Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm

Yuping Derek LiDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;

Search for other papers by Yuping Derek Li in
jns
Google Scholar
PubMed
Close
 MD
,
Andrew T. CoxonDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;

Search for other papers by Andrew T. Coxon in
jns
Google Scholar
PubMed
Close
 BS
,
Jiayi HuangDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Jiayi Huang in
jns
Google Scholar
PubMed
Close
 MD
,
Christopher D. AbrahamDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Christopher D. Abraham in
jns
Google Scholar
PubMed
Close
 MD
,
Joshua L. DowlingDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Joshua L. Dowling in
jns
Google Scholar
PubMed
Close
 MD
,
Eric C. LeuthardtDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Eric C. Leuthardt in
jns
Google Scholar
PubMed
Close
 MD
,
Gavin P. DunnDepartment of Neurosurgery, Harvard Medical School, Boston, Massachusetts;

Search for other papers by Gavin P. Dunn in
jns
Google Scholar
PubMed
Close
 MD
,
Albert H. KimDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Albert H. Kim in
jns
Google Scholar
PubMed
Close
 MD
,
Ralph G. DaceyDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Ralph G. Dacey in
jns
Google Scholar
PubMed
Close
 MD
,
Gregory J. ZipfelDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and

Search for other papers by Gregory J. Zipfel in
jns
Google Scholar
PubMed
Close
 MD
,
John EvansDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;

Search for other papers by John Evans in
jns
Google Scholar
PubMed
Close
 BS
,
Eric A. FiliputDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

Search for other papers by Eric A. Filiput in
jns
Google Scholar
PubMed
Close
 BS
, and
Michael R. ChicoineDepartment of Neurosurgery, Washington University School of Medicine, St. Louis;
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;
The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis; and
Department of Neurosurgery, University of Missouri, Columbia, Missouri

Search for other papers by Michael R. Chicoine in
jns
Google Scholar
PubMed
Close
 MD
Free access

OBJECTIVE

For patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity during surgery. A neoadjuvant (preoperative) approach to radiation therapy avoids these limitations and offers improved patient convenience. This study assessed the efficacy of neoadjuvant SRS as a new treatment paradigm for patients with brain metastases.

METHODS

A retrospective review was performed at a single institution to identify patients who had undergone neoadjuvant SRS (specifically, Gamma Knife radiosurgery) followed by resection of a brain metastasis. Kaplan-Meier survival and log-rank analyses were used to evaluate risks of progression and death. Assessments were made of local recurrence and leptomeningeal spread. Additionally, an analysis of the contemporary literature of postoperative and neoadjuvant SRS for metastatic disease was performed.

RESULTS

Twenty-four patients who had undergone neoadjuvant SRS followed by resection of a brain metastasis were identified in the single-institution cohort. The median age was 64 years (range 32–84 years), and the median follow-up time was 16.5 months (range 1 month to 5.7 years). The median radiation dose was 17 Gy prescribed to the 50% isodose. Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months. In 4 patients who had local treatment failure, salvage therapy included repeat resection, laser interstitial thermal therapy, or repeat SRS. One hundred thirty patients (including the current cohort) were identified in the literature who had been treated with neoadjuvant SRS prior to resection. Overall rates of local control at 1 year after neoadjuvant SRS treatment ranged from 49% to 91%, and rates of leptomeningeal dissemination from 0% to 16%. In comparison, rates of local control 1 year after postoperative SRS ranged from 27% to 91%, with 7% to 28% developing leptomeningeal disease.

CONCLUSIONS

Neoadjuvant SRS for the treatment of brain metastases is a novel approach that mitigates the shortcomings of postoperative SRS. While additional prospective studies are needed, the current study of 130 patients including the summary of 106 previously published cases supports the safety and potential efficacy of preoperative SRS with potential for improved outcomes compared with postoperative SRS.

ABBREVIATIONS

GKRS = Gamma Knife radiosurgery; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy.

OBJECTIVE

For patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity during surgery. A neoadjuvant (preoperative) approach to radiation therapy avoids these limitations and offers improved patient convenience. This study assessed the efficacy of neoadjuvant SRS as a new treatment paradigm for patients with brain metastases.

METHODS

A retrospective review was performed at a single institution to identify patients who had undergone neoadjuvant SRS (specifically, Gamma Knife radiosurgery) followed by resection of a brain metastasis. Kaplan-Meier survival and log-rank analyses were used to evaluate risks of progression and death. Assessments were made of local recurrence and leptomeningeal spread. Additionally, an analysis of the contemporary literature of postoperative and neoadjuvant SRS for metastatic disease was performed.

RESULTS

Twenty-four patients who had undergone neoadjuvant SRS followed by resection of a brain metastasis were identified in the single-institution cohort. The median age was 64 years (range 32–84 years), and the median follow-up time was 16.5 months (range 1 month to 5.7 years). The median radiation dose was 17 Gy prescribed to the 50% isodose. Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months. In 4 patients who had local treatment failure, salvage therapy included repeat resection, laser interstitial thermal therapy, or repeat SRS. One hundred thirty patients (including the current cohort) were identified in the literature who had been treated with neoadjuvant SRS prior to resection. Overall rates of local control at 1 year after neoadjuvant SRS treatment ranged from 49% to 91%, and rates of leptomeningeal dissemination from 0% to 16%. In comparison, rates of local control 1 year after postoperative SRS ranged from 27% to 91%, with 7% to 28% developing leptomeningeal disease.

CONCLUSIONS

Neoadjuvant SRS for the treatment of brain metastases is a novel approach that mitigates the shortcomings of postoperative SRS. While additional prospective studies are needed, the current study of 130 patients including the summary of 106 previously published cases supports the safety and potential efficacy of preoperative SRS with potential for improved outcomes compared with postoperative SRS.

