Background While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumour progression which may impact on patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M=7 and T2 M=13 years after diagnosis). Methods Participants completed HRQOL (SF-36; EORTC-BN20), fatigue (Checklist Individual Strength (CIS)), and depression (Center for Epidemiological Studies-Depression (CES-D)) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Change over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumour was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. Results Thirty patients and nineteen caregivers participated. Of N=11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M=26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers’ HRQOL was similar to controls, but reported high rates of fatigue (63.2%). Over time, patients’ mental health improved (p<.05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. Conclusions While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent.

BACKGROUND Our previous study among 195 low-grade glioma (LGG) patients six years after initial diagnosis, showed that high radiation doses (>2 Gy) were associated with neurocognitive disability. Follow-up at 12 years in 64 LGG patients showed patients without radiotherapy to have stable neurocognitive and radiological status while attentional functioning deteriorated between 6 and 12 years in irradiated patients. The present assessment at a mean of 26 years after initial diagnosis and treatment, investigates the neurocognitive sequelae of radiotherapy in long-term survivors. METHODS Patients who were alive since the 12 year follow-up were invited for assessment of the same neurocognitive domains as tested at 6 and 12 years: attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed. Using a mixed model, standardized scores of neurocognitive performance were compared between treatment (radiotherapy versus no radiotherapy) and over time. FINDINGS: 32 patients, of whom 13 (41%) had received radiotherapy, completed the assessment at a mean of 26 years (range 20–35 years) after initial diagnosis. Patients who had radiotherapy had more attentional deficits at the present assessment, than those who did not (–1·0 [SD 1·6] vs 0·33 [0·65], p=0·01; mean difference 1·3, 95% CI 0·3–2·3). Furthermore, patients who had radiotherapy had reduced attentional functioning over time (p=0·03), regardless of antiepileptic drug use. Three (23%) patients who had radiotherapy developed neurocognitive disabilities deficits in at least four of the 20 neuropsychological test parameters compared with five (26%) patients who did not have radiotherapy. INTERPRETATION: Extreme long-term, and probably surviving LGG patients who had radiotherapy show relatively stable and adequate neurocognitive functioning when compared to patients who did not have radiotherapy. Apart from attentional functioning, no progression of neurocognitive deficits at 26 years after initial diagnosis were found.