Does earlier diagnosis and treatment of brain tumours matter? Time-to-treatment intervals and tumour size at detection; impact on survival and other patient outcomes
Ewan Gray, James Cameron, Abigail Lishman, Peter Hall, Piyumanga Karunaratne, Giovanni Tramonti, Maheva Vallet, Luke Pike, Matthew Baker, Paul M BrennanAbstract
Background
The importance of timely diagnosis of brain tumours is well recognised but how this translates to impact on important patient outcomes is not well described. This observational study aimed to quantify the effect of time-to-treatment interval and tumour size at diagnosis on six patient outcomes: tumour-specific survival, overall survival, new or worsened neurological deficit, 30-day mortality, recurrence and inpatient length of stay.
Methods
A retrospective cohort study including 1196 patients from Southeast Scotland diagnosed with brain tumours between 2010 and 2020. Analysis was stratified by tumour type in three categories: Glioblastoma (GBM) and other grade 4 brain tumours, grade 1-3 tumours and brain metastases. Regression methods (Cox, Logistic & Linear) were used to estimate per day impact of time-to treatment and tumour size impact on outcomes.
Results
The mean time from first presentation to treatment was 161 days (median: 57 days. Time-to-treatment results showed an association between longer intervals and reduced mortality. The mean tumour size was 4.06cm (SD: 1.75cm). For GBM and grade 4 tumours, each 1cm increase in tumour size increased tumour-specific mortality risk by approximately 11% (HR: 1.11, 95%CI: 1.05-1.16) and increased all-cause mortality by 10% (HR: 1.10, 1.05-1.16). Associations between tumour size and the outcomes of brain tumour mortality, all-cause mortality and inpatient length of stay were consistent across tumour subgroups.
Conclusions
Larger tumour size was consistently associated with increased hazard ratios for mortality. Applying these estimates together with estimates of mean tumour growth rates available in the literature, if a 6cm Glioblastoma tumour were diagnosed 3 months earlier then we would expect a 17-26% reduction in hazard of brain tumour mortality.
Importance of the Study
These findings reinforce the potential positive impact of earlier diagnosis for brain tumour patients. Building upon the accumulated evidence that tumour size is a critical factor influencing prognosis, this study is the first to focus on estimating causal associations with patient outcomes. Earlier detection, through influence on tumour size at diagnosis, may offer measurable survival benefits and potential reductions in healthcare resource use. There are limitations of an observational study design, but we believe our large, robust dataset and detailed analysis provide a stronger foundation for advocating further prospective research such as trials or pilots of early diagnostic interventions.