Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

• Published in: International journal of radiation oncology, biology, physics Vol. 86; no. 4; pp. 609 - 615
• Main Authors: Lee, Percy, MD, Eppinga, Wietse, MD, Lagerwaard, Frank, MD, PhD, Cloughesy, Timothy, MD, Slotman, Benjamin, MD, PhD, Nghiemphu, Phioanh L., MD, Wang, Pin-Chieh, PhD, Kupelian, Patrick, MD, Agazaryan, Nzhde, PhD, Demarco, John, PhD, Selch, Michael T., MD, Steinberg, Michael, MD, Kang, Jung Julie, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-07-2013
• Subjects: Analysis of Variance; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Brain Neoplasms - radiotherapy; Brain Neoplasms - surgery; Cerebral Ventricles - pathology; COMPUTERIZED TOMOGRAPHY; Disease-Free Survival; Female; Glioblastoma - mortality; Glioblastoma - pathology; Glioblastoma - radiotherapy; Glioblastoma - surgery; GLIOMAS; HEALTH HAZARDS; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; MULTIVARIATE ANALYSIS; Neoplastic Stem Cells - physiology; Neoplastic Stem Cells - radiation effects; PATIENTS; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOSENSITIVITY; RADIOTHERAPY; Radiotherapy Dosage; STEM CELLS; SURGERY
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2013.01.009

Purpose Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P =.042) and longer OS (25.8 vs 19.2 months, P =.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.