The Case Against Prophylactic Cranial Irradiation for Patients With SCLC

Daniel Gomez, MD, Memorial Sloan Kettering Cancer Center, summarizes his argument against prophylactic cranial irradiation (PCI) for patients with small-cell lung cancer, a stance he defended in a debate session at the Great Debates and Updates in Lung Cancer conference in Chicago, Illinois.

Dr Gomez discusses the lack of evidence for benefit from PCI in extensive-stage small cell lung cancer, whether the benefit in limited-stage small cell lung cancer is clinically meaningful, and stereotactic radiosurgery vs whole-brain radiotherapy.

Transcript:

My name's Daniel Gomez. I am a thoracic radiation oncologist with a focus in lung cancer, and I'm a faculty member at Memorial Sloan Kettering Cancer Center.

I am going to be debating the benefit of prophylactic cranial irradiation (PCI) in the context of small cell lung cancer. And my position is that there's no clear role for PCI at this time, and I will make my case in four concrete points. Number one, that in extensive stage small cell lung cancer, the debate is over. Prior data from 15 years ago seemed to potentially show a benefit. That study had major limitations, and when the study was repeated in the modern era with the advent of MRI studies, there was shown to be no benefit in survival. we can put extensive stage aside and focus on limited stage small cell lung cancer.

In limited stage small cell lung cancer, much of the evidence that is quoted is in the context of the Aupérin meta-analysis, demonstrating a 5% improvement in overall survival. However, I would argue that the 5% improvement at 3 years, which then continues to go down, is while statistically significant, clinically how meaningful it is can be debated, particularly in the context of the side effects from small cell lung cancer, and I'll go into those further in just a minute.

My third point is that while more patients develop brain metastases in this context without prophylactic cranial radiation, and the studies have been relatively consistent on that, in the area of stereotactic radiosurgery (SRS), these lesions can be treated effectively. And a recent large clinical study published in JAMA Oncology with over 700 patients demonstrated the effectiveness of treating with SRS in small cell lung cancer and with time to [central nervous system] CNS progression and neurologic mortality that was similar to the indications that we see in other scenarios of metastatic disease in which SRS is indicated. Therefore, for those patients that don't get prophylactic cranial radiation, SRS remains a viable option.

And finally, I would argue that even in the era of hippocampal avoidance radiation and the implementation of mementine, that the side effects from small cell lung cancer are still too high and that the risks of the treatment, the toxicity, outweighs the benefits. These toxicities include fatigue, substantial fatigue, hair loss, which is a significant quality of life issue, and cognitive effects, primarily those such as short-term memory loss and even neurocognitive failure, which has been shown to be relatively high with whole brain radiation therapy.

Even in this scenario where we implement these preventative measures and advanced radiation techniques, particularly for elderly patients, those that have preexisting cognitive conditions, which represent a large percentage of patients, given that many of these patients are also on other systemic therapies, that other therapies such as systemic therapy that can affect their cognition, the quality of life impact on these patients in the context of permanent cognitive side effects, albeit subtle, remains excessive in the setting of a relatively limited benefit in survival and in the framework of an available salvage option with the advent of stereotactic radiosurgery.

Sources:

Gomez D. Debate: Prophylactic Cranial Irradiation (PCI) in SCLC — No. Presented at Great Debates & Updates in Lung Cancer; May 4-6; Chicago, IL

Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476-84. doi:10.1056/NEJM199908123410703

Rusthoven CG, Yamamoto M, Bernhardt D, et al. Evaluation of first-line radiosurgery vs whole-brain radiotherapy for small cell lung cancer brain metastases: The FIRE-SCLC cohort study. JAMA Oncol. 2020;6(7):1028-1037. doi:10.1001/jamaoncol.2020.1271