scholarly journals Optimal Combinations of Chemotherapy and Radiotherapy in Low-Grade Gliomas: A Mathematical Approach

2021 ◽  
Vol 11 (10) ◽  
pp. 1036
Author(s):  
Luis E. Ayala-Hernández ◽  
Armando Gallegos ◽  
Philippe Schucht ◽  
Michael Murek ◽  
Luis Pérez-Romasanta ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
In Silico ◽  
Treatment Options ◽  
Patient Specific ◽  
Low Grade ◽  
Treatment Schedule ◽  
Imaging Data ◽  
Low Grade Gliomas ◽  
Combination Treatments ◽  
Longitudinal Imaging

Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits.

scholarly journals OS06.6 Optimized radiotherapy protocols delay the malignant transformation of low-grade gliomas in-silico

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii12-iii12
Author(s):  
A. Henares-Molina ◽  
S. Benzekry ◽  
P. Lara ◽  
M. García-Rojo ◽  
V. Pérez-García ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
In Silico ◽  
Low Grade ◽  
Low Grade Gliomas

scholarly journals Old meet new—the path to combination treatments in pediatric low-grade gliomas

2018 ◽  
Vol 21 (2) ◽  
pp. 143-145
Author(s):  
Jessica Clymer ◽  
Pratiti Bandopadhayay
Keyword(s):  
Low Grade ◽  
Low Grade Gliomas ◽  
Combination Treatments

scholarly journals Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis

PLoS Medicine ◽  
2016 ◽  
Vol 13 (12) ◽  
pp. e1002192 ◽  
Author(s):  
Brian J. Reon ◽  
Jordan Anaya ◽  
Ying Zhang ◽  
James Mandell ◽  
Benjamin Purow ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
In Silico ◽  
In Silico Analysis ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Silico Analysis

The Vascular Model Repository: A Public Resource of Medical Imaging Data and Blood Flow Simulation Results

2013 ◽  
Author(s):  
Nathan M. Wilson ◽  
Ana K. Ortiz ◽  
Allison B. Johnson
Keyword(s):  
Blood Flow ◽  
Treatment Options ◽  
Unmet Need ◽  
Flow Simulation ◽  
Image Data ◽  
Patient Specific ◽  
Imaging Data ◽  
Medical Software ◽  
Public Resource ◽  
Simulation Results

Patient-specific blood flow simulations may provide insight into disease progression, treatment options, and medical device design that would be difficult or impossible to obtain experimentally. However, publicly available image data and computer models for researchers and device designers are extremely limited. The NHLBI sponsored Open Source Medical Software Corporation (Contracts No: HHSN268200800008C & HHSN268201100035C) and its university collaborators to build a public repository including realistic, image-based anatomic models and related hemodynamic simulation results to address this unmet need.

scholarly journals Clinical Management of Diffuse Low-Grade Gliomas

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3008
Author(s):  
Giuseppe Lombardi ◽  
Valeria Barresi ◽  
Antonella Castellano ◽  
Emeline Tabouret ◽  
Francesco Pasqualetti ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Targeted Therapy ◽  
Operative Management ◽  
Molecular Profile ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Therapeutic Modalities ◽  
Molecular Features ◽  
Prognostic Stratification

Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care.

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas

2022 ◽  
pp. 1-11
Keyword(s):  
Extent Of Resection ◽  
Neurological Complications ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Imaging Data ◽  
Volumetric Imaging ◽  
Exact Test ◽  
Low Grade Gliomas ◽  
Presenting Symptoms ◽  
Piecemeal Resection

OBJECTIVE Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors’ institution they have increasingly used a circumferential, perilesional, sulcus-guided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome. METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher’s exact test. Multivariate analyses were performed using multivariate logistic regression. RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1–2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR. CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 510-510
Author(s):  
Karim Chamie ◽  
Sam Chang ◽  
Mark L. Gonzalgo ◽  
Eugene V. Kramolowsky ◽  
Wade J. Sexton ◽  
...  
Keyword(s):  
T Cells ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Complete Response ◽  
Clinical Results ◽  
Low Grade ◽  
Treatment Schedule ◽  
Open Label ◽  
Muscle Invasive

510 Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase Ib data in BCG-naive patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter phase II/III study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report here the interim analysis of Cohort A, BCG-unresponsive (CIS) [with or without Ta or T1 disease], as of December 2020 data cutoff. Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A of this phase II/III study is incidence of complete response (CR) of CIS at any time. Results: To date, 80 patients have enrolled in cohort A of this phase II/III trial. Evaluable analysis at this time shows CR rate at any time of 72% (N=51/71); for patients achieving CR, the probability of maintaining a CR for 12 months is 59%, with a median duration of complete response of 19.2 (7.6, 26.4) months. Low-grade treatment related AEs include dysuria, hematuria, and pollakiurua (all 16%), urgency (14%), and bladder spasm (8%), all other AEs were seen at 6% or less. A total of 9 subjects experienced at least 1 treatment emergent SAE (Severe Adverse event), the SAE rate is 1% for any given AE. No treatment emergent SAE’s were considered treatment related. No immune related SAE’s have been seen. To date, 10/80 (12.5%) patients proceeded to cystectomy in this BCG unresponsive population. Conclusions:With a CR rate of 72%, N-803 has met its primary endpoint with 59% probability of CR patients maintaining CR for at least 12 months. With the observed strong efficacy and an SAE rate of 1%, N-803 represents a novel treatment option for BCG unresponsive CIS with a favorable benefit:risk ratio, in a therapeutically challenging disease. Clinical trial information: NCT03022825.

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