Age-dependent prognostic effects of EGFR/p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients

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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Relationship between Patient Age and Disease Features in a Prospective Cohort of 1560 Women Affected by Endometriosis

Journal of Minimally Invasive Gynecology ◽

10.1016/j.jmig.2019.09.004 ◽

2020 ◽

Vol 27 (5) ◽

pp. 1158-1166 ◽

Cited By ~ 2

Author(s):

Emanuela Stochino-Loi ◽

Jenny-Claude Millochau ◽

Stefano Angioni ◽

Salma Touleimat ◽

Carole Abo ◽

...

Keyword(s):

Prospective Cohort ◽

Patient Age ◽

Patient Âgé

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Impact of EGFR amplification status in newly diagnosed glioblastoma treated with Stupp protocol.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13569 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13569-e13569

Author(s):

Addison Barnett ◽

Anas Saeed Bamashmos ◽

Assad Ali ◽

Xuefei Jia ◽

Wei (Auston) Wei ◽

...

Keyword(s):

Statistical Significance ◽

Tertiary Care ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Egfr Amplification ◽

Newly Diagnosed Glioblastoma ◽

Cox Proportional Hazard Models ◽

Tertiary Care Institution ◽

Stupp Protocol

e13569 Background: Standard post-surgical glioblastoma (GBM) treatment, per Stupp protocol, includes six-weeks of concurrent Temozolomide chemoradiation followed by at least six cycles of adjuvant-Temozolomide. Previous investigations into epidermal growth factor receptor (EGFR) amplification as a prognostic factor in GBM have yielded contradicting results, requiring further investigation. The primary aim of this study was to determine the degree to which EGFR amplification, in newly diagnosed GBM, impacted progression free survival (PFS) and overall survival (OS). Methods: Data from 582 patients who underwent surgical intervention for GBM at a tertiary care institution between 2012 and 2018 were analyzed. Only adult patients who underwent treatment per Stupp protocol and had pathological analysis on EGFR and CEP7 were included. Amplification and non-amplification status was calculated by a ratio of EGFR/CEP7 > 2 and < 2, respectively. PFS and OS outcomes were compared using Cox proportional hazard models stratified by surgery type and sex. Results: Of the original 582 patients, 122 were treated per Stupp protocol and had documented EGFR analysis. Of patients who were EGFR amplified, 41 (58.5%) were male and 25 (48.1%) were female (p = 0.38) and median amplification was 1.07 and 1.16 (p < 0.001), respectively. EGFR non-amplified patients had a PFS hazard ratio, HR = 0.70 (95% CI = 0.44 – 1.12, p = 0.14); and an OS HR = 0.60 (95% CI = 0.35 – 1.03, p = 0.065). When the EGFR/CEP7 ratio was stratified by quartile, it was found that Q4 compared to Q1 (Q4 > 6.50 vs 0 < Q1 ≤ 1.06) had a PFS HR = 2.1 (95% CI = 1.11 – 4.07, p = 0.024); and an OS HR = 2.48 (95% CI = 1.10 – 5.60, p = 0.028). Conclusions: There was no statistical difference in prevalence of EGFR amplification by sex. However, despite statistical significance, there was minimal difference in median degree of amplification by sex (0.09). Trends begin to show that patients who were EGFR non-amplified had better PFS and OS outcomes than patients who were EGFR amplified, although this was not statistically significant. Patients with very high EGFR amplification (Q4) had significantly poorer PFS and OS outcomes than patients with very low EGFR amplification (Q1).

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Multicenter validation of the prognostic value of patient age in patients treated with radical cystectomy

World Journal of Urology ◽

10.1007/s00345-011-0772-2 ◽

2011 ◽

Vol 30 (6) ◽

pp. 753-759 ◽

Cited By ~ 22

Author(s):

Thomas F. Chromecki ◽

Julian Mauermann ◽

Eugene K. Cha ◽

Robert S. Svatek ◽

Harun Fajkovic ◽

...

Keyword(s):

Radical Cystectomy ◽

Prognostic Value ◽

Patient Age ◽

Patient Âgé ◽

Multicenter Validation

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

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2022.5 ◽

2022 ◽

pp. 1-22

Author(s):

Mohammed H Ahmed ◽

Isaias Hernández-Verdin ◽

Franck Bielle ◽

Maite Verreault ◽

Julie Lerond ◽

...

Keyword(s):

Tumor Microenvironment ◽

Prognostic Value ◽

Newly Diagnosed ◽

Newly Diagnosed Glioblastoma

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Laparoscopic Testicular Preservation in Adults with Intra-Abdominal Cryptorchidism: Is It Beneficial?

Advances in Urology ◽

10.1155/2012/329237 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Fábio César Miranda Torricelli ◽

Marco Antonio Arap ◽

Ricardo Jordão Duarte ◽

Anuar Ibrahim Mitre ◽

Miguel Srougi

Keyword(s):

Postoperative Complications ◽

Hospital Stay ◽

Operative Time ◽

Testicular Tumor ◽

Adult Patients ◽

Patient Age ◽

Testis Development ◽

Patient Âgé ◽

Laparoscopic Evaluation ◽

Prospective Database

Purpose. To present the results in a midterm followup of laparoscopic testicular preservation in adults with intra-abdominal cryptorchidism.Methods. We analyzed 14 adult patients with cryptorchidism (19 testes) submitted to transabdominal laparoscopic evaluation and treatment of the condition. Data was collected retrospectively from a prospective database from August 2005 to May 2010. It analyzed patient age, affected side, procedure, mean operative time, mean hospital stay, postoperative testis position, intra- and postoperative complications, presence of malignancy in the removed testis, and midterm outcomes: size of the testis, development of tumors, and fertility.Results. Mean patient age was 29 (18–54) years. Thirteen (68.4%) testes were preserved. There were no intra- or postoperative complications. After a mean followup of 48.7 (20–64) months, all patients submitted to orchiopexy had the organs correctly positioned, although 2 testes were significantly smaller than before the procedure. No patient presented any signs of malignancy during the followup. Fertility was not preserved in bilateral cases.Conclusion. Laparoscopic testicular evaluation and eventual preservation are feasible and safe. In a midterm followup, testicular tumor is not a concern, and unfortunately, fertility may not be preserved in bilateral cases.

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Present epidemiology of chronic subdural hematoma in Japan: analysis of 63,358 cases recorded in a national administrative database

Journal of Neurosurgery ◽

10.3171/2016.9.jns16623 ◽

2018 ◽

Vol 128 (1) ◽

pp. 222-228 ◽

Cited By ~ 21

Author(s):

Hiroyuki Toi ◽

Keita Kinoshita ◽

Satoshi Hirai ◽

Hiroki Takai ◽

Keijiro Hara ◽

...

Keyword(s):

Subdural Hematoma ◽

Age Distribution ◽

Chronic Subdural Hematoma ◽

Japanese Patients ◽

Administrative Database ◽

Newly Diagnosed ◽

Patient Age ◽

Chronological Change ◽

Disturbance Of Consciousness ◽

Patient Âgé

OBJECTIVEAging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system.METHODSThis study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge.RESULTSA total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale [mRS] score 0–2) of cases and poor in 28.4% (mRS score 3–6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%.CONCLUSIONSThis study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.

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