A new retrospective study published in Advances in Radiation Oncology in November 2026 suggests that both single-fraction stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are feasible preoperative treatment approaches for patients undergoing surgical resection of brain metastases.
The study, titled “Preoperative Single-Fraction Versus Fractionated Stereotactic Radiation Therapy: A Single-Institutional Analysis of 299 Resected Metastases,” was conducted by Haley K. Perlow, Joshua D. Palmer, and colleagues at The Ohio State University Wexner Medical Center.
Among 299 resected brain metastases, both approaches were associated with relatively low rates of local failure, symptomatic radiation necrosis, and meningeal disease. Although fractionated treatment demonstrated numerically fewer local recurrences, the study did not establish a statistically significant difference in the primary composite outcome.
The findings contribute to growing interest in delivering stereotactic radiation before, rather than after, surgical resection of brain metastases.
Study Design and Patient Population
The single-institution retrospective analysis included 260 patients with 299 surgically resected brain metastases treated with preoperative stereotactic radiation between 2016 and 2023.
Patients were divided into two groups according to their preoperative radiation schedules:
- Single-fraction SRS: 64 metastases treated with 20 Gy in one fraction.
- Fractionated stereotactic radiotherapy (FSRT): 235 metastases treated with 24 Gy in three fractions or 25 Gy in five fractions.
Among lesions receiving FSRT, 92% were treated in three fractions, while approximately 8% received five fractions. The most common primary malignancies were lung cancer (48%), genitourinary cancers (14%), and melanoma (13%).
Nearly all metastases underwent gross total surgical resection following radiotherapy.
The primary endpoint was a composite of local failure, nodular meningeal disease, or grade 2 or higher symptomatic radiation necrosis. Outcomes were evaluated per lesion, while survival was assessed at the patient level.
Fractionated Radiotherapy Shows Numerically Lower Local Failure Rates
After a median follow-up of 10.4 months, local failure was uncommon in both treatment groups.
Local progression occurred in:
- 6.3% (4/64) of metastases treated with single-fraction SRS.
- 2.6% (6/235) of metastases treated with fractionated radiotherapy.
Although the local failure rate was numerically lower with FSRT, the difference was not statistically significant.
An important consideration is that patients receiving fractionated treatment generally had larger metastases. The median gross tumor volume was 10 cm³ with FSRT compared with 4 cm³ with single-fraction SRS, while the median planning target volume was 16 cm³ versus 6 cm³, respectively.
These differences reflect potential selection bias, as fractionation is frequently preferred for larger lesions to balance tumor control against radiation-related toxicity. The results suggest that preoperative FSRT can achieve favorable local control even in patients with larger brain metastases, although superiority over single-fraction treatment remains unproven.
Symptomatic Radiation Necrosis Remains Relatively Uncommon
Radiation necrosis is a clinically important complication of stereotactic brain radiotherapy, potentially causing neurological symptoms, edema, and the need for corticosteroids or additional interventions.
In this study, the incidence of grade 2 or higher radiation necrosis was:
- 6.3% (4/64) following single-fraction SRS.
- 8.9% (21/235) following FSRT.
The difference was not statistically significant.
Grade 3 radiation necrosis occurred in two SRS-treated metastases (3.1%) and nine FSRT-treated metastases (3.9%).
No grade 4 or higher radiation necrosis was reported.
The slightly higher numerical incidence with FSRT should be interpreted in the context of the significantly larger treatment volumes in that group.
Overall, both approaches demonstrated relatively low rates of symptomatic radiation necrosis during the available follow-up.
Meningeal Disease Rates Are Similar Between Treatment Approaches
Preoperative radiation has attracted interest because treating the intact metastasis before surgery may reduce viable tumor-cell dissemination during resection. This approach may potentially decrease the risk of leptomeningeal disease compared with postoperative irradiation.
In the current study, leptomeningeal disease occurred in 4.7% of metastases in both treatment groups.
Specifically:
- Three metastases in the single-fraction SRS group developed leptomeningeal disease.
