence and survival in newly diagnosed glioblastoma patients.

Similar Datasets

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