scholarly journals A retrospective comparison of intensity-modulated arc therapy and 3-dimensional conformal approaches in the planning of grade 3 gliomas

2018 ◽  
Vol 17 (3) ◽  
pp. 266-273
Author(s):  
Lubna Sheazadi ◽  
Robert Appleyard ◽  
Natalie Foley ◽  
Bernadette Foran
Keyword(s):  
Optic Chiasm ◽  
Rank Test ◽  
Normal Brain ◽  
High Grade ◽  
Optic Chiasma ◽  
Dose Volume Histograms ◽  
Intensity Modulated ◽  
Arc Therapy ◽  
High Grade Gliomas ◽  
Grade 3

AbstractPurposeTo evaluate the extent to which intensity-modulated arc therapy (IMAT) for high-grade gliomas is comparable with three-dimensional conformal radiotherapy (3DCRT) in relation to the dose delivered to normal brain tissue (NBT), planning target volume (PTV) conformity and the dose delivered to brainstem and optic chiasma.MethodA total of 16 randomly selected 3DCRT treatment plans of grade 3 gliomas were re-planned using an IMAT planning technique and dose–volume histograms were compared. Primary outcomes were maximum, mean, 1/3 and 2/3 doses to NBT outside the PTV. Also the maximum, mean, D50 and D20 doses to PTV. Secondary outcomes were maximum and mean doses to the brainstem and optic chiasm. Wilcoxon signed rank test was used to compare data.ResultsIMAT led to a statistically significant increase in mean dose to NBT (34·4 versus 33·3 Gy, (p=0·047) but a statistically significant reduction in maximum dose to NBT (62·7 versus 63·8 Gy, p=0·004) compared with 3DCRT. IMAT led to statistically significant reductions in maximum, D50 and D20 doses to the PTV (63·3 versus 64·7 Gy, p=0·001; 60·0 versus 60·7 Gy, p=0·001 and 60·5 versus 61·8 Gy, p=0·002, respectively). No statistically significant differences were seen in doses to brainstem and optic chiasm.ConclusionIMAT is at least comparable with 3DCRT in relation to minimising dose to NBT and ensuring good PTV conformity. Doses delivered to organs at risk using IMAT were also comparable with 3DCRT. This study supports the continued use of IMAT for the treatment of high-grade gliomas.

scholarly journals TAMI-54. THE PRESENCE OF IMMUNE CELL INFILTRATES IN THE TISSUE MICROENVIRONMENT OF HIGH-GRADE GLIOMAS AND THEIR ASSOCIATION WITH OVERALL SURVIVAL

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii225
Author(s):  
Anupam Rishi ◽  
Homan Mohammadi ◽  
Daniela Martir ◽  
Eric Welsh ◽  
Timothy Robinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Surgical Resection ◽  
Immune Cell ◽  
Cox Regression ◽  
Tumor Biology ◽  
Rank Test ◽  
High Grade ◽  
High Grade Gliomas ◽  
Grade 3

Abstract OBJECTIVE Tumor-associated microglia and macrophages (TAMs) influence brain tumor biology and promote tumor-proliferating phenotype. Studies have shown these cell types predict outcomes in various tumor sites with limited evidence in high-grade gliomas (HGG). In this study, we assessed the presence of immune cell infiltrate (ICI) and overall survival (OS) in HGGs. METHODS A total of 97 consecutively treated patients with primary HGG with complete gene expression profiling were identified from our IRB-approved institutional tissue biorepository. Patients underwent primary surgical resection between 02/2004 and 03/2011. Gene expression levels were assessed by Affymetrix Hu-RSTA assays (Affymetrix; Santa Clara, CA). CIBERSORT estimated the presence of ICI via gene expression deconvolution. Tumor characteristics and the presence of 22 individual ICI subtypes were assessed with respect to OS. Time-to-event analyses were performed with Kaplan-Meier estimates and compared via log-rank test. Associations between the ICI and outcomes were explored using Cox-regression. P< 0.05 (two-tailed) was considered statistically significant. RESULTS Median follow-up from primary surgical resection was 12.8 months (range: 0.1-162.8), and median age was 58 years (20-85). Most patients were male (n=63; 65%) and had grade 4 tumors (n=71; 73%). OS differed by grade with 24-month actuarial OS rates of 81% and 34% (P< 0.0001) for grade 3 and 4 gliomas, respectively. The presence of M0 (HR 2.2; 95% CI 1.4-3.6; P=0.001), M1 (HR 1.8; 95%CI 1.1-2.9; P=0.01), and M2 macrophages (HR 1.9; 95%CI 1.2-3.2; P=0.007) predicted OS. No other ICI subtypes were predictive of OS. The presence of M0- and M2-polarized macrophages were more common in grade 4 compared to grade 3 gliomas 46% vs. 11% (P=0.002) and 69% vs. 31% (P=0.0007), respectively. CONCLUSION The increased presence of non-polarized or M2 TAMs within the glioma microenvironment was significantly associated with OS in HGG. Their presence may serve as unique stratification and a potential therapeutic target.

