If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Department of Radiation Oncology, Duke University Medical Center, Durham, North CarolinaDepartment of Neurosurgery, Duke University Medical Center, Durham, North Carolina
Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-SRS.
Methods and Materials
Patients undergoing HF-SRS for intact (iHF-SRS) or resected (rHF-SRS) BMs from 2008 to 2018 were retrospectively identified. Linear accelerator-based image-guided HF-SRS consisted of 5 fractions at 5, 5.5, or 6 Gy per fraction. Time to local progression (LP), time to distant brain progression (DBP), and overall survival (OS) were calculated. Cox models assessed effect of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined effect of factors on LP and DBP. The occurrence of leptomeningeal disease (LMD) was determined. Logistic regression examined predictors of LMD.
Results
Among 445 patients, median age was 63.5 years; 87% had Karnofsky performance status ≥70. Fifty-three % of patients underwent surgical resection, and 75% received 5 Gy per fraction. Patients with resected BMs had higher Karnofsky performance status (90-100, 41 vs 30%), less extracranial disease (absent, 25 vs 13%), and fewer BMs (multiple, 32 vs 67%). Median diameter of the dominant BM was 3.0 cm (interquartile range, 1.8-3.6 cm) for intact BMs and 4.6 cm (interquartile range, 3.9-5.5 cm) for resected BMs. Median OS was 5.1 months (95% confidence interval [CI], 4.3-6.0) following iHF-SRS and 12.8 months (95% CI, 10.8-16.2) following rHF-SRS (P < .01). Cumulative LP incidence was 14.5% at 18 months (95% CI, 11.4-18.0%), significantly associated with greater total GTV (hazard ratio, 1.12; 95% CI, 1.05-1.20) following iFR-SRS, and with recurrent versus newly diagnosed BMs across all patients (hazard ratio, 2.28; 95% CI, 1.01-5.15). Cumulative DBP incidence was significantly greater following rHF-SRS than iHF-SRS (P = .01), with respective 24-month rates of 50.0 (95% CI, 43.3-56.3) and 35.7% (95% CI, 29.2-42.2). LMD (57 events total; 33% nodular, 67% diffuse) was observed in 17.1% of rHF-SRS and 8.1% of iHF-SRS cases (odds ratio, 2.46; 95% CI, 1.34-4.53). Any radionecrosis and grade 2+ radionecrosis events were observed in 14 and 8% of cases, respectively.
Conclusions
HF-SRS demonstrated favorable rates of LC and radionecrosis in postoperative and intact settings. Corresponding LMD and RN rates were comparable to those of other studies.
Introduction
Stereotactic radiosurgery (SRS) is the preferred local treatment for many patients with brain metastasis (BMs). Radiation Therapy Oncology Group 90-05 prospectively established a standardized single-fraction SRS (SF-SRS) dosing regimen based on lesion size;
Alternatively, hypofractionated SRS (HF-SRS) with or without surgical resection may maximize the therapeutic ratio for larger BMs, reducing toxicity and/or improving LC.
In the absence of randomized comparisons between SF- and HF-SRS, several series demonstrate equivocal rates of LC and decreased risk of RN following HF-SRS.
Single-fraction versus multifraction (3× 9 Gy) stereotactic radiosurgery for large (>2 cm) brain metastases: A comparative analysis of local control and risk of radiation-induced brain necrosis.
Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection.
Despite the emerging central role of HF-SRS for larger BMs, optimal target volumes and planning parameters remain a matter of debate. Moreover, within the evolving context of multidisciplinary BM management, associations of patient- and tumor-specific parameters to clinical outcomes following HF-SRS remain poorly understood. Herein, we report clinical outcomes, associated predictive factors, and toxicity rates following 5-fraction HF-SRS.
Methods and Materials
For this institutional review board–approved retrospective review, we identified all patients who completed an initial HF-SRS course for intact (iHF-SRS) and resected (rHF-SRS) brain metastases at our institution between 2008 and 2018. Prior SF-SRS, surgical resection, or whole brain radiation therapy were allowed. Demographic variables, clinical characteristics, and treatment parameters were obtained.