Brain metastases are one of the most common neurological complications of cancer, occurring in approximately 20% of all patients with cancer.1 In addition, with increased surveillance imaging and detection rates as well as improved systemic treatments, the incidence of brain metastases continues to rise.1 Management of brain metastases involves a combination of radiation therapy, resection, and, in certain cancers, immunotherapy and targeted small molecule inhibitors.24

For patients with solitary brain metastases or oligometastatic disease (≤ 5 lesions), resection is an effective therapy with increased survival and duration of functional independence, but local recurrence rates of up to 50% have been reported after surgery alone.5,6 Consequently, postoperative radiation therapy is recommended and has been demonstrated in multiple studies including randomized prospective trials to decrease the risk of local recurrence.5,7,8,31 Traditionally, postoperative whole-brain radiation therapy (WBRT) was recommended after resection of cerebral metastases for disease control, but because of the risks of long-term neurotoxicity and cognitive dysfunction, there has been a paradigm shift toward stereotactic radiosurgery (SRS) after resection for solitary metastases or oligometastatic disease.710 Multiple studies have shown that SRS provides effective tumor control, as well as maintenance of a higher quality of life in comparison with postoperative WBRT.11,12 There remain several practical challenges with coordinating postoperative radiosurgery. Targeting of the tumor resection cavity for SRS may be challenging due to the irregular margins of the tumor resection and other postoperative changes on imaging.13 Medical and neurological complications of surgery as well as waiting for adequate wound healing can result in delayed radiation treatment. Additionally, there is a risk of "seeding" tumor cells to intracranial or spinal sites distant from the tumor cavity itself during surgery, leading to further metastatic or leptomeningeal disease and potentially decreasing the efficacy of postoperative radiation therapy.14 Furthermore, recent data have suggested that if SRS is delayed more than 4 weeks after surgery, local recurrence at the site of resection is higher, indicating that the efficiency of completion surgery and radiosurgery can be clinically important.15

To mitigate these limitations of postoperative SRS, a neoadjuvant (preoperative) approach to radiosurgery has been gaining interest but has not been widely adopted or reported in larger series. Initial studies have demonstrated neoadjuvant SRS as a safe and effective treatment strategy with comparable rates of local disease control.1619 Here, we report a single-institution experience with neoadjuvant SRS combined with resection in 24 patients with brain metastases, and we analyze and summarize cases reported in the literature to date on this strategy.

Methods

Records Review

The study was completed with IRB approval using data from a single center extracted from a multicenter database of patients undergoing procedures for brain tumors and other conditions.2029 Data were collected and managed via Research Electronic Data Capture (REDCap)30 servers, and the database was approved by the IRB at the host institution. Patients undergoing neoadjuvant Gamma Knife radiosurgery (GKRS) for the treatment of brain metastases were retrospectively identified by cross-referencing a radiosurgery treatment database with a surgical database. Neoadjuvant GKRS (either Perfexion or Icon, Elekta AB) was performed prior to craniotomy for resection of brain metastases. Preoperative SRS dosing was selected based on a consensus between the radiation oncologist and neurosurgeon at the time of treatment based on tumor diameter and volume. Over time, there was a gradual increase in radiation dosage based on physician experience as well as with emerging literature suggesting a higher dose escalation for larger brain metastases.31

Medical records of identified patients were reviewed to obtain demographic information, including age, sex, Eastern Cooperative Oncology Group performance scores, prior cranial radiation treatments, and time from SRS to surgery. Radiation treatment records, oncology treatment records, surgical pathology reports, and radiology reports were also reviewed for each patient. A retrospective analysis was subsequently performed to examine the clinical experience of these patients. Primary outcome measures were local progression-free survival, defined as the time of total freedom from local recurrence in the tumor bed, and overall survival.

Statistical Analysis

All statistical analyses were performed using IBM SPSS (version 28, IBM Corp.) and Prism version 9 (GraphPad). The endpoints of interest were local progression-free survival as defined above and overall survival, measured as the time from SRS to the date of death or date of last follow-up. The independent variables analyzed included maximum tumor diameter (> 3 cm), tumor volume (> 10 cm3), dose (> 16 Gy), and primary diagnosis (e.g., breast, lung, and melanoma) for both overall survival and local control. Survival curves were estimated by Kaplan-Meier analysis, and the log-rank test was used to determine significant differences in survival between cohorts; p < 0.05 was considered statistically significant.

Literature Review

A literature review and tabulation of contemporary studies of postoperative and neoadjuvant SRS for metastatic disease was performed using the PubMed database. Five neoadjuvant SRS studies (including the present study) have been published to date. Twenty-two postoperative SRS studies with local recurrence rate and leptomeningeal disease rate data were included for comparison purposes. Postoperative SRS studies were reviewed by two authors (Y.D.L. and M.R.C.) with regard to relevance prior to inclusion. In total, 130 patients underwent neoadjuvant SRS and 2180 patients underwent postoperative SRS. Rates of local disease control and leptomeningeal dissemination were extracted from each study when possible.

Results

Illustrative Case

A 64-year-old woman was diagnosed with lung cancer seen on chest radiography after a fall. On further staging workup, brain MRI demonstrated a contrast-enhancing left frontal lesion (Fig. 1). On examination, the patient was neurologically intact. She underwent SRS (15 Gy to 50% isodose line) followed by left frontal craniotomy for tumor resection the next day. After surgery, the patient recovered overnight in the neurointensive care unit per protocol and was discharged home on postoperative day 1. At 6 months postsurgery, surveillance MRI demonstrated four new distant brain metastases that were then treated with SRS alone. At 2 years of follow-up, the patient has not had any further disease progression or local recurrence of the resected metastasis. This case highlights how neoadjuvant SRS expedites tumor treatment and can be particularly convenient for patients.

FIG. 1.
FIG. 1.