scholarly journals EPCT-19. A PHASE I STUDY OF RIBOCICLIB AND EVEROLIMUS FOLLOWING RADIATION THERAPY IN CHILDREN WITH NEWLY DIAGNOSED NON-BIOPSIED DIFFUSE PONTINE GLIOMAS (DIPG) AND RB+ BIOPSIED DIPG AND HIGH GRADE GLIOMAS (HGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii307-iii307
Author(s):  
Mariko DeWire ◽  
James Leach ◽  
Christine Fuller ◽  
Peter de Blank ◽  
Trent Hummel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
High Grade ◽  
Newly Diagnosed ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Expansion Cohort

Abstract Genomic aberrations in the cell cycle and mTOR pathways have been reported in diffuse pontine gliomas (DIPG) and high-grade gliomas (HGG). Dual inhibition of CDK4/6 (ribociclib) and mTOR (everolimus) has strong biologic rationale, non-overlapping single-agent toxicities, and adult clinical experience. The maximum tolerated dose (MTD) and/or recommended phase two dose (RP2D) of ribociclib and everolimus administered during maintenance therapy following radiotherapy was determined in the phase I study as a rolling 6 design. Ribociclib and everolimus were administered once daily for 21 days and 28 days, respectively starting two-four weeks post completion of radiotherapy. All HGG patients and any DIPG patient who had undergone biopsy were screened for RB protein by immunohistochemistry. Eighteen eligible patients enrolled (median age 8 years; range: 2–18). Six patients enrolled at dose levels 1,2, and 3 without dose limiting toxicities (DLT). Currently, five patients are enrolled at dose level 3 expansion cohort. The median number of cycles are 4.5 (range: 1–20+). Among the expansion cohort, one dose limiting toxicity included a grade 3 infection and one patient required a dose reduction in course 3 due to grade 3 ALT and grade 4 hypokalemia. The most common grade 3/4 adverse events included neutropenia. Preliminary pharmacokinetic studies on 12 patients suggest an impact of ribociclib on everolimus pharmacokinetics. The MTD/RP2D of ribociclib and everolimus following radiotherapy in newly diagnosed DIPG and HGG is anticipated to be 170 mg/m2/day x 21 days and 1.5 mg/ m2/day every 28 days which is equivalent to the adult RP2D.

scholarly journals Hypofractionated Stereotactic Re-Irradiation with Pembrolizumab and Bevacizumab in Patients with Recurrent High Grade Gliomas: Results from a Phase 1 Study

2020 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Peter A Forsyth ◽  
Nam D Tran ◽  
John A Arrington ◽  
Robert Macaulay ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
High Grade ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Abstract Background Radiotherapy may synergize with programmed death 1 (PD-1)/PD-1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended Phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high grade gliomas (HGGs). Methods Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. Results Thirty two patients were enrolled (bevacizumab naïve, n = 24; bevacizumab resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab naïve cohort, twenty patients (83%) had a complete response (CR) or partial response (PR). The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (20/26 pts; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. Conclusions The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Intensity modulated radiotherapy in high grade gliomas: Clinical and dosimetric results

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1532-1532
Author(s):  
A. Narayana ◽  
J. Yamada ◽  
M. Hunt ◽  
P. Shah ◽  
P. Gutin ◽  
...  
Keyword(s):  
Intensity Modulated Radiotherapy ◽  
High Grade ◽  
Intensity Modulated ◽  
High Grade Gliomas
Sign in / Sign up

Export Citation Format

Share Document