Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 -3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α -strong and TERT -strong" and the "HIF-1α -weak and TERT -weak" patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.
A dosimetric comparison of linear accelerator (LA)-based (BrainLAB) and robotic radiosurgery (RS) (CyberKnife) systems for acoustic schwannoma (Acoustic neuroma, AN) was carried out. Seven patients with radiologically confirmed unilateral AN were planned with both an LA-based (BrainLAB) and robotic RS (CyberKnife) system using the same computed tomography (CT) dataset and contours. Gross tumour volume (GTV) was contoured on post-contrast magnetic resonance imaging (MRI) scan [planning target volume (PTV) margin 2 mm]. Planning and calculation were done with appropriate calculation algorithms. The prescribed isodose in both systems was considered adequate to cover at least 95% of the contoured target. Plan evaluations were done by examining the target coverage by the prescribed isodose line, and high- and low-dose volumes. Isodose plans and dose volume histograms generated by the two systems were compared. There was no statistically significant difference between the contoured volumes between the systems. Tumour volumes ranged from 380 to 3,100 mm(3). Dose prescription was 13-15 Gy in single fraction (median prescribed isodose 85%). There were no significant differences in conformity index (CI) (0.53 versus 0.58; P = 0.225), maximum brainstem dose (4.9 versus 4.7 Gy; P = 0.935), 2.5-Gy volume (39.9 versus 52.3 cc; P = 0.238) or 5-Gy volume (11.8 versus 16.8 cc; P = 0.129) between BrainLAB and CyberKnife system plans. There were statistically significant differences in organs at risk (OAR) doses, such as mean cochlear dose (6.9 versus 5.4 Gy; P = 0.001), mean mesial temporal dose (2.6 versus 1.7 Gy; P = 0.07) and high-dose (10 Gy) volume (3.2 versus 5.2 cc; P = 0.017). AN patients planned with the CyberKnife system had superior OAR (cochlea and mesial temporal lobe) sparing compared with those planned with the Linac-based system. Further evaluation of these findings in prospective studies with clinical correlation will provide actual clinical benefit from the dosimetric superiority of CyberKnife.
PurposeTo evaluate long-term outcome of high-dose-rate brachytherapy and perioperative brachytherapy in early mobile tongue cancer.Material and methodsSeventy-three patients with clinically staged T1/T2 N0 M0 of mobile tongue cancer were studied retrospectively. Between January 2000 and September 2010, 47 patients underwent high-dose-rate brachytherapy (HDR-BT) alone and 26 patients underwent perioperative brachytherapy (PB). Endpoints were overall survival, disease-free survival, loco-regional control, and late side effects.ResultsMedian age was 52 years and median follow-up was 74 months (range, 60-180). There were no local recurrences in the PB group. Overall survival at 6 years was 74.7% vs. 92.3% in HBR BT and PB group, respectively (p = 0.032). Disease-free survival at 6 years was 55.3% vs. 92.3% respectively in HDR-BT and PB (p = 0.002). Disease-free survival at 6 years in tumor histologic grade 1/2 patients was 76.3 months versus 40% in grade 3 patients. Nodal recurrence-free rate at 6 years was 67.5% with HDR-BT only, and 96.2% with PB (p = 0.007). In HDR BT only group, nodal recurrence-free rate at 6 years in T1 patients was 89.8% versus 29.4% in T2 patients. 16% and 7% patients developed soft tissue necrosis and osteoradionecrosis, respectively. Multivariate Cox proportional hazards analysis revealed significant correlation of local recurrence with tumor grade (p = 0.029), nodal recurrence with T-stage (p = 0.007), and disease-free survival with age (p = 0.003) and T stage (p = 0.026).ConclusionsHDR-BT alone gives acceptable loco-regional control in T1 tumors. T2 stage tumors should not be treated by brachytherapy alone in view of high failure rates in nodal regions and should undergo either neck dissection or nodal irradiation. Perioperative brachytherapy is investigational and can be considered in patients who are at high-risk for local recurrence in patients undergoing surgery alone.
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