Prophylactic Cranial Irradiation in Small‐Cell Lung Cancer: Is It Still Controversial or Is It a No‐Brainer?

The Oncologist 2000;5:299-301 www.TheOncologist.com Correspondence: Andrew T. Turrisi, III, M.D., Professor and Chair, Department of Radiation Oncology, Medical University of South Carolina, 169 Ashley Avenue, Box 250318, Charleston, South Carolina 29425, USA. Telephone: 843-792-3273; Fax: 843792-5498; e-mail: turrisi@radonc.musc.edu Received June 26, 2000; accepted for publication June 26, 2000. ©AlphaMed Press 1083-7159/2000/$5.00/0 This past summer’s meta-analysis and this issue’s review article would seem to ice the cake for making prophylactic cranial irradiation (PCI) for patients with small cell lung cancer a no-brainer. The long-awaited proof of a survival advantage is now in hand [1]. Seemingly this should silence those that decried PCI as unnecessary and even dangerous. Perhaps if all who were treated stood such a substantial chance of being injured by PCI, even a survival gain would be considered counter-productive because of the toxicity. Recently, I dined with a lung cancer expert whom I hold in high regard. He waxed prophetic that he would refuse this treatment for himself, and would not recommend it to a relative. Even the respected leaders are not always enlightened by the emerging facts. I guess it is hard to bury a legend no matter how weak the data bolstering it. It’s hard to accept a banished warrior even when the indictment has been dismissed and the jury not only finds for acquittal but even finds him a hero rather than a perpetrator. This is especially true when usually sober opinion leaders have been immoderate in their premature damning of what ultimately turns out to be a valuable tactic. Are there continuing credible facts about the neurocognitive risk of PCI? The case reports and series summaries calling attention to the risks of PCI are all aged and weakened by faulty methodology. Yang and Matthews [2] in the current review and analysis include some of these, and the labored analysis by Suwinski et al. [3] includes all of the studies in an attempt to define a dose-response and timing relationship with PCI. The problems with these data studies are legion: crude versus actuarial survivals; lack of cumulative frequency of relapse; short survival leading to many patients dying with poor systemic or local control before they metastasize to the brain, and retrospective data with lack of uniform screening for the relapse of the brain event. My largest irritation with these reports is the extraordinary reporting bias: problems with long-term survivor neurocognitive dysfunction fall on PCI, but no one tallies the dysfunction caused by brain metastasis in those not receiving PCI. Today we know that many patients present with neurocognitive dysfunction before any systemic, local or brain treatment is applied [4]. In the reports from the 1970s and 1980s, patients received months and months of post-PCI chemotherapy with the likes of lomustine, procarbazine, doxorubicin, vincristine, methotrexate, and alkylators—many cross damaged blood-brain barriers and perhaps all chemotherapy drugs after PCI have been applied. Sometimes the systemic therapy lasted as long as two years! Median survivals and two-year survivals for limitedstaged patients treated in this era were half what it is today, so the long-term surviving population was less than today. In North America and Japan, the 1990s brought an era of cisplatin and etoposide as systemic therapy and a shortened duration of systemic therapy to only four to six cycles. Those physicians who continued, despite adverse publicity, to use PCI, did so after completion of systemic therapy. If the idea was that the central nervous system was the only site where chemotherapy was barred, why would one use PCI if viable or resistant systemic disease persisted and required further chemotherapy? Sensibly one would clean up systemic and The Oncologist Dialogues In Oncology