All patients underwent linear accelerator-based, image-guided HF-SRS, for which patients were simulated in the supine position with head immobilization using a frameless stereotactic mask. Gross tumor volume (GTV) was defined as contrast enhancing tumor on T1 contrast enhanced thin-sliced axial magnetic resonance image (MRI) (typically an axial 3-dimensional spoiled gradient with a 1-mm thickness), fused with treatment planning axial computed tomography (CT) images (- mm thickness).
The decision to hypofractionate SRS was at the discretion of the treating physician, according to tumor size (PTV > 3 cm in greatest dimension), volume of normal brain parenchyma that would receive a dose of ≥12 Gy if delivered in a single fraction (V12, >15 mL), and tumor location (eg, brain stem, motor strip, or other eloquent location).
All patients received 5, 5.5, or 6 Gy per fraction, prescribed to the 100% isodose line. The decision to treat to 5, 5.5, or 6 Gy per fraction was left to the discretion of the individual radiation oncologist, generally based on BM size, histology, and location. In general, for cases involving multiple BMs, HF-SRS was used across all BMs if indicated for ≥1 dominant lesions. HF-SRS was delivered using a Varian TrueBeam STx linear accelerator (Varian, Palo Alto, CA, USA) or, before 2011, a Novalis Tx (Varian, Palo Alto, CA, USA) with daily cone beam CT and 6° of freedom motion couch.
RN and LC were determined by multidisciplinary clinical consensus, which retrospectively incorporated findings from serial MRI brain scans, response to steroids, and, when available, histopathologic diagnosis. Where histopathologic diagnosis was not available, subsequent serial MRI was used to confirm initial RN/LC diagnoses, the latter defined per Response Assessment in Neuro-Oncology criteria.
Distant brain progression (DBP) was recorded independently from LC. RN events were graded using Common Terminology Criteria for Adverse Events v5.0 criteria.
Time to local progression (LP) (eg, LC), time to DBP, and overall survival (OS) were calculated. Univariate and multivariate Cox proportional hazard models assessed the effect of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined the effect of clinical factors on LP and DBP. The occurrence of leptomeningeal disease (LMD) was determined, and multivariable logistic regression examined predictors of LMD. Analyses were performed using SAS version 9.4 (Cary, NC, USA).
Results
Across 445 patients, median follow-up was 39.4 months. The length of follow-up of patients alive at the time of analysis ranged between .23 and 87.8 months. Patients were predominantly female (53%) and Karnofsky performance status ≥70 (87%), with a median age of 63.5 years at time of HF-SRS. Common primary tumor sites were lung (43%), breast (16%), gastrointestinal (11%), skin (11%), and genitourinary (11%), with evidence of extracranial metastatic disease in 77% of cases at time of HF-SRS (Table 1). rHF-SRS and iHF-SRS comprised 53 and 47% of cases, respectively, with ≥2 brain metastases present in 32% of rHF-SRS and 67% of iHF-SRS cases. Following HF-SRS, 70% of patients received immunotherapy, a small molecule inhibitor (IT/SMI).
