Radiosurgery for re-irradiation of brain metastasis: results in 54 patients

Abstract

Purpose: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory.

Patients and methods: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2–70). Median age was 53 years (24–80), and median Karnofski performance status (KPS) 70 (60–100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6–59) and 1.2 cc (0.1–95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8–23), and median maximal dose 21.2 Gy (14– 42).

Results: Median follow-up was 9 months (1–57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia.

Conclusion: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.

Introduction

The life expectancy of patients with brain metastasis is short. Once brain metastasis develop, the therapeutic goal is to palliate debilitating neurological symptoms and signs. Moreover, the incidence of brain metastasis may be increasing. A combination of factors probably accounts for this increased life expectancy with including systemic chemotherapy and the rising incidence of lung cancer. Without any treatment, the median survival after diagnosis of brain metastasis is only one month; medical treatment which includes corticosteroids results in an increase of one month in median survival [41]. The radiotherapy effectiveness in the treatment of brain metastasis was first shown by Chao et al. in 1954 [7]. Since that time, a variety of different dose and fractionation schedules have been evaluated and whole brain radiotherapy (WBRT) is the standard of care for the majority of patients with brain metastasis [19], [34], [41]. Although such irradiation moderately prolonged survival from 2 to 4.2 months, 31–49% of these patients still died of local central nervous system (CNS) failure [4], [15], [26], [41]. Re-treatment of progressive metastases with external beam radiation therapy is usually not beneficial [14], [18], [40]. Chemotherapy cannot cure brain metastasis relapse and surgery is uncommonly proposed to patients with such recurring brain metastasis [25], [36], [41]. An alternative therapy for these patients is stereotactic radiosurgery (SR) [20], [22], [27], [31]. A high single dose of radiation is delivered to a limited volume of tissue, while normal brain is minimally irradiated. This is due to the sharp dose gradient of radiation at the treatment fields edges, which markedly reduces the dose to the surrounding normal structures. In addition, this minimally invasive technique is applicable to surgically inaccessible lesions.

The purpose of the present analysis was to review results obtained with radiosurgery as salvage treatment for recurrent metastases after WBRT.