scholarly journals Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival

2019 ◽  
Vol 6 (5) ◽  
pp. 364-374 ◽  
Author(s):  
Christopher H Chapman ◽  
Jared H Hara ◽  
Annette M Molinaro ◽  
Jennifer L Clarke ◽  
Nancy Ann Oberheim Bush ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Systemic Therapy ◽  
Performance Status ◽  
Area Under The Curve ◽  
High Grade Glioma ◽  
Target Volume ◽  
Initial Therapy ◽  
Prognostic Scores ◽  
High Grade ◽  
Who Grade

Abstract Background Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores. Methods A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients. Results Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively. Conclusions Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.

scholarly journals Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Goodness Of Fit ◽  
Clinical Target Volume ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Grade Glioma ◽  
Target Volume ◽  
Tumor Location ◽  
High Grade ◽  
Clinical Trial Registry

Abstract Introduction In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. Materials and methods The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. Results Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). Conclusion ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

scholarly journals Safety and Efficacy of Hypofractionated Stereotactic Radiosurgery for High-Grade Gliomas at First Recurrence: A Single-Center Experience

2020 ◽  
Author(s):  
Yun Guan ◽  
Ji Xiong ◽  
Mingyuan Pan ◽  
Wenyin Shi ◽  
Jing Li ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Performance Status ◽  
Target Volume ◽  
Salvage Treatment ◽  
High Grade ◽  
Who Grade ◽  
Cyberknife Radiosurgery ◽  
High Grade Gliomas ◽  
First Recurrence ◽  
Grade 3

Abstract Background: The optimal treatment for recurrent high-grade gliomas (rHGG) remains uncertain. This research aimed to investigate the efficacy and safety of CyberKnife radiosurgery as a salvage treatment for high-grade gliomas at first recurrence that within the radiation field.Methods: Between January 2016 and October 2019, rHGG patients treated with CyberKnife radiosurgery were retrospectively analyzed. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and toxicity. Toxicity was assessed using CTCAE 5.0. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) were evaluated.Results: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis Glioblastoma (GBM), and rest (21) were WHO Grade 3 Gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). Median baseline Karnofsky Performance Status (KPS) is 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas; p = 0.039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed concurrent bevacizumab with radiosurgery and KPS>70 were favorable prognostic factors for grade 4 patients.Conclusions: Salvage CyberKnife radiosurgery showed a favorable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of HSRS in rHGG.

Long-term outcomes after irradiation (RT) for pediatric low-grade glioma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10549-10549
Author(s):  
Derek S. Tsang ◽  
Erin Sennett Murphy ◽  
Thomas E. Merchant
Keyword(s):  
Systemic Therapy ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Extent Of Surgery

10549 Background: Treatment for pediatric low-grade glioma (LGG) is variable, depending on age and tumor location. Systemic therapy (ST) is often used to delay RT, but ST does not result in durable local control. The goal of this study was to evaluate event-free survival (EFS) and toxicities for pediatric LGG treated with RT over a 30-year period. Methods: All patients age ≤21 with intracranial pediatric LGG (WHO grade I-II) treated with RT at a single institution since May 1986 were included in this retrospective review. Patients with metastatic disease (M+) received craniospinal irradiation (CSI); otherwise, RT was conformal. EFS and overall survival (OS) were measured from the first day of RT. Events included death, progression, or secondary high-grade glioma. Results: 221 patients were eligible. Median follow-up was 11.3 yrs (range, 0.1-30.5). Median RT dose was 54 Gy. 10-yr EFS and OS were 67.9% (95% CI 60.4-74.3) and 91.1% (95% CI 85.8-94.5) for non-metastatic patients, respectively. For 12 M+ patients treated with CSI, 10-yr EFS and OS were 58.9% (95% CI 23.4-82.5) and 70.0% (32.9-89.2), respectively. 28.6% developed pseudoprogression (PP) with median time to onset and resolution of 6.1 months (IQR 3.6-14.6) and 6.4 months (IQR 3.5-11.7), respectively. Patients with PP had improved 10-yr EFS (83.4% vs. 61.0%, HR 0.40, p = .006). Patients with grade II tumors and who received pre-RT ST had lower EFS (Table). Sex, NF-1, tumor location, extent of surgery and CSI were not independently associated with EFS. 10-yr cumulative incidence of grade ≥2 vasculopathy was 7.5% (95% CI 4.9-11.4). There were 12 cases of secondary high-grade glioma, with a 20-yr cumulative incidence of 5.5% (95% CI 2.6-11.4). Conclusions: Irradiation provides long-term control of pediatric LGG in a majority of patients. Receipt of pre-RT systemic therapy was associated with reduced EFS; this association requires further investigation. [Table: see text]

scholarly journals Radiotherapy versus combination radiotherapy-bevacizumab for the treatment of recurrent high-grade glioma: a systematic review