- Eleven metastases in the FSRT group developed leptomeningeal disease.
Classical meningeal disease occurred in 4.7% of lesions treated with SRS and approximately 3.4% of those treated with FSRT. Nodular meningeal disease was not observed in the SRS group, compared with approximately 1.7% of lesions treated with FSRT.
These findings suggest that both preoperative strategies may offer acceptable meningeal disease outcomes, although longer follow-up and prospective comparisons are needed.
Composite Endpoint Shows No Significant Difference.
The study’s primary composite endpoint combined three clinically relevant adverse outcomes: local failure, symptomatic radiation necrosis, and nodular meningeal disease.
The composite endpoint occurred in:
- 11% (7/64) of metastases receiving single-fraction SRS.
- 12% (28/235) of metastases receiving FSRT.
After adjustment for treatment method, patient characteristics, number of lesions, and tumor volume, the hazard ratio for the composite endpoint was 0.65 (95% CI, 0.25–1.71) for FSRT compared with SRS.
Although the point estimate numerically favored FSRT, the wide confidence interval and lack of statistical significance mean that the study cannot establish superiority or equivalence between the two strategies.
A sensitivity analysis restricted to patients with overlapping tumor volumes produced a similar direction of association, but uncertainty remained substantial.
The findings therefore support the feasibility of both approaches rather than identifying a preferred preoperative fractionation schedule.
Overall Survival and Clinical Outcomes
The estimated 12-month overall survival probability across the study population was 57% (95% CI, 51–64%).
The adjusted hazard ratio for mortality among patients receiving FSRT compared with SRS was 1.23 (95% CI, 0.79–1.93), without a statistically significant difference.
The study was not designed to demonstrate an overall survival advantage for either fractionation approach.
Furthermore, differences in tumor burden, extracranial disease status, and treatment selection may have influenced survival outcomes.
The investigators emphasized that outcomes following preoperative radiation should be interpreted within the broader context of disease prognosis and multidisciplinary treatment planning.
What Do These Findings Mean for Clinical Practice?
Surgical resection followed by postoperative stereotactic radiation remains an established treatment strategy for selected patients with large or symptomatic brain metastases. However, preoperative stereotactic radiotherapy is increasingly being investigated as an alternative that may reduce treatment-related complications while preserving local tumor control.
Potential advantages include treating a clearly defined intact tumor rather than an irregular postoperative cavity and sterilizing viable tumor cells before surgical manipulation.
The current findings suggest that both single-fraction and fractionated preoperative stereotactic radiation can achieve relatively favorable early outcomes.
Nevertheless, several limitations must be considered. The retrospective, nonrandomized design introduces selection bias, particularly because larger metastases were more frequently treated with fractionated radiotherapy.
The median follow-up of approximately 10 months may also underestimate late radiation necrosis and subsequent local or meningeal failures. Additionally, the study included relatively few adverse events, limiting statistical power, and patient-reported quality of life and neurocognitive outcomes were not collected.
Importantly, the analysis directly compared two preoperative radiation approaches rather than preoperative versus postoperative treatment. Therefore, any apparent advantages over postoperative SRS remain based on comparisons with historical data rather than the study’s own randomized evidence.
Toward More Individualized Preoperative Radiotherapy
The study adds to the growing evidence supporting preoperative stereotactic radiation as a potential treatment strategy for patients with resectable brain metastases. Both single-fraction SRS and fractionated stereotactic radiotherapy demonstrated low observed rates of local failure, symptomatic radiation necrosis, and meningeal disease.
Although fractionated treatment showed numerically lower local failure rates, the study did not demonstrate a statistically significant advantage over single-fraction treatment.
The findings suggest that fractionation can be individualized according to tumor size, location, and surrounding critical structures, while emphasizing the need for prospective randomized comparisons.
Further evaluation in larger, matched patient populations and ongoing clinical trials will be important to determine whether fractionated preoperative radiotherapy offers meaningful improvements in disease control, toxicity, and patient outcomes.
