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PT-06RANDOMIZED TRIAL OF HIGH-PRECISION CONFORMAL RADIATION THERAPY COMPARED TO CONVENTIONAL RADIOTHERAPY IN PRESERVATION OF LONG-TERM NEURO-COGNITIVE OUTCOMES IN YOUNG PATIENTS WITH PROGRESSIVE OR RESIDUAL BENIGN/LOW-GRADE BRAIN TUMORS.

ABSTRACT: BACKGROUND: To report neuro-psychological outcomes in young patients with progressive benign and low-grade brain tumors treated with high-precision stereotactic conformal radiotherapy (SCRT) versus conventional radiotherapy (Conv RT) (NCT00517959). METHODS: Between 2001-10, 200 patients (median age 13 years, commonest histology craniopraryngioma) were randomized to SCRT (n = 105; 6MV, non-coplanar fields using micromultileaf collimators) or Conv RT (n = 95; 6MV, 2-4 open fields) to 54 Gy/30 fractions. Neuropsychological battery included full-scale IQ (FSIQ), verbal quotient (VQ), performance quotient (PQ), memory quotient (MQ in patients > 16 years) by Wechsler scores, LOTCA battery and state-trait Anxiety Inventory and Hamilton Anxiety-Depression Scales. Serial evaluations were performed at baseline (pre-RT), 6-months and 2, 3, 4, and 5-years post-RT and analyzed using generalized linear-mixed model (GLMM). RESULTS: Pre- RT baseline revealed considerable proportion of patients with low intelligence in both arms indicating effects of tumor and prior treatments. GLMM for repeated measures demonstrated significantly better preservation of FSIQ over time in SCRT versus Conv RT arm at 3 years (p = 0.0003) and 5 years (p = 0.012). There was significantly better preservation of VQ (age < 16 years) (p = 0.047) and MQ (age > 16 years) (p = 0.049) in SCRT than Conv RT arm. Anxiety scores between two arms was not significant at 5 years but mean depression scores at 5 years in age group <16 years was found significantly higher in Conv RT arm (p = 0.01). Patients in Conv RT also had significantly more neurocognitive decline in LOTCA battery at 5 years (p = 0.019), particularly in visuomotor organization and attention-concentration domains. CONCLUSIONS: We demonstrate high-precision conformal radiotherapy superior to conventional radiotherapy in preservation of neuropsychological functions in young patients with benign/low grade brain tumors. This is among few trials generating evidence for use of modern conformal RT from an appropriately-powered trial with clinically relevant endpoints and act as suitable benchmark for testing newer RT- technologies.

SUBMITTER: Jalali R

PROVIDER: S-EPMC4218463 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Project description:ImportanceEvidence for application of stereotactic and other conformal radiotherapy techniques in treating brain tumors is largely based on data derived from dosimetric, retrospective, or small prospective studies. Therefore, we conducted a randomized clinical trial of stereotactic conformal radiotherapy (SCRT) compared with conventional radiotherapy (ConvRT) evaluating clinically meaningful end points.ObjectiveTo compare neurocognitive and endocrine functional outcomes and survival at 5 years in young patients with residual and/or progressive benign or low-grade brain tumors treated with SCRT and ConvRT techniques.Design, setting, and participantsThis phase 3 randomized clinical trial enrolled 200 young patients (ages 3-25 years) with residual or progressive benign or low-grade brain tumors at a single center between April 2001 to March 2012. Patients were randomly allocated (1:1) to either SCRT (n = 104) or ConvRT (n = 96) arms.InterventionsPatients were randomly assigned to either high-precision SCRT or ConvRT to a dose of 54 Gy in 30 fractions over 6 weeks.Main outcomes and measuresDetailed neuropsychological and neuroendocrine assessments were performed at preradiotherapy baseline, at 6 months, and annually thereafter until 5 years on longitudinal follow-up. Change in these functional parameters was compared between the 2 arms as the primary end point and overall survival (OS) as the secondary end point.ResultsIn total, 200 young patients (median [interquartile range] age, 13 [9-17] years; 133 males and 67 females) were enrolled. Mean full-scale or global intelligence quotient (IQ) and performance IQ scores over a period of 5 years were significantly superior in patients treated with SCRT compared with those treated with ConvRT (difference in slope = 1.48; P = .04 vs difference in slope = 1.64; P = .046, respectively). Cumulative incidence of developing new neuroendocrine dysfunction at 5 years was significantly lower in patients treated with SCRT compared with ConvRT (31% vs 51%; P = .01) while developing a new neuroendocrine axis dysfunction in patients with preexisting dysfunction in at least 1 axis at baseline was also significantly lower in the SCRT arm compared with the ConvRT arm (29% vs 52%; P = .02). Five-year OS in SCRT and ConvRT arms was 86% and 91%, respectively (P = .54).Conclusions and relevanceIn young patients with residual and/or progressive benign or low-grade brain tumors requiring radiotherapy for long-term tumor control, SCRT compared with ConvRT achieves superior neurocognitive and neuroendocrine functional outcomes over 5 years without compromising survival.Trial registrationclinicaltrials.gov Identifier: NCT00517959.

Project description:Accurate regional brain quantitative PET measurements, particularly when using partial volume correction, rely on robust image registration between PET and MR images. We argue here that the precision, and hence the uncertainty, of MR-PET image registration is mainly driven by the registration implementation and the quality of PET images due to their lower resolution and higher noise compared to the structural MR images. We propose a dedicated uncertainty analysis for quantifying the precision of MR-PET registration, centred around the bootstrap resampling of PET list-mode events to generate multiple PET image realisations with different noise (count) levels. The effects of PET image reconstruction parameters, such as the use of attenuation and scatter corrections and different number of iterations, on the precision and accuracy of MR-PET registration were investigated. In addition, the performance of four software packages with their default settings for rigid inter-modality image registration were considered: NiftyReg, Vinci, FSL and SPM. Four distinct PET image distributions made of two early time frames (similar to cortical FDG) and two late frames using two amyloid PET dynamic acquisitions of one amyloid positive and one amyloid negative participants were investigated. For the investigated four PET frames, the biggest impact on the uncertainty was observed between registration software packages (up to 10-fold difference in precision) followed by the reconstruction parameters. On average, the lowest uncertainty for different PET frames and brain regions was observed with SPM and two iterations of fully quantitative image reconstruction. The observed uncertainty for the varying PET count-level (from 5% to 60%) was slightly lower than for the reconstruction parameters. We also observed that the registration uncertainty in quantitative PET analysis depends on amyloid status of the considered PET frames, with increased uncertainty (up to three times) when using post-reconstruction partial volume correction. This analysis is applicable for PET data obtained from either PET/MR or PET/CT scanners.

Dataset Information

PT-06RANDOMIZED TRIAL OF HIGH-PRECISION CONFORMAL RADIATION THERAPY COMPARED TO CONVENTIONAL RADIOTHERAPY IN PRESERVATION OF LONG-TERM NEURO-COGNITIVE OUTCOMES IN YOUNG PATIENTS WITH PROGRESSIVE OR RESIDUAL BENIGN/LOW-GRADE BRAIN TUMORS.

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