To Radiate Upfront or at Initial Recurrence after Gross Total Resection of Newly Diagnosed WHO II Meningiomas? A Propensity Score–Adjusted Analysis

2529 Background: Despite multimodality approaches, survival with GBM is dismal. Induction of immune responses to suppress the infiltrative, residual component with an easily manufactured and administered immunotherapy has been a theoretical ideal. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface protein expressed on approximately 40% of GBMs. Methods: Newly-diagnosed GBM patients with a gross-total resection, a KPS ≥70, and EGFRvIII+, after undergoing radiation with concurrent temozolomide without tumor progression, were eligible to receive EGFRvIII peptide vaccination i.d. with GM-CSF. Primary endpoint was safety. Results: Accrual began in 06/14/2004 and is now complete. 19 patients were enrolled. Median follow-up is 18 months. Toxicity was minimal and without evidence of autoimmunity. Humoral and cellular immune responses were generated. Median TTP from surgery in vaccine-treated patients is 12 months (n = 12), comparing favorably with a historical matched unvaccinated cohort (gross total resection without progression during radiation, KPS≥70, EGFRvIII+) that had a median TTP of 7.1 months (n = 39) (p = 0.0058). These results also compared favorably with those reported for concurrent temozolomide and radiation followed by adjuvant temozolomide, with a median TTP of 6.9 months. Median survival in this trial has exceeded 18 months which compares favorably to all published analyses accounting for all known prognostic indicators. Among recurrent tumors evaluated by immunohistochemistry, 100% no longer expressed the EGFRvIII, suggesting immunological activation that eliminated EGFRvIII-expressing cells, as well as one potential mechanism of treatment failure. Conclusions: EGFRvIII peptide vaccination warrants further investigation in a larger randomized clinical trial in patients with EGFRvIII-expressing tumors. No significant financial relationships to disclose.

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BIOM-30. BLOOD COUNTS THROUGH TREATMENT COURSE IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS RECEIVING CHEMORADIATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.061 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi17-vi17

Author(s):

Davy Deng ◽

Lubna Hammoudeh ◽

Daniel Cagney ◽

J Ricardo McFaline-Figueroa ◽

Ugonma Chukwueke ◽

...

Keyword(s):

Multivariable Analysis ◽

Progression Free Survival ◽

Older Age ◽

Neutrophil To Lymphocyte Ratio ◽

Gross Total Resection ◽

Newly Diagnosed ◽

Total Resection ◽

Lymphocyte Ratio ◽

Newly Diagnosed Glioblastoma ◽

First Recurrence

Abstract BACKGROUND Glioblastoma (GBM) patients are treated with radiation therapy (RT), temozolomide, and corticosteroids which can affect hematologic and immunologic parameters. We examined lymphocytes, neutrophil-to-lymphocyte ratio and platelet measurements and their association with progression-free survival (PFS) overall survival (OS). METHODS We identified 759 newly diagnosed adult GBM patients treated at our institution in the temozolomide (TMZ) era with blood counts that could be automatically extracted from the electronic medical record during chemoradiation (CRT, defined as within 42 days of RT) and at first recurrence. Linear regression and Cox modeling were used to evaluate outcomes. RESULTS Median age was 60.3 years; 87% had KPS ≥ 70, 37.5% had gross total resection, and 90% received TMZ. Prior to RT, 56.4% (375/665) patients had a lymphocyte measurement < 1.0 × 1000 cells [K]/μL. Within 42 days of CRT, 81.7% (536/656) had a lymphocyte measurement < 1.0 K/μL, 37.8% (248/656) < 0.5 K/μL. 10.7% (58/544) patients developed grade 2 or higher neutropenia, 9.1% (50/547) patients developed grade 2 or higher thrombocytopenia. On multivariable analysis (MVA), older age (AHR1.03, p< 0.001), unmethylated MGMT status (AHR2.56,p< 0.001), lower RT dose (<54Gy, AHR 3.45, p< 0.001), male sex (AHR1.45, p=0.02), non-gross total resection (AHR1.63, p< 0.001), lymphopenia during CRT (AHR0.63, p=0.008) and higher NLR during CRT (AHR1.02, p=0.001) were significantly associated with worse OS. Older age (AHR1.01, p=0.02), unmethylated MGMT status (AHR2.44, p< 0.001), lower RT dose (AHR1.82, p=0.02), higher NLR during CRT (AHR1.03, p < 0.001) were significantly associated with worse PFS on MVA. At first recurrence, median lymphocyte count was 0.7 K/μL with 74% (348/468) patients < 1.0 K/μL and 27% < 0.5 K/μL. CONCLUSION Lymphopenia and higher neutrophil-to-lymphocyte ratio are associated with inferior outcomes. Persistent lymphopenia at time of first recurrence may have implications for clinical trial eligibility and immunotherapy approaches in recurrent GBM.

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Phase I Trial of Gross Total Resection, Permanent Iodine-125 Brachytherapy, and Hyperfractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2007.03.061 ◽

2007 ◽

Vol 69 (3) ◽

pp. 825-830 ◽

Cited By ~ 22

Author(s):

Allen M. Chen ◽

Susan Chang ◽

Jean Pouliot ◽

Penny K. Sneed ◽

Michael D. Prados ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Phase I ◽

Phase I Trial ◽

Gross Total Resection ◽

Newly Diagnosed ◽

Total Resection ◽

Hyperfractionated Radiotherapy ◽

Newly Diagnosed Glioblastoma ◽

Iodine 125

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Patterns of care and outcomes in gliosarcoma: an analysis of the National Cancer Database

Journal of Neurosurgery ◽

10.3171/2016.12.jns162291 ◽

2018 ◽

Vol 128 (4) ◽

pp. 1133-1138 ◽

Cited By ~ 16

Author(s):

Jonathan Frandsen ◽

Andrew Orton ◽

Randy Jensen ◽

Howard Colman ◽

Adam L. Cohen ◽

...

