scholarly journals RADI-05. Metastatic Neoplasm Volume Kinetics Following Two-Staged Stereotactic Radiosurgery

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii18-iii19
Author(s):  
Ethan Damron ◽  
Antonio Dono ◽  
Hatim Chafi ◽  
Magda Martir ◽  
Tse-Kuan Yu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Progression ◽  
Alternative Approach ◽  
Large Brain ◽  
Metastatic Neoplasm ◽  
Grade 3 ◽  
Volume Kinetics ◽  
To Receive

Abstract Introduction Multisession staged stereotactic radiosurgery (2-SSRS) represents an alternative approach for management of large brain metastases (LBMs), with potential theoretical advantages over fractionated SRS and represents an alternative to surgery in poor surgical candidates. We aimed to investigate the clinical efficacy and safety of 2-SSRS in patients with LBMs. Methods LBMs of patients treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic information was obtained. Volumetric measurements at first SSRS, second SSRS, and follow-up imaging studies were obtained. Results Twenty-six patients with 28 LBMs were included in the study. Fifteen patients (58%) were male. Median age at 2-SSRS was 61 years (range: 31–84). Median marginal doses for first and second SSRS were 15 Gy (range: 12–18 Gy) and 15 Gy (range: 12–16 Gy), respectively. Median duration between sessions was 32 days. Two patients (8%) failed to receive their second SSRS due to local progression. Median tumor volumes at first SSRS, second SSRS, 3-month follow-up, and 6-month follow-up were 8.7 cm3 (range: 1.5–34.7 cm3), 3.3 cm3 (range: 0.8–26.1 cm3), 1.7 cm3 (range: 0.2–10.1 cm3), and 1.4 cm3 (range: .04–20.7 cm3), respectively. The median absolute and relative decrement between S-SRS sessions was 3.7 cm3 (range: 2.8–16.5 cm3) and 49.5% (range: 17.1- 87.1%), respectively. Overall, 26 of the 28 lesions (93%) demonstrated early local control following the first SSRS with 18 lesions (69%) demonstrating a decrease in volume of >30% and 3 lesions (12%) remaining stable. Six lesions (23%) showed disease progression. There were no grade 3 adverse events. Conclusions Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with large, symptomatic brain metastases, especially in non-surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery series.

Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20502-e20502 ◽  
Author(s):  
Sai-Hong Ignatius Ou ◽  
Marcello Tiseo ◽  
D. Ross Camidge ◽  
Myung-Ju Ahn ◽  
Rudolf M. Huber ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Review Committee ◽  
Small Cell Lung ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
A Site ◽  
To Receive ◽  
Clinical Trial Information

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]

scholarly journals Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

2018 ◽  
Vol 129 (2) ◽  
pp. 366-382 ◽  
Author(s):  
Lilyana Angelov ◽  
Alireza M. Mohammadi ◽  
Elizabeth E. Bennett ◽  
Mahmoud Abbassy ◽  
Paul Elson ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Binary Data ◽  
Tumor Volume ◽  
Demographic Data ◽  
Maximum Diameter ◽  
Local Progression ◽  
Imaging Results ◽  
Increased Risk

OBJECTIVEStereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%–62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy.METHODSFifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board–approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient.RESULTSAmong 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23–83 years), 23 patients (43%) had non–small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12–18 Gy) and 15 Gy (range 12–15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm3 (range 2.4–31.3 cm3) and 7.0 cm3 (range 1.0–29.7 cm3). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm3 (range 0.1–23.1 cm3). The median change in volume compared with baseline was a decrease of 54.9% (range −98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3–7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively.CONCLUSIONS2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.

scholarly journals Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET

2020 ◽  
Author(s):  
Francesco Cicone ◽  
Luciano Carideo ◽  
Claudia Scaringi ◽  
Andrea Romano ◽  
Marcelo Mamede ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Radiation Necrosis ◽  
Standardized Uptake Value ◽  
Longitudinal Assessment ◽  
Metabolic Evolution ◽  
Local Progression ◽  
Pet Ct

Abstract Background The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, we characterized the long-term metabolic evolution of RN by sequential PET/CT imaging with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (F-DOPA) in patients with brain metastases following stereotactic radiosurgery (SRS). Methods Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI. Results Ninety-nine F-DOPA PET scans were acquired over a median period of 18 (range: 12–66) months. Median follow-up from the baseline F-DOPA PET/CT was 48 (range 21–95) months. Overall, 24 (70.6%) and 10 (29.4%) lesions were classified as RN and LP, respectively. LP occurred after a median of 18 (range: 12–30) months from baseline PET. F-DOPA tumor-to-brain ratio (TBR) and relative standardized uptake value (rSUV) increased significantly over time in LP lesions, while remaining stable in RN lesions. The parameter showing the best diagnostic performance was rSUV (accuracy = 94.1% for the optimal threshold of 1.92). In contrast, variations of the longest tumor dimension measured on contrast-enhancing MRI did not distinguish between RN and LP. Conclusion F-DOPA PET has a high diagnostic accuracy for assessing the long-term evolution of brain metastases following SRS.