Table 1Demographic, clinical, and treatment parameters are provided for all patients by postoperative status
Postoperative status
No
Yes
Characteristic
N
%
N
%
Sex
Female
124
58.8
114
48.7
Male
87
41.2
120
51.3
Age at SRS (y)
Mean (SD)
62.4 (11.8)
-
61.7 (11.9)
-
Range
22-87
-
25-84
-
White race
No
41
19.4
58
24.8
Yes
170
80.6
176
75.2
KPS
30
1
0.5
0
0.0
40
4
1.9
2
0.9
50
12
5.7
4
1.7
60
19
9.0
16
6.8
70
56
26.5
44
18.8
80
56
26.5
72
30.8
90
54
25.6
88
37.6
100
9
4.3
8
3.4
Primary site
Breast
36
17.1
37
15.8
GI
18
8.5
32
13.7
GU
27
12.8
22
9.4
Lung
92
43.6
101
43.2
Other
16
7.6
14
6.0
Skin
22
10.4
28
12.0
Systemic burden
Present
182
86.3
162
69.2
Absent
27
12.8
59
25.2
Unknown
2
1.0
13
5.6
Newly diagnosed or recurrent
Newly diagnosed
163
77.3
195
83.3
Recurrent
48
22.8
39
16.7
Dural contact
No
77
36.5
54
23.1
Yes
134
63.5
180
76.9
Location
Frontal
21
10.0
67
28.6
Parietal
18
8.5
33
14.1
Cerebellum
34
16.1
66
28.2
Brain stem
19
9.0
0
0.0
Temporal
6
2.8
26
11.1
Occipital
6
2.8
32
13.7
Cavernous sinus/BOS
13
6.2
0
0.0
Multiple
94
44.6
10
4.3
Number of metastases
1
69
32.7
159
68.0
2
39
18.5
42
18.0
3-5
57
27.0
27
11.5
≥6
46
21.8
6
2.6
Receipt of immunotherapy or small molecule inhibitor
Lesion-specific parameters are provided in Table E1 for 781 intact BMs (76%) and 249 resected BMs (24%). Nineteen percecnt of BMs had received local treatment before HF-SRS, primarily consisting of whole brain radiation therapy (16%) or SRS (5%). Dural contact was observed for 230 of 781 intact BMs (29%) and 191 of 249 resected BMs (77%). More than 99% of BMs received <6 Gy per fraction; 69% and 75% of intact and resected BMs received 5 Gy per fraction, respectively. Across all patients, median maximum diameter of the dominant BM was 3.0 cm (interquartile range [IQR], 2.3-3.7) axially and 3.9 cm (IQR, 3.1-4.9) across any orientation. For all intact BMs, mean values included a maximum axial diameter of 1.33 cm (standard deviation [SD], 1.08), GTV of 3.31 cc (SD, 6.67), conformity index of 1.60 (SD, 0.68), and GTV maximum dose of 30.09 Gy (SD, 2.14), while the maximum diameter of the dominant BM was 3.0 cm (IQR, 1.8-3.6) across any orientation. For all resected BMs, mean values included a maximum axial diameter of 3.47 cm (SD, 1.09), GTV of 19.37 cc (SD, 14.88), conformity index of 1.14 (SD, 0.09), and GTV maximum dose of 29.22 Gy (SD, 1.95), while the maximum diameter of the dominant resection cavity was 4.6 cm (IQR, 3.9-5.5) across any orientation.
As shown in Fig. 1A, median OS across all patients was 8.3 months (95% confidence interval [CI],7.2-9.7). Median OS was 5.1 months (95% CI, 4.3-6.0) following iHF-SRS and 12.8 months (95% CI, 10.8-16.2) following rHF-SRS (P < .01). At 12, 24, and 60 months following rHF-SRS, OS was 52.1 (95% CI, 45.5-58.4), 34.2 (27.9-40.6%), and 19.7% (95% CI, 13.3-27.0), respectively (Fig. 1B). At the same time points following iHF-SRS, OS was 20.4 (95% CI, 15.2-26.1), 10.3% (95% CI, 6.6-15.0), and 3.8% (95% CI, 1.4-8.1) at 12, 24, and 60 months, respectively. For patients completing iHF-SRS, clinical factors associated with OS on multivariate analysis included post-SRS receipt of IT/SMI (hazard ratio [HR], 0.48; 95% CI, 0.33-0.69) and ≥6 versus 1 brain metastases (HR, 1.71; 95% CI, 1.08-2.70; Table 2). For patients completing rHF-SRS, clinical factors associated with OS included post-SRS receipt of IT/SMI (HR, 0.42, 95% CI, 0.28-0.64), BM-related neurologic symptoms (HR, 1.95; 95% CI, 1.32-2.88) and dural contact (HR, 0.68; 95% CI, 0.44-0.99; Table 2).
Figure 1Kaplan-Meier plots are shown for A, B, overall survival; C, D, cumulative incidence of local intracranial progression; and E, F, cumulative incidence of distant brain progression across all patients and stratified by postoperative status, respectively. Abbreviation: post-op = postoperative; SRS = stereotactic radiosurgery.
