A new retrospective study provides some of the strongest support yet for considering first-line stereotactic radiosurgery (SRS) over whole-brain radiotherapy (WBRT) in carefully selected patients with brain metastases from small-cell lung cancer (SCLC), the researchers say.
As expected, WBRT was superior to focused SRS in lengthening the time to disease progression in the brain. However, this advantage did not appear to provide an improvement in overall survival (OS).
“This study suggests that the trade-offs inherent to first-line SRS without WBRT, including a shorter time to new brain metastases without an apparent difference in overall survival, may be similar to other settings where SRS alone is already well established,” lead author Chad Rusthoven, MD, told Medscape Medical News.
Upfront SRS may be “particularly attractive for SCLC patients with limited brain metastases and those at a higher risk of developing neurocognitive toxicity from WBRT, including older patients and those with a poor baseline performance status,” said Rusthoven, of the Department of Radiation Oncology, University of Colorado School of Medicine, Aurora.
Results of the FIRE-SCLC study – the largest analysis of first-line SRS for patients with SCLC brain metastases – were published online June 4 in JAMA Oncology.
The coauthors of an editorial in JAMA Oncology say the FIRE-SCLC study investigators should be “commended for conducting this important work and also for highlighting the inherent limitations of retrospective data.”
“Even after multivariable adjustment, OS may not be directly compared between the SRS and WBRT groups because selection bias is likely,” caution Cecile Le Pechoux, MD, and Antonin Levy, MD, PhD, from Institut Gustave-Roussy in Villejuif, France.
“Impressive” Outcomes
The researchers analyzed the outcomes of 710 patients (mean age, 68.5 years; 75% men; Karnofsky Performance Status score, ≥90) who underwent first-line SRS without prior treatment with WBRT or prophylactic cranial irradiation. They compared the SRS outcomes with outcomes of a cohort of 219 patients treated with first-line WBRT for SCLC brain metastases.
The SRS outcomes are “encouraging,” with a median OS of 8.5 months, median time to central nervous system (CNS) progression (TTCP) of 8.1 months, and median CNS progression-free survival (PFS) of 5.0 months, the study investigators say.
The outcomes are “particularly impressive” in patients with a single brain metastasis (median OS and TTCP, 11.0 months and 11.7 months, respectively), they note.
They found no significant differences in OS or TTCP after SRS in patients with two to four lesions and those with five to 10 lesions.
Median OS was 8.7 months with two to four lesions, 8.0 months with five to 10 lesions, and 5.5 months with 11 or more lesions. Corresponding median TTCP was 6.8, 6.1, and 4.7 months.
Local failures after SRS were rare. Most CNS progression occurred in the form of new lesions, which is in line with what’s been shown with SRS in other settings.
In propensity score–matched analyses that compared SRS with WBRT, median OS was higher with SRS (6.5 months vs 5.2 months with WBRT; P = .003). Median TTCP was improved with WBRT (SRS, 9.0 months vs WBRT, not reached; hazard ratio, 0.38; 95% confidence interval, 0.26 – 0.55; P < .001), with no significant difference in CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79).
The results were similar in multivariable analyses that compared SRS and WBRT, including subgroup analyses that controlled for extracranial metastases and extracranial disease control status.