The purpose of this study is to evaluate the accuracy and precision of the Clarity 3D ultrasound system to track prostate gland positional variations due to setup error and organ motion. Seventeen patients (n=17) undergoing radical external beam radiation therapy for localized prostate cancer were studied. Subsequent to initial reference ultrasound and planning CT scans, each patient underwent seven repeat weekly tracking CT and ultrasound (US) scans during the course of treatment. Variations in the location of the prostate between reference and tracking scans were measured. Differences reported by CT and ultrasound scans are compared. Ultrasound tracking was initially performed clinically by a group of trained general users. Retrospective prostate localization was then performed by a trained dedicated user upon the original raw data set and also a reduced data set derived from the original by an expert user from Resonant Medical. Correlation accuracy between ultrasound and CT shifts acquired and delineated by a pool of trained general users was deemed unacceptable for radiotherapy purposes. A mean discrepancy between CT and US localizations of greater than 10 mm, with a 5 mm or greater discrepancy rate of nearly 90%, was observed. Retrospective analysis by a dedicated user of both the original and Resonant Medical reduced data sets yielded mean CT‐Us discrepancies of 8.7 mm and 7.4 mm, respectively. Unfortunately, the 5 mm or greater CT‐US discord rate for these retrospective analyses failed to drop below 80%. The greatest disparity between CT and ultrasound was consistently observed in the superior–inferior direction, while greatest agreement was achieved in the lateral dimension. Despite an expert reanalysis of the original data, the Clarity ultrasound system failed to deliver an acceptable level of geometric accuracy required for modern radiotherapy purposes.PACS numbers: 8755ne, 87.56Da, 87.63dh

PurposeTo determine the safety and efficacy of hypofractionated intensity modulated radiation therapy (Hypo-IMRT) using helical tomotherapy (HT) with concurrent low dose temozolomide (TMZ) followed by adjuvant TMZ in patients with glioblastoma multiforme (GBM).Methods and materialsAdult patients with GBM and KPS > 70 were prospectively enrolled between 2005 and 2007 in this phase I study. The Fibonacci dose escalation protocol was implemented to establish a safe radiation fractionation regimen. The protocol defined radiation therapy (RT) dose level I as 54.4 Gy in 20 fractions over 4 weeks and dose level II as 60 Gy in 22 fractions over 4.5 weeks. Concurrent TMZ followed by adjuvant TMZ was given according to the Stupp regimen. The primary endpoints were feasibility and safety of Hypo-IMRT with concurrent TMZ. Secondary endpoints included progression free survival (PFS), pattern of failure, overall survival (OS) and incidence of pseudoprogression. The latter was defined as clinical or radiological suggestion of tumour progression within three months of radiation completion followed by spontaneous recovery of the patient.ResultsA total of 25 patients were prospectively enrolled with a median follow-up of 12.4 months. The median age at diagnosis was 53 years. Based on recursive partitioning analysis (RPA) criteria, 16%, 52% and 32% of the patients were RPA class III, class IV and class V, respectively. All patients completed concurrent RT and TMZ, and 19 patients (76.0%) received adjuvant TMZ. The median OS was 15.67 months (95% CI 11.56 - 20.04) and the median PFS was 6.7 months (95% CI 4.0 – 14.0). The median time between surgery and start of RT was 44 days (range of 28 to 77 days). Delaying radiation therapy by more than 6 weeks after surgery was an independent prognostic factor associated with a worse OS (4.0 vs. 16.1 months, P = 0.027). All recurrences occurred within 2 cm of the original gross tumour volume (GTV). No cases of pseudoprogression were identified in our cohort of patients. Three patients tolerated dose level I with no dose limiting toxicity and hence the remainder of the patients were treated with dose level II according to the dose escalation protocol. Grade 3–4 hematological toxicity was limited to two patients and one patient developed Grade 4 Pneumocystis jiroveci pneumonia.ConclusionHypo-IMRT using HT given with concurrent TMZ is feasible and safe. The median OS and PFS are comparable to those observed with conventional fractionation. Hypofractionated radiation therapy offers the advantage of a shorter treatment period which is imperative in this group of patients with limited life expectancy.

The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

Dose escalation and hypofractionated radiation treatment with IMRT treating the prostate and proximal SV concurrently with the pelvic lymph nodes and distal SV and long-term androgen suppression therapy is well tolerated with respect to acute and late toxicity with 5-year actuarial overall survival 86.67%, freedom from biochemical failure 91.38%, and freedom from clinical failure 96.67%. Longer follow-up will provide more information on 10-year survival outcomes.