Discussion

We found in this large database analysis that SRS is being increasingly utilized for the management of brain metastases. We found several factors, including updated clinical guidelines, regional availability, and the use of SRS-adjacent techniques, to be associated with increased utilization. One such SRS-adjacent technique is fSRS, which combines the steep-dose gradients and smaller margins of SRS with the radiobiologic advantages of fractionation. The odds of receiving SRS also vary by primary disease type and socioeconomic factors, such as insurance status and proximity to metropolitan environments.

Over the past decade, SRS has been increasingly employed to minimize the risk of neurocognitive decline associated with WBRT while still maintaining similar survival rates for patients with 3 BMs.^{6 - 8} Within the last couple of years, however, its use has been expanded to patients with 4-15 BMs, where WBRT may traditionally have been used.⁹ Several studies, including a large-scale retrospective review in 2020 and a meta-analysis in 2022, support the effectiveness of first-line SRS in patients with a primary SCLC diagnosis who would have otherwise been treated with WBRT.^{10 , 11} Continued evidence depicting SRS’s decreased parenchymal tissue damage and comparable effectiveness to WBRT supports relaxing the clinical guidelines and promoting the widespread adoption of SRS over time. Additionally, the rise of frameless GK treatment reduces the logistical constraints and increases patient satisfaction, further explaining the observed increase in SRS use.^{12 , 13} Furthermore, adopting fSRS allows for the treatment of metastases that are large or in unfavorable locations.¹⁴

Our study also demonstrated that regional and socioeconomic discrepancies determine a patient’s odds of receiving SRS. A 2012 Canadian study found that on-site SRS availability was the most important factor in receiving SRS treatment.¹⁵ The distribution of SRS systems was surveyed in 2019, and researchers found that most states in the United States have a ratio of at least 1 SRS machine (GK,linear accelerator, CK) per 1,000,000 people, with a few exceptions. Several states in the South Atlantic, West North Central, West South Central, and New England regions had ratios less than 1, while Vermont, South Dakota, and Wyoming all had 0 machines per 1,000,000 people.¹⁶ Even within certain geographic regions of the United States, proximity to a metropolitan area correlates with higher odds of being treated with SRS in addition to a higher probability of survival.¹⁷ Likewise, multiple studies concur that insured patients have much higher odds of receiving SRS and a higher probability of survival compared with uninsured populations.^{18 - 20} However, lower survival in uninsured patients and those distant from metro centers may be confounded by an increased disease burden at clinical presentation from a lack of preventative and continued health care.

Scenarios in which patients receive WBRT include extensive intracranial disease, multiple distant failures, or poor performance status.⁷ As a result of these confounding variables, we observed that the risk of mortality was almost halved at the post-treatment 3-year mark among patients who were treated with SRS compared with WBRT. However, a recent 2021 study showed that short-term survival rates are significantly higher for SRS patients than WBRT patients (1-year survival; SRS = 46.4% vs WBRT = 38.8%), when examining crude mortality between a propensity-matched SRS and WBRT cohort.²¹ Another study in 2016 claimed that SRS had a larger survival benefit than WBRT in the first 6 months after treatment for postoperative resection cavities ( P = .003).²² In our study, we also observed patients living longer with their diagnoses as median overall survival increased by 50% over the last decade. With patients’ post-diagnosis life expectancy increasing, the long-term neurocognitive effects of WBRT must be given greater consideration when developing treatment plans. Investigating the long-term survival rates and neurocognitive preservation for different RT strategies is therefore warranted in future studies.

Primary tumor subtype remains an important prognostic factor for BM patients. In consensus with existing literature, our study found that breast cancer patients (excluding TN subtypes) survived the longest following treatment.^{23 , 24} Within breast cancer subtypes, patients with luminal B and HER2 diagnoses demonstrated the greatest survival, both in this analysis and the literature.²⁵ Improved survival in BMs associated with HER2-positive breast cancer may be associated with the advent of newer agents such as Enhertu (T-DXd). T-DXd has been proven to have intracranial activity with minimal toxicity when treating advanced breast cancer patients with BMs.²⁶ Interestingly, within lung cancer subtypes, patients with SCLC had better survival following treatment than patients with SCC or NOS NSCLC subtypes. Other studies support that patients with SCLC have an increased risk of developing BMs; however, there is no evidence suggesting survival rates are lower among this subgroup compared with other lung cancer subtypes.²⁷

This study has several limitations to consider when interpreting results. The NCDB has limited available data, so all analyses used phase I RT data, which do not account for subsequent treatments, such as salvage SRS or WBRT. Furthermore, the NCDB lacks data on the size, number, or location of BMs as well as prognostic factors, such as performance score or tumor grade. It also does not include BM-specific surgical data, even though surgery remains an important treatment for BMs. Additionally, there is a lack of information regarding other downstream effects of BM treatments in the literature, such as leptomeningeal disease and radiation necrosis. Finally, because patients were partitioned into the general SRS and WBRT groups, it is possible that some treated with unconventional or experimental doses/fractions were excluded.

SRS usage over the last decade has increased nationwide due to relaxation of guidelines, improved techniques, and accessibility of technology. The increase in patient survival over this same period indicates a possible relationship between SRS usage and improved survival. Finally, patient characteristic discrepancies in RT usage should be explored to identify ways to overcome BM treatment limitations.