T1-weighted postcontrast MR images of the brain. A: A rim-enhancing left frontal lesion with surrounding vasogenic edema is seen on axial, coronal, and sagittal images. B: SRS radiation therapy protocol, 15 Gy to the 50% isodose line on axial, coronal, and sagittal images. C: Axial postoperative image demonstrating gross-total resection.

Patient Cohort

Twenty-four patients were identified who had undergone neoadjuvant SRS followed by resection. Patient characteristics at the time of SRS are summarized in Table 1. The patients’ median age was 64 years (range 32–84 years), and 15 patients (62.5%) were female. The median follow-up duration was 16.5 months (range 1–69 months). The median duration between preoperative SRS and resection was 2 days (range 0–9 days). The median maximum diameter of the lesions was 3.0 cm (range 1.60–3.60 cm), and the median tumor volume was 10.1 cm3 (range 1.8–14.9 cm3). The median delivered dose was 17 Gy (range 14–21 Gy) prescribed to the 50% isodose line. There were no perioperative difficulties with wound infections or other surgical complications, and no perioperative mortality was observed.

TABLE 1.

Patient demographics of the single-institution retrospective case series

Value
No. of pts24
Median age at SRS (range), yrs64 (32–84)
Sex, n (%)
 Female15 (62.5)
 Male9 (37.5)
ECOG performance status, n (%)
 09 (37.5)
 114 (58.3)
 ≥21 (4.2)
Histology, n (%)
 Lung10 (41.7)
 Breast5 (20.8)
 Melanoma2 (8.3)
 Other (colorectal, renal cell, thyroid, neuroendocrine, ovarian)7 (29.2)
Median tumor vol (range), cm310.1 (1.8–14.9)
Median tumor diameter (range), cm3.0 (1.6–3.6)
Median radiation dose to 50% isodose line (range), Gy17 (14–21)
Median follow-up (range), mos16.5 (1–69)

ECOG = Eastern Cooperative Oncology Group; pt = patient.

The median overall survival was 2.2 years, with 75.0% survival at 6 months and 70.0% survival at 12 months (Fig. 2A). Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months (Fig. 2B). The overall distant failure rate was 54.2%, with a median overall progression-free survival of 11 months. Of the 13 patients who developed distant intracranial disease, 11 underwent additional GKRS for the new lesions, and two underwent salvage WBRT.

FIG. 2.
FIG. 2.

Overall survival (A) and local progression-free survival (B) for the single-institution cohort of 24 patients.

The tumor in one of the 4 patients with local treatment failure was pathologically confirmed to be recurrent tumor after a repeat craniotomy for resection. The other 3 patients with local treatment failure had surveillance imaging that demonstrated increased contrast enhancement in the tumor bed, which was favored to be tumor recurrence following review by a multidisciplinary team (radiologist, neurosurgeon, medical oncologist, and radiation oncologist). One patient underwent laser interstitial thermal therapy (without biopsy) and the other two had repeat SRS to the area of contrast enhancement. None of the patients in our cohort developed leptomeningeal carcinomatosis.

On univariate analysis, local disease progression was more likely in patients with a tumor volume > 10 cm3 (p = 0.025; Fig. 3A) and a maximum tumor diameter ≥ 3.0 cm (p = 0.005; Fig. 3B). These parameters were also associated with decreased overall survival (p < 0.05; Fig. 4). Radiation dose was not associated with statistically significant differences in overall survival or local disease control.

FIG. 3.
FIG. 3.

Kaplan-Meier plots of local progression-free survival for the single-institution cohort of 24 patients comparing tumors by volume (A) or by maximum tumor diameter (B). Local progression is more likely in larger tumors.

FIG. 4.
FIG. 4.

Kaplan-Meier plots of overall survival for the single-institution cohort of 24 patients comparing tumors by volume (A) and by maximum tumor diameter (B). Patients with larger tumors had decreased overall survival.

Literature Review

In the literature, 130 patients were treated with neoadjuvant SRS, and 2180 patients underwent postoperative SRS (Table 2). The median follow-up ranged from 7 to 49 months. All studies on neoadjuvant SRS were retrospective in nature except for data from 24 patients that were collected prospectively in the study by Asher et al.16 Rates of local disease control and leptomeningeal dissemination are reported in Table 2. In patients who underwent preoperative SRS, rates of local disease control ranged from 49% to 91% compared with 27% to 91% for postoperative SRS (Fig. 5A). Rates of leptomeningeal dissemination ranged from 0% to 16% in patients after neoadjuvant SRS (Fig. 5B) compared with 7% to 28% for postoperative SRS.

TABLE 2.

Studies of postoperative and preoperative SRS

Authors & YearNo. of PtsMedian Follow-Up (mos)Local Control RateLeptomeningeal Dissemination
Neoadjuvant SRS studies
 Current series2416 87.6% at 1 yr, 73.5% at 2 yrsNone
 Udovicich et al., 2022192812.891.3% at 1 yr4% at 1 yr
 Patel et al., 2018531213 82% at 6 mos, 49% at 1 yr16% at 1 yr
 Patel et al., 201617*6611.1 84.1% at 1 yr3.2% at 2 yrs
 Asher et al., 2014164712 85.6% at 1 yr, 71.8% at 2 yrsNone
Postop SRS studies
 Bander et al., 20213428249 85.7% at 5 yrs14.9% at 5 yrs
 Bachmann et al., 2019387511.2 72% at 1 yrNR
 Mahajan et al., 20173613211.1 72% at 1 yr vs 43% w/ op alone28% at 1 yr
 Brown et al., 20173319411.1 80.4% at 6 mos, 60.5% at 1 yr7.2% at 1 yr
 Patel et al., 201617*11411.1 87.4% at 1 yr16.6% at 2 yrs
 Rava et al., 201639877.1 82% at 1 yrNR
 Johnson et al., 2016401129 84.4% at 1 yr16.9% at 1 yr
 Strauss et al., 20154110016.3 84% at 1 yr9.8% at 1 yr
 Abel et al., 2015428516.4 87% at 1 yrNR
 Ojerholm et al., 201443919.8 81% at 1 yrNR
 Iorio-Morin et al., 2014441101084% at 6 mos, 73% at 1 yr11% at 1 yr
 Brennan et al., 2014454912 78% at 1 yrNR
 Atalar et al., 20134616512.4 91.2% at 1 yr & 87.0% at 2 yrs11% at 1 yr
 Luther et al., 20134712012.6 87% at 1 yrNR
 Kelly et al., 2012481712.7 89% at 1 yrNR
 Robbins et al., 2012498511.2 81.4% at 1 yrNR
 Prabhu et al., 201252629.7 78% at 1 yrNR
 Rwigema et al., 2011507713.8 76% at 1 yrNR
 Jensen et al., 201151106NR80.3% at 1 yr7% overall
 Limbrick et al., 200971520 26.7% at 1 yr (2 pts had STR)NR
 Soltys et al., 200813728.188% at 6 mos & 79% at 1 yrNR
 Do et al., 2009830NR82% at 1 yrNR

