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

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).

scholarly journals PATH-13. SEX-LINKED TUMORAL MGMT STATUS AND OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi145-vi145
Author(s):  
Addison Barnett ◽  
Anas Saeed Bamashmos ◽  
Assad Ali ◽  
Hong Li ◽  
David Bosler ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Newly Diagnosed ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Newly Diagnosed Glioblastoma ◽  
Cox Proportional Hazard Models ◽  
Tertiary Care Institution ◽  
The Impact

Abstract INTRO/OBJECTIVE Glioblastoma (GBM) and MGMT have been reported to have sexual dimorphism. The primary objective of this study was to analyze the impact and association between sex and MGMT status on progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed GBM. METHODS 582 patients with newly diagnosed GBM who underwent first surgical intervention at a single tertiary care institution between 2012 and 2018 were reviewed. Adults with documented methylated (≥ 12) and un-methylated (≤ 7) MGMT status were included. A Kaplan-Meier and Cox proportional hazard models were used to analyze the association between sex and MGMT status on PFS and OS. RESULTS 464 adult patients (median age 63.4, 36.6% female) had documented MGMT status. Overall rate of MGMT methylated patients was 42.5%, while females were more often methylated than males (52.1% vs 37.4%, p=0.004). MGMT methylated compared to un-methylated females (median: 12.8 vs 7.4 months; 1-yr: 53% vs 27%) had a greater PFS benefit than males (median: 9.6 vs 6.8 months; 1-yr: 44% vs 23%). OS was significantly improved in MGMT methylated compared to un-methylated patients among females (p=0.001) but not among males (p=0.22). Among MGMT methylated patients, females had significantly better OS compared to males (median: 18.7 vs 12.4 months; 2-yr OS: 36.8% vs 24.3%, p=0.03). Although statistically not significant, a similar pattern was observed on PFS (median: 12.8 vs 9.6 months; 1-yr PFS: 52.6% vs 44.4%). Compared to MGMT methylated females, MGMT methylated males had a PFS HR=1.22 (95% CI=0.80 – 1.85, p=0.36), and an OS HR=1.45 (95% CI=1.03 – 2.04, p=0.032). CONCLUSION MGMT methylation is more common in females and methylation had a larger impact on both PFS and OS in females compared to males. These analyses highlight the need to further investigate sex differences that can inform clinical management of GBM.

scholarly journals Radiosensitizers in the temozolomide era for newly diagnosed glioblastoma

2019 ◽  
Vol 7 (3) ◽  
pp. 268-276
Author(s):  
Peter Mathen ◽  
Lindsay Rowe ◽  
Megan Mackey ◽  
DeeDee Smart ◽  
Philip Tofilon ◽  
...  
Keyword(s):  
Histone Deacetylase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Antiangiogenic Agents ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Molecularly Targeted Agents ◽  
Newly Diagnosed Glioblastoma ◽  
Epidermal Growth ◽  
Potential Methods

Abstract Glioblastoma (GBM) is a challenging diagnosis with almost universally poor prognosis. Though the survival advantage of postoperative radiation (RT) is well established, around 90% of patients will fail in the RT field. The high likelihood of local failure suggests the efficacy of RT needs to be improved to improve clinical outcomes. Radiosensitizers are an established method of enhancing RT cell killing through the addition of a pharmaceutical agent. Though the majority of trials using radiosensitizers have historically been unsuccessful, there continues to be interest with a variety of approaches having been employed. Epidermal growth factor receptor inhibitors, histone deacetylase inhibitors, antiangiogenic agents, and a number of other molecularly targeted agents have all been investigated as potential methods of radiosensitization in the temozolomide era. Outcomes have varied both in terms of toxicity and survival, but some agents such as valproic acid and bortezomib have demonstrated promising results. However, reporting of results in phase 2 trials in newly diagnosed GBM have been inconsistent, with no standard in reporting progression-free survival and toxicity. There is a pressing need for investigation of new agents; however, nearly all phase 3 trials of GBM patients of the past 25 years have demonstrated no improvement in outcomes. One proposed explanation for this is the selection of agents lacking sufficient preclinical data and/or based on poorly designed phase 2 trials. Radiosensitization may represent a viable strategy for improving GBM outcomes in newly diagnosed patients, and further investigation using agents with promising phase 2 data is warranted.

MGMT status through the ages, literally.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13550-e13550
Author(s):  
Assad Ali ◽  
Anas Saeed Bamashmos ◽  
Addisson Barnett ◽  
Hong Li ◽  
Soumya Sagar ◽  
...  
Keyword(s):  
Reference Group ◽  
Cox Model ◽  
Tertiary Care ◽  
Gene Promoter ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Newly Diagnosed ◽  
Tertiary Care Institution ◽  
Methylguanine Methyltransferase ◽  
And Gender

e13550 Background: It is known that in the setting of glioblastoma (GBM) having a methylated O6-Methylguanine Methyltransferase (MGMT) gene promoter confers a greater response to Temozolomide (TMZ) and an increased progression free survival (PFS) and overall survival (OS). Recent literature has uncovered interesting results when dichotomizing patients by demographics (i.e. age and gender) and analyzing response to the various available GBM therapies. Our primary objective is to analyze the effect of both age and MGMT status on OS and PFS in patients with newly diagnosed GBM. Understanding the role of MGMT on age in the setting of GBM can allow for a better understanding of disease course and treatment. Methods: 464 adult patients with newly diagnosed GBM and documented MGMT status were analyzed from a single major tertiary care institution between 2012 and 2018. Patients were stratified into four groups based on age (above or below 65 years) and MGMT status. A univariate Cox model was used to analyze the effect of age and MGMT status on PFS and OS, where our reference group was the group with the highest OS ( < 65/methylated). Results: The median age of the whole dataset was 63.4 years, and 65.2 years for patients who were MGMT methylated. Patients less than 65 years and were MGMT methylated had the best prognosis with a PFS and an OS of 10.9 months and 18.9 (Table), respectively. Patients above the age of 65 were more likely to be MGMT methylated (p = 0.002). There was an association between IDH1-mutant status and MGMT methylation (p = 0.006). Conclusions: Using MGMT status and age of the patient, our model predicts outcomes that can vary from 7.4 months to 18.9 months (HR = 3.41 p < 0.001).[Table: see text]

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

scholarly journals Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients

Neurosurgery ◽  
2018 ◽  
Vol 85 (6) ◽  
pp. 762-772 ◽  
Author(s):  
Alireza M Mohammadi ◽  
Mayur Sharma ◽  
Thomas L Beaumont ◽  
Kevin O Juarez ◽  
Hanna Kemeny ◽  
...  
Keyword(s):  
Laser Ablation ◽  
Tumor Volume ◽  
Cleveland Clinic ◽  
Damage Threshold ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Newly Diagnosed ◽  
Prognostic Groups ◽  
Newly Diagnosed Glioblastoma ◽  
Disease Specific

Abstract BACKGROUND Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM). OBJECTIVE To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort. METHODS Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (&lt; 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (&lt;11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines. RESULTS The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (&lt;70 yr, P = .02) and tumor volume (&lt;11 cc, P = .03) were favorable prognostic factors for OS. CONCLUSION The maximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patients with nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA.

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