Small Cell Lung (PCI): Perhaps Cancer and Prophylactic Cranial Irradiation the Question is Not who Needs PC1 but who Wants PCI?

WITH 175 000 new cases annually, lung cancer is the most frequent malignancy in adults in the European Community. Approximately 20% of these tumours are of the small cell subtype and roughly a third, chiefly when disease is confined to the thorax, will be in complete remission after aggressive induction therapy combining multidrug chemotherapy (CT) and thoracic radiation therapy. However, the majority of these patients will relapse and ultimately only 15-20% of complete responders will be long-term survivors (i.e. alive beyond 30 months). The major problems the physician is confronted with in these cases are how to preclude recurrences and how to cure them without generating unacceptable toxicity and without impairing the patient’s quality of life. The central nervous system (CNS) is one of the main organs invaded by small cell lung cancer (SCLC) and a tiequent site of relapse. CNS metastases are found in up to 65% of patients at autopsy with the brain traditionally being considered a sanctuary for tumour cells [ 11. Although the bloodbrain barrier is supposed to bar the entry to harmful substances (in particular most cytotoxic agents) and thus protect the CNS, this shield does not function systematically since dramatic responses to CT have been achieved in brain metastases from SCLC and brain metastases also arise even when clear responses are being observed at all other sites [2]. ranging from 24 to 36 Gy. However, at the same time, it was incriminated in the emergence of adverse effects such as neuropsychological syndromes and brain abnormalities, detected perhaps because of the advent of more sophisticated imaging techniques such as computed tomography and magnetic resonance imaging. In any case, just how significant these changes were is hard to tell and could not be appreciated from an analysis of retrospective studies because investigators were unaware of the initial clinical status of patients who had received PC1 and those who had not [4,5]. Toxicity appeared to be more frequent and severe when PC1 and CT were administered simultaneously, when PC1 preceded CT containing radiosensitising cytotoxics, when the total RT dose exceeded 30 Gy or when fractions were above 3 Gy. Consequently, the systematic use of PC1 was abandoned by some teams while others sought to deliver more cautiously administered PC1 (total dose < 30 Gy, fractions 5 3 Gy) to complete responders after induction therapy. Alternatively, the spectacular radiosensitivity of SCLC, which has been well established for decades, prompted the strategy of delivering prophylactic cranial irradiation (PCI) during induction treatment in order to prevent the development of metastases and their cohort of clinical symptoms. Several randomised trials were conducted in the 1970s [3]. Most of them concluded that PC1 reduced the rate of brain metastases, but no clear gain was afforded for overall survival. Restrospective analyses of these studies suggest that any potential benefit would only be gained by patients in complete remission, a finding which is not at all surprising since they are the only ones likely to enjoy long-term survival and thus possibly benefit from adjuvant treatments. In the early 198Os, PC1 was largely an integral part of the standard treatment of SCLC limited to the thorax with total doses usually