A secondary analysis of the phase II NRG-RTOG 0424 trial—which initially reported a 73.1% 3-year overall survival rate—has shown a decline in neurocognitive function for half of the trial participants with high-risk, low-grade gliomas up to a year after receiving concurrent chemoradiotherapy with temozolomide. However, the analysis also concluded that, on average, the quality of life of patients either remained stable or improved up to a year following temozolomide-based chemoradiotherapy treatment. These results were presented during the Plenary Session at the 2019 Society for Neuro-Oncology Annual Meeting and were published by Wefel et al in Neuro-Oncology.
Methods
The trial accrued 129 evaluable patients with high-risk, low-grade gliomas to receive daily temozolomide plus concurrent radiotherapy for 6 weeks followed by temozolomide for 12 cycles. A total of 93 patients completed at least one neurocognitive function and quality-of-life measurement. Neurocognitive function tests were performed at the end of treatment, again at 6 months following treatment, and at 1 year following treatment. At 6 months after treatment, 55% to 59% of trial participants completed neurocognitive function and quality-of-life measurements, and 54% to 57% of participants completed measurements at 1 year following treatment.
Findings
Neurocognitive function deterioration occurred in 50% of patients at 6 months and 40% of patients at 1 year posttreatment. These functional declines were most notable in Hopkins Verbal Learning Test (HVLT) and Trail Making Tests (TMTA and TMTB). Patients who exhibited deterioration in the HVLT at 1 year posttreatment had a significantly greater decrease in MOS-Cognitive Function (MOS-CF). FACT Emotional and Functional Well-Being subscales improved over time. No neurocognitive function test at baseline was independently associated with overall survival.
KEY POINTS
- Neurocognitive function deterioration occurred in 50% of patients at 6 months and 40% of patients at 1 year posttreatment.
- While general quality of life subscales were stable on average, a subset of patients reported diminished brain-related quality of life over time.
- Patients in the EORTC High-Risk Group and with tumors crossing the midline were at greater risk for these adverse outcomes.
Patients who completed neurocognitive function and quality-of-life measurements had better clinician-rated neurologic function than patients who did not complete the measurements.
“The secondary analysis of NRG-RTOG 0424 shows that a large subset of patients [is] vulnerable to neurocognitive decline after chemoradiotherapy with temozolomide followed by adjuvant temozolomide. Similarly, while general quality-of-life subscales were stable on average, a subset of patients reported diminished brain-related quality of life over time. Patients in the EORTC High-Risk Group and with tumors crossing the midline were at greater risk for these adverse outcomes. These data further support the importance of monitoring neurocognitive function and quality of life in trials comparing this treatment regimen with other active treatment regimens such as the CODEL trial (Alliance N0577; EORTC 26081-22086; NRG 1071; NCIC CEC.6) and for further developing our understanding of risk factors for such outcomes,” stated lead author Jeffrey S. Wefel, PhD, ABPP, of The University of Texas MD Anderson Cancer Center, in an NRG Oncology press release.
Disclosure: The trial was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit academic.oup.com.
