A randomized trial of stereotactic versus conventional radiotherapy in young patients with low-grade brain tumors: occupational therapy-based neurocognitive data

Abhishek Chatterjee, Jayant S Goda, Tejpal Gupta, Rashmi Kamble, Smruti Mokal, Rahul Krishnatry, Rajiv Sarin, Rakesh Jalali, Abhishek Chatterjee, Jayant S Goda, Tejpal Gupta, Rashmi Kamble, Smruti Mokal, Rahul Krishnatry, Rajiv Sarin, Rakesh Jalali

Abstract

Background: Radiotherapy for brain tumors in young patients is not only associated with improved survival but also long-term neurocognitive sequelae. We aimed to compare group differences in the executive neurocognitive outcomes in young patients with low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) and conventional RT (ConvRT) techniques.

Methods: This a phase 3 randomized trial that enrolled 200 young patients with benign brain tumors and low-grade gliomas. Patients were randomly allocated (1:1) to either SCRT or ConvRT arms and treated to a dose of 54 Gy in 30 fractions over 6 weeks. Lowenstein Occupational Therapy Cognitive Assessment battery was performed at preradiotherapy baseline, 6 months, and annually thereafter until 5 years. Executive functions measures included orientation, visual perception, spatial perception, motor praxis, visuomotor organization, thinking operations, and attention and concentration. The trajectory of these parameters was compared between the treatment arms over 5 years.

Results: Two hundred patients were enrolled in the study (SCRT: 104 and ConvRT: 96). The median age was 13 years (interquartile range: 9-17); mean total neurocognitive scores over 5 years were significantly superior in SCRT arm as compared to ConvRT (difference in slope: 2.27, P = .024). Outcomes improved in the SCRT arm vis-à-vis ConvRT for the subdomain of visuomotor organization (difference in slope: 0.66, P < .001). Visuomotor organization scores significantly improved in majority of the substratification groups. Spatial perception improved in craniopharyngioma patients with SCRT technique as opposed to ConvRT.

Conclusions: SCRT achieved superior outcomes compared to ConvRT in certain executive neurocognitive functional domains. We provide high level of evidence in favor of SCRT. Trial Registration. ClinicalTrials.gov Identifier: NCT00517959.

Keywords: executive neurocognitive functions; randomized trial; stereotactic conformal radiotherapy.

© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Figures

Figure 1.
Figure 1.
(A) The trends and the difference in slopes of the total Lowenstein’s Occupational Therapy and Cognitive Assessment (LOTCA) scores in patients longitudinally followed up for 5 years; the difference in slopes between the stereotactic conformal radiotherapy (SCRT) and conventional radiotherapy (ConvRT) arms were compared by linear mixed effect model. (B) The trends and the difference in slopes of the Visuomotor domain scores in patients longitudinally followed up for 5 years; the difference in slopes between the SCRT and ConvRT arms were compared by linear mixed effect model. (C, D) The trends and the difference in slopes of the total LOTCA scores in patients with Neurological Performance Score (NPS) 0–1 (Figure 1C) and NPS 2–3 (Figure 1D) longitudinally followed up for 5 years; the difference in slopes between the stereotactic conformal radiotherapy (SCRT) and conventional radiotherapy (ConvRT) arms were compared by linear mixed effect model.
Figure 2.
Figure 2.
(A–H) The trends and the difference in slopes of various subdomains scores that were statistically significant in different subgroups of patients longitudinally followed up for 5 years; the difference in slopes between the stereotactic conformal radiotherapy (SCRT) and conventional radiotherapy (ConvRT) arms were compared by linear mixed effect model.

