Prophylactic Cranial Radiation Revisited: Significant Change in Cognitive Function Not Found
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: Prophylactic cranial radiation (PCI) has been shown to reduce the incidence of CNS metastases and prolong survival for patients presenting with limited-stage small cell lung cancer (SCLC). However, concern that such treatment results in cognitive decline has tempered enthusiasm, but this claim has not been satisfactorily addressed. Grosshans and colleagues at M.D. Anderson Cancer Center performed comprehensive neuropsychological testing before and after PCI in a series of SCLC patients. Of 96 patients completing systemic chemotherapy +/- thoracic radiotherapy for limited stage disease and considered eligible for PCI, only 69 went on to receive the additional therapy, and of these, 37 had repeat testing. There was significant cognitive impairment in this cohort, but the testing indicated it was present prior to PCI and only minimally, and transiently worse after treatment. Thus, PCI should be considered both effective and safe for patients at risk for the development of CNS metastases.
Source: Grosshans DR, et al. Neurocognitive function in patients with small cell lung cancer. Effect of prophylactic cranial irradiation. Cancer. 2008;112:589-595.
There have been concerns raised about the use of prophylactic cranial irradiation (PCI) for patients with small cell lung cancer because of the risk for associated declining cognitive function.1 However, the data in this regard have been obtained primarily retrospectively and without pretreatment comprehensive neuropsychologic testing.1-3 The current report by Grosshans and colleagues from M.D. Anderson Cancer Center in Huston is a follow-up report from their earlier series published a decade ago.4 Ninety-six patients, who completed initial therapy for small cell lung cancer, typically concurrent chemotherapy and radiation therapy to the chest, underwent a battery of neuropsychological testing prior to PCI. Of these, 69 patients completed PCI and, of these, 37 patients underwent repeat testing at a mean follow-up time of 23 months after PCI. The other 32 patients did not have follow-up testing primarily because of a disease recurrence either in the brain or elsewhere.
Baseline (pre-PCI) cognitive impairment, defined as ≥ 1.5 standard deviations below the normative mean, occurred in 47% of the patients. For those retested after PCI, there was further decline in cognitive function, observed only in certain domains. These deficits, however, were small in magnitude and transient. Over time, significant improvements in language and motor coordination were recorded. Importantly, by multivariate analysis, there was no significant difference in overall neurocognitive function associated with PCI treatment.
Commentary
Brain metastases remain common in patients with small cell lung cancer, occurring as frequently as 50% of cases.5 Prophylactic cranial irradiation has been shown to decrease the incidence of brain metastasis and provide overall survival benefit.6 Despite this, however, some have argued against PCI for fear of its adverse effect on CNS function.1 Yet the data in this regard has been limited, obligating clinicians to rely on anecdotal experience. In this regard, this report is of considerable importance as it demonstrates a deficit in neurocognitive function in patients with SCLC prior to PCI, and only modest changes produced by cranial radiation. Why this should be the case is unclear, but perhaps it relates to either a particular paraneoplastic process associated with small cell lung cancer, or a more generalized CNS toxicity from the prior systemic chemotherapy. In either event, the study points out the importance of carefully examining previously unproven, but commonly accepted biases. In this case, it made perfect sense to accept that PCI resulted in clear and often marked cognitive decline. Only by prospective analysis incorporating a comprehensive panel of neuropsychological testing could this bias be debunked and certainly the absence of dramatic changes were seen with PCI may go a long way to reopen this issue. This study, although reassuring; included a relatively small sample size, and unfortunately the majority of patients receiving PCI did not receive repeat testing. Furthermore, it would be scientifically more satisfying if such neuropsychologic testing could be performed in parallel on individuals who did, vs did not, receive PCI.
Yet, whole brain irradiation has been shown to affect cognitive function under other circumstances. For example, in children with acute lymphoblastic leukemia in remission, it had been the practice to provide CNS irradiation in an effort to reduce the chance for relapse. Long-term studies have demonstrated cognitive impairments in those who had received radiation. In fact, for this reason some pediatric oncologists refer only those children with "high risk" ALL for prophylactic CNA irradiation. Of course, the effects of radiation on CNS function in children vs adults may be quite different.
Thus the definitive answer is not on the risk/benefit ratio for PCI in patients with small cell lung cancer. This study would suggest that the risks are small that sustained neurocognitive decline will be the result of PCI. This, in light of the known high rate of CNS recurrence would seem to favor this approach under selected circumstances. In order to be certain that such an approach does not significantly impair cognitive function, a larger experience of testing before and after treatment is warranted.
References
1. Fonseca R, et al. Cerebral toxicity in patients treated for small cell carcinoma of the lung. Mayo Clin Proc. 1999 May;74(5):461-465.
2. Fleck JF, et al. Is prophylactic cranial irradiation indicated in small-cell lung cancer? J Clin Oncol. 1990;Feb(2):209-214.
3. Johnson BE, et al. Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors. J Clin Oncol. 1990; Jan;8(1):48-56.
4. Komaki R, et al. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. International Journal of Radiation Oncology, Biology, Physics. 1995 Aug 30;33(1):179-182.
5. Komaki R, et al. Cancer Treat Rep. 1981 Sep-Oct;65(9-10):811-814.
6. Auperin A, et al. N Engl J Med. 1999;341(7):476-484.
Prophylactic cranial radiation (PCI) has been shown to reduce the incidence of CNS metastases and prolong survival for patients presenting with limited-stage small cell lung cancer (SCLC). However, concern that such treatment results in cognitive decline has tempered enthusiasm, but this claim has not been satisfactorily addressed.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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