Keyword(s):

Propensity Score ◽

Promoter Methylation ◽

Cox Regression ◽

Propensity Score Analysis ◽

Gross Total Resection ◽

National Cancer Database ◽

Total Resection ◽

Chi Square ◽

Trimodality Therapy ◽

Chi Square Analysis

OBJECTIVEThe authors compared presenting characteristics and survival for patients with gliosarcoma (GS) and glioblastoma (GBM). Additionally, they performed a survival analysis for patients who underwent GS treatments with the hypothesis that trimodality therapy (surgery followed by radiation and chemotherapy) would be superior to nontrimodality therapy (surgery alone or surgery followed by chemotherapy or radiation).METHODSAdults diagnosed with GS and GBM between the years 2004 and 2013 were queried from the National Cancer Database. Chi-square analysis was used to compare presenting characteristics. Kaplan-Meier, Cox regression, and propensity score analyses were employed for survival analyses.RESULTSIn total, data from 1102 patients with GS and 36,658 patients with GBM were analyzed. Gliosarcoma had an increased rate of gross-total resection (GTR) compared with GBM (19% vs 15%, p < 0.001). Survival was not different for patients with GBM (p = 0.068) compared with those with GS. After propensity score analysis for GS, patients receiving trimodality therapy (surgery followed by radiation and chemotherapy) had improved survival (12.9 months) compared with those not receiving trimodality therapy (5.5 months). In multivariate analysis, GTR, female sex, fewer comorbidities, trimodality therapy, and age < 65 years were associated with improved survival. There was a trend toward improved survival with MGMT promoter methylation (p = 0.117).CONCLUSIONSIn this large registry study, there was no difference in survival in patients with GBM compared with GS. Among GS patients, trimodality therapy significantly improved survival compared with nontrimodality therapy. Gross-total resection also improved survival, and there was a trend toward increased survival with MGMT promoter methylation in GS. The major potential confounder in this study is that patients with poor functional status may not have received aggressive radiation or chemotherapy treatments, leading to the observed outcome. This study should be considered hypothesis-generating; however, due to its rarity, conducting a clinical trial with GS patients alone may prove difficult.

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Prognostic Factors For Intermediate-Risk Atypical Meningiomas Determining Early Postoperative Adjuvant Radiotherapy Versus Active Monitoring After Gross Total Resection

10.21203/rs.3.rs-1017992/v1 ◽

2021 ◽

Author(s):

Muhammet Enes Gurses ◽

Hatice Yagmur Zengin ◽

Aysel Shıkhaliyeva ◽

Cengiz Savas Askun ◽

Melike Mut

Keyword(s):

Prognostic Factors ◽

Gross Total Resection ◽

Subtotal Resection ◽

Recurrence Rates ◽

Total Resection ◽

Active Monitoring ◽

Risk Of Recurrence ◽

Initial Recurrence ◽

Increased Risk ◽

Atypical Meningiomas

Abstract Background Atypical meningiomas (AMs) constitute 18% of meningiomas. Predictors of recurrence are still indeterminate, and the timing of RT whether to treat with radiation upfront or at initial recurrence remains controversial, especially after gross total resection (GTR). Methods A retrospective study of AMs with uni-and multivariate analyses was conducted with clinical, surgical, radiological, and histopathological parameters. The prognostic factors associated with increased risk of recurrence were elucidated in the whole series and in the subgroup with GTR only. Results Subtotal resection (STR), skullbase-tentorium localization, no adjuvant RT, and progesterone-negativity caused tumor recurrence in 37 patients with a median follow-up of 48 (2-120) months. Among subgroup of 23 patients GTR only, 30.8% showed recurrence in a median of 39.65 months. AMs with a preoperative volume ≥27.5 cm3 disclosed a significantly higher risk of recurrence (a 9.3 fold increase) than those with <27.5 cm3 (66.7% vs. 14.3%, respectively). Skullbase-tentorium localization and progesterone negativity tend to have higher recurrence rates after GTR. Conclusions Preoperative volume was found to be a prognostic factor for AMs with a cut-off value of 27.5 cm3 for the first time in the literature. Our results disclosed that RT could be delayed with active monitorization after GTR for AMs, which are smaller than 27.5 cm3, not localized in skullbase-tentorium and progesterone-positive. Otherwise, early postop RT would be a safer approach without waiting the recurrence for AMs.

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Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score–adjusted analysis

Journal of Neurosurgery ◽

10.3171/2021.4.jns21559 ◽

2021 ◽

pp. 1-8

Author(s):

Arbaz A. Momin ◽

Pranay Soni ◽

Jianning Shao ◽

Amy S. Nowacki ◽

John H. Suh ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Adjuvant Radiation ◽

Newly Diagnosed ◽

Total Resection ◽

Who Grade ◽

Free Survival ◽

Cox Regression Analysis ◽

Initial Recurrence ◽

Grade Ii

OBJECTIVE After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary. METHODS The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed. RESULTS A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01). CONCLUSIONS In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.

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