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




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BMC Cancer

, 10:384

Clinical oncology

Abstract

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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-384 contains supplementary material, which is available to authorized users.

Patrick Evers, Percy P Lee contributed equally to this work.

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Autor: Patrick Evers - Percy P Lee - John DeMarco - Nzhde Agazaryan - James W Sayre - Michael Selch - Frank Pajonk

Fuente: https://link.springer.com/







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