NR = not reported; STR = subtotal resection.

Preoperative and postoperative SRS cohorts from the Patel et al. 2016 study were included in both categories.

FIG. 5.
FIG. 5.

Comparison of rates of local disease control and leptomeningeal dissemination in the literature. A: Comparison of rates of local control at 1 year in studies of neoadjuvant SRS (light gray bars) and postoperative SRS (dark gray bars). B: Comparison of rates of leptomeningeal dissemination in studies of neoadjuvant SRS and postoperative SRS. Horizontal dashed lines demarcate the weighted average among each treatment group.

Discussion

Brain metastases and their associated deficits are among the most debilitating sequelae experienced by patients with cancer. Previously, WBRT was a fundamental component of treatment after Patchell et al. demonstrated that local recurrence rates were as high as 50% in the absence of adjuvant WBRT after resection of solitary metastases.5 However, WBRT is associated with multiple potential toxicities including hair loss, fatigue, and neurocognitive decline.32 Chang et al. conducted a randomized controlled trial demonstrating a decrease in learning and memory function by 4 months in patients treated with WBRT in addition to SRS in comparison with SRS alone.9 Consequently, investigators challenged the necessity of WBRT, particularly as focused therapies such as SRS were becoming more readily available. Brown et al. demonstrated that there was no difference in overall survival between postoperative WBRT and SRS, but decline in cognitive function was more frequent with WBRT.33 A recent retrospective study also confirmed that adjuvant SRS provides durable local control up to 5 years.34

While adjuvant SRS has become a mainstay of treatment, there are several limitations.35 Delineation of the radiation target for postoperative SRS is often a challenge given the irregular contours of the resection cavity and the postoperative changes on imaging. Local recurrence rates following postoperative SRS are not insignificant, with a rate as high as 44% at 1 year for lesions greater than 3 cm in diameter.36 In addition, Nguyen et al. reported that patients who had SRS to the resection cavities versus intact lesions were at increased risk of developing leptomeningeal disease.37 One explanation is that tumor cells may be "spilled" during surgery, resulting in viable cells that can persist outside of the radiation treatment volume. By treating the tumor with radiosurgery prior to surgery, any spilled tumor cells would have been irradiated and thus less likely to be replication competent. Preoperative SRS also requires less complex target delineation when contouring an intact tumor. Higher marginal tumor doses may be tolerated with neoadjuvant SRS, as resection of the lesion after SRS may alleviate some of the edema or other possible delayed consequences of SRS. Coordination of SRS in the postoperative period may be confounded by competing needs for patient rehabilitation and recovery after surgery. Delays in the initiation of SRS after surgery decrease its efficacy; time from surgery to SRS of greater than 38 days resulted in significantly decreased local control rates in one study.34 By undergoing SRS within 1 to 2 days prior to surgery, patients can move from diagnosis to completion of treatment in a shorter period of time. In some cases, SRS and craniotomy for resection can be performed on the same day, which expedites tumor treatment and can be particularly convenient for patients.

The current study demonstrated that neoadjuvant SRS can be a safe and effective treatment strategy for brain metastases. In our single-institution cohort, neoadjuvant SRS provided effective local control with rates of 100% at 6 months and 87.6% at 12 months. No cases of leptomeningeal carcinomatosis were identified in this study group. These data are consistent with previous studies by Asher et al., Patel et al., and Udovicich et al., as summarized in Table 2.1619 From our review of the literature, rates of local control are comparable between preoperative SRS and postoperative SRS (Table 2).7,8,13,16,17,19,33,34,36,3853 Rates of local disease control at 1 year were extracted from the listed studies, and then a weighted average was calculated based on the number of patients included in each study. In patients who received neoadjuvant SRS prior to resection, the average rate of local control was 82.8% compared with 78.8% in patients who had postoperative SRS (Fig. 5A).

Brown et al. demonstrated that WBRT results in decreased rates of leptomeningeal disease compared with postoperative SRS.33 Comparing WBRT and preoperative neoadjuvant SRS, Patel et al. reported similar rates of leptomeningeal disease, although further confirmatory and neurocognitive studies are needed.18 From the cases in the literature analyzed in this study, the weighted average rate of leptomeningeal disease in neoadjuvant SRS studies was 4.1% compared with 13.2% in postoperative SRS studies (Fig. 5B). This could be due to the aforementioned preirradiation effect, which prevents the dissemination of replication-competent tumor cells at the time of surgery. While the data suggest that preoperative SRS provides similar rates of local disease control with decreased leptomeningeal disease, there are also several limitations to this approach. One potential disadvantage of neoadjuvant SRS is that the radiation is delivered prior to pathologic diagnosis. This is mitigated by modern developments in MRI such as perfusion and spectroscopy, resulting in an approximate risk of misdiagnosis in patients with a recent history of systemic cancer to be less than 3%, and typically patients have a tissue diagnosis from the primary site of the malignancy or another site of metastasis.16 In their cohort, Asher et al. reported 1 case of presumed metastatic neuroendocrine carcinoma that was discovered to be glioblastoma after SRS and resection.16 A second disadvantage concerns wound healing. Often following resection, patients will have a grace period prior to starting adjuvant radiation therapy to allow for the wound to mature. This grace period is forgone in the setting of neoadjuvant SRS. However, in our cohort of 24 patients, there were no wound complications noted. Lastly, while preoperative SRS has the potential to offer patients convenience and expedited treatment, feasibility and care coordination provide a challenge to making preoperative SRS widely available.

