DOSE EFFECT RELATIONSHIPS FOR BRAIN METASTASES/

Purpose: Only in selected patients with brain metastases, e.g. those w ith controlled or absent extracranial tumour, may application of highe r total doses of radiotherapy improve survival. However, local control is the prerequisite for long-term survival. This study aimed to answe r the question whether or not local control call be improved by dose e scalation. Methods: Computed tomography scans of 322 patients were ana lysed in order to evaluate the best local result after radiotherapy an d the time to local progression. Total doses of 25-60 Gy were administ ered (single doses 1.8-5 Gy). The biologically effective dose (BED10) was calculated for statistical evaluation according to the linear-quad ratic model assuming an alpha/beta-value of Gy. It ranged between 37.5 Gy and 72 Gy. Results: The best local result was dependent on the num ber of brain metastases, BED and the histology of the primary tumour ( small-cell and breast carcinoma had higher remission rates than squamo us-cell carcinoma, non-breast adenocarcinoma and others). Partial remi ssion rates significantly increased with BED, whereas complete remissi on rates did not improve. Histology was the only significant factor in multivariate tests. The 1-year-failure rate improved with increased B ED from 44% to 31% (P > 0.05). Overall survival (median 3 months) was not dependent on total dose. Conclusions: Previous studies suggested t hat a prolongation of survival can be achieved through better local ma nagement (e.g. surgery plus radiotherapy, radiosurgery). However, it i s still uncertain whether conventional external-beam radiotherapy with higher total doses leads to comparable results. The optimum dose leve l still has to be established. For squamous-cell carcinoma and adenoca rcinoma 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 sufficien t. The important influence of tumour histology on local remission and progression-free survival should be considered when planning future cl inical trials.