scholarly journals Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases 

2020 ◽  
Author(s):  
Morgan Guénolé ◽  
François Lucia ◽  
Vincent Bourbonne ◽  
Gurvan Dissaux ◽  
Emmanuelle Reygagne ◽  
...  

Abstract Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. IT was used concurrently with SRT in 30 patients. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Variables analyzed included histology, age, gender, diagnosis-specific Graded Prognostic Assessment score, recursive partitioning analysis score, number of BM, presence of extracranial metastases, tumor volume, Karnofsky performance status and the timing of ST. Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT had better 1-year LC, FFDBM and RN rate compared to patient who did not: 96% versus 78% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03).Conclusion: SRT delivered concurrently with IT improved LC, FFDBM, OS with a higher RN rate.

2020 ◽  
Author(s):  
Morgan Guénolé ◽  
François Lucia ◽  
Vincent Bourbonne ◽  
Gurvan Dissaux ◽  
Emmanuelle Reygagne ◽  
...  

Abstract Introduction: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. IT was used concurrently with SRT in 30 patients. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Variables analyzed included histology, age, gender, diagnosis-specific Graded Prognostic Assessment score, recursive partitioning analysis score, number of BM, presence of extracranial metastases, tumor volume, Karnofsky performance status and the timing of ST. Results: After a median follow-up of 11.9 months (range 0.7-29.7), the 1-year LC, FFDBM and RN rate in group 1 and group 2 were 96% versus 78% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03). Conclusion: SRT delivered concurrently with IT improved LC, FFDBM, OS with a higher RN rate.


2020 ◽  
Author(s):  
Morgan Guénolé ◽  
François Lucia ◽  
Vincent Bourbonne ◽  
Gurvan Dissaux ◽  
Emmanuelle Reygagne ◽  
...  

Abstract Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n=30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p=0.02), 89% versus 77% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03).Conclusion: SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Morgan Guénolé ◽  
François Lucia ◽  
Vincent Bourbonne ◽  
Gurvan Dissaux ◽  
Emmanuelle Reygagne ◽  
...  

Abstract Background The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results After a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03). Conclusion SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.


2019 ◽  
Vol 26 (1) ◽  
Author(s):  
E. Hamel-Perreault ◽  
D. Mathieu ◽  
L. Masson-Cote

Background Stereotactic radiosurgery (srs) for patients with 5 or more brain metastases (bmets) is a matter of debate. We report our results with that approach and the factors influencing outcome.Methods In the 103 patients who underwent srs for the treatment of 5 or more bmets, primary histology was nonsmall- cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (rpa) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 bmets had been given to 56 patients (54%). The mean number of treated bmets was 7 (range: 5–19), and the median cumulative bmets volume was 2 cm3 (range: 0.06–28 cm3).Results Multivariate analyses showed that stable extracranial disease (p < 0.001) and rpa (p = 0.022) were independent prognostic factors for overall survival (os). Moreover, a cumulative treated bmets volume of less than 6 cm3 (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better os. The total number of bmets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The rpa was significant (p = 0.027) in terms of distant recurrence.Conclusions Our study suggests that srs is a reasonable option for the management of patients with 5 or more bmets, especially with a cumulative treatment volume of less than 6 cm3.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7153-7153
Author(s):  
G. M. Videtic ◽  
C. A. Reddy ◽  
S. T. Chao ◽  
T. W. Rice ◽  
D. J. Adelstein ◽  
...  

7153 Background: To explore gender, race and their interactions in the setting of NSCLC brain metastases only, a single-institution brain database was analyzed, using the RTOG recursive partitioning analysis (RPA) brain metastases classification. Methods: From 1/82 to 9/04, 831 NSCLC pts with brain metastases were registered. RPA criteria for analysis were: class I- Karnofsky performance status (KPS) ≥ 70, age<65 years, primary tumor controlled, no extracranial metastases; class III- KPS<70; class II- all others. Results: Median follow-up was 5.4 months (m) (range 0–122.9). Median age was 62.4 (range 25–90). Median KPS was 80 (range 20–100). There were 485 males [M] (58.4%) and 346 females [F] (41.6%). 824 pts (99%) were either African-American (AA; n = 142[17%]) or White (W; n = 682[83%]). Pts characteristics were balanced when stratified by RPA class and by treatments. Median survival (MS) in months from time of brain metastasis diagnosis for all pts was 5.8. MS in months by gender [F vs. M] and race [W vs. AA] was: 6.3 vs. 5.5, p = 0.013; 6.0 vs. 5.2, p = 0.08, respectively. By RPA class for gender, MS trends (in months) favored F over M in classes I and II but not III: 17.1 vs. 9.5 (p = 0.11); 6.8 vs. 6.0 (p = 0.09), 2.7 vs. 2.5 (p = 0.42), respectively. By RPA class for gender and race, MS trends (in months) favored AAF over AAM in classes I and II but not III: 30.0 vs. 12.4, p = 0.50; 11.2 vs. 4.6, p = 0.021; 3.2 vs. 3.2, p = 0.64, respectively; and WF over WM in classes I but not II or III: 14.4 vs. 9.5, p = 0.11; 6.6 vs. 6.3, p = 0.38; 2.4 vs. 2.3, p = 0.49, respectively. On multivariable analysis, significant variables were gender (p = 0.041; RR 0.83); RPA class (p < 0.0001; RR 0.28, for I vs. III; p < 0.0001; RR 0.51, for II vs. III). Conclusions: Gender significantly influences NSCLC brain metastasis survival while race trends to significance. MS trends by RTOG RPA class suggest race may interact with genderprimarily in class I but pt numbers limited significance. Further characterization of these factors is warranted. No significant financial relationships to disclose.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 487-487
Author(s):  
Stefan Stremitzer ◽  
Anna Sophie Berghoff ◽  
Nico Benjamin Volz ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  

