Delivery of prophylactic cranial irradiation to patients with extensive-stage small cell lung cancer (SCLC) has declined significantly since the publication of a study by Takahashi et al, according to a recent survey of academic radiation oncologists.¹

Data presented at the 2019 Multidisciplinary Thoracic Cancers Symposium showed a ~30% drop in prophylactic cranial irradiation utilization for extensive-stage SCLC following the publication of the Japanese study demonstrating no overall survival advantage when compared to observation with close magnetic resonance imaging (MRI) surveillance.² Results of the survey indicated that the majority of respondents (67%) altered their practice patterns in response to the Takahashi et al trial.

Although both MRI surveillance and prophylactic cranial irradiation are acceptable options, MRI surveillance has become more predominant since the publication of the Takahashi et al trial.

— Olsi Gjyshi, MD, PhD

Tweet this quote

“The practice of prophylactic cranial irradiation in patients with extensive-stage SCLC is rapidly evolving,” said Olsi Gjyshi, MD, PhD, initial author of the study who is a radiation oncology resident at The University of Texas MD Anderson Cancer Center, Houston, when the abstract was written. “Although both MRI surveillance and prophylactic cranial irradiation are acceptable options, MRI surveillance has become more predominant since the publication of the Takahashi study. However, careful consideration should be given to future studies and trials that are planning on investigating the role of prophylactic cranial irradiation in this patient population.”

Controversy Surrounding Prophylactic Cranial Irradiation

As Dr. Gjyshi explained, despite recent advances in cancer therapy, SCLC continues to be associated with very poor outcomes, with 5-year overall survival ranging in the single digits. One of the main reasons for these poor outcomes, said Dr. Gjyshi, is the fact that most of these patients will develop brain metastases during the course of their disease, especially those with extensive-stage disease. After the results of a phase III trial demonstrated a doubling in overall survival advantage at 1 year with prophylactic cranial irradiation vs observation in extensive-stage SCLC, prophylactic cranial irradiation became the standard of care in the United States for this patient population.³ However, as Dr. Gjyshi reported, with the recent improvements in imaging technology, the practice of prophylactic cranial irradiation has come into question.

To address this issue, Takahashi et al decided to run the same trial with the addition of MRI screening instead of screening by clinical symptoms and observation with MRI on a 3-month basis. Despite a reduced incidence in brain metastasis in patients who underwent prophylactic cranial irradiation, the investigators found no overall survival benefit compared with those followed closely with MRI surveillance. In fact, noted Dr. Gjyshi, the investigators actually saw a trend toward decreased overall survival, which led to the early interruption of the trial. Based on these results, the National Comprehensive Cancer Network^® (NCCN^®) changed its 2019 NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer to recommend either prophylactic cranial irradiation or MRI brain surveillance in managing these patients.⁴

Survey Reveals Change in Practice Patterns

To see how these changes in guidelines affected current practice patterns in patients with extensive-stage SCLC, Dr. Gjyshi and colleagues contacted 205 attending radiation oncologists from large academic institutions within the United States via e-mail to participate in an anonymous 24-question survey regarding the use of prophylactic cranial irradiation before and after publication of the Takahashi et al study. As Dr. Gjyshi reported, a total of 49 radiation oncologists (24%) responded to the survey, with responders evenly distributed geographically within the United States.

Although 78% of respondents stated that they routinely offered prophylactic cranial radiation for extensive-stage SCLC, 38% continued to do so after publication of the trial (P < .001). What’s more, the majority of respondents (67%) indicated that they had changed their practice patterns in response to the Takahashi et al trial.

To ensure that results were not simply due to sample bias, Dr. Gjyshi and colleagues surveyed an additional cohort of 3,600 American Society for Radiation Oncology–registered radiation oncologists throughout the United States. The results at the national level strongly mirrored the results of the academic institutions. Prior to the Takahashi study, approximately 72% of respondents stated that they had routinely offered prophylactic cranial radiation to patients with extensive-stage disease, whereas after publication of the Japanese study, 43% of participants continued to do so.

“Remarkably, there was no difference between academic radiation oncologists or private practice and government radiation oncologists, with both groups offering a similar rate of prophylactic cranial irradiation use before or after publication of the trial,” said Dr. Gjyshi. He emphasized that increased awareness about the current body of literature on the topic is important for both physicians and patients in making educated treatment decisions. ■

DISCLOSURE: Dr. Gjyshi reported no conflicts of interest.

REFERENCES

1. Gjyshi O, Ludmir EB, Pezzi TA, et al: The impact of the stage III randomized trial by Takahashi et al. on the use of prophylactic cranial irradiation in patients with extensive-stage small-cell lung cancer. 2019 Multidisciplinary Thoracic Cancers Symposium. Abstract 3. Presented March 14, 2019.

2. Takahashi T, Yamanaka T, Seto T, et al: Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 18:663-671, 2017.

3. Slotman B, Faivre-Finn C, Kramer G, et al: Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664-672, 2007.

4. Kalemkerian GP, Loo BW, Akerley W, et al: NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer, version 1.2019. Available at https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed March 29, 2019.