As I described in prior post, prophylactic cranial irradiation (PCI) is established as a treatment approach for patients with LD-SCLC who have had a complete or "good partial" response to chemo and radiation. Some physicians also recommend PCI for patients with ED-SCLC who have experienced a very good response, since about 10% of the patients on the PCI trials that led to our current recommendations had ED-SCLC. But a trial presented by the European Organization for the Research and Treatment of Cancer (EORTC) at the plenary session of ASCO (abstract here) demonstrated a survival benefit from PCI for a much broader range of ED-SCLC patients that is likely to change our practice patterns.

The trial was designed to test whether PCI for patients with ED-SCLC who had any response to 4-6 cycles of chemotherapy would demonstrate a significant reduction in the development of symptomatic brain metastases. The trial design was as shown below:

(click to enlarge)

A total of 286 patients were enrolled, a median of just over 4 months after initial diagnosis (remember, patients didn't start this trial until after completing first-line chemo). Patients were not required to have a screening head CT or MRI unless they had neurological symptoms. In contrast with the most typical ways of giving PCI in the US, the majority of patients received their PCI in 5 sessions over the course of one week only, a schedule that many in the US would be concerned would give patients a higher risk of complications, including neurocognitive problems. Nevertheless, PCI was generally well tolerated, with the main side effects being headache in just over 40% of patients, nausea and/or vomiting in about 1/3, and a smaller proportion of around 10% or less with fatigue. Skin reactions like a local burn were rarely seen as well. A total of 3 patients (accounting for around 2% of the total getting PCI) experienced long-term significant headaches or neurologic problems, the big fears about brain radiation.

About 90% of the patients were followed until the time of progression or death. The study demonstrated significant improvements for the group receiving PCI in multiple endpoints. The primary endpoint was symptomatic brain metastases, which were seen in 16.8% of those who received PCI, vs. 41.3% who didn't receive it, so a more than two-fold difference. But progression outside of the brain was also less common after PCI (85% vs 93%), as were deaths from SCLC during the period of follow-up (76% vs 87%).

Importantly, although the trial wasn't aiming to show a survival benefit, it did show a 32% improvement in overall survival during the time of follow-up on the trial, and survival at one year after enrollment was more than twice as high on the PCI arm:

Keep in mind, when reviewing these numbers, that they're on the low side for one-year survival in SCLC, probably because the patients had actually been diagnosed and treated for several months before going on this trial.

Finally, the investigators also investigated patient quality of life (QoL) on the trial and found that the people on PCI had a transient drop in QoL that lasted for three months, and then both groups had the same ratings of QoL after that.

So the trial demonstrated that patients with ED-SCLC who responded to initial chemo (4-6 cycles) not only showed a reduction in symptomatic brain metastases after PCI, but also a reduction in progression outside of the brain and overall survival in general. This was not associated with significant side effects except in very rare patients, and quality of life was only transiently lower in recipients of PCI. These results are likely to be enough to change our practice patterns to lead us to administer PCI in SCLC much more liberally.