With regard to radiation dosing, a recent phase I study by Qiao-Guan et al. demonstrated that larger brain metastases (> 2–3 cm in diameter) could be treated with 22 Gy with a reasonable risk of acute toxicity and radiation necrosis.31 A fractionated SRS approach has also been suggested, with the goal of improved local control following delivery of higher biological effective doses. This strategy has been studied primarily in the setting of postoperative SRS, but Palmer et al. recently demonstrated that fractionated preoperative SRS may offer improved rates of local disease recurrence, radiation necrosis, and leptomeningeal disease compared with postoperative SRS as well as single-fraction preoperative SRS.54 Faruqi et al. reported that the risks of adverse radiation effects were higher in patients who underwent fractionated SRS for intact lesions compared with resection cavities.55 Of note, the median planning target volume was significantly smaller in the cohort of intact lesions. Also, in their study, patients who received SRS to intact lesions were not planning for resection. Thereby, the higher rate of symptomatic adverse radiation effects could be in part due to mass effect from the unresected tumor. In addition to the other limitations of preoperative SRS, fractionated SRS delivery requires more patient follow-up and compliance. Also, given the time course of fractionated SRS therapy, patients with large or symptomatic brain metastases are less likely to be able to tolerate the delay to surgery.

Given the retrospective nature and nonrandomized selection of the 24 patients who underwent preoperative SRS, these data are limited by selection bias. Most patients who underwent preoperative SRS presented in an outpatient setting, as this approach requires careful coordination between multiple medical specialties. In the single-institution cohort, 7 patients were treated between 2011 and 2016 compared with 17 patients treated between 2017 and 2021, suggesting that the process for setting up neoadjuvant SRS became more streamlined and available over time. Prospective randomized trials comparing preoperative SRS with postoperative SRS are currently ongoing, including the Mayo Clinic study (ClinicalTrials.gov identifier NCT03750227). In summary, while data from these prospective trials are still needed, the development of a neoadjuvant SRS treatment pathway could provide a new and potentially improved treatment paradigm for patients with brain metastases.

Conclusions

For patients who undergo resection for solitary brain metastases or oligometastatic disease, the current treatment paradigm often includes postoperative SRS. This strategy has several limitations with regard to SRS planning and treatment in the postoperative period. Neoadjuvant SRS is a novel approach that circumvents many of those challenges. In patients with oligometastatic disease, neoadjuvant SRS provides effective and potentially improved local disease control, diminished postoperative leptomeningeal spread, and logistical benefits for patients including expedited completion of the combination SRS and resection. While large-volume studies are needed to further characterize the risks and benefits of a neoadjuvant radiosurgery regimen, the current study confirms the favorable outcomes previously demonstrated in multiple single-institution studies, particularly the low rate of leptomeningeal disease. In conjunction with recent studies examining dose escalation and fractionated delivery of SRS for brain metastases,31,54 this study helps to lay the groundwork for prospective trials utilizing more aggressive SRS dosing in combination with preoperative radiosurgery.

Acknowledgments

I-MiND is maintained in The REDCap server at Washington University in St. Louis and is supported by Clinical and Translational Science Award (CTSA) Grant (UL1 TR000448) and The Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant (P30 CA091842).

Disclosures

Dr. Chicoine: funding from IMRIS Inc. for an unrestricted educational grant to support an intraoperative MRI and brain tumor database and outcomes analysis project (the IMRIS Multicenter intraoperative MRI Neurosurgery Database [I-MiND]), The Head for the Cure Foundation, Mrs. Carol Rossfeld and The Alex & Alice Aboussie Family Charitable Foundation, and Mr. and Mrs. Barbara and George Holtzman. Dr. Dunn: cofounder of Immunovalent. Dr. Kim: consultant for Monteris Medical and non–study-related clinical or research effort from Monteris Medical, Stryker, and Collagen Matrix. Dr. Zipfel: grant funding via the NIH National Institute of Neurological Disorders and Stroke (NINDS). Dr. Leuthardt: ownership in Neurolutions, Sora Neuroscience, Inner Cosmos, and Inner Cosmos; and consultant for E15.

Author Contributions

Conception and design: Li, Huang, Abraham, Chicoine. Acquisition of data: Li, Coxon, Evans, Filiput. Analysis and interpretation of data: Li, Coxon. Drafting the article: Li. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Li. Study supervision: Chicoine.

References

  • 1

    Sacks P, Rahman M. Epidemiology of brain metastases. Neurosurg Clin N Am. 2020;31(4):481488.

  • 2

    Nieblas-Bedolla E, Nayyar N, Singh M, Sullivan RJ, Brastianos PK. Emerging immunotherapies in the treatment of brain metastases. Oncologist. 2021;26(3):231241.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Niranjan A, Lunsford LD, Ahluwalia MS. Targeted therapies for brain metastases. Prog Neurol Surg. 2019;34:125137.

  • 4

    Arvold ND, Lee EQ, Mehta MP, et al. Updates in the management of brain metastases. Neuro Oncol. 2016;18(8):10431065.

