The Impact of Perioperative Adverse Events on Adjuvant Therapy and Overall Survival in Patients with High-Grade Glioma

2018 ◽  
Author(s):  
M.C. Neidert ◽  
L. Weber ◽  
L. Regli ◽  
J. Sarnthein
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Adverse Events ◽  
High Grade Glioma ◽  
High Grade ◽  
The Impact

scholarly journals INNV-39. THE IMPACT OF MULTIDISCIPLINARY MANAGEMENT ON THE OVERALL SURVIVAL OF GLIOBLASTOMA AND ANAPLASTIC GLIOMA PATIENTS IN THE ERA OF PRECISION MEDICINE-A COMMUNITY PHYSICIAN’S EXPERIENCE AND DILEMMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi138-vi138
Author(s):  
Tulika Ranjan ◽  
Alexander Yu ◽  
Rodney Wegner ◽  
Stephen Karlovits ◽  
Linda Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Precision Medicine ◽  
High Grade Glioma ◽  
Idh1 Mutation ◽  
High Grade ◽  
Multidisciplinary Management ◽  
T Cell Therapy ◽  
Anaplastic Gliomas ◽  
The Impact

Abstract The newer modalities of GBM treatment on the horizon are targeted therapy utilizing precision medicine, immunotherapy, Laser interstitial thermal therapy (LITT), ChemoID, CAR-T cell therapy, etc. There is always dilemma about referring a patient to the clinical trials which restrict the patient to one therapeutic agent Vs using a multi-disciplinary approach to improve patient’s survival. We present a single- institution retrospective data of the multidisciplinary management of our high grade glioma patients and their outcome. A chart review is being performed on high grade glioma patients (GBM, Gliosarcoma, Anaplastic Astrocytomas and Anaplastic Oligodendrogliomas) who had genomic alterations identified by commercial next generation sequencing. Thus far 100 patients had molecular profiling done at our institution and precision medicine was implemented in >50 patients along with other treatments. Of 100 patients 82 were GBM and 18 were Anaplastic gliomas. There were 61 males and 39 females. MGMT methylation was seen in 36 patients and 12 patients had IDH1 mutation. The actionable mutations seen EGFR, EGFRvIII, TERT, PDGFR, CDKN2A-20, BRAF, PTEN, NF1- PD/PD-L1. The targeted therapy used were imatinib, sirolimus, afinotor, debrfenib, pembrolizumab, EGFR vIII vaccine. The chemotherapies utilized were BCNU,CCNU, CPT-11, Etoposide, carboplatin. Of 100 high grade glioma patients 8 patients underwent LITT, 24 patients received SRS, 58 patients received Avastin. All patients are being followed for overall survival (OS) and progression free survival (PFS-6) at this point. Of the 82 GBM patients 35 are still alive at a median 21 months. The median overall survival of the 47 dead GBM patients was 24 months. CONCLUSION: In high grade Glioma patients a multi-disciplinary approach may prolong the survival and the genomic analysis does impact the outcome of these patients. When we implement more than one therapy at the same time overall survival can’t be credited to one specific mode of therapy.

scholarly journals The Impact of Radiation Therapy Variables on Pediatric High-Grade Glioma Outcomes: A National Cancer Database Analysis

2021 ◽  
Author(s):  
Christopher Williamson ◽  
Shayla Williamson ◽  
Renjian Jiang ◽  
Lisa Sudmeier ◽  
Natia Esiashvili ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Private Insurance ◽  
Multivariable Analysis ◽  
High Grade Glioma ◽  
National Cancer Database ◽  
High Grade ◽  
Who Grade ◽  
The Impact ◽  
Pediatric High Grade Glioma