2021 ◽  
Author(s):  
Daniel P. Kulinich ◽  
John P. Sheppard ◽  
Thien Nguyen ◽  
Aditya M. Kondajji ◽  
Ansley Unterberger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Target Volume ◽  
Adult Brain ◽  
High Grade ◽  
Who Grade ◽  
Fractionated Radiotherapy ◽  
Meta Analyses

Abstract Background High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. Objective To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). Methods We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT ± BVZ. Cohorts were stratified by BVZ treatment status and re-irradiation modality (SRS, HFSRT, and FFRT). Outcome variables were overall survival (OS), progression-free survival (PFS), and radiation necrosis (RN). Results Data on 1399 patients was analyzed, with 954 patients receiving reRT alone and 445 patients receiving reRT + BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO grade, RT dosing, reRT fractionation regimen, time between primary and re-irradiation, and re-irradiation target volume, BVZ therapy was associated with significantly improved OS (2.51, 95% CI [0.11, 4.92] months, P = .041) but no significant improvement in PFS (1.40, 95% CI [− 0.36, 3.18] months, P = .099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 6.5%, P < .001). Conclusions Combination of reRT + BVZ may improve OS and reduce RN rates in recurrent HGG, but further controlled studies are needed to confirm these effects.

scholarly journals RADT-33. RADIOSURGERY VERSUS COMBINATION RADIOSURGERY-BEVACIZUMAB FOR THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMA: A SYSTEMATIC REVIEW

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii188-ii188
Author(s):  
Daniel Kulinich ◽  
John Sheppard ◽  
Thien Nguyen ◽  
Aditya Kondajji ◽  
Ansley Unterberger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Target Volume ◽  
Adult Brain ◽  
High Grade ◽  
Who Grade ◽  
Reported Data ◽  
Meta Analyses

Abstract BACKGROUND High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination re-radiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed. OBJECTIVE To assess clinical outcomes after reRT±BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypo-fractionated (HFSRT), or fully fractionated RT (FSRT). METHODS We performed a systematic review of PubMed, Web of Science, Scopus, Embase, and Cochrane databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified studies reporting outcomes for patients with recurrent HGG treated via reRT±BVZ. Cohorts were stratified by BVZ treatment status and reRT modality (SRS, HFSRT, and FSRT). Outcome variables were overall survival (OS), and progression-free survival (PFS). RESULTS 34 of 1,742 identified articles survived inclusion criteria (2%) and reported data on 954 patients receiving reRT alone and 445 patients receiving reRT+BVZ. All patients initially underwent standard-of-care therapy for their primary HGG. In a multivariate analysis that adjusted for median patient age, WHO Grade, RT dosing, reRT fractionation regimen, time between primary and reRT, and reRT target volume, BVZ therapy was associated with significantly improved OS (2.51 [0.11, 4.92] months, P=.041) but no significant improvement in PFS (1.40 [-0.36, 3.18] months, P=.099). Patients receiving BVZ also had significantly lower rates of RN (2.2% vs 9.5%, P &lt; .001). CONCLUSIONS Combination reRT+BVZ may improve OS and reduce rates of RN in recurrent HGG, but further controlled studies are needed to confirm these effects.

Prognostic Factors in Patients Diagnosed with High Grade Glioma Managed with Radiotherapy: Experience at the Federico Gómez Children's Hospital of Mexico

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
María Fátima Chilaca-Rosas ◽  
Heynar de Jesús Pérez-Villanueva ◽  
Noé Trinidad-Hernández ◽  
Juan Carlos Heredia-Gutiérrez ◽  
Héctor Urueta-Cuéllar
Keyword(s):  
Prognostic Factors ◽  
High Grade Glioma ◽  
High Grade ◽  
Children's Hospital ◽  
Children’S Hospital

scholarly journals CTIM-06. DENDRITIC CELL VACCINE STUDY FOR RECURRENT, HIGH-GRADE GLIOMA: TISSUE-BASED RNA SEQUENCING AND SERUM CYTOKINE LEVELS AS POTENTIAL BIOMARKERS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii34
Author(s):  
Macarena De La Fuente ◽  
Tulay Koru-Sengul ◽  
Deborah Heros ◽  
Feng Miao ◽  
Alain Fernandez Marrero ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Rna Sequencing ◽  
Tumor Antigens ◽  
High Grade Glioma ◽  
Treatment Discontinuation ◽  
Sequencing Analysis ◽  
High Grade ◽  
Who Grade ◽  
Cytokine Levels ◽  
Grade 3