  • 5

    Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):14851489.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494500.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Limbrick DD Jr, Lusis EA, Chicoine MR, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol. 2009;71(3):280289.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Do L, Pezner R, Radany E, Liu A, Staud C, Badie B. Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases. Int J Radiat Oncol Biol Phys. 2009;73(2):486491.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):10371044.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Sahgal A, Aoyama H, Kocher M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710717.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Chang EL, Wefel JS, Maor MH, et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery. 2007;60(2):277284.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Serizawa T, Ono J, Iichi T, et al. Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non-small cell carcinoma. J Neurosurg. 2002;97(5 suppl):484488.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Soltys SG, Adler JR, Lipani JD, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2008;70(1):187193.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Jung JM, Kim S, Joo J, Shin KH, Gwak HS, Lee SH. Incidence and risk factors for leptomeningeal carcinomatosis in breast cancer patients with parenchymal brain metastases. J Korean Neurosurg Soc. 2012;52(3):193199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Roth O’Brien DA, Kaye SM, Poppas PJ, et al. Time to administration of stereotactic radiosurgery to the cavity after surgery for brain metastases: a real-world analysis. J Neurosurg. 2021;135(6):16951705.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Asher AL, Burri SH, Wiggins WF, et al. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014;88(4):899906.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Patel KR, Burri SH, Asher AL, et al. Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery. 2016;79(2):279285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Patel KR, Burri SH, Boselli D, et al. Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis. J Neurooncol. 2017;131(3):611618.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Udovicich C, Ng SP, Tange D, Bailey N, Haghighi N. From postoperative to preoperative: a case series of hypofractionated and single-fraction neoadjuvant stereotactic radiosurgery for brain metastases. Oper Neurosurg (Hagerstown). 2022;22(4):208214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Akbari SHA, Sylvester PT, Kulwin C, et al. Initial experience using intraoperative magnetic resonance imaging during a trans-sulcal tubular retractor approach for the resection of deep-seated brain tumors: a case series. Oper Neurosurg (Hagerstown). 2019;16(3):292301.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Chicoine MR. Low subfrontal dural opening for anterior clinoid meningioma. J Neurol Surg B Skull Base. 2018;79(suppl 3):S273S275.

  • 22

    Hawasli AH, Rubin JB, Tran DD, et al. Antiangiogenic agents for nonmalignant brain tumors. J Neurol Surg B Skull Base. 2013;74(3):136141.

  • 23

    Karsy M, Akbari SH, Limbrick D, et al. Evaluation of pediatric glioma outcomes using intraoperative MRI: a multicenter cohort study. J Neurooncol. 2019;143(2):271280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Leuthardt EC, Lim CCH, Shah MN, et al. Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience. Neurosurgery. 2011;69(1):194206.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Shah MN, Leonard JR, Inder G, et al. Intraoperative magnetic resonance imaging to reduce the rate of early reoperation for lesion resection in pediatric neurosurgery. J Neurosurg Pediatr. 2012;9(3):259264.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Sylvester PT, Evans JA, Zipfel GJ, et al. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas. Pituitary. 2015;18(1):7285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Yahanda AT, Patel B, Shah AS, et al. Impact of intraoperative magnetic resonance imaging and other factors on surgical outcomes for newly diagnosed grade II astrocytomas and oligodendrogliomas: a multicenter study. Neurosurgery. 2020;88(1):6373.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Yahanda AT, Patel B, Sutherland G, et al. A multi-institutional analysis of factors influencing surgical outcomes for patients with newly diagnosed grade I gliomas. World Neurosurg. 2020;135:e754e764.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Zenga J, Sharon JD, Santiago P, et al. Lower trapezius flap for reconstruction of posterior scalp and neck defects after complex occipital-cervical surgeries. J Neurol Surg B Skull Base. 2015;76(5):397408.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Qiao-Guan G, Murphy ES, Suh JH, et al. Dose escalation for larger brain metastases: a phase I study. Int J Radiat Oncol Biol Phys. 2019;105(1):E87E88.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Gaspar LE, Mehta MP, Patchell RA, et al. The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):1732.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):10491060.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Bander ED, Yuan M, Reiner AS, et al. Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. Neurooncol Pract. 2021;8(3):278289.

    • Search Google Scholar
    • Export Citation
  • 35

    Tsao MN, Rades D, Wirth A, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):10401048.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Nguyen TK, Sahgal A, Detsky J, et al. Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases. Neuro Oncol. 2020;22(1):8493.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38

    Bachmann N, Leiser D, Ermis E, et al. Impact of regular magnetic resonance imaging follow-up after stereotactic radiotherapy to the surgical cavity in patients with one to three brain metastases. Radiat Oncol. 2019;14(1):45.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Rava P, Rosenberg J, Jamorabo D, et al. Feasibility and safety of cavity-directed stereotactic radiosurgery for brain metastases at a high-volume medical center. Adv Radiat Oncol. 2016;1(3):141147.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Johnson MD, Avkshtol V, Baschnagel AM, et al. Surgical resection of brain metastases and the risk of leptomeningeal recurrence in patients treated with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2016;94(3):537543.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Strauss I, Corn BW, Krishna V, et al. Patterns of failure after stereotactic radiosurgery of the resection cavity following surgical removal of brain metastases. World Neurosurg. 2015;84(6):18251831.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Abel RJ, Ji L, Yu C, et al. Stereotactic radiosurgery to the resection cavity for brain metastases: prognostic factors and outcomes. J Radiosurg SBRT. 2015;3(3):179186.