References

    1. Gupta P, Jalali R. Long-term survivors of childhood brain tumors: impact on general health and quality of life. Curr Neurol Neurosci Rep. 2017;17(12):99.
    1. Taphoorn MJB. Neurocognitive sequelae in the treatment of low-grade gliomas. Semin Oncol. 2003;30(6 Suppl 19):45–48.
    1. Tucha O, Smely C, Preier M, Lange KW. Cognitive deficits before treatment among patients with brain tumors. Neurosurgery. 2000;47(2):324–333; discussion 333.
    1. Jalali R, Mallick I, Dutta D, et al. Factors influencing neurocognitive outcomes in young patients with benign and low-grade brain tumors treated with stereotactic conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2010;77(4):974–979.
    1. Jalali R, Goswami S, Sarin R, More N, Siddha M, Kamble R. Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63:S156.
    1. Coomans MB, van der Linden SD, Gehring K, Taphoorn MJB. Treatment of cognitive deficits in brain tumour patients: current status and future directions. Curr Opin Oncol. 2019;31(6):540–547.
    1. Wefel JS, Noll KR, Scheurer ME. Neurocognitive functioning and genetic variation in patients with primary brain tumours. Lancet Oncol. 2016;17(3):e97–e108.
    1. Jalali R, Gupta T, Goda JS, et al. Efficacy of stereotactic conformal radiotherapy vs conventional radiotherapy on benign and low-grade brain tumors: a randomized clinical trial. JAMA Oncol. 2017;3(10):1368–1376.
    1. Katz N, Itzkovich M, Averbuch S, Elazar B. Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery for brain-injured patients: reliability and validity. Am J Occup Ther. 1989;43(3):184–192.
    1. Annes G, Katz N, Cermak SA. Comparison of younger and older healthy American adults on the loewenstein occupational therapy cognitive assessment. Occup Ther Int. 1996;3(3):157–173.
    1. Carpentieri SC, Waber DP, Scott RM, et al. Memory deficits among children with craniopharyngiomas. Neurosurgery. 2001;49(5):1053–1057; discussion 1057.
    1. Klein M, Heimans JJ, Aaronson NK, et al. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study. Lancet. 2002;360(9343):1361–1368.
    1. Gondi V, Hermann BP, Mehta MP, Tomé WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys. 2012;83(4):e487–e493.
    1. Goda JS, Dutta D, Krishna U, et al. Hippocampal radiotherapy dose-constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors. Neuro Oncol. 2020. [Online ahead of print]. doi:10.1093/neuonc/noaa076
    1. Merchant TE, Kiehna EN, Kun LE, et al. Phase II trial of conformal radiation therapy for pediatric patients with craniopharyngioma and correlation of surgical factors and radiation dosimetry with change in cognitive function. J Neurosurg. 2006;104(2 Suppl): 94–102.
    1. Radcliffe J, Bunin GR, Sutton LN, Goldwein JW, Phillips PC. Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: age-dependent effects of whole brain radiation. Int J Dev Neurosci. 1994;12(4):327–334.
    1. Hirsch JF, Renier D, Czernichow P, Benveniste L, Pierre-Kahn A. Medulloblastoma in childhood. Survival and functional results. Acta Neurochir (Wien). 1979;48(1-2):1–15.
    1. Cohen MA, Horowitz TS, Wolfe JM. Auditory recognition memory is inferior to visual recognition memory. Proc Natl Acad Sci USA. 2009;106(14):6008–6010.
    1. Armstrong C, Ruffer J, Corn B, DeVries K, Mollman J. Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms. J Clin Oncol. 1995;13(9):2263–2271.
    1. Armstrong CL, Fisher MJ, Li Y, et al. Neuroplastic response after radiation therapy for pediatric brain tumors: a pilot study. Int J Radiat Oncol Biol Phys. 2016;95(3):991–998.
    1. Josman N, Abdallah TM, Engel-Yeger B. Using the LOTCA to measure cultural and sociodemographic effects on cognitive cultural and sociodemographic effects on cognitive skills in two groups of children. Am J Occup Ther. 2011;65(3):e29–e37.
    1. Seibert TM, Karunamuni R, Kaifi S, et al. Cerebral cortex regions selectively vulnerable to radiation dose-dependent atrophy. Int J Radiat Oncol Biol Phys. 2017;97(5):910–918.
    1. Ingle D, Goodale MA, Mansfield RJW, NATO Advanced Study Institute (1978 : Brandeis University) Analysis of Visual Behavior. Cambridge, MA: MIT Press; 1982. . Accessed June 3, 2020.
    1. Born RT, Bradley DC. Structure and function of visual area MT. Annu Rev Neurosci. 2005;28:157–189.
    1. Harrison BJ, Pujol J, López-Solà M, et al. Consistency and functional specialization in the default mode brain network. Proc Natl Acad Sci USA. 2008;105(28):9781–9786.
    1. Sours Rhodes C, Zhang H, Patel K, et al. The feasibility of integrating resting-state fMRI networks into radiotherapy treatment planning. J Med Imaging Radiat Sci. 2019;50(1):119–128.
    1. Karunamuni R, Bartsch H, White NS, et al. Dose-dependent cortical thinning after partial brain irradiation in high-grade glioma. Int J Radiat Oncol Biol Phys. 2016;94(2):297–304.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa