The Case for Prophylactic Cranial Irradiation in Small-Cell Lung Cancer

At the Great Debates & Updates in Lung Cancer meeting in New York, New York, Charles Simone, MD, Memorial Sloan Kettering Cancer Center, New York, New York, debated in favor of prophylactic cranial irradiation when considering treatment options for patients with small-cell lung cancer.

Transcript:

Hi, my name is Dr Charles Simone, I'm the Chief Medical Officer of the New York Proton Center and professor in radiation oncology at Memorial Sloan Kettering Cancer Center. I'm going to be speaking about the use of prophylactic cranial irradiation for small-cell lung cancer and the reason why it has been, is, and should continue to be the standard of care.

We know that about 1 in 6 people are diagnosed with brain metastases at the time of their diagnosis for small cell lung cancer. We also know that up to about 50% of patients with small cell lung cancer develop brain metastases at some point during the course of their disease. There's been a lot of evidence showing that the use of low-dose radiation to the brain, called prophylactic cranial irradiation, can help to reduce the risk of brain metastases and, quite significantly, 2- or 3-fold reduction in the risk of developing brain disease, and that directly correlates with an improvement in overall survival. That's been shown in randomized trials, both for a limited stage and for extensive-stage small-cell lung cancer.

Really, the question is, why would you not do prophylactic cranial irradiation? And the answer is historically, there's been a concern of neurocognitive toxicity. The most common concern is: What does the radiation to the brain actually do to neurocognitive function in patients? The answer, fortunately, today, is either not much or nothing at all. Historically, we have seen that if you deliver very, very high doses of radiation in a total dose or each individual day; or if you do that radiation in people who are getting concurrent chemotherapy or in patients with preexisting neurocognitive dysfunction, they do have neurocognitive decline after radiation. There's no question about that. As we've done randomized trials showing that you can do lower doses of radiation for prophylactic cranial irradiation, as we know not to do it with concurrent chemotherapy or in patients with significant dementia or preexisting cognitive decline, numerous studies now for 30 years have shown there's really no decrement in neurocognitive function, no changes on imaging relative to patients who do not get prophylactic cranial irradiation.

And then lastly, the question is, in today's era, in the era where we're seeing increasing use of immunotherapy or consolidative thoracic radiation therapy, should we continue the practice of prophylactic cranial irradiation that has been standard of care until today? And I would say it's actually more important than ever, as we now have multiple randomized trials showing that doing consolidative thoracic radiation reduces the failure rate in the chest, and people are now more likely to fail in the brain, as we now have immunotherapy that reduces the risk of failing outside of the chest, and they're more likely to fail in the brain we really do need to control brain disease, and we now have emerging data showing that the use of prophylactic cranial irradiation in a chemo-immunotherapy era significantly improves overall survival.

Really, the question is not should we be using it, but probably why are we not considering it in all of our patients who don't have preexisting cognitive decline? With things like memantine to help to prevent neurocognitive dysfunction today, hippocampal avoidance radiation and more advanced radiation techniques, we certainly can do prophylactic cranial radiation safely, and it could directly impact the survival for our patients.

Source:

Simone, C. Debate: Prophylactic Cranial Irradiation (PCI) in SCLC – Yes. Presented at Great Debates & Updates in Lung Cancer; September 21-23; New York, NY.