Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity.
OBJECTIVE
To prospectively evaluate efficacy and side effects of hypofractionated stereotactic radiotherapy (hfSRT) for irresectable brain metastases not amenable to radiosurgery (SRS).


METHODS
From 1/2003 to 2/2005, 51 patients with 72 brain metastases were included in a prospective phase II-trial and accepted for treatment at the dedicated stereotactic radiosurgery system Novalis (BrainLAB, Heimstetten, Germany). In case of planned or prior whole brain radiotherapy (WBRT), hfSRT was to be performed with 5 x 6 Gy, otherwise with 5 x 7 Gy. This dose was prescribed to the 90% isodose line which should cover 100% of the planning target volume (PTV).


RESULTS
Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 66.7%, 18.1%, 12.5% and 2.8%, respectively, after a median follow-up of 7 months. Median survival was 11 months. Disease-specific survival and survival related to brain metastases were strongly associated with the size of gross tumor volume (GTV), the planning target volume (PTV), Karnofsky Performance Score (KPS) and number of metastases. Side effects, i.e., increase in T2w-signal area, duration of steroid intake and size of new or progressive necrotic centre of metastasis, were dependent on the volume of normal brain irradiated with more than 4 Gy per fraction (V(4Gy)). Significantly more patients with a V(4Gy)> or =23 cc developed radiological signs of side effects from hfSRT.


CONCLUSIONS
Hypofractionated stereotactic radiotherapy with 5 x 6-7 Gy is an effective and safe treatment for brain metastases not amenable to single high-dose radiosurgery. The normal brain volume receiving >4 Gy per fraction may not exceed 20 cc.
Ernst-Stecken
Antje
A
Department of Radiation Therapy and Novalis Shaped Beam Surgery Center, University of Erlangen, Germany. antje.ernst-stecken@strahlen.imed.uni-erlangen.de
Ganslandt
Oliver
O
Lambrecht
Ulrike
U
Sauer
Rolf
R
Grabenbauer
Gerhard
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001929:Brain Edema / Q000209:etiology; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D019583:Dose Fractionation, Radiation; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods; D012074:Remission Induction; D019233:Retreatment; D016896:Treatment Outcome