Abstract Purpose Pediatric high-grade glioma (HGG) is a devastating disease with a poor prognosis. The purpose of this analysis is to evaluate the impact of Radiation Therapy (RT) variables on outcomes of pediatric HGG patients in the National Cancer Database (NCDB). Methods The NCDB was used to select patients age < 22 with histologically proven WHO Grade III and IV gliomas treated with ≥ 50Gy and < 76Gy RT between 2004 and 2013. RT variables including RT dose, timing between diagnosis and RT initiation (< 4 weeks, 4–6 weeks, or > 6 weeks), and RT modality were analyzed along with baseline demographic, tumor and treatment variables to assess the impact on overall survival in univariate and multivariable analyses. Results 498 pediatric HGG patients were included. Histologies included glioblastoma (30%), astrocytoma (55%), oligogendroglioma (5%) and gliomas not otherwise specific (10%). The median RT dose was 59.4 Gy (SD 2.9 Gy) starting a median of 4.4 weeks from diagnosis (SD 2.5 weeks). Median follow-up was 19.6 months with 1- and 3-year OS of 78.4% and 40.4%, respectively. On Multivariable analysis, female gender, older age, and private insurance remained independently associated with lower rate of overall death. Radiation initiation ≤ 4 weeks from diagnosis, and glioblastoma histology were significantly associated with higher rate of overall death. There was no relationship between radiation dose or whether radiation was delivered with proton or photon therapy and overall survival. Conclusions Outcomes for pediatric HGG are poor. Early initiation of RT within 4 weeks from diagnosis was negative associated with overall survival and may be related to unknown prognostic factors.

CTNI-41. INITIAL RESULTS OF A PHASE I WINDOW OF OPPORTUNITY TRIAL EVALUATING A FIRST-IN-CLASS CD29 INHIBITOR, OS2966, IN RECURRENT HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi69-vi69
Author(s):  
James Liu ◽  
Chibueze D Nwagwu ◽  
Amanda V Immidisetti ◽  
Gabriela Bukanowska ◽  
Anne-Marie Carbonell ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Underlying Disease ◽  
Tissue Level ◽  
High Grade ◽  
Convection Enhanced Delivery ◽  
Tumor Biopsy ◽  
Safety Issues

Abstract BACKGROUND OS2966 is a first-in-class, humanized and deimmunized monoclonal antibody which antagonizes CD29/β1integrin, a mechanosignaling receptor prominently upregulated in glioblastoma. Preclinical studies in mice and non-human primates have demonstrated safety and encouraging efficacy. A two-part, ascending concentration, phase I clinical trial was therefore initiated to evaluate the safety and feasibility of delivering OS2966 directly to the site of disease via convection-enhanced delivery (CED) in recurrent high-grade glioma patients. METHODS This study has a 2-part design: In part 1, patients undergo stereotactic tumor biopsy followed by placement of a multiport CED catheter for delivery of OS2966 to the bulk contrast enhancing tumor. Subsequently, patients undergo a clinically-indicated tumor resection followed by placement of two CED catheters and delivery of OS2966 to the surrounding tumor-infiltrated brain. A unique concentration-based accelerated titration design is utilized for dose escalation. Given availability of pre and post infusion samples, pharmacodynamic data will be analyzed to explore mechanism of action of OS2966. RESULTS Two subjects have been treated at two corresponding dose levels (0.2mg/mL and 0.4 mg/mL). No dose-limiting toxicity or unexpected safety issues have been identified. To date, reported adverse events were mild (i.e., grade 1) and consistent with underlying disease and surgical procedures. No adverse events were attributed to OS2966 or CED catheter placement. Further, no clinically significant changes from baseline neurological exam have been noted for either patient through initial follow-up. Maximal tumor coverage and concomitant gross total resection were achieved for both patients. Tumor volume measured 1.63 cm3 and 16 cm3 for Patient 1 and 2 respectively with an intratumoral Vd/Vi ratio of 1.3. and 0.94. Pharmacodynamic analysis via tissue-level biomarkers is ongoing and will be presented. CONCLUSION Initial data demonstrates the safety and feasibility of direct intracranial delivery of OS2966.

OS03.4.A Irradiation of the subventricular and subgranular zone and overall survival in high-grade glioma patients

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
D Bruil ◽  
S David ◽  
S Nagtegaal ◽  
J Verhoeff
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
High Grade Glioma ◽  
Radiotherapy Planning ◽  
Intracranial Volume ◽  
High Grade ◽  
Subgranular Zone ◽  
Median Dose ◽  
Repair Capacity ◽  
The Mean

