scholarly journals Clinical and volumetric predictors of local control after robotic stereotactic radiosurgery for cerebral metastases: active systemic disease may affect local control in the brain

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Sławomir Blamek ◽  
Magdalena Stankiewicz ◽  
Bogusław Maciejewski

AbstractBackgroundThe aim of the study was to assess the association between physical and biological dose normalized to volume of the metastatic tumor as well as clinical factors with local control in patients with brain metastases who underwent robotic stereotactic radiosurgery.Patients and methodsA cohort of 69 patients consecutively treated with robotic radiosurgery between 2011 and 2016 was analyzed. The patients were treated with either single fraction radiosurgery or hypofractionated regimens. Biologically effective dose (BED) was calculated assuming alpha/beta value = 10 and both physical dose and BED were normalized to the tumor volume to allow dose-volume effect evaluation. Moreover, clinical and treatment-related variables were evaluated to asses association with local control.ResultsA total of 133 tumors were irradiated and their volumes ranged between 0.001 and 46.99 cm3. Presence of extracranial progression was associated with worse local control whereas higher total dose, BED10 > 59 Gy and single metastasis predicted statistically significantly better local outcome. BED10/cm3 > 36 Gy, and BED2 > 60 Gy negatively affected local control in univariate analysis. In multivariate analysis performed on all these variables, presence of a single metastasis, BED10 > 59 Gy and extracranial progression retained their significance. Excluding a priori the BED2/ cm3 parameter resulted with a Cox model confirming significance of all remaining variables.ConclusionsHypofractionated treatment schemes have similar efficiency to single fraction treatment in terms of local control and the effect depends on BED irrespective of fractionation schedule. Effective control of extracranial sites of the disease is associated with higher probability of local control in the brain which in turn is consistently lower in patients with multiple lesions.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6086
Author(s):  
Maxime Loo ◽  
Jean-Baptiste Clavier ◽  
Justine Attal Khalifa ◽  
Elisabeth Moyal ◽  
Jonathan Khalifa

For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.


2016 ◽  
Vol 16 (3) ◽  
pp. 344-351 ◽  
Author(s):  
Mark J. Amsbaugh ◽  
Mehran B. Yusuf ◽  
Jeremy Gaskins ◽  
Anthony E. Dragun ◽  
Neal Dunlap ◽  
...  

Purpose/Objective(s): To establish a dose–volume response relationship for brain metastases treated with single-fraction robotic stereotactic radiosurgery and identify predictors of local control. Materials/Methods: We reviewed a prospective institutional database of all patients treated for intact brain metastases with stereotactic radiosurgery alone using the CyberKnife robotic radiosurgery system from 2012 to 2015. Tumor response was determined based on Response Evaluation Criteria In Solid Tumors version 1.1. Survival was estimated using the Kaplan-Meier method. Logistic regression modeling was used to identify predictors of outcome and establish a dose–volume response relationship. Receiver operating characteristic curves were constructed to evaluate the predictive capability of the relationship. Results: There were 357 metastases evaluated in 111 patients with a median diameter of 8.14 mm (2.00-40.77 mm). At 6 and 12 months, local control was 86.9% and 82.2%, respectively. For lesions of similar volumes, higher maximum dose, mean dose, and minimum dose (all P values <.05) predicted for better local control. Tumor volume and diameter were strongly correlated, and a dose–volume response relationship was constructed using mean dose per lesion diameter (Gy/mm) that was predictive of local control (odds ratio: 1.34, 95% confidence interval: 1.06-1.70). Area under the receiver operating characteristic curve for local control and mean dose by volume was 0.6199 with a threshold of 2.05 Gy/mm (local failure 7.6% above and 17.3% below 2.05 Gy/mm). Conclusion: A dose–volume response relationship exists for brain metastases treated with robotic stereotactic radiosurgery. Mean dose per volume is strongly predictive of local control and can be potentially useful during stereotactic radiosurgery plan evaluation while respecting previously established dose constraints.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
Michael Tjong ◽  
Fabio Moraes ◽  
David Shultz

