A systematic review of pediatric neuropsychological outcomes with proton versus photon radiation therapy: A call for equity in access to treatment

Abstract

Objective: There is increasing interest in the utilization of proton beam radiation therapy (PRT) to treat pediatric brain tumors based upon presumed advantages over traditional photon radiation therapy (XRT). PRT provides more conformal radiation to the tumor with reduced dose to healthy brain parenchyma. Less radiation exposure to brain tissue beyond the tumor is thought to reduce neuropsychological sequelae. This systematic review aimed to provide an overview of published studies comparing neuropsychological outcomes between PRT and XRT. Method: PubMed, PsychINFO, Embase, Web of Science, Scopus, and Cochrane were systematically searched for peer-reviewed published studies that compared neuropsychological outcomes between PRT and XRT in pediatric brain tumor patients. Results: Eight studies were included. Six of the studies utilized retrospective neuropsychological data; the majority were longitudinal studies (n = 5). XRT was found to result in lower neuropsychological functioning across time. PRT was associated with generally stable neuropsychological functioning across time, with the exception of working memory and processing speed, which showed variable outcomes across studies. However, studies inconsistently included or considered medical and sociodemographic differences between treatment groups, which may have impacted neuropsychological outcomes. Conclusions: Despite methodological limitations, including limited baseline neuropsychological evaluations, temporal variability between radiation treatment and first evaluation or initial and follow-up evaluations, and heterogenous samples, there is emerging evidence of sociodemographic inequities in access to PRT. With more institutions dedicating funding towards PRT, there may be the opportunity to objectively evaluate the neuropsychological benefits of patients matched on medical and sociodemographic variables.

Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study

“…However, efforts to reduce radiation exposure to the primary site has often been met with an increased risk of relapse, particularly in high‐risk patients 45–48 . Proton radiotherapy can deliver radiation with less dose deposition to adjacent healthy tissue than conventional photon radiotherapy 49 and has been associated with fewer late effects 50–54 . It will be important to assess whether reduced radiation exposure adjacent to the primary tumor bed will result in improvement in functional outcomes in RMS survivors.…”

“…[45][46][47][48] Proton radiotherapy can deliver radiation with less dose deposition to adjacent healthy tissue than conventional photon radiotherapy 49 and has been associated with fewer late effects. [50][51][52][53][54] It will be important to assess whether reduced radiation exposure adjacent to the primary tumor bed will result in improvement in functional outcomes in RMS survivors.…”

Limited Research Investigating the Value of MRI in Predicting Future Cognitive Morbidity in Survivors of Paediatric Brain Tumours: A Call to Action for Clinical Neuroimaging Researchers

“…Whilst developments in treatment have mitigated some neurocognitive toxicity (e.g. proton beam radiotherapy [22]), there is still need for clinicians to navigate treatment decisions in terms of risk to QoL based upon known disease and age related risk factors [20,21].…”

“…Whilst developments in treatment have mitigated some risk of neurocognitive toxicity (e.g. proton beam radiotherapy [21]), there is still need for clinicians to make decisions about treatment strategy to further reduce risk to a child’s neurocognitive development, using existing disease and age related risk factors [19, 20]. More accurate prediction of individual-level risk of cognitive morbidity (even across domain and severity), would enable clinicians to further adapt and personalise treatment schedules with a greater focus on risk to quality-of-life whilst maintaining efficacy in treating disease [22].…”

Predicting neuropsychological late effects in pediatric brain tumor survivors using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity

“…Moreover, concomitant chemotherapy and radiation results in greater neurocognitive deficits and academic difficulties than CRT alone (Bull et al, 2007; Butler et al, 1994). Poorer neurocognitive outcomes are also associated with other neurological risk factors, such as endocrine disruption and seizures (Reimers et al, 2003; Vingerhoets, 2006), and patient/demographic factors, such as age at the time of treatment, time since treatment, socioeconomic status (SES), and sex (Radcliffe et al, 1994; Peterson & King, 2022; Sands et al, 2001; Torres et al, 2021).…”