scholarly journals Gamma Knife versus Frameless Linear Accelerator Based Stereotactic Radiosurgery for Brain Metastases: Clinical Outcomes and Factors Associated with Local Failure and Radiation Necrosis

Author(s):  
Gregory S. Alexander ◽  
Jill S. Remick ◽  
Emily S. Kowalski ◽  
Kai Sun ◽  
Yannick Poirer ◽  
...  

Abstract BackgroundSingle-fraction stereotactic radiosurgery (SF-SRS) for the treatment of brain metastases can be delivered with either a Gamma-Knife platform (GK-SRS) or with a frameless linear accelerator (LA-SRS) which vary based on patterns of prescribing, patient setup and radiation delivery. Whether these differences affect clinical outcomes is unknown. MethodsPatients treated for metastatic brain cancer treated with SF-SRS from 2014-2020 were retrospectively reviewed and clinical outcomes were recorded on a per lesion basis. Covariates between groups were compared using a Chi-square analysis for dichotomous variables and t-test for continuous variables. Median follow up was calculated using the reverse Kaplan Meier (KM) method. Primary endpoints of local failure (LF) and symptomatic radiation necrosis (RN) were estimated using the KM method with salvage WBRT used as a censoring event. Outcome estimates were compared using the log-rank test. Multivariate analysis (MVA) and Cox proportional hazards modeling were used for statistical analyses. Propensity score (PS) adjustments were used to reduce the effects confounding variables.ResultsOverall, 119 patients with 287 lesions were included for analysis which included 57 patients (127 lesions) treated with LA-SRS compared to 62 patients (160 lesions) treated with GK-SRS. On both multivariate and univariate analysis, there was no statistically significant differences between GK-SRS and LA-SRS for LF, RN, or the combined endpoint of either LF or RN (multivariate p-value=0.17).ConclusionsIn our retrospective cohort, we found no statistically significant differences in the incidence of RN or LF in patients treated with GK-SRS when compared to LA-SRS.Trial Registration: Retrospectively registered

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Tatsuya Takezaki ◽  
Haruaki Yamamoto ◽  
Naoki Shinojima ◽  
Jun-ichiro Kuroda ◽  
Shigeo Yamashiro ◽  
...  

Abstract Recent advances in the systemic treatment of various cancers have resulted in longer survival and higher incidence of brain metastases. Phase 3 trials in north America and in Japan have demonstrated that stereotactic radiosurgery will be a standard adjuvant modality following surgery for resectable brain metastases. However, we don’t know the optimal sequence of this combination therapy. We hypothesized that pre-operative stereotactic radiosurgery for resectable brain metastases provides favorable rates of local control, overall survival, leptomeningeal dissemination and symptomatic radiation necrosis. We have experienced 4 cases of resected brain metastases within 1–7 days after Gamma-knife surgery (median margin dose:22Gy) and have been following their clinical course. We will show the repressive cases.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i22-i22
Author(s):  
Jameson Mendel ◽  
Ankur Patel ◽  
Toral Patel ◽  
Robert Timmerman ◽  
Tu Dan ◽  
...  

Abstract PURPOSE/OBJECTIVE(S): Stereotactic radiosurgery with Gamma Knife is a common treatment modality for patients with brain metastasis. The Gamma Knife ICON allows for immobilization with an aquaplast mask, permitting fractionated treatments. We describe one of the first experiences utilizing this technique with brain metastasis and evaluate outcomes. MATERIALS/METHODS: From June 2017 to November 2018, 29 patients with 43 separate intracranial lesions were treated with fractionated stereotactic radiotherapy using the gamma knife ICON at a single institution. Patients received between 20–30 Gy in 3–5 fractions with no margin over the course of 5 to 23 days. Local control was physician assessed. Local failure over time was modeled using cumulative incidence; lesions were censored at last radiographic follow up. RESULTS: Median tumor volume and prescription isodose was 7.7 cm3 (range 0.3–43.9) and 50% (range 40–65), respectively. Median radiographic follow-up was 7 months and median survival was 9 months. Radiation necrosis occurred in 3/3 patients treated with 27 Gy in 3 fractions, one requiring therapeutic resection. Incidence of local failure for all treated lesions was 9% at 1 year. Tumor volume >7 cm3 was associated with local failure on univariate analysis (p=0.025). 100% (2/2) lesions treated with 20 Gy in 5 fractions developed local recurrence. CONCLUSION: Fractionated stereotactic radiotherapy with the Gamma Knife ICON provides excellent local control for small and large brain metastases with minimal toxicity. Tumors >7 cm3 should receive at least 30 Gy in 5 fractions for optimal control. Treatment with 27 Gy in 3 fractions appears to have high rates of treatment related toxicity and should be avoided.


Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Ammoren Dohm ◽  
Emory R McTyre ◽  
Catherine Okoukoni ◽  
Adrianna Henson ◽  
Christina K Cramer ◽  
...  

Abstract BACKGROUND Treatment options are limited for large, unresectable brain metastases. OBJECTIVE To report a single institution series of staged stereotactic radiosurgery (SRS) that allows for tumor response between treatments in order to optimize the therapeutic ratio. METHODS Patients were treated with staged SRS separated by 1 mo with a median dose at first SRS of 15 Gy (range 10-21 Gy) and a median dose at second SRS of 14 Gy (range 10-18 Gy). Overall survival was evaluated using the Kaplan-Meier method. Cumulative incidences were estimated for neurological death, radiation necrosis, local failure (marginal or central), and distant brain failure. Absolute cumulative dose–volume histogram was created for each treated lesion. Logistic regression and competing risks regression were performed for each discrete dose received by a certain volume. RESULTS Thirty-three patients with 39 lesions were treated with staged radiosurgery. Overall survival at 6 and 12 mo was 65.0% and 60.0%, respectively. Cumulative incidence of local failure at 6 and 12 mo was 3.2% and 13.3%, respectively. Of the patients who received staged therapy, 4 of 33 experienced local failure. Radiation necrosis was seen in 4 of 39 lesions. Two of 33 patients experienced a Radiation Therapy Oncology Group toxicity grade > 2 (2 patients had grade 4 toxicities). Dosimetric analysis revealed that dose (Gy) received by volume of brain (ie, VDose(Gy)) was associated with radiation necrosis, including the range V44.5Gy to V87.8Gy. CONCLUSION Staged radiosurgery is a safe and effective option for large, unresectable brain metastases. Prospective studies are required to validate the findings in this study.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10555-10555
Author(s):  
R. Gutt ◽  
S. Yovino ◽  
L. Chin ◽  
W. Regine ◽  
P. Amin ◽  
...  

10555 Background: Outcomes of gamma knife stereotactic radiosurgery (GK-SRS) for patients with brain metastases specifically from breast cancer have not been well-defined. This study was undertaken to report the long-term experience with GK-SRS in this subset of patients. Methods: From 1995 to 2005, 75 patients with 162 brain lesions were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up data were available in 65 patients. Additional whole brain radiation therapy (WBRT) was administered to 53 (81.5%) patients. The median WBRT dose was 36.75 Gy (30.0–45.0 Gy). The median number of lesions treated with GK-SRS was 2 (1–8 lesions). The median follow-up, age, and KPS were 7.2 months (0.4–75.7 months), 53.5 years (23–81 years), and 90 (40–100), respectively. The factors included in the univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) were age, Karnofsky Performance Status (KPS), tumor histology, estrogen receptor status, Her-2-neu status, number of intracranial lesions, and presence of systemic disease. Results: Median PFS and OS from GK-SRS were 5.3 months (0.4–33.2 months) and 8.1 months (0.4–75.7 months), respectively. The 6, 12, and 24 month actuarial PFS were 47.8%, 24.9%, and 9.6% respectively. The 6, 12, and 24 month actuarial OS were 60.7%, 39.1%, and 18.1% respectively. The tumor local control after WBRT and GK-SRS was 87.7%. Radiation necrosis was a complication in 10.8% of patients. Forty-seven (72.3%) patients had neurological symptoms prior to gamma knife treatment. Seven (14.9%) and 9 (19.1%) of these patients experienced symptom resolution and significant symptomatic improvement, respectively. Multivariate and univariate analysis did not reveal any of the prognostic factors in question to be significantly associated with OS nor PFS. Conclusions: This relatively large cohort of patients experienced poor survival outcomes despite aggressive therapy with WBRT and GK-SRS. However, GK-SRS can provide significant symptomatic relief, with acceptable complication rates. More research is required to improve the survival of breast cancer patients with intracranial metastases. No significant financial relationships to disclose.


ISRN Surgery ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Andrew F. Lamm ◽  
Ameer L. Elaimy ◽  
Wayne T. Lamoreaux ◽  
Alexander R. Mackay ◽  
Robert K. Fairbanks ◽  
...  

Only 3%–5% of all brain metastases are located in the brainstem. We present a comprehensive review of the clinical outcomes from modern studies that treated patients with brainstem metastasis using either a Gamma Knife or a linear accelerator-based stereotactic radiosurgery. The median survival time of patients was compared to better understand what clinical or treatment factors are predictive of improved survival. This information can then be utilized to optimize patient care. The data suggests that higher prescribed marginal dose and the associated greater local control of brainstem lesions are associated with longer patient survival. Further research is necessary to better describe the most effective dose for individual brainstem lesions and to tailor optimum therapy to specific patient subgroups.


2017 ◽  
Vol 127 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Will H. McKay ◽  
Emory R. McTyre ◽  
Catherine Okoukoni ◽  
Natalie K. Alphonse-Sullivan ◽  
Jimmy Ruiz ◽  
...  

OBJECTIVEThere are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS.METHODSBetween 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis.RESULTSForty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14–22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%–94%). Estimated 1-year OS was 70% (95% CI 55%–88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%–88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%–28%), 0.76 cm3 (95% CI 9%–39%), 1.60 cm3 (95% CI 26%–74%).CONCLUSIONSRepeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.


2021 ◽  
pp. 1-11

OBJECTIVE In the era in which more patients with greater numbers of brain metastases (BMs) are being treated with stereotactic radiosurgery (SRS) alone, it is critical to understand how patient, tumor, and treatment factors affect functional status and overall survival (OS). The authors examined the survival outcomes and dosimetry to critical structures in patients treated with Gamma Knife radiosurgery (GKRS) for ≥ 25 metastases in a single session or cumulatively over the course of their disease. METHODS A retrospective analysis was conducted at a single institution. The institution’s prospective Gamma Knife (GK) SRS registry was queried to identify patients treated with GKRS for ≥ 25 cumulative BMs between June 2013 and April 2020. Ninety-five patients were identified, and their data were used for analysis. Treatment plans for dosimetric analysis were available for 89 patients. Patient, tumor, and treatment characteristics were identified, and outcomes and OS were evaluated. RESULTS The authors identified 1132 patients with BMs in their institutional registry. Ninety-five patients were treated for ≥ 25 cumulative metastases, resulting in a total of 3596 tumors treated during 373 separate treatment sessions. The median number of SRS sessions per patient was 3 (range 1–12 SRS sessions), with nearly all patients (n = 93, 98%) having > 1 session. On univariate analysis, factors affecting OS in a statistically significant manner included histology, tumor volume, tumor number, diagnosis-specific graded prognostic assessment (DS-GPA), brain metastasis velocity (BMV), and need for subsequent whole-brain radiation therapy (WBRT). The median of the mean WB dose was 4.07 Gy (range 1.39–10.15 Gy). In the top quartile for both the highest cumulative number and highest cumulative volume of treated metastases, the median of the mean WB dose was 6.14 Gy (range 4.02–10.15 Gy). Seventy-nine patients (83%) had all treated tumors controlled at last follow-up, reflecting the high and durable control rate. Corticosteroids for tumor- or treatment-related effects were prescribed in just over one-quarter of the patients. Of the patients with radiographically proven adverse radiation effects (AREs; 15%), 4 were symptomatic. Four patients required subsequent craniotomy for hemorrhage, progression, or AREs. CONCLUSIONS In selected patients with a large number of cumulative BMs, multiple courses of SRS are feasible and safe. Together with new systemic therapies, the study results demonstrate that the achieved survival rates compare favorably to those of larger contemporary cohorts, while avoiding WBRT in the majority of patients. Therefore, along with the findings of other series, this study supports SRS as a standard practice in selected patients with larger numbers of BMs.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi212-vi212
Author(s):  
Shearwood McClelland III ◽  
Catherine Degnin ◽  
Yiyi Chen ◽  
Gordon Watson ◽  
Jerry Jaboin

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) for brain metastases is predominantly delivered via single-fraction Gamma Knife SRS (GKRS) or linear accelerator (LINAC) in 1–5 fractions. Predictors of SRS modality have been sparsely examined on a nationwide level. METHODS The 2010–2016 National Cancer Database identified brain metastases patients from non-small cell lung cancer throughout the United States (US) having undergone SRS. A multivariable logistic regression model characterized SRS receipt, adjusting for patient age, dose, geographic location of treatment, facility type, and distance from treatment facility. RESULTS A total of 1,760 patients received GKRS, while 1,064 patients received LINAC SRS. Treatment at non-academic facilities was associated with increased LINAC SRS receipt, most prominently in the Midwestern (OR= 6.23; p< 0.001), Northeastern (OR= 4.42; p< 0.001), and Southern US (OR= 1.96;p< 0.001). Administered doses of 18–19 Gy (OR= 1.42;p= 0.025), 20–21 Gy (OR= 1.82;p< 0.001), and 22–24 Gy (OR= 3.11;p< 0.001) were associated with increased LINAC SRS receipt, as was patient location within 20 miles of a radiation treatment facility (OR= 1.27;p= 0.007). CONCLUSIONS Despite Gamma Knife being more prominently used over LINAC for SRS, patients treated at non-academic facilities outside of the Western US were substantially more likely to receive LINAC over Gamma Knife. Patients located in the Midwest were 523% more likely, Northeast 342% more likely, and South 96% more likely to receive LINAC when treated at a non-academic facility. Increasing dose independently predicted LINAC over GKRS, indicating that smaller tumors – particularly those less than two centimeters (consistent with RTOG 90-05 recommendations) – are being treated with LINAC. Finally, patients residing in close proximity to a treatment center were 27% more likely to receive LINAC, likely indicative of the increased geographic accessibility of LINAC compared with GKRS. These findings should result in hypothesis-generating questions to further explore predictors of LINAC versus GKRS.


2016 ◽  
Vol 124 (4) ◽  
pp. 1018-1024 ◽  
Author(s):  
Henry S. Park ◽  
Elyn H. Wang ◽  
Charles E. Rutter ◽  
Christopher D. Corso ◽  
Veronica L. Chiang ◽  
...  

OBJECT Single-fraction stereotactic radiosurgery (SRS) is a crucial component in the management of limited brain metastases from non-small cell lung cancer (NSCLC). Intracranial SRS has traditionally been delivered using a frame-based Gamma Knife (GK) platform, but stereotactic modifications to the linear accelerator (LINAC) have made an alternative approach possible. In the absence of definitive prospective trials comparing the efficacy and toxicities of treatment between the 2 techniques, nonclinical factors (such as technology accessibility, costs, and efficiency) may play a larger role in determining which radiosurgery system a facility may choose to install. To the authors’ knowledge, this study is the first to investigate national patterns of GK SRS versus LINAC SRS use and to determine which factors may be associated with the adoption of these radiosurgery systems. METHODS The National Cancer Data Base was used to identify patients > 18 years old with NSCLC who were treated with single-fraction SRS to the brain between 2003 and 2011. Patients who received “SRS not otherwise specified” or who did not receive a radiotherapy dose within the range of 12–24 Gy were excluded to reduce the potential for misclassification. The chi-square test, t-test, and multivariable logistic regression analysis were used to compare potential demographic, clinicopathologic, and health care system predictors of GK versus LINAC SRS use, when appropriate. RESULTS This study included 1780 patients, among whom 1371 (77.0%) received GK SRS and 409 (23.0%) underwent LINAC SRS. Over time, the proportion of patients undergoing LINAC SRS steadily increased, from 3.2% in 2003 to 30.8% in 2011 (p < 0.001). LINAC SRS was adopted more rapidly by community versus academic facilities (overall 29.2% vs 17.2%, p < 0.001). On multivariable analysis, 4 independent predictors of increased LINAC SRS use emerged, including year of diagnosis in 2008–2011 versus 2003–2007 (adjusted OR [AOR] 2.04, 95% CI 1.52–2.73, p < 0.001), community versus academic facility type (AOR 2.04, 95% CI 1.60–2.60, p < 0.001), non-West versus West geographic location (AOR 4.50, 95% CI 2.87–7.09, p < 0.001), and distance from cancer reporting facility of < 20 versus ≥ 20 miles (AOR 1.57, 95% CI 1.21–2.04, p = 0.001). CONCLUSIONS GK remains the most commonly used single-fraction SRS modality for NSCLC brain metastases in the US. However, LINAC-based SRS has been rapidly disseminating in the past decade, especially in the community setting. Wide geographic variation persists in the distribution of GK and LINAC SRS cases. Further comparative effectiveness research will be needed to evaluate the impact of these shifts on SRS-related toxicities, local control, and survival, as well as treatment costs and efficiency.


2020 ◽  
Vol 132 (5) ◽  
pp. 1473-1479 ◽  
Author(s):  
Eun Young Han ◽  
He Wang ◽  
Dershan Luo ◽  
Jing Li ◽  
Xin Wang

OBJECTIVEFor patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.METHODSTen patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.RESULTSPlans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.CONCLUSIONSAll 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.


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