E-33. Prevention and management of brain metatsases

Abstract

Between 25%30%% of all patients with lung cancer develop brain metastases at some stage of their life and this percentage is likely to increase with lengthening survival and more aggressive multi-modality treatment of patients with advanced stage of disease at presentation [l]. Until recently brain metastases were considered to be a terminal event and their treatment was essentially palliative. With increasing frequency of failure in the brain together with development of new techniques and reports of prolonged survival after aggressive treatment we need to reassess our approach to patients with brain metastases and develop new treatment algorithms to ensure that they receive the optimal therapy. This should not only maximise their opportunity for survival but also provide functional improvements and improved quality of life. The initial evaluation of lung cancer patients with neurological symptoms requires confirmation of diagnosis and assessment of prognostic factors that will determine the optimal approach to treatment. Radiological evaluation with CT and in patients with apparently solitary lesion MRI confirms the diagnosis and establishes the extent of involvement. This is important as solitary lesions have a different prognosis to multiple tumours or patients with wider dissemination through the CSF pathways Steroids to control peri-tumoral oedema and anticonvulsants in patients with seizures provide immediate palliation and allows time for decisions on further therapy. Number of studies confirmed that solitary metastases, time of their appearance (synchronous/metachronous), presence of active tumour at other sites, PS, functional neurological status and age of the patients are significant prognostic factors. Using recursivepartitioning models such as the RTOG [2] one can pick individual patients who fall into a favourable prognostic group. Radiation therapy to the whole brain (WBRT) is the mainstay of treatment for the majority of patients. For those in favourable prognostic category consideration should be given to additional ways of enhancing local control in the brain either by resecting [3] the solitary metastasis or stereotactically delivered radiation boost [4]. Both methods can improve rates of local response and prolong time to relapse at this site. Which one to choose will depend on the accessibility of the lesion, need for and value of fast internal decompression and availability of surgical expertise. Evidence suggests comparable results in expert hands, although surgery achieves faster response at a cost of higher immediate morbidity. The disruption of blood brain barrier by metatstatic disease enables access of many chemotherapy agents and in the presence of metatsatic disease at other sites this is a logical option. The prediction of response in the brain can be determined by sensitivity rules applicable to primary tumour. There is evidence that addition of WBRT improves rates and prolongs local control without influencing survival [5]. Most of lung cancer patients develop brain metastases in the context of advanced extra-cranial disease and fall in the poor prognostic category. The aims of treatment are palliative and role of radiotherapy or chemotherapy, particularly when accompanied by significant toxicity, is much less clear. Increasing radiation dose does not improve survival and may be detrimental to quality of life. Utility of currently available chemotherapy is limited by low response rates and significant toxicity of treatment. Studies assessing neurological function and quality of life have consistently demonstrated poor symptom control and low and rapidly deteriorating functional status despite treatment in most patients. Can we do better? Increasing the biological radiation dose using accelerated hyper fractionation schedules has not improved survival when compared to conventional radiotherapy in a randomised trial of good prognosis patients [6]. Is prevention the way forward? The ability of prophylactic cranial irradiation (PCI) to significantly reduce rates of brain relapse and improve survival has been convincingly demonstrated in small cell lung cancer (SCLC) [7]. Can this be replicated for patients with other histological types and can we identify a group most likely to benejit? Proposals to test this have been regularly raised over the last decade and promising results observed in exploratory studies. The lessons learned from the PC1 experience in SCLC should make progress faster than it has been so far and groups investigating multimodality treatment approaches should come together to run simple pragmatic randomised trials to evaluate the effectiveness of this approach. Until we have these results PC1 remains experimental and the group of lung cancer patients at risk of relapse in the brain is increasing. For majority of these the currently available therapy produces disappointing results.