Expression and prognostic value of CD80 and CD86 in the tumor microenvironment of newly diagnosed glioblastoma

AimsTo assess the prognostic influence of EGFR amplification/overexpression, p53 immunoreactivity and their age-dependent prognostic effects in a large prospective cohort of uniformly treated adult patients with newly diagnosed glioblastoma.MethodsTumours from a uniformly treated prospective cohort of adult patients with newly diagnosed glioblastoma (n=140) were examined for EGFR amplification by fluorescence in situ hybridisation and EGFR/p53 expression by immunohistochemistry. Statistical methods were employed to assess the degree of association between EGFR amplification/overexpression and p53 immunopositivity. Survival analyses were performed by employing Cox proportional hazard models to assess the independent prognostic value of EGFR/p53 alterations and test the propensity for risk with age by assessing their interaction with patient age.ResultsA strong positive correlation between EGFR amplification and EGFR overexpression (ρ=0.5157; p<0.0001; CI 0.3783 to 0.6309) and a negative association of EGFR amplification (ρ=−0.3417; p<0.0001; CI −0.4842 to −0.1816) and EGFR overexpression (ρ=−0.3095; p<0.001; CI −0.4561 to −0.1465) with p53 immunopositivity was observed. Only patient age (HR: 1.029; p=0.004; CI 1.009 to 1.049) was associated with shorter survival by univariate Cox regression analysis. Multivariable Cox proportional hazards models revealed a statistically significant interaction between EGFR overexpression and age to be associated with shorter survival (HR: 1.001; p<0.0001; CI 1.000 to 1.002), thus predicting a higher hazard with increasing age. No age interaction of EGFR amplification status (HR: 1.001; p=0.642; CI 0.995 to 1.008) and p53 immunopositivity (HR: 1.000; p=0.841; CI 0.999 to 1.001) was noted in this cohort.ConclusionsThe prognostic value of EGFR overexpression is age-dependent, and there is a propensity for a higher hazard with increasing patient age. Identifying such groups of patients with more aggressive disease becomes mandatory, since they would benefit from intense therapeutic protocols targeting EGFR.

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Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Scientific Reports ◽

10.1038/s41598-018-34820-x ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 4

Author(s):

K. Ina Ly ◽

Bella Vakulenko-Lagun ◽

Kyrre E. Emblem ◽

Yangming Ou ◽

Xiao Da ◽

...

Keyword(s):

Tumor Microenvironment ◽

Functional Mri ◽

Newly Diagnosed ◽

Adjuvant Temozolomide ◽

Newly Diagnosed Glioblastoma

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The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-016-3494-2 ◽

2016 ◽

Vol 44 (3) ◽

pp. 373-381 ◽

Cited By ~ 21

Author(s):

Sidsel Højklint Poulsen ◽

Thomas Urup ◽

Kirsten Grunnet ◽

Ib Jarle Christensen ◽

Vibeke Andrée Larsen ◽

...

Keyword(s):

Prognostic Value ◽

Radiotherapy Planning ◽

Newly Diagnosed ◽

Fet Pet ◽

Newly Diagnosed Glioblastoma

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Prognostic value of 18FET positron emission tomography (18FET-PET) for the clinical course in newly diagnosed glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2045 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2045-2045

Author(s):

Joerg Christian Tonn ◽

Bogdana Suchorska ◽

Natalie Jansen ◽

Jennifer Linn ◽

Hans A Kretzschmar ◽

...

Keyword(s):

Prognostic Value ◽

Response To Therapy ◽

Therapeutic Effects ◽

Newly Diagnosed ◽

Prognostic Information ◽

Prospective Longitudinal Study ◽

Cox Regression Analysis ◽

Fet Pet ◽

Newly Diagnosed Glioblastoma ◽

Prospective Longitudinal

2045 Background: Aim of this prospective longitudinal study was to evaluate whether 18FET-PET allow to monitor and quantify the therapeutic effects of surgery, radiotherapy and chemotherapy in newly diagnosed glioblastoma and whether 18FET-PET can provide additional prognostic information on response to therapy and outcome. Methods: 92 patients with newly diagnosed glioblastoma considered eligible for radiochemotherapy (RcX) were included; diagnosis was obtained by biopsy (n=46) or resection (n=46). Patients were to undergo 18FET-PET and cocomitant MRI scans prior to surgery, following RcX and as well as after three cycles of adjuvant temozolomide (TMZ). At each time point, biological tumor volume (BTV), maximal 18FET uptake as ratio to background (SUVmax/BG), and tumor uptake kinetics (TAC) were obtained. Overall survival (OS) was primary endpoint, progression-free survival (PFS) as defined by MRI using Macdonald criteria was a secondary endpoint. ROC analyses were done to determine optimal cut-off values of 18FET-PET parameters for survival outcome. To identify predictors for OS/PFS, Cox regression analysis was performed. Results: 79 patients were eligible for further evaluation. ROC analysis revealed cut-off values for pre-RCX BTV (9.5 ccm) and SUVmax/BG (2.95) with a sensitivity and specificity of both 70% for BTV and 68/73% for SUVmax/BG. Both pre-therapeutic BTV and SUVmax/BG were associated with PFS and OS (p<0.05). In contrast to MRI-based volume, the prognostic value of BTV remained highly significant in the multivariate Cox analysis independently of MGMT status.. Furthermore, 18FET TAC pattern and its changes were related to OS and PFS. Conclusions: Serial 18FET-PET imaging in glioblastoma before and after concomitant radio-/chemotherapy is a highly powerful tool to provide prognostic information for the outcome in newly diagnosed glioblastoma patients. These findings might help to personalize therapy and response evaluation in forthcoming clinical investigations. Clinical trial information: NCT01089868.

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