Across all patients, cumulative incidence of LP was 7.4% (95% CI, 5.2-10.1) at 6 months, 13.6% (95% CI, 10.6-17.0) at 12 months, and 14.5% (95% CI, 11.4-18.0) at 18 months (Fig. 1C). No significant differences in LP were observed across resected versus intact cases (Fig. 1D; P = .41). On multivariable analyses for patients completing iHF-SRS, greater total GTV (cc) was significantly associated with greater LP risk (HR, 1.12; 95% CI, 1.05-1.20). No significant associations to LP were found among those completing rHF-SRS. Across all patients, LP was significantly associated with recurrent rather than newly diagnosed BMs (HR, 2.28; 95% CI, 1.01-5.15; Table 3).
Table 3Multivariable analyses of cumulative incidence of local progression across all patients, intact cases, and postoperative cases
Fig. 1E provides cumulative incidence of DBP across all patients, which was significantly greater following rHF-SRS than iHF-SRS (P = .01). Cumulative incidence of DBP following rHF-SRS was 32.6% (95% CI, 26.7-38.7) at 6 months, 46.1% (95% CI, 39.5-52.4) at 12 months, and 50.0% (95% CI, 43.3-56.3) at 24 months (Fig. 1F). Following iHF-SRS, cumulative incidence of DBP was 28.9% at 6 months (95% CI, 22.9-35.1), 33.7% at 12 months (95% CI, 27.3-40.1), and 35.7% at 24 months (95% CI, 29.2-42.2). On multivariable analysis, cumulative incidence of DBP was not associated with any patient- or tumor-specific factors aside from postoperative status (Table E2).
LMD was identified in 57 patients (33% nodular, 67% diffuse) following HF-SRS, including 40 patients treated with rHF-SRS (22% nodular, 78% diffuse) and 17 patients treated with iHF-SRS (59% nodular, 41% diffuse). LMD involvement was regional in 37 patients (65%); across all patients with LMD, involved sites included right hemisphere (33%), left hemisphere (26%), posterior fossa (28%), cistern (25%), lateral and/or third ventricles (11%), and fourth ventricle (21%). On multivariable analysis among all patients (Table 4), clinical factors associated with LMD included postoperative status (rHF-SRS, 17.1%, iHF-SRS, 8.1%; odds ratio [OR], 2.10; 95% CI, 1.03-4.27) and primary site (lung vs breast OR, 0.45; 95% CI, 0.22-0.93; other vs breast OR, 0.32; 95% CI, 0.15-0.68). The percentage of rHF-SRS and iHF-SRS patients who experienced LMD were 17.1% and 8.1%, respectively. Following iHF-SRS, presence of LMD was associated with lung vs breast (OR, 0.18; 95% CI, 0.05-0.68) and other vs breast (OR, 0.23; 95% CI, 0.07-0.79) primary sites, while no clinical factors were associated with LMD following rHF-SRS. On exploratory analysis, rates of LMD were proportionally greater following rHF-SRS than iHF-SRS within cases of lung and other primary sites origin in comparison to breast (Table E1). Similarly, rates of LMD were proportionally greater following rHF-SRS than iHF-SRS in cases without IT/SMI receipt (Table E3).
Table 4Multivariate analyses of leptomeningeal disease across all patients, intact cases, and postoperative cases
All patients (n = 445)
Intact (n = 211)
Postoperative (n = 234)
Effect
OR
95% Wald CI
P value
OR
95% Wald CI
P value
OR
95% Wald CI
P value
Postoperative: yes vs no
1.977
0.942
4.318
0.0783
N/A
N/A
Primary site: lung vs breast
0.451
0.219
0.933
0.0302
0.173
0.040
0.636
0.0107
0.173
0.040
0.636
0.0107
Primary site: other vs breast
0.314
0.144
0.676
0.0031
0.216
0.058
0.739
0.0164
0.216
0.058
0.739
0.0164
Number of brain metastases: >1 vs 1
0.749
0.379
1.458
0.3979
0.660
0.222
2.043
0.4554
0.66
0.222
2.043
0.4554
Dural contact: no vs yes
0.477
0.207
0.999
0.0627
0.477
0.112
1.708
0.2770
0.477
0.112
1.708
0.2770
Immunotherapy or small molecular inhibitor: yes vs no
0.903
0.455
1.721
0.7622
1.434
0.434
4.535
0.5400
1.434
0.434
4.535
0.5400
GTV (cc)
0.997
0.936
1.06
0.9210
1.049
0.878
1.211
0.5706
1.049
0.878
1.211
0.5706
PTV (cc)
1.000
0.955
1.044
0.9980
0.949
0.848
1.072
0.3971
0.949
0.848
1.072
0.3971
Prior WBRT
0.734
0.236
1.894
0.5539
0.858
0.175
3.193
0.8307
0.858
0.175
3.193
0.8307
Abbreviations: CI = confidence interval; GTV = gross tumor volume; N/A = not applicable; OR = odds ratio; PTV = planned target volume; WBRT = whole brain radiation therapy.
