Re: Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: Longitudinal evidence of cognitive awareness from EORTC brain tumour trials

Dear Editor, We read with great interest the recent study [[1]Caramanna I. Reijneveld J.C. van de Ven P.M. van den Bent M. Idbaih A. Wick W. et al.Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: longitudinal evidence of cognitive awareness from EORTC brain tumour trials.Eur J Cancer. 2023; 186: 38-51Google Scholar] exploring the association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma. The study provided valuable longitudinal evidence of cognitive awareness derived from the European Organization for Research and Treatment of Cancer (EORTC) brain tumour trials. The authors conducted a rigorous investigation, employing a longitudinal design to assess neurocognitive functioning and neurocognitive complaints over time. This approach allowed them to capture the dynamic nature of cognitive impairment in patients with recurrent high-grade glioma. The results of the study [[1]Caramanna I. Reijneveld J.C. van de Ven P.M. van den Bent M. Idbaih A. Wick W. et al.Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: longitudinal evidence of cognitive awareness from EORTC brain tumour trials.Eur J Cancer. 2023; 186: 38-51Google Scholar] revealed a significant association between objective neurocognitive functioning and neurocognitive complaints. This finding is crucial as it highlights the importance of considering patients' subjective experiences alongside objective measurements when evaluating cognitive functioning in this population. By demonstrating the link between these two domains, the study adds to our understanding of the lived experiences of individuals with recurrent high-grade glioma. Furthermore, the longitudinal design of the study provides valuable insights into the trajectory of cognitive awareness in patients with recurrent high-grade glioma. The observed changes in cognitive functioning and complaints over time underscore the need for ongoing monitoring and support for patients throughout their disease course. However, we believe that the following issues require further clarification. Firstly, it is unclear from the study [[1]Caramanna I. Reijneveld J.C. van de Ven P.M. van den Bent M. Idbaih A. Wick W. et al.Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: longitudinal evidence of cognitive awareness from EORTC brain tumour trials.Eur J Cancer. 2023; 186: 38-51Google Scholar] the baseline characteristics of the neurocognitively impaired and intact patients, as described in the study with 437 patients classified as impaired and 109 as intact. The baseline characteristics of the impaired and intact patients may have significant differences, which could influence the subsequent follow-up outcomes. It is worth noting that the impaired group showed a declining trend in cognitive status from baseline (80%) to 12 weeks (78.1%), 24 weeks (77.2%), and 36 weeks (67.8%), while the intact group exhibited an increasing trend in cognitive status from baseline (20%) to 12 weeks (21.9%), 24 weeks (22.8%), and 36 weeks (32.2%). One possible hypothesis for this phenomenon is that the impaired group had a higher proportion of corticosteroid usage. Previous studies [2Montero-López E. Santos-Ruiz A. Navarrete-Navarrete N. Ortego-Centeno N. Pérez-García M. Peralta-Ramírez M.I. The effects of corticosteroids on cognitive flexibility and decision-making in women with lupus.Lupus. 2016; 25: 1470-1478Google Scholar, 3Prado C.E. Crowe S.F. Corticosteroids and cognition: a meta-analysis.Neuropsychol Rev. 2019; 29: 288-312Google Scholar] have shown an association between corticosteroid use and a decline in cognitive status. Thus, further clarification and exploration of the baseline characteristics of the impaired and intact groups would strengthen the study. Understanding potential confounding factors and their impact on the observed cognitive outcomes over time is crucial for interpreting the study's findings accurately. Moreover, it would be valuable to discuss the potential mechanisms underlying the observed trends in cognitive status within the impaired and intact groups. Exploring factors such as corticosteroid use, tumour characteristics, and comorbidities could provide insights into the drivers of cognitive changes in patients with recurrent high-grade glioma. This would contribute to a more comprehensive understanding of the relationship between neurocognitive functioning and neurocognitive complaints in this population. Secondly, while the study focuses on the association between objective neurocognitive functioning and neurocognitive complaints, it would be beneficial to consider the impact of psychological and emotional factors on cognitive awareness [[4]Karsdorp P.A. Everaerd W. Kindt M. Mulder B.J. Psychological and cognitive functioning in children and adolescents with congenital heart disease: a meta-analysis.J Pediatr Psychol. 2007; 32: 527-541Google Scholar]. Patients' subjective experiences, education, mood, anxiety, and quality of life could potentially influence their perception of neurocognitive functioning. Incorporating measures of psychological well-being and patient-reported outcomes would enhance the understanding of the complex interplay between objective and subjective cognitive measures. Thirdly, it is crucial to consider whether the patients with recurrent high-grade glioma included in the study had previously undergone surgical resection. Previous research has shown that surgical resection is a significant factor in improving prognosis for patients with recurrent high-grade glioma [5Keles G.E. Chang E.F. Lamborn K.R. Tihan T. Chang C.J. Chang S.M. et al.Volumetric extent of resection and residual contrast enhancement on initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma.J Neurosurg. 2006; 105: 34-40Google Scholar, 6Sanai N. Polley M.Y. McDermott M.W. Parsa A.T. Berger M.S. An extent of resection threshold for newly diagnosed glioblastomas.J Neurosurg. 2011; 115: 3-8Google Scholar]. However, the study does not provide detailed information regarding the patients' history of surgical treatment. Specifically, it is known that cognitive dysfunction is often associated with lesions in the frontal and temporal regions of the left hemisphere [7Campanella F. Del Missier F. Shallice T. Skrap M. Localizing memory functions in brain tumor patients: anatomical hotspots over 260 patients.World Neurosurg. 2018; 120: e690-e709Google Scholar, 8Habets E.J.J. Hendriks E.J. Taphoorn M.J.B. Douw L. Zwinderman A.H. Vandertop W.P. et al.Association between tumor location and neurocognitive functioning using tumor localization maps.J Neurooncol. 2019; 144: 573-582Google Scholar]. If the location of the recurrent high-grade glioma or the surgical resection coincided with the structures in the left hemisphere, particularly the frontal and temporal lobes, it is highly likely that the cognitive functioning of these patients would be impaired. Therefore, it is essential to describe whether the included patients underwent surgical resection. Additionally, conducting subgroup analyses based on tumour location could provide more accurate and meaningful conclusions. Furthermore, considering the potential influence of adjuvant treatments on neurocognitive functioning is also important [[9]Acevedo-Vergara K. Perez-Florez M. Ramirez A. Torres-Bayona S. Dau A. Salva S. et al.Cognitive deficits in adult patients with high-grade glioma: a systematic review.Clin Neurol Neurosurg. 2022; 219107296Google Scholar]. It would be valuable to explore whether the patients received treatments such as chemotherapy or radiation therapy, as these modalities have been associated with cognitive side effects. Including information on adjuvant treatments in the analysis would allow for a more comprehensive assessment of the factors contributing to cognitive awareness in patients with recurrent high-grade glioma. The study was conceived and designed by DeHua Liu and Jian Wang. They both contributed to the drafting and critical revision of the manuscript. The final version of the manuscript received approval from all authors. None.