    • Search Google Scholar
    • Export Citation
  • 43

    Ojerholm E, Lee JYK, Thawani JP, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(suppl):75-83

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44

    Iorio-Morin C, Masson-Côté L, Ezahr Y, Blanchard J, Ebacher A, Mathieu D. Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121(suppl):69-74

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45

    Brennan C, Yang TJ, Hilden P, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46

    Atalar B, Modlin LA, Choi CY, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47

    Luther N, Kondziolka D, Kano H, et al. Predicting tumor control after resection bed radiosurgery of brain metastases. Neurosurgery. 2013;73(6):10011006.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Kelly PJ, Lin YB, Yu AY, et al. Stereotactic irradiation of the postoperative resection cavity for brain metastasis: a frameless linear accelerator-based case series and review of the technique. Int J Radiat Oncol Biol Phys. 2012;82(1):95101.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49

    Robbins JR, Ryu S, Kalkanis S, et al. Radiosurgery to the surgical cavity as adjuvant therapy for resected brain metastasis. Neurosurgery. 2012;71(5):937943.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50

    Rwigema JCM, Wegner RE, Mintz AH, et al. Stereotactic radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review. Stereotact Funct Neurosurg. 2011;89(6):329337.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51

    Jensen CA, Chan MD, McCoy TP, et al. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. 2011;114(6):15851591.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52

    Prabhu R, Shu HK, Hadjipanayis C, et al. Current dosing paradigm for stereotactic radiosurgery alone after surgical resection of brain metastases needs to be optimized for improved local control. Int J Radiat Oncol Biol Phys. 2012;83(1):e61e66.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53

    Patel AR, Nedzi L, Lau S, et al. Neoadjuvant stereotactic radiosurgery before surgical resection of cerebral metastases. World Neurosurg. 2018;120:e480e487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54

    Palmer JD, Perlow HK, Matsui JK, et al. Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis. J Neurooncol. 2022;159(2):389395.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55

    Faruqi S, Ruschin M, Soliman H, et al. Adverse radiation effect after hypofractionated stereotactic radiosurgery in 5 daily fractions for surgical cavities and intact brain metastases. Int J Radiat Oncol Biol Phys. 2020;106(4):772779.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • View in gallery
    FIG. 1.

    T1-weighted postcontrast MR images of the brain. A: A rim-enhancing left frontal lesion with surrounding vasogenic edema is seen on axial, coronal, and sagittal images. B: SRS radiation therapy protocol, 15 Gy to the 50% isodose line on axial, coronal, and sagittal images. C: Axial postoperative image demonstrating gross-total resection.

  • View in gallery
    FIG. 2.

    Overall survival (A) and local progression-free survival (B) for the single-institution cohort of 24 patients.

  • View in gallery
    FIG. 3.

    Kaplan-Meier plots of local progression-free survival for the single-institution cohort of 24 patients comparing tumors by volume (A) or by maximum tumor diameter (B). Local progression is more likely in larger tumors.

  • View in gallery
    FIG. 4.

    Kaplan-Meier plots of overall survival for the single-institution cohort of 24 patients comparing tumors by volume (A) and by maximum tumor diameter (B). Patients with larger tumors had decreased overall survival.

  • View in gallery
    FIG. 5.

    Comparison of rates of local disease control and leptomeningeal dissemination in the literature. A: Comparison of rates of local control at 1 year in studies of neoadjuvant SRS (light gray bars) and postoperative SRS (dark gray bars). B: Comparison of rates of leptomeningeal dissemination in studies of neoadjuvant SRS and postoperative SRS. Horizontal dashed lines demarcate the weighted average among each treatment group.

  • 1

    Sacks P, Rahman M. Epidemiology of brain metastases. Neurosurg Clin N Am. 2020;31(4):481488.

  • 2

    Nieblas-Bedolla E, Nayyar N, Singh M, Sullivan RJ, Brastianos PK. Emerging immunotherapies in the treatment of brain metastases. Oncologist. 2021;26(3):231241.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Niranjan A, Lunsford LD, Ahluwalia MS. Targeted therapies for brain metastases. Prog Neurol Surg. 2019;34:125137.

  • 4

    Arvold ND, Lee EQ, Mehta MP, et al. Updates in the management of brain metastases. Neuro Oncol. 2016;18(8):10431065.

  • 5

    Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):14851489.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494500.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Limbrick DD Jr, Lusis EA, Chicoine MR, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol. 2009;71(3):280289.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Do L, Pezner R, Radany E, Liu A, Staud C, Badie B. Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases. Int J Radiat Oncol Biol Phys. 2009;73(2):486491.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):10371044.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Sahgal A, Aoyama H, Kocher M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710717.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Chang EL, Wefel JS, Maor MH, et al. A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery. 2007;60(2):277284.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Serizawa T, Ono J, Iichi T, et al. Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non-small cell carcinoma. J Neurosurg. 2002;97(5 suppl):484488.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Soltys SG, Adler JR, Lipani JD, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2008;70(1):187193.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Jung JM, Kim S, Joo J, Shin KH, Gwak HS, Lee SH. Incidence and risk factors for leptomeningeal carcinomatosis in breast cancer patients with parenchymal brain metastases. J Korean Neurosurg Soc. 2012;52(3):193199.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Roth O’Brien DA, Kaye SM, Poppas PJ, et al. Time to administration of stereotactic radiosurgery to the cavity after surgery for brain metastases: a real-world analysis. J Neurosurg. 2021;135(6):16951705.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Asher AL, Burri SH, Wiggins WF, et al. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014;88(4):899906.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Patel KR, Burri SH, Asher AL, et al. Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery. 2016;79(2):279285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Patel KR, Burri SH, Boselli D, et al. Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis. J Neurooncol. 2017;131(3):611618.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Udovicich C, Ng SP, Tange D, Bailey N, Haghighi N. From postoperative to preoperative: a case series of hypofractionated and single-fraction neoadjuvant stereotactic radiosurgery for brain metastases. Oper Neurosurg (Hagerstown). 2022;22(4):208214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Akbari SHA, Sylvester PT, Kulwin C, et al. Initial experience using intraoperative magnetic resonance imaging during a trans-sulcal tubular retractor approach for the resection of deep-seated brain tumors: a case series. Oper Neurosurg (Hagerstown). 2019;16(3):292301.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Chicoine MR. Low subfrontal dural opening for anterior clinoid meningioma. J Neurol Surg B Skull Base. 2018;79(suppl 3):S273S275.

