Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

BMC Cancer

Research Article

Nzhde Agazaryan¹  Patrick Evers¹  John DeMarco¹  Michael Selch²  Percy P Lee²  Frank Pajonk²  James W Sayre³ 

[1] Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA;Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA;Jonsson Comprehensive Cancer Center at UCLA, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA;UCLA School of Public Health, Biostatistics and Radiological Sciences, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA;

关键词: Cancer Stem Cell;    Neural Stem Cell;    Stem Cell Niche;    Periventricular Region;    Dosimetry Data;   

DOI  :  10.1186/1471-2407-10-384

 received in 2010-02-26, accepted in 2010-07-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGlioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.Methods55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.ResultsUsing Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.ConclusionsOur study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.

【 授权许可】

Unknown   
© Evers et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.