Abstract BACKGROUND Glioblastoma is the most common primary malignant brain tumor. Despite multimodality treatment approach, median progression-free survival (PFS) is only 8 months, median overall-survival (OS) 14 months and 5-year survival rate of under 10%. Dendritic cells (DCs) are the professional antigen presenting cells of the immune system. The rationale for sensitizing dendritic cells to a pool of non-selected tumor antigens is based on the marked heterogeneity present within glioblastoma tumor cells. METHODS Phase 1/feasibility study of DC vaccine for recurrent high-grade glioma was conducted. Pooled, non-selected tumor antigens collected via tumor cell lysate were used for DC sensitization. RNA sequencing analysis was performed on all tumor samples. Cytokine levels in serum were detected using a Luminex cytokine panel. RESULTS A total of 20 patients were enrolled onto this study (median age 58yrs, range: 39–74, 65% male). Pathology showed WHO grade IV glioblastoma in 14 (70%) and grade III anaplastic astrocytoma in 6 (30%) patients. IDH wild type in 19 (95%) patients. Treatment emergent adverse events (all grades, regardless of attribution) occurred in more than 15% of the patients (20% fatigue, 15% dizziness, 15% headache, none leading to treatment discontinuation). There were five grade 3–4 and none grade 5 events. One grade 4 event (seizure) probable related to investigational treatment leading to treatment discontinuation. Four grade 3 events (dysphasia, possible related; intracranial hemorrhage unrelated; muscle weakness, unlikely related and hematoma, unrelated). Median PFS was 3.8 months. Median OS was 11 months. RNA sequencing in tumor samples and correlation with cytokine levels in serum is currently been analyzed. CONCLUSION Tumor lysate pulsed DC vaccination demonstrates acceptable safety and tolerability in high-grade glioma patients. Evaluations of integrating molecular profiling RNA sequencing information and cytokine levels to identify potential subset of patients with significant clinical benefit will be provided.

CTNI-22. A PHASE 0/1 ‘TRIGGER’ TRIAL OF RIBOCICLIB PLUS EVEROLIMUS IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi64-vi64
Author(s):  
Nader Sanai ◽  
An-Chi Tien ◽  
Jun Jiang ◽  
Yu-Wei Chang ◽  
Chelsea Pennington-Krygier ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Mtor Inhibition ◽  
Who Grade ◽  
Expansion Phase ◽  
Pik3ca Mutations ◽  
Pten Loss ◽  
Drug Concentrations ◽  
Phase 0 ◽  
Unbound Concentration

Abstract BACKGROUND mTOR activation is a mechanism of resistance in CDK4/6 targeting. We evaluated tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of combined CDK4/6 and mTOR inhibition in recurrent high-grade glioma (HGG) patients. METHODS Recurrent HGG patients with (1) intact RB, (2) CDKN2A/B deletion or CDK4/6 amplification, and (3) PTEN loss or PIK3CA mutations receive five days of presurgical ribociclib plus everolimus prior to resection at 2, 8 or 24 hours after the final dose. Beginning at 400mg QD ribociclib plus 2.5mg QD everolimus, six dose-escalations summit at 600mg QD plus 60mg QW. Gadolinium [Gd]-enhancing and nonenhancing tumor regions, CSF, and plasma are collected. Total and unbound drug concentrations are determined using validated LC-MS/MS methods. RB and S6 phosphorylation are compared to matched archival tissue. To select patients for a therapeutic expansion phase of combined drug therapy, the protocol includes a PK ‘trigger’ (i.e., for each drug, unbound concentration in Gd-nonenhancing tumor &gt; 5-fold biochemical IC50) and a PD ‘trigger’ (i.e., for each tumor, &gt; 30% decrease in pRB and pS6). RESULTS 21 patients with WHO Grade III (n=2) and IV (n=19) gliomas were enrolled into the Phase 0 component of the study. No dose-limiting toxicities were observed. In Gd-nonenhancing tumor regions, the median unbound concentration of ribociclib was 719 nM, whereas unbound everolimus tumor concentrations were undetectable. Across all dose-levels, 62% (13/21) and 22% (5/21) of tumors demonstrated decreased tumor RB and S6 phosphorylation, respectively. Tumor proliferation (MIB-1) was decreased in 67% (14/21) of all patients. No patients qualified for the therapeutic expansion phase. CONCLUSION In adult HGG, ribociclib achieves pharmacologically-relevant concentrations in Gd-nonenhancing tumor whereas everolimus exhibits no meaningful tumor penetration. These findings support further clinical development of ribociclib, but not everolimus, for the treatment of high-grade glioma patients.

scholarly journals High-grade glioma with anterior skull base erosion and intranasal extension: case report

2017 ◽  
Vol 126 (5) ◽  
pp. 1484-1487 ◽  
Author(s):  
Matthew T. Stib ◽  
Michael Johnson ◽  
Alan Siu ◽  
M. Isabel Almira-Suarez ◽  
Zachary Litvack ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Skull Base ◽  
Radiation Treatment ◽  
High Grade Glioma ◽  
Brain Parenchyma ◽  
Anterior Skull Base ◽  
High Grade ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment.

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