Abstract PURPOSE/OBJECTIVE(S): Melanoma commonly metastasizes to the brain and is radioresistant. Stereotactic radiosurgery (SRS) confers durable local control of brain metastases (BM) while maintaining neurocognitive function. These advantages are increasingly important as survival among these patients improves secondary to advances in systemic therapies. This study investigated the local control (LC), intracranial PFS (iPFS), freedom from radionecrosis (FFRN), and overall survival (OS) among melanoma patients receiving SRS for BM. MATERIALS/METHODS: We retrospectively reviewed clinical outcomes of melanoma patients with brain metastases treated with SRS between October 2008 and January 2017 in a large academic centre. Post-SRS, patients were followed in a multidisciplinary clinic with clinical examination and brain MRI every 3 months. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: In total, 97 patients with 283 brain metastases (including 12 surgical cavities) treated with SRS were identified. Median age was 60.5 (24.4–90.7). Median follow-up was 9.6 (2.2–74.7) months after first SRS. Median prescription dose was 21 (10–24) Gy delivered in a single fraction. Thirty (30.9%) patients had WBRT post-SRS, 36 (37.1%) patients had BRAF-positive disease. Per lesion (N=283), 1-year LC and FFRN were 84.4%, and 90.1%, respectively; medians were not achieved for either LC or FFRN. Radionecrosis (RN) occurred in 20 (7.1%) lesions. Per patient (N=97), median OS and iPFS were 16.0 and 5.3 months, respectively; 1-year OS and iPFS rates were 62.0%, and 30.1%, respectively. CONCLUSION: SRS resulted in excellent rates of LC, with a low risk of RN. However, most patients developed intracranial progression within 1 year. Further analyses to establish correlates (lesion size, SRS dose, and molecular status) to LC, FFRN, OS, and iPFS will be performed prior to the final presentation.


2013 ◽  
Vol 119 (5) ◽  
pp. 1131-1138 ◽  
Author(s):  
Eric K. Oermann ◽  
Marie-Adele S. Kress ◽  
Jonathan V. Todd ◽  
Brian T. Collins ◽  
Riane Hoffman ◽  
...  

Object Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2–5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. Methods The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2–5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. Results There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83–6.91, p = 0.032). Conclusions Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.


2016 ◽  
Vol 125 (Supplement_1) ◽  
pp. 89-96 ◽  
Author(s):  
Charles A. Valery ◽  
Matthieu Faillot ◽  
Ioannis Lamproglou ◽  
Jean-Louis Golmard ◽  
Catherine Jenny ◽  
...  

OBJECTIVEGrade II meningiomas, which currently account for 25% of all meningiomas, are subject to multiple recurrences throughout the course of the disease and represent a challenge for the neurosurgeon. Radiosurgery is increasingly performed for the treatment of Grade II meningiomas and is quite efficient in controlling relapses locally at the site of the lesion, but it cannot prevent margin relapses. The aim of this retrospective study was to analyze the technical parameters involved in producing marginal relapses and to optimize loco-marginal control to improve therapeutic strategy.METHODSEighteen patients presenting 58 lesions were treated by Gamma Knife radiosurgery (GKRS) between 2010 and 2015 in Hopital de la Pitié-Salpêtrière. The median patient age was 68 years (25%−75% interval: 61–72 years), and the sex ratio (M/F) was 13:5. The median delay between surgery and first GKRS was 3 years. Patients were classified as having Grade II meningioma using World Health Organization (WHO) 2007 criteria. The tumor growth rate was computed by comparing 2 volumetric measurements before treatment. After GKRS, iterative MRI, performed every 6 months, detected a relapse if tumor volume increased by more than 20%. Patterns of relapse were defined as being local, marginal, or distal. Survival curves were estimated using the Kaplan-Meier method, and the relationship between criterion and potential risk factors was tested by the log-rank test and univariable Cox model.RESULTSThe median follow-up was 36 months (range 8–57 months). During this period, 3 patients presented with a local relapse, 5 patients with a marginal relapse, and 7 patients with a distal relapse. Crude local control was 84.5%. The local control actuarial rate was 89% at 1 year and 71% at 3 years. The marginal control actuarial rate was 81% at 1 year and 74% at 2 years. The distal control actuarial rate was 100% at 1 year, 81% at 2 years, and 53% at 3 years. Median distal control was 38 months. Progression-free survival (PFS) was 71% at 1 year, 36% at 2 years, and 23% at 3 years. Median PFS was 18 months. Lesions treated with a minimum radiation dose of ≤ 12 Gy had significantly more local relapses than those treated with a dose > 12 Gy (p = 0.04) in univariate analysis.Marginal control was significantly influenced by tumor growth rate, with a lower growth rate being highly associated with improved marginal control (p = 0.002). There was a trend toward a relationship between dose and marginal control, but it was not significant (p = 0.09). PFS was significantly associated with delay between first surgery and GKRS (p = 0.03). The authors noticed few complications with no sequelae.CONCLUSIONSIn order to optimize loco-marginal control, radiosurgical treatment should require a minimum dose of > 12 Gy and an extended target volume along the dural insertion. Ideally, these parameters should correspond to the aggressiveness of the lesion, based on genetic features of the tumor.


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.


2009 ◽  
Vol 110 (1) ◽  
pp. 181-186 ◽  
Author(s):  
Benjamin D. Fox ◽  
Akash Patel ◽  
Dima Suki ◽  
Ganesh Rao

Object Metastatic sarcoma to the brain is rare and represents a therapeutic challenge due to its relative resistance to radio- and chemotherapy. Resection has traditionally been the mainstay of treatment. The authors reviewed a series of patients with metastatic sarcoma to the brain treated surgically to determine outcomes and identify predictors of survival in these patients. Methods A retrospective review of prospectively collected data was undertaken on patients undergoing surgery between 1993 and 2005 for metastatic sarcoma to the brain at The University of Texas, M.D. Anderson Cancer Center. Results During the study period, 62 patients underwent 84 operations for metastatic sarcoma to the brain. The median postoperative overall and progression-free survival rates were 7.5 and 4.7 months, respectively. Fifty-nine (95%) of 62 patients had a gross-total resection. The 30-day mortality rate was 4.2%. The Karnofsky Performance Scale scores at discharge from the hospital and 3 months postoperatively were the same or improved in 50 (85%) of 59 and 26 (51%) of 51, respectively. Overall postcraniotomy survival was 62% at 6 months, 39% at 1 year, 21% at 2 years, and 8% at 5 years. In multivariate and univariate analysis, control of systemic disease, and sarcomas originating from bone, cartilage, or soft tissue were predictors of survival. Patients with control of systemic disease had survival advantage when compared with those who did not. In patients with alveolar soft-part sarcoma, there was a significantly increased survival advantage compared with all other histological subgroups. Conclusions The authors' results suggest that in selected patients, resection of metastatic sarcoma to the brain is associated with a relatively low risk of operative death and results in improvement in neurological function. Patients with systemic control of their primary disease and certain histological subtypes (specifically alveolar soft-part sarcoma) have improved overall and progression-free survival.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9501-9501
Author(s):  
Michael Ryan Folkert ◽  
Mark Bilsky ◽  
Ashlyn K. Tom ◽  
Kaled M. Alektiar ◽  
Ilya Laufer ◽  
...  