  • 22

    Hawasli AH, Rubin JB, Tran DD, et al. Antiangiogenic agents for nonmalignant brain tumors. J Neurol Surg B Skull Base. 2013;74(3):136141.

  • 23

    Karsy M, Akbari SH, Limbrick D, et al. Evaluation of pediatric glioma outcomes using intraoperative MRI: a multicenter cohort study. J Neurooncol. 2019;143(2):271280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Leuthardt EC, Lim CCH, Shah MN, et al. Use of movable high-field-strength intraoperative magnetic resonance imaging with awake craniotomies for resection of gliomas: preliminary experience. Neurosurgery. 2011;69(1):194206.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Shah MN, Leonard JR, Inder G, et al. Intraoperative magnetic resonance imaging to reduce the rate of early reoperation for lesion resection in pediatric neurosurgery. J Neurosurg Pediatr. 2012;9(3):259264.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Sylvester PT, Evans JA, Zipfel GJ, et al. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas. Pituitary. 2015;18(1):7285.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Yahanda AT, Patel B, Shah AS, et al. Impact of intraoperative magnetic resonance imaging and other factors on surgical outcomes for newly diagnosed grade II astrocytomas and oligodendrogliomas: a multicenter study. Neurosurgery. 2020;88(1):6373.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Yahanda AT, Patel B, Sutherland G, et al. A multi-institutional analysis of factors influencing surgical outcomes for patients with newly diagnosed grade I gliomas. World Neurosurg. 2020;135:e754e764.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Zenga J, Sharon JD, Santiago P, et al. Lower trapezius flap for reconstruction of posterior scalp and neck defects after complex occipital-cervical surgeries. J Neurol Surg B Skull Base. 2015;76(5):397408.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Qiao-Guan G, Murphy ES, Suh JH, et al. Dose escalation for larger brain metastases: a phase I study. Int J Radiat Oncol Biol Phys. 2019;105(1):E87E88.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Gaspar LE, Mehta MP, Patchell RA, et al. The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010;96(1):1732.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):10491060.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Bander ED, Yuan M, Reiner AS, et al. Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. Neurooncol Pract. 2021;8(3):278289.

    • Search Google Scholar
    • Export Citation
  • 35

    Tsao MN, Rades D, Wirth A, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):10401048.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Nguyen TK, Sahgal A, Detsky J, et al. Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases. Neuro Oncol. 2020;22(1):8493.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38

    Bachmann N, Leiser D, Ermis E, et al. Impact of regular magnetic resonance imaging follow-up after stereotactic radiotherapy to the surgical cavity in patients with one to three brain metastases. Radiat Oncol. 2019;14(1):45.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Rava P, Rosenberg J, Jamorabo D, et al. Feasibility and safety of cavity-directed stereotactic radiosurgery for brain metastases at a high-volume medical center. Adv Radiat Oncol. 2016;1(3):141147.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Johnson MD, Avkshtol V, Baschnagel AM, et al. Surgical resection of brain metastases and the risk of leptomeningeal recurrence in patients treated with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2016;94(3):537543.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Strauss I, Corn BW, Krishna V, et al. Patterns of failure after stereotactic radiosurgery of the resection cavity following surgical removal of brain metastases. World Neurosurg. 2015;84(6):18251831.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Abel RJ, Ji L, Yu C, et al. Stereotactic radiosurgery to the resection cavity for brain metastases: prognostic factors and outcomes. J Radiosurg SBRT. 2015;3(3):179186.

    • Search Google Scholar
    • Export Citation
  • 43

    Ojerholm E, Lee JYK, Thawani JP, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(suppl):75-83

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44

    Iorio-Morin C, Masson-Côté L, Ezahr Y, Blanchard J, Ebacher A, Mathieu D. Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121(suppl):69-74

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45

    Brennan C, Yang TJ, Hilden P, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46

    Atalar B, Modlin LA, Choi CY, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47

    Luther N, Kondziolka D, Kano H, et al. Predicting tumor control after resection bed radiosurgery of brain metastases. Neurosurgery. 2013;73(6):10011006.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Kelly PJ, Lin YB, Yu AY, et al. Stereotactic irradiation of the postoperative resection cavity for brain metastasis: a frameless linear accelerator-based case series and review of the technique. Int J Radiat Oncol Biol Phys. 2012;82(1):95101.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49

    Robbins JR, Ryu S, Kalkanis S, et al. Radiosurgery to the surgical cavity as adjuvant therapy for resected brain metastasis. Neurosurgery. 2012;71(5):937943.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50

    Rwigema JCM, Wegner RE, Mintz AH, et al. Stereotactic radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review. Stereotact Funct Neurosurg. 2011;89(6):329337.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51

    Jensen CA, Chan MD, McCoy TP, et al. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. 2011;114(6):15851591.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52

    Prabhu R, Shu HK, Hadjipanayis C, et al. Current dosing paradigm for stereotactic radiosurgery alone after surgical resection of brain metastases needs to be optimized for improved local control. Int J Radiat Oncol Biol Phys. 2012;83(1):e61e66.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53

    Patel AR, Nedzi L, Lau S, et al. Neoadjuvant stereotactic radiosurgery before surgical resection of cerebral metastases. World Neurosurg. 2018;120:e480e487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54

    Palmer JD, Perlow HK, Matsui JK, et al. Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis. J Neurooncol. 2022;159(2):389395.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55

    Faruqi S, Ruschin M, Soliman H, et al. Adverse radiation effect after hypofractionated stereotactic radiosurgery in 5 daily fractions for surgical cavities and intact brain metastases. Int J Radiat Oncol Biol Phys. 2020;106(4):772779.

    • Crossref
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 631 631 360
PDF Downloads 603 603 321
EPUB Downloads 0 0 0