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Title: Concurrent thermochemoradiotherapy for brain high-grade glioma

Abstract

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards themore » increase in disease-free survival in the patients with newly diagnosed malignant gliomas.« less

Authors:
; ; ; ;  [1];  [1];  [2];  [1];  [2];  [3]
  1. Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation)
  2. (Russian Federation)
  3. National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)
Publication Date:
OSTI Identifier:
22608288
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1760; Journal Issue: 1; Conference: PC'16: International conference on physics of cancer: Interdisciplinary problems and clinical applications 2016, Tomsk (Russian Federation), 22-25 Mar 2016; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRAIN; CHEMOTHERAPY; DIAGNOSIS; GLIOMAS; HYPERTHERMIA; PATIENTS; RADIOTHERAPY; SKIN; SURGERY

Citation Formats

Ryabova, A. I., E-mail: ranigor@mail.ru, Novikov, V. A., Startseva, Zh. A., Bober, E. E., Frolova, I. G., Choinzonov, E. L., Siberian State Medical University, Tomsk, 634050, Gribova, O. V., National Research Tomsk Polytechnic University, Tomsk, 634050, and Baranova, A. V.. Concurrent thermochemoradiotherapy for brain high-grade glioma. United States: N. p., 2016. Web. doi:10.1063/1.4960277.
Ryabova, A. I., E-mail: ranigor@mail.ru, Novikov, V. A., Startseva, Zh. A., Bober, E. E., Frolova, I. G., Choinzonov, E. L., Siberian State Medical University, Tomsk, 634050, Gribova, O. V., National Research Tomsk Polytechnic University, Tomsk, 634050, & Baranova, A. V.. Concurrent thermochemoradiotherapy for brain high-grade glioma. United States. doi:10.1063/1.4960277.
Ryabova, A. I., E-mail: ranigor@mail.ru, Novikov, V. A., Startseva, Zh. A., Bober, E. E., Frolova, I. G., Choinzonov, E. L., Siberian State Medical University, Tomsk, 634050, Gribova, O. V., National Research Tomsk Polytechnic University, Tomsk, 634050, and Baranova, A. V.. 2016. "Concurrent thermochemoradiotherapy for brain high-grade glioma". United States. doi:10.1063/1.4960277.
@article{osti_22608288,
title = {Concurrent thermochemoradiotherapy for brain high-grade glioma},
author = {Ryabova, A. I., E-mail: ranigor@mail.ru and Novikov, V. A. and Startseva, Zh. A. and Bober, E. E. and Frolova, I. G. and Choinzonov, E. L. and Siberian State Medical University, Tomsk, 634050 and Gribova, O. V. and National Research Tomsk Polytechnic University, Tomsk, 634050 and Baranova, A. V.},
abstractNote = {Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.},
doi = {10.1063/1.4960277},
journal = {AIP Conference Proceedings},
number = 1,
volume = 1760,
place = {United States},
year = 2016,
month = 8
}
  • Purpose: Concurrent bevacizumab with hypofractionated stereotactic radiation therapy (HSRT) is safe and effective for the treatment of recurrent high-grade gliomas (HGG). The objective of this study was to characterize the patterns of failure after this treatment regimen. Methods and Materials: Twenty-four patients with recurrent enhancing HGG were previously treated on an institutional review board-approved protocol of concurrent bevacizumab and reirradiation. Patients received 30 Gy in 5 fractions to the recurrent tumor with HSRT. Brain magnetic resonance imaging (MRI) was performed every 2 cycles, and bevacizumab was continued until clinical or radiographic tumor progression according to the criteria of Macdonald etmore » al. MRI at the time of progression was fused to the HSRT treatment plan, and the location of recurrence was classified on the basis of volume within the 95% isodose line. Outcomes based on patient characteristics, tumor grade, recurrence pattern, and best response to treatment were analyzed by the Kaplan-Meier method. Results: Twenty-two patients experienced either clinical or radiographic progression. Recurrent tumor was enhancing in 15 (71.4%) and nonenhancing in 6 (28.6%) patients. Eleven patients (52.4%) had recurrence within the radiation field, 5 patients (23.8%) had marginal recurrence, and 5 patients had recurrence outside the radiation field. Pattern of enhancement and location of failure did not correlate with overall survival or progression-free survival. Radiographic response was the only variable to significantly correlate with progression-free survival. Conclusions: Despite the promising initial response seen with the addition of HSRT to bevacizumab as salvage treatment for recurrent HGG, approximately half of patients ultimately still experience failure within the radiation field. The rate of local failure with the addition of HSRT seems to be lower than that seen with bevacizumab alone in the salvage setting. Our data underscore the radioresistance of HGG and the need for better salvage treatments.« less
  • Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine themore » most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.« less
  • Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thicknessmore » between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.« less
  • Malignant glioma cells, known to overexpress the epidermal growth factor receptor (EGF-r), have been targeted both in vitro and in vivo by the murine monoclonal antibody MAb-425 ({alpha}-EGF-r). MAb-425, radiolabeled with Iodine-125 (I-125), demonstrates substantial cell kill when the energetic cascade of Auger electrons is deposited close to the DNA. Due to the short range of the electron cascade, nearby normal brain cells with negligible EGF-r are not harmed by the radiation`s energy, making it a good choice for radioimmunotherapy. Human high grade glioma cell lines were evaluated in vitro for intracellular as well as nuclear accumulation of I-125 MAb-425.more » Binding and internalization studies revealed that this MAb is degraded following receptor-mediated endocytosis. In an attempt to inhibit lysosomal degradation and subsequently increase tumor cell uptake, lysomotropic agents such as chloroquine and monensin were employed. Glioma cell lines with varying EGF-r densities were incubated with and without these inhibitors (2-48 hr) and analyzed for cellular and nuclear accumulation. At a 50 {mu}M concentration, chloroquine significantly increased the intracellular concentration (3-fold) and nuclear accumulation (3-10-fold) compared to untreated cells. Monensin, under comparable conditions, showed modestly enhanced nuclear uptake (2-fold). Our data suggest that the use of lysosomal inhibitors in combination with I-125 MAb-425 can enhance intracellular as well as nuclear accumulation in glioma cells, improving radiotoxic effects in vitro. This approach could benefit the ongoing radioimmunotherapy of glioma patients treated with I-125 MAb 425.« less
  • Short communication.