RN was identified in 63 patients (14%). The maximum RN grade experienced was grade 2 or higher in 37 patients (8%), 18 of whom underwent biopsy confirmation (Table 5). Grade 2 or higher RN was observed in 6% of patients completing iHF-SRS including a single grade 5 event (0.5%), as well as 11% of patients completing rHF-SRS including a single grade 4 event (0.4%). Among patients with documented RN, median time from SRS completion to any grade 1 to 5 RN event was 8.0 months (IQR, 5.3-19.1).
Table 5Radionecrosis frequency by maximum event grade experienced by a patient
HF-SRS is commonly used for BMs that are >2 cm, resected, or adjacent to critical organs at risk. For consecutive BM patients undergoing HF-SRS with or without surgical resection at a single institution between 2008 to 2018, we report rates of OS, time to LP, time to DBP, leptomeningeal progression, and RN. Clinical outcomes and toxicity rates of the present report compare favorably to prior HF-SRS series across intact
Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection.
despite greater proportions of recurrent disease, multiple BMs, and comparatively smaller RT doses (75% patients receiving 5 Gy per fraction).
The distribution of demographic and clinical parameters across iHF-SRS and rHF-SRS cases appears consistent with clinical criteria for surgical resection, many of which are associated with favorable OS: greater Karnofsky performance status, younger age, limited extracranial disease, and fewer brain metastases.
Estimating survival in melanoma patients with brain metastases: An update of the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA).
The graded prognostic assessment (GPA) for lung cancer patients with brain metastases: Initial report of the small cell lung cancer GPA and update of the non-small cell lung cancer GPA including the effect of programmed death ligand-1 (PD-L1) and other prognostic factors.
Notably, our institutional series contained a relatively large proportion (32%) of patients treated with rHF-SRS with multiple BMs. For patients with multiple BMs, resection was considered in the presence of BM-related neurologic symptoms and otherwise favorable clinical characteristics.
Global determinants of OS for BM patients are largely independent of local intracranial therapy, and include overall performance status, extracranial disease burden, and receipt of post-SRS systemic therapy.
Assessment of extracranial metastatic disease in patients with brain metastases: How much effort is needed in the context of evolving survival prediction models?.
As median OS continues to improve across BM populations, durable LC and late toxicity mitigation following SRS are increasingly important considerations. Time to LP (eg, LC) observed in this study compares favorably to those of prior HF-SRS reports, which typically range from 70 to 90% ≥12 months following SRS.
Single-fraction versus multifraction (3× 9 Gy) stereotactic radiosurgery for large (>2 cm) brain metastases: A comparative analysis of local control and risk of radiation-induced brain necrosis.
We similarly identified significant association between greater total GTV (cc) and LP; however, we found no association to SRS dose or surgical resection among a population with a larger number of BMs of similar size, with >99 and 69% BMs receiving 5-fraction HF-SRS total doses <30 and 25 Gy, respectively. Comparatively, in a recent 5-fraction HF-SRS series with just 38% patients who received <6 Gy per fraction, a total radiation therapy dose of ≥30 Gy prescribed to 99% PTV coverage was associated with superior LC.
Notably, this series reported a median maximum lesion diameter of 1.9 versus 3.9 cm in the present data. Accordingly, these data may support the utility of 5-fraction HF-SRS at 5 to 5.5 Gy per fraction, particularly for cases where minimization of brain V24 or dose to adjacent normal structures is of primary concern.