9501 Background: Conventional radiation treatment (20-40 Gy total dose, 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses and results in poor local control (58-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of control and salvage for these lesions. Methods: Patients with pathologically-proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. Local control (LC) and overall survival (OS) were analyzed using Kaplan-Meier statistics; univariate/multivariate analyses were performed using Cox regression. Toxicities were assessed according to CTCAE v4.0 criteria. Results: From 5/2005 and 11/2012, 88 patients with 120 discrete metastases were treated with HF (3-6 fractions, median dose 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose 24 Gy, n=68, 56.7%). Median followup was 12.3 months. LC at 12 months was 87.9% (95% CI 81.3-94.5%). OS at 12 months was 60.6% (95% CI 49.6-71.6%) with a median survival of 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (P=.007) (Table). SF IG-SRS retained its significance in terms of improved LC on multivariate analysis, HR 0.304 (95% CI: 0.117-0.790); variables tested included prior radiation therapy, histology, IG-SRS fractionation, surgery, and chemotherapy. Treatment was well-tolerated with 1% acute Grade 3 toxicity and 4.5% chronic Grade 3 toxicity observed; there were no > Grade 3 toxicities. Conclusions: In the largest series of metastatic sarcoma to the spine to date, image-guided stereotactic radiosurgery provides excellent local control in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction image-guided stereotactic radiosurgery demonstrates the highest rates of local control with minimal toxicity. [Table: see text]


2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 146-146
Author(s):  
Diogo Bugano Diniz Gomes ◽  
Rita Elias Deeba ◽  
Vicente Valero ◽  
Stacy L. Moulder ◽  
Banu Arun ◽  
...  

146 Background: There are various treatment modalities for metastatic breast cancer to the brain (MBC-b), with wide variation of reported outcomes. Methods: There were 1,513 patients (pts) with MBC-b treated at MD Anderson Cancer Center October 2009-December 2012. We reviewed medical records of the first consecutive 1015 and included 792 with confirmed brain metastases (BM). A Cox multivariate model was used to identify the effect of treatment on time-to-progression in the brain (TTP-b) and overall survival (OS). Results: Disease subtypes: ER+/HER2- (27%); ER+/HER2+ (16%); ER-/HER2+ (18%); ER-/HER2- (29%), missing (10%). Number of BM: 1 (20%), >1 (73%), missing (7%). Local treatment: metastasectomy (S) (13%), radio-surgery (SRS) (12%), whole-brain radiation (WBRT) (57%), combination of S/SRS with WBRT (11%), no treatment (7%). Systemic treatment: Any (64%), HER2 directed (24%). Median OS was 11.33 months(m) (4.4-25.8). Clinical characteristics associated with OS in multivariate analysis: ER+, HER2+, age < 60, ECOG 0-1, single BM, controlled systemic disease at time of BM and <3 treatment lines before BM. After correction for covariates, use of systemic therapy was associated with longer OS (HR 0.35 CI 0.20-0.60, p < 0.001) regardless of subgroup: HER2+ (19.9 vs 3.5m), ER+/HER2- (12.7 vs 2.2m), ER-/HER- (10.5 vs 2.3m). In pts receiving trastuzumab at diagnosis of BM, continuation of HER2 therapy increased OS (HR 0.44 CI 0.25-0.77, p = 0.004) regardless of agent used (lapatinib vs trastuzumab p=0.7). OS was the same for S and SRS (p=0.7) and either one increased OS (HR 0.41 CI 0.21-0.79 p=0.008). WBRT prolonged OS in multiple BM (HR 0.61 CI 0.38-0.96); Median TTP-b was 11.07m (5-24). WBRT added to S/SRS had longer TTP-b than either modality alone (17.6m vs 10.4m HR 0.56 CI 0.37-0.85 p=0.006). Use of systemic therapy after diagnosis of BM increased TTP-b (11.8 vs 5.1m HR 0.55 CI 0.33-0.92 p = 0.024), but there was no difference between agents used (lapatininib vs trastuzumab p=0.79; capecitabine vs others p= 0.96). Conclusions: WBRT improved local control when done after S/SRS. The use of chemotherapy after local therapy improved time to progression in the brain and survival.


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