Prophylactic Cranial Irradiation: More Questions Than Answers

Cerebral metastases are a common problem in patients with small cell lung cancer, with a crude incidence of approximately 25%. However, a review of the published data shows that, in patients who achieve a complete response with chemotherapy, the incidence of cerebral metastasis as the first or only site of treatment failure is approximately 14%. This is the proportion of patients who might be expected to obtain a survival benefit if their cerebral metastases could have been prevented. The incidence of cerebral metastases varies with the length of survival and the administration of prophylactic cranial irradiation (PCI). The incidence may also be influenced by the administration of systemic chemotherapy and the timing of thoracic irradiation (in patients with limited disease). PCI has been shown in randomized trials to reduce the crude incidence of cerebral metastases to 7%, but this has not resulted in a detectable survival advantage, possibly because the numbers of randomized patients in complete response have been too small. Numerous retrospective studies now link PCI with late neurotoxicity, with an overall crude incidence of approximately 19%, but with considerable variation from study to study, ranging from less than 10% to over 80%. This toxicity may have been reduced if small doses per fraction had been used, and chemotherapy had not been given concurrently with PCI. Because of these concerns about late toxicity and the small proportion of patients who might obtain a survival benefit from PCI, it is not possible to recommend it as a routine treatment at this time. Nevertheless, the treatment of established cerebral metastases is unsatisfactory, with complete response to radiotherapy in the range 20% to 30% and median survivals of 4 months or less. Because cerebral metastasis is likely to become an increasing cause of primary failure as patients survive longer, further studies should aim to define an optimum dose/fractionation schedule for PCI, and also evaluate its effect not only on survival and neurotoxicity, but also any benefits resulting from a reduction in morbidity resulting from the development of cerebral metastases.