487 Background: Brain metastases (BM) in colorectal cancer (CRC) are rare, developing in only 0.3-9% of the patients, and considered a late-stage manifestation of the disease. The aim of this study was to investigate whether genetic variants of genes involved in BM-related pathways, such as integrin, invasion- and adhesion-mediating, angiogenic and tumor suppressing pathways, are associated with outcome. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected BM from 70 patients with histologically proven CRC. Single nucleotide polymorphisms (SNP) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed by direct Sanger DNA sequencing and evaluated for association with overall survival (OS) from resection of BM. Only SNPs with an allele frequency of ≥ 10% were analyzed. Results: In univariate analysis, rs17577 (MMP9) and rs4642 (ITGB3) showed a significant difference in OS [(G/G 7.4 months, G/A 5.1 months; HR (95% CI) 1.83 (0.95-3.53), p = 0.0440) and (A/A 9.4 months, A/G 4.8 months, G/G 4.3 months; HR (95% CI) 0.81 (0.44-1.49) and 2.14 (0.98-4.67), p = 0.0354), respectively]. In multivariate analysis adjusted for baseline characteristics [primary tumor site (right colon, left colon, rectal), chemotherapy before BM (yes/no), BM location (supratentorial, infratentorial, both), Karnofsky performance status (<80, 80-100)], rs2236599 (KLF4), and rs10171481 (ITGAV) are significant in OS [(G/G 7.4 months, G/A or A/A 4.8 months; HR (95% CI) 3.19 (1.55-6.53), p = 0.0016) and (A/A 5.7 months, A/G 4.4 months, G/G 15.5 months; HR (95% CI) 0.61 (0.29-1.29) and 0.25 (0.10-0.60), p = 0.0082), respectively]. Conclusions: This study suggests for the first time a prognostic effect of the SNPs involved in the BM pathway. Further analyses are needed to confirm these findings.


2021 ◽  
Vol 52 (3) ◽  
pp. e2004567
Author(s):  
José Manuel Sánchez-Villalobos ◽  
Alfredo Serna-Berna ◽  
Juan Salinas-Ramos ◽  
Pedro Pablo Escolar-Pérez ◽  
Emma Martínez-Alonso ◽  
...  

Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyze retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival compared to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes are factors that significantly influence patient survival.


2019 ◽  
Vol 26 (1) ◽  
pp. 64-69 ◽  
Author(s):  
E. Hamel-Perreault ◽  
D. Mathieu ◽  
L. Masson-Cote

Background: Stereotactic radiosurgery (SRS) for patients with 5 or more brain metastases (BMets) is a matter of debate. We report our results with that approach and the factors influencing outcome. Methods: In the 103 patients who underwent SRS for the treatment of 5 or more BMets, primary histology was non-small-cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (RPA) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 BMets had been given to 56 patients (54%). The mean number of treated BMets was 7 (range: 5–19), and the median cumulative BMets volume was 2 cm3 (range: 0.06–28 cm3). Results: Multivariate analyses showed that stable extracranial disease (p < 0.001) and RPA (p = 0.022) were independent prognostic factors for overall survival (OS). Moreover, a cumulative treated BMets volume of less than 6 cm3 (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better OS. The total number of BMets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The RPA was significant (p = 0.027) in terms of distant recurrence. Conclusions: Our study suggests that SRS is a reasonable option for the management of patients with 5 or more BMets, especially with a cumulative treatment volume of less than 6 cm3.


Author(s):  
Sergej Telentschak ◽  
Daniel Ruess ◽  
Stefan Grau ◽  
Roland Goldbrunner ◽  
Niklas von Spreckelsen ◽  
...  

Abstract Purpose The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. Methods All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). Results We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%. Conclusion Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.


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