Abstract
Purpose
To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide.
Methods and materials
Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models. Covariates included: age, sex, surgery, tumor location, and concomitant and adjuvant temozolomide.
Results
Median progression-free survival and overall survival were 11.5 ± 9.96 and 18.8 ± 18.5 months, respectively. The p75 doses to the ipsilateral, contralateral and bilateral subventrivular zone were, respectively, 57.30, 48.8, and 52.7 Gy. Patients who received a dose ≥48.8 Gy in the contralateral subventricular zone had better progression-free survival than those who received lower doses (HR 0.46; 95% CI 0.23–0.91 P = 0.028). This association was not found for overall survival (HR 0.60; 95% CI 0.30–1.22 P = 0.16). Administration of adjuvant temozolomide was significantly associated with improved progression-free survival (HR 0.19; 95% CI 0.09–0.41 P < 0.0001) and overall survival (HR 0.11; 95% CI 0.05–0.24 P = 0.001). In the subgroup of 46 patients whose O6-methylguanine-DNA methyltransferase gene promoter status was known, the methylation had no effect on either progression-free survival (P = 0.491) or overall survival (P = 0.203).
Conclusion
High-dose radiation in the contralateral subventricular zone was associated with a significant improvement in progression-free survival but not overall survival in patients treated for glioblastoma multiforme.
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References
Gupta T, Nair V, Jalili R. Stem cell niche irradiation in glioblastoma providing a ray of hope? CNS Oncol. 2014;3(5):367–76.
Evers P, Lee PP, DeMarco J, Agazaryan N, Sayre JW, Selch M, et al. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma. BMC Cancer. 2010;10:384.
Gupta T, Nair V, Paul SN, Kannan S, Moiyadi A, Epari S, et al. Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma? J Neurooncol. 2012;109:195–203.
Lee P, Eppinga W, Lagerwaard F, Cloughesy T, Slotman B, Nghiemphu PL, et al. Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis. Int J Radiat Oncol Biol Phys. 2013;86(4):609–15.
Chen L, Guerrero-Cazares H, Ye X, Ford E, McNutt T, Kleinberg L, et al. Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys. 2013;86(4):616–22.
Elicin O, Inac E, Uzel EK, Karacam S, Uzel OE, et al. Relationship between survival and increased radiation dose to ventricular zone in glioblastoma is controversial. J Neurooncol. 2014;118:413–9.
Gibbs IC, Haas-Kogan D, Terezakis S, Kavanagh BD. The subventricular zone neural progenitor cell hypothesis in glioblastoma: epiphany, Trojan Horse, or Cheshire fact? Int J Radiat Oncol Biol Phys. 2013;86(4):606–8.
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5 years analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–66.
Bleehen NM, Stenning SP. A Medical research council trial of two radiotherapy doses in the treatment of grade 3 and 4 astrocytoma. The medical research Council Brain Tumour Working Party. Br J Cancer. 1991;64(4):769–74.
Slotman BJE, de Han PF, Lagerwaard J. Is irradiation of potential cáncer stem cell niches in the subventricular zones indicated in GBM? Int J Radiat Oncol Biol Phys. 2011;81(2):S184 (Abstract 1058).
Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, et al. Assaciation of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016;11:1460–9.
Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S. Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro-oncology. 2013;15(1):91–6.
Adeberg S, König L, Bostel T, Harrabi S, Welzel T, Debus J, et al. Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol Biool Phys. 2014;90(4):886–93.
Adeberg S, Bostel T, König L, Welzel T, Debus J, Combs SE. A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement. A predictive factor for survival? Radiat Oncol. 2014;90(9):95.
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Foro Arnalot, P., Pera, O., Rodriguez, N. et al. Influence of incidental radiation dose in the subventricular zone on survival in patients with glioblastoma multiforme treated with surgery, radiotherapy, and temozolomide. Clin Transl Oncol 19, 1225–1231 (2017). https://doi.org/10.1007/s12094-017-1659-5
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DOI: https://doi.org/10.1007/s12094-017-1659-5