Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033

Abstract

Background EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or Temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of radiotherapy on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Methods Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model memory functioning was compared between treatment arms and over time. Results Neuropsychological assessment was performed in 98 patients ( 53 RT, 46 TMZ). At 12 months compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, gender, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (p = 0.017) and total number of words recalled (Total Recall; p < 0.001, albeit with delayed improvement in radiotherapy patients (group by time; p = 0.011). Memory functioning was not associated with radiotherapy gross, clinical, or planned target volumes. Conclusion In patients with high-risk low-grade glioma there is no indication that in the first year after treatment radiotherapy has a deleterious effect on memory function when compared to TMZ chemotherapy.

Effects of brain radiotherapy on cognitive performance in adult low-grade glioma patients: A systematic review

“…Concerns about the impact of radiation therapy on the cognitive function of grade II glioma patients are legitimate, however, current data fail to produce a consistent, coherent and ultimately convincing picture of the RT associated cognitive deficits. Notably, the most recent neurocognitive study in this cohort by Klein et al [65] produced results in line with this conclusion. Upcoming studies may very well provide higher quality data to the contrary, but at present it is tenuous to argue that radiation associated cognitive morbidity outweighs the benefit of prolonged survival.…”

“…Vigliani and colleagues failed to show a substantial cognitive decline using a detailed battery in a 4 year follow up. The most current data on the cognitive effects of radiotherapy stem from the EORTC 20033-26033 trial; within the one year follow up period no significant deficit in memory functioning (tested using the Visual Verbal Learning Test) was documented in the 53 patients receiving radiation therapy compared to 46 patients receiving temozolomide chemotherapy [65]. The Vigliani et al [64] and the Klein et al [65] studies were not incorporated in our analysis as their cohorts admitted patients receiving chemotherapy and hence did not meet our inclusion criteria.…”

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis

“…However, we should also consider the role of surgical resection in developing the side effects, especially late neurotoxicity [32][33][34]. In the recent EORTC trial, Klein and colleagues [35] proved that memory functioning was not associated with RT target volumes in low-grade glioma patients. Moreover, radiotherapy does not have a deleterious effect on memory function after one year of treatment, compared to chemotherapy.…”

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

“…This need has previously been pointed out 46 . Recent randomised trials include long-term neurocognitive outcomes (for example EORTC study 22033–26033 47 ; CATNON 2017 48 ). Ongoing observational studies include NCT00457210 49 , NCT02544178 50 and NCT03055364 51 .…”