The Volumetric Response of Brain Metastases After Stereotactic Radiosurgery and Its Post-treatment Implications

Neurosurgery ◽  
2013 ◽  
Vol 74 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Suzanne R. Sharpton ◽  
Eric K. Oermann ◽  
Dominic T. Moore ◽  
Eric Schreiber ◽  
Riane Hoffman ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Tumor Volume ◽  
Neurological Symptoms ◽  
Volume Reduction ◽  
Whole Brain Radiation ◽  
Local Progression ◽  
Tumor Volume Reduction

Abstract BACKGROUND: Changes in tumor volume are seen on magnetic resonance imaging within weeks after stereotactic radiosurgery (SRS), but it remains unclear what clinical outcomes early radiological changes portend. OBJECTIVE: We hypothesized that rapid, early reduction in tumor volume post-SRS is associated with prolonged local control and favorable clinical outcome. METHODS: A retrospective review of patients treated with CyberKnife SRS for brain metastases at the University of North Carolina from 2007 to 2009 was performed. Patients with at least 1 radiological follow-up, minimal initial tumor volume of 0.1 cm3, no previous focal radiation, and no recent whole-brain radiation therapy were eligible for inclusion. RESULTS: Fifty-two patients with 100 metastatic brain lesions were analyzed and had a median follow-up of 15.6 months (range, 2-33 months) and a median of 2 (range, 1–8) metastatic lesions. In treated metastases in which there was a significant tumor volume reduction by 6 or 12 weeks post-SRS, there was no local progression for the duration of the study. Furthermore, patients with metastases that did not reduce in volume by 6 or 12 weeks post-SRS were more likely to require corticosteroids (P = .01) and to experience progression of neurological symptoms (P = .003). CONCLUSION: Significant volume reductions of brain metastases measured at either 6 or 12 weeks post-SRS were strongly associated with prolonged local control. Furthermore, early volume reduction was associated with less corticosteroid use and stable neurological symptoms.

scholarly journals MRI Texture Analysis for the Prediction of Stereotactic Radiosurgery Outcomes in Brain Metastases from Lung Cancer

2021 ◽  
Vol 10 (2) ◽  
pp. 237
Author(s):  
Jung Hyun Park ◽  
Byung Se Choi ◽  
Jung Ho Han ◽  
Chae-Yong Kim ◽  
Jungheum Cho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Texture Analysis ◽  
Multivariable Analysis ◽  
Texture Features ◽  
Progression Free Survival ◽  
Clinical Parameter ◽  
Imaging Biomarker ◽  
Local Progression

This study aims to evaluate the utility of texture analysis in predicting the outcome of stereotactic radiosurgery (SRS) for brain metastases from lung cancer. From 83 patients with lung cancer who underwent SRS for brain metastasis, a total of 118 metastatic lesions were included. Two neuroradiologists independently performed magnetic resonance imaging (MRI)-based texture analysis using the Imaging Biomarker Explorer software. Inter-reader reliability as well as univariable and multivariable analyses were performed for texture features and clinical parameters to determine independent predictors for local progression-free survival (PFS) and overall survival (OS). Furthermore, Harrell’s concordance index (C-index) was used to assess the performance of the independent texture features. The primary tumor histology of small cell lung cancer (SCLC) was the only clinical parameter significantly associated with local PFS in multivariable analysis. Run-length non-uniformity (RLN) and short-run emphasis were the independent texture features associated with local PFS. In the non-SCLC (NSCLC) subgroup analysis, RLN and local range mean were associated with local PFS. The C-index of independent texture features was 0.79 for the all-patients group and 0.73 for the NSCLC subgroup. In conclusion, texture analysis on pre-treatment MRI of lung cancer patients with brain metastases may have a role in predicting SRS response.

161: Surgical Resection(S) Plus Stereotactic Radiosurgery (SRS) Versus SRS Alone for Large Brain Metastases: A Comparative Study

2021 ◽  
Vol 163 ◽  
pp. S68
Author(s):  
Barbara-Ann Millar ◽  
Normand Laperriere ◽  
Tatiana Conrad ◽  
Aristotelis Kalyvas ◽  
Gelareh Zadeh ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Comparative Study ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Large Brain

Phase 1, 2 trial of concurrent anti-PD1 and stereotactic radiosurgery for melanoma and non-small cell lung cancer brain metastases (NCT02858869).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2022-2022
Author(s):  
Mohammad Khurram Khan ◽  
Tahseen Nasti ◽  
Troy Kleber ◽  
David H. Lawson ◽  
Melinda Lynne Yushak ◽  
...  
Keyword(s):  
T Cells ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Free Survival ◽  
Early Activation ◽  
Previously Treated ◽  
The Mean ◽  
Grade 3

2022 Background: The safety and efficacy of concurrent pembrolizumab (anti-PD1) and stereotactic radiosurgery (SRS) for brain metastases (BM) is unknown. Methods: Patients with melanoma or NSCLC, 1-10 brain metastases, ≥ 1 extra-cranial lesion, age ≥ 18, and ECOG 0-1 were treated with anti-PD1 every 3 weeks. SRS was administered 1-2 days after starting anti-PD1. SRS used three different radiation arms: Arm A used 6 Gray (Gy) in 5 fractions (fx), Arm B used 9 Gy in 3 fx, and Arm C used 18-21 Gy in single fx. Primary endpoint was grade 3 CNS toxicity at 3 months (CTCAE v 4.0). Secondary endpoints were overall survival (OS), local control (LC) within the SRS field, intra-cranial progression free survival (IC-PFS), extra-cranial progression free survival (EC-PFS), rate of extra-cranial clinical benefit, and immunological changes. OS, LC, IC-PFS, and EC-PFS were estimated using the Kaplan-Meier method, and covariates were compared using log-rank tests. 95% confidence intervals for 6-month and 12-month were estimated using Greenwood’s formula. Results: 25 patients were treated from 2016 until 2020. The mean age was 61. The mean number of CNS lesions was 2.7. The mean number of extra-cranial lesions was 2.5. Six were enrolled on Arm A, 12 on Arm B, and 7 on Arm C. 21 had melanoma. 4 had NSCLC. Of the melanoma, 8 were BRAF-, 10 were BRAF+, and 3 had unknown mutation status. 12 patients (48%) had progressed on prior immunotherapy and/or other oncological therapies. The trial met its primary endpoint, with no grade 3 CNS toxicity at 3 months. Two patients (8%) experienced ≥ Grade 3 anti-PD1 related toxicity, and no grade 5 toxicity was noted. The median OS was 32.8 months. The 6 and 12 month OS were 79.1% (56.5-90.8%) and 67.8% (43.3-83.5%), respectively. The 1 year OS was similar between previously treated and treatment naïve patients (71.8% vs. 65.6%), suggesting some role for SRS in overcoming therapy resistance. However, with longer follow-up, the OS trended worse (p=0.07) for previously treated patients. LC was 95.7% (72.9-99.4%) at 6 and 12 months. IC-PFS at 6 months was 69.1% (45.8-83.9%), and at 12 months was 57.5% (33.7-75.5%). The EC-PFS at 6 and 12 month was 54.5% (32.1-72.4%) and 43.6% (22.3-63.2%), respectively. Clinical benefit, which was defined as a best overall response of stable disease or better according to RECIST 1.1, occurred in 12 patients (48%). No outcome differences were noted amongst the three different SRS arms. 70% of the patients demonstrating early activation (within 3 weeks of starting SRS/anti-PD1) of CD8+PD1+Ki67+ T cells demonstrated a clinical benefit. 100% of patients that failed to show early activation of CD8+PD1+Ki67+ T cells progressed. Conclusions: Concurrent pembrolizumab (Anti-PD-1) and SRS is safe and effective. Early activation of CD8+PD1+Ki67+ T cells correlates with improved outcome. Further trials testing pembrolizumab and SRS are justified. Clinical trial information: NCT02858869.

Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials

2019 ◽  
Vol 103 (3) ◽  
pp. 618-630 ◽  
Author(s):  
Eric J. Lehrer ◽  
Jennifer L. Peterson ◽  
Nicholas G. Zaorsky ◽  
Paul D. Brown ◽  
Arjun Sahgal ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Meta Analysis ◽  
Large Brain ◽  
Single Versus

scholarly journals CMET-41. OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY (SRS) FOR LIMITED BRAIN METASTASES - AN AUSTRALIAN SINGLE INSTITUTIONAL EXPERIENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi60-vi60
Author(s):  
Lilly Shen ◽  
Wee Loon Ong ◽  
Briana Farrugia ◽  
Anna Seeley ◽  
Carlos Augusto Gonzalvo ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Cumulative Incidence ◽  
Multivariate Analyses ◽  
Primary Lung Cancer ◽  
Factors Associated ◽  
Distant Failure ◽  
Kaplan Meier ◽  
Institutional Experience

Abstract INTRODUCTION Despite increasing use of stereotactic radiosurgery (SRS) for management of brain metastases (BM), published Australian data is scarce. We aim to report on the outcomes following SRS for limited BM in a single Australian institution. METHODS This is a retrospective cohort of patients with limited BM treated with SRS between August 2015 and March 2019. A dose of 24Gy/3# were prescribed to intact lesion, and 21Gy/3# to surgical cavity post-surgical resection. All patients were followed with 3-monthly surveillance MRI brain. Primary outcomes were: local failure (LF: increased in size of SRS-treated BM lesion/ recurrence in surgical cavity), distant failure (DF: intracranial progression outside of the SRS-treated lesion/ cavity), and overall survival (OS). LF, DF and OS were estimated using the Kaplan-Meier method. Multivariate Cox regressions were used to evaluate factors associated with outcomes of interest, with death as competing-risk events for LF and DF. RESULTS 76 courses of SRS were delivered in 65 patients (54 unresected