Dose/effect relationships for brain metastases

Abstract

Purpose: Only in selected patients with brain metastases, e.g. those with controlled or absent extracranial tumour, may application of higher total doses of radiotherapy improve survival. However, local control is the prerequisite for long-term survival. This study aimed to answer the question whether or not local control can be improved by dose escalation. Methods: Computed tomography scans of 322 patients were analysed in order to evaluate the best local result after radiotherapy and the time to local progression. Total doses of 25–60 Gy were administered (single doses 1.8–5 Gy). The biologically effective dose (BED₁₀) was calculated for statistical evaluation according to the linear-quadratic model assuming an α/β-value of Gy. It ranged between 37.5 Gy and 72 Gy. Results: The best local result was dependent on the number of brain metastases, BED and the histology of the primary tumour (small-cell and breast carcinoma had higher remission rates than squamous-cell carcinoma, non-breast adenocarcinoma and others). Partial remission rates significantly increased with BED, whereas complete remission rates did not improve. Histology was the only significant factor in multivariate tests. The 1-year-failure rate improved with increased BED from 44% to 31% (P > 0.05). Overall survival (median 3 months) was not dependent on total dose. Conclusions: Previous studies suggested that a prolongation of survival can be achieved through better local management (e.g. surgery plus radiotherapy, radiosurgery). However, it is still uncertain whether conventional external-beam radiotherapy with higher total doses leads to comparable results. The optimum dose level still has to be established. For squamous-cell carcinoma and adenocarcinoma a BED of at least 72 Gy seems to be necessary, for small-cell and breast carcinoma, doses between 48 Gy and 60 Gy might be sufficient. The important influence of tumour histology on local remission and progression-free survival should be considered when planning future clinical trials.