# Brain Dose–Volume Thresholds and Survival in Dogs With Intracranial Tumours Treated With the 10 × 4 Gy Radiotherapy Schedule: A Combined Analysis of Two Trials

## TL;DR

This study identifies brain dose-volume thresholds in dogs with brain tumors that are linked to better survival outcomes after radiotherapy.

## Contribution

The study provides species-specific, evidence-based dose-volume thresholds for canine brain tumor radiotherapy.

## Key findings

- Limiting Brain–GTV V32 Gy to ≤13 cm³ was associated with longer overall survival in dogs.
- Whole-brain gEUD >30 Gy predicted poorer survival outcomes.
- A brain-volume-adjusted gEUD ceiling improved risk prediction for survival.

## Abstract

Dogs with intracranial tumours routinely receive radiotherapy, yet species‐specific dose–volume constraints for normal brain tissue remain undefined. In human radiation oncology, exceeding certain brain dose–volume thresholds markedly increases the risk of radiation‐induced injury (e.g., radionecrosis). Current veterinary practice often extrapolates human guidelines without validation in discrete species, creating a gap in evidence‐based planning. This study aimed to identify brain dose–volume thresholds associated with overall survival (OS) in canine brain‐tumour patients. We pooled data from two prospective randomised trials (n = 105 dogs) treated with 10 daily fractions of 4 Gy (total 40 Gy) for intracranial tumours at a single institution. Semi‐automated scripting extracted multiple dose–volume metrics, including generalised equivalent uniform dose (gEUD), for the whole brain and brain minus gross tumour volume (Brain–GTV). An iterative Kaplan–Meier and Cox proportional hazards approach identified optimal dosimetric cutoffs, which were then adjusted for tumour volume and body weight via a regression residual method. A brain‐volume‐adjusted gEUD threshold was also derived to account for variation in brain size. Exposure to normal brain to doses around 30–40 Gy emerged as the strongest predictor of OS. Brain–GTV V32 Gy ≤ 13 cm3 was associated with longer OS (covariate‐adjusted cutoff 13.4 cm3, HR = 1.74; p = 0.022, unadjusted optimal split 11.5 cm3, HR = 2.08; p = 0.001). Whole‐brain gEUD > 30 Gy similarly predicted poorer survival (HR = 1.72; p = 0.034). Implementing a personalised gEUD ceiling increased 2‐year sensitivity from 31% to 38% with only a three‐point drop in specificity. In a 10 × 4 Gy canine intracranial radiotherapy model, limiting Brain–GTV V32 Gy to ≤ 13 cm3 and whole‐brain gEUD to ≤ 30 Gy was associated with longer overall survival. A brain‐volume‐adjusted gEUD ceiling further refined risk prediction. These evidence‐based thresholds provide actionable guidance for veterinary treatment planning, with the potential to improve outcomes in canine brain tumour therapy.