The discrepancy between medial lesion axial diameter (1.3 cm) and median maximum lesion diameter (3.9 cm) reflects both the high proportion of patients with multiple BMs and our institutional practice of treating all BMs with HF-SRS via single-isocenter multitarget technique where hypofractionation is indicated for a single dominant BM. Given the lack of significant association to LP across a comprehensive list of clinical and treatment parameters, future analyses of LP may wish to examine radiomic and genomic parameters as predictors of clinical outcomes. To guide clinical management of patients undergoing resection of 1 to 3 BMs, the ongoing Alliance A071801 phase III trial (NCT04114981) compares LC rates following SF-SRS versus HF-SRS.
Clinical Trials. Single fraction stereotactic radiosurgery compared with fractionated stereotactic radiosurgery in treating patients with resected metastatic brain disease. Available at: https://clinicaltrials.gov/ct2/show/NCT04114981. Accessed September 21, 2022.
The clinical significance of LMD risk is difficult to ascertain across studies, given that LMD subtype (ie, nodular versus diffuse) is often not reported despite its prognostic and therapeutic implications.
Breast brain metastases are associated with increased risk of leptomeningeal disease after stereotactic radiosurgery: A systematic review and meta-analysis.
This report has several limitations. In a nonrandomized setting, utilization of HF-SRS and surgical resection both reflect significant selection bias. Patient inclusion from 2008 to 2018 may incorporate significant chronological bias consistent with improved clinical outcomes in recent years. Novel systemic agents confer superior central nervous system activity and OS,
Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data.
as well as technological advances in both surgery and SRS. Generalizability of linear accelerator-based HF-SRS to patients completing CyberKnife or GammaKnife SRS may be limited. While multidisciplinary consensus regarding RN and LP were retrospectively confirmed through serial radiographic images, histopathologic confirmation was not available for the majority of RN cases. Furthermore, the relatively short OS following iHF-SRS in particular limits analysis of non-OS outcomes. Infrequent LMD events precluded analysis of potential interactions across parameters. Nevertheless, to our knowledge, this report provides the largest single institution 5-fraction HF-SRS series to date, with favorable rates of OS, LC, DBP, LMD, and RN across both rHF-SRS and iHF-SRS cases despite a patient population with a relatively advanced intracranial disease burden and relatively low HF-SRS doses.
Conclusions
Patients completing 5-fraction HF-SRS with and without surgical resection represent distinct subgroups within the BM population, with superior OS following rHF-SRS versus iHF-SRS despite higher rates of distant brain progression and LMD. Patient- and tumor-specific factors associated with OS and LP varied across rHF-SRS and iHF-SRS cases. DBP incidence was greater following rHF-SRS than iHF-SRS. Across all patients, rates of LP, LMD, and RN compared favorably to those of other series despite a relatively advanced intracranial disease burden and slightly lower HF-SRS doses.
Single-fraction versus multifraction (3× 9 Gy) stereotactic radiosurgery for large (>2 cm) brain metastases: A comparative analysis of local control and risk of radiation-induced brain necrosis.
Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection.
Estimating survival in melanoma patients with brain metastases: An update of the graded prognostic assessment for melanoma using molecular markers (Melanoma-molGPA).
The graded prognostic assessment (GPA) for lung cancer patients with brain metastases: Initial report of the small cell lung cancer GPA and update of the non-small cell lung cancer GPA including the effect of programmed death ligand-1 (PD-L1) and other prognostic factors.
Assessment of extracranial metastatic disease in patients with brain metastases: How much effort is needed in the context of evolving survival prediction models?.
Clinical Trials. Single fraction stereotactic radiosurgery compared with fractionated stereotactic radiosurgery in treating patients with resected metastatic brain disease. Available at: https://clinicaltrials.gov/ct2/show/NCT04114981. Accessed September 21, 2022.
Breast brain metastases are associated with increased risk of leptomeningeal disease after stereotactic radiosurgery: A systematic review and meta-analysis.
Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data.
Sources of support: The funding source for this study (National Institute of Health grant R38CA24520401) had no role in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit it for publication.
Disclosures: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Research data are stored in an institutional repository and will be shared upon request to the corresponding author.
A single patient received 6 Gy per fraction.
00271-8&id=gr1.jpg){kind=link}