Abstract BACKGROUND Previous research has shown that neural stem cells (NSCs) in the subventricular zone (SVZ) may support the growth of glioma by recruiting new cells to the tumor. NSCs are located in the SVZ as well as in the subgranular zone (SGZ) of the hippocampus, the two neurogenic niches of the brain. This might indicate that irradiation of the SVZ and SGZ, and thereby damaging NSCs, reduces tumor growth and improves overall survival (OS). However, irradiation may also inhibit the repair capacity of healthy brain tissue by these neurogenic niches. Therefore, we investigated the effects of SVZ and SGZ irradiation dose on OS, in a cohort of high-grade glioma patients. MATERIAL AND METHODS We have retrospectively selected 221 patients (2014–2020) with WHO grade III and IV gliomas that underwent radiotherapy. Next to clinical baseline characteristics, T1 weighted MRI- and CT-images were collected. The SVZ and SGZ regions on the individual T1 images were delineated via non-linear registration of brain atlases. SVZ labels were created in 0.5mm isotropic MNI T1 and T2 templates, while SGZ atlas labels were available via the Hippocampus and Subfields CoBrA atlas. Next, the mean dose from the acquired SVZ and SGZ labels were extracted. The relationship between SVZ doses, SGZ doses and OS were examined using the Cox proportional hazards model and the Kaplan-Meier method (using the Log Rank test for significance). RESULTS For the mean dose in the SVZ, the hazard ratio (HR) was 1.024 per Gy (P = 0.002, [95% confidence interval, 1.009–1.040]) and the mean SGZ dose had a HR of 1.021 per Gy (P&lt; 0.001, [95% confidence interval, 1.012–1.031]). These results were then corrected for the following covariates: sex, age, total intracranial volume and extent of surgery. This resulted in a HR of 1.031 per Gy (P = 0,001, [95% confidence interval, 1.014–1.050]) for the mean SVZ dose, and a HR of 1.025 per Gy (P&lt; 0.001, [95% confidence interval, 1.015–1.036]) for the mean SGZ dose. Patients whose SVZ received greater than the median SVZ dose (= 31.3 Gy) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 13.5 months median OS, P = 0.001). Patients whose SGZ received greater than the median SGZ dose (= 31.9) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 15.1 months median OS, P&lt; 0.001). CONCLUSION Here, we present a large cohort of high-grade glioma patients, in which we show a statistically significant decrease in overall survival with increasing radiation dose on the SGZ and SVZ. This correlation suggests that both neurogenic niches might need to be spared during radiotherapy treatment to improve overall survival even in high-grade glioma patients. Modern radiotherapy planning and delivery options are available to implement this.

scholarly journals SURG-24. OVERALL SURVIVAL IN A SYNGENEIC RODENT ORTHOTOPIC HIGH-GRADE GLIOMA MODEL IS SIGNIFICANTLY PROLONGED BY NEUROSURGICAL DELIVERY OF PLGA/PEG INTERSTITIAL CHEMOTHERAPY

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi240-vi240
Author(s):  
Stuart Smith ◽  
Toby Gould ◽  
Betty Tyler ◽  
Alison Ritchie ◽  
Gareth Veal ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Interstitial Chemotherapy ◽  
Glioma Model

scholarly journals Brain atlas for assessing the impact of tumor location on perioperative quality of life in patients with high-grade glioma: A prospective population-based cohort study

2019 ◽  
Vol 21 ◽  
pp. 101658 ◽  
Author(s):  
Lisa Millgård Sagberg ◽  
Daniel Høyer Iversen ◽  
Even Hovig Fyllingen ◽  
Asgeir Store Jakola ◽  
Ingerid Reinertsen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cohort Study ◽  
High Grade Glioma ◽  
Tumor Location ◽  
Population Based ◽  
Brain Atlas ◽  
High Grade ◽  
The Impact

scholarly journals An Unusual Case of Aplastic Anemia Caused by Temozolomide

2010 ◽  
Vol 2010 ◽  
pp. 1-2 ◽  
Author(s):  
Gazi Comez ◽  
Alper Sevinc ◽  
Ozlem Nuray Sever ◽  
Taner Babacan ◽  
Ibrahim Sarı ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adjuvant Therapy ◽  
Aplastic Anemia ◽  
Adjuvant Treatment ◽  
Unusual Case ◽  
English Literature ◽  
Bone Marrow Aspiration ◽  
High Grade Glioma ◽  
High Grade ◽  
Life Threatening

Radiotherapy and concomitant/adjuvant therapy with temozolomide are a common treatment regimen for children and adults with high-grade glioma. Although temozolomide is generally safe, it can rarely cause life-threatening complications. Here we report a case of a 31-year-old female patient who underwent surgical resection followed by radiotherapy plus concomitant temozolomide. She developed pancytopenia after adjuvant treatment with temozolomide. A bone marrow aspiration and biopsy showed hypocellularity with very few erythroid and myeloid cells, consistent with aplastic anemia. In the English literature, aplastic anemia due to temozolomide is extremely rare.

scholarly journals Navigated Intraoperative 2-Dimensional Ultrasound in High-Grade Glioma Surgery: Impact on Extent of Resection and Patient Outcome

2019 ◽  
Author(s):  
Alessandro Moiraghi ◽  
Francesco Prada ◽  
Alberto Delaidelli ◽  
Ramona Guatta ◽  
Adrien May ◽  
...  
Keyword(s):  
Real Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Intraoperative Ultrasound ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Grade ◽  
Glioma Surgery ◽  
Supratentorial Gliomas ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) and reducing residual tumor volume (RTV) while preserving neurological functions is the main goal in the surgical treatment of gliomas. Navigated intraoperative ultrasound (N-ioUS) combining the advantages of ultrasound and conventional neuronavigation (NN) allows for overcoming the limitations of the latter. OBJECTIVE To evaluate the impact of real-time NN combining ioUS and preoperative magnetic resonance imaging (MRI) on maximizing EOR in glioma surgery compared to standard NN. METHODS We retrospectively reviewed a series of 60 cases operated on for supratentorial gliomas: 31 operated under the guidance of N-ioUS and 29 resected with standard NN. Age, location of the tumor, pre- and postoperative Karnofsky Performance Status (KPS), EOR, RTV, and, if any, postoperative complications were evaluated. RESULTS The rate of gross total resection (GTR) in NN group was 44.8% vs 61.2% in N-ioUS group. The rate of RTV > 1 cm3 for glioblastomas was significantly lower for the N-ioUS group (P < .01). In 13/31 (42%), RTV was detected at the end of surgery with N-ioUS. In 8 of 13 cases, (25.8% of the cohort) surgeons continued with the operation until complete resection. Specificity was greater in N-ioUS (42% vs 31%) and negative predictive value (73% vs 54%). At discharge, the difference between pre- and postoperative KPS was significantly higher for the N-ioUS (P < .01). CONCLUSION The use of an N-ioUS-based real-time has been beneficial for resection in noneloquent high-grade glioma in terms of both EOR and neurological outcome, compared to standard NN. N-ioUS has proven usefulness in detecting RTV > 1 cm3.

scholarly journals Temozolomide radiochemotherapy for high-grade glioma patients with hemodialysis: a case series of 7 patients

2019 ◽  
Vol 7 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Jun Muto ◽  
Tomoo Matsutani ◽  
Ryosuke Matsuda ◽  
Masashi Kinoshita ◽  
Mitsuteru Oikawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Case Series ◽  
High Grade Glioma ◽  
Patient Characteristics ◽  
The Body ◽  
Study Patient ◽  
Treatment Schedule ◽  
High Grade ◽  
Concomitant Radiochemotherapy ◽  
High Grade Gliomas

Abstract Background The pharmacokinetics of temozolomide (TMZ) in patients with severe renal impairments (creatinine clearance, &lt;36 mL/min/m2) or in hemodialysis (HD) patients has not been investigated. TMZ and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in HD patients. Methods Seven HD patients with high-grade gliomas from 6 institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated. Results The histopathological diagnoses were isocitrate dehydrogenase (IDH) wild-type glioblastoma in 4 cases, not other specified (NOS) glioblastoma in 2 cases, and IDH-mutant anaplastic astrocytoma in 1 case. Five of the 7 patients completed radiotherapy (48-60 Gy) with concomitant TMZ (75 mg/m2) followed by adjuvant 5-day TMZ (150 mg/m2) every 28 days. During the entire course of treatment with TMZ, severe (Common Terminology Criteria for Adverse Events [CTCAE] ≥ Grade 3) lymphocytopenia occurred in 57%, neutropenia in 0%, and thrombocytopenia in 14% of the patients. Generally, the frequency and degree of myelosuppression do not increase in HD patients with high-grade gliomas. Two of the 7 (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression; that is similar to the death rate of 21.9% resulting from infection in HD patients in Japan. Conclusions Decreasing the dose of TMZ might not be required in HD patients with high-grade gliomas during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.

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