Dataset Information

Efficacy of Stereotactic Conformal Radiotherapy vs Conventional Radiotherapy on Benign and Low-Grade Brain Tumors: A Randomized Clinical Trial.

ABSTRACT:

Importance

Evidence 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.

Objective

To 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 participants

This 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.

Interventions

Patients 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 measures

Detailed 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.

Results

In 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 relevance

In 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 registration

clinicaltrials.gov Identifier: NCT00517959.

SUBMITTER: Jalali R

PROVIDER: S-EPMC5710529 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT).Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score ?-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD(2)) assuming an ?/? ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model.Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD(2) to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD(2) to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068).EQD(2) to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

Project description: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.