Background
Patients with anaplastic glioma (AG) harbouring the isocitrate dehydrogenase (IDH) mutation have the potential for long survival duration following intensity modulated radiation therapy (IMRT) and chemotherapy. Thus, to guide future decision-making, there is an importance of understanding the level of long term functioning following management, and the factors that may impact on later adverse effects.
Methods:
Consecutive AG patients managed with IMRT from January 2008 to December 2017 were reviewed regarding features associated with impact of IMRT on Six Survivorship Domains. These included Performance Status; Treatment Late Toxicity; Neurological Status, Medical Co-morbidity Events; Functional Status with Employment and Driving; and Psychosocial Events. Overall survival was calculated from date of IMRT, and assessments were performed at baseline pre-RT, month+6, Year +1, Yr+3 and Yr+5. Analysis was performed in relation to the patient, tumour and treatment factors potentially associated with the two primary endpoints, ECOG performance status and Employment at year +3.
Results:
146 patients with median age 43 years were included with a median follow-up for survivors of 5.1 years. The 6-year overall survival from start of RT was 78.7% (95% CI: 71.1-87.0). Baseline ECOG Performance status, was 0 or 1 in 82.2% of patients but improved at Y+1 and Yr+3 of 95.7% and 97.2% of patients respectively. In the 51 patients evaluable at Yr+5, the ECOG was 0,1 in 96.1% of patients. For Employment Status at Yr+3 and Yr+5 the proportion of potential employable patients fully or partially employed was 70.1% and 76.5% respectively. This compared with baseline preIMRT of 61.6% being at a point of working or being able to return to work. The proportion of patients who were retired prior to IMRT remained consistent across the three time points with 8.2%, 8.9% and 9.8% at baseline, Yr+3 and Yr+5 respectively. The factors associated with worse ECOG Score at Yr+3 included WHO Path of AAmut (p=0.001), delayed timing of RT (p=0.081), multiple craniotomies prior to RT (p=0.002), worse ECOG preRT (p<0.001), worse MRC Score preRT (p<0.001), seizures at Yr+1 (p=0.038), neurocognitive disturbance at Yr+1(p<0.001) and presence of relapse (p=0.004). The factors associated with absent or impaired Employment at this timepoint included: older age (p=0.007), delayed timing of RT (p=0.023), multiple craniotomies prior to RT (p=0.005), worse ECOG preRT (p<0.001), worse MRC Score preRT (p<0.001), and neurocognitive disturbance at Yr+1(p<0.001).
Conclusion:
AG with IDH mutation have prolonged survival. Functional status at Year+3 post treatment is good with > 95% of patients having high performance status and greater than 75% in employment. Deficits relate more to the initial tumour and surgery, especially when IMRT is delayed to second or later relapse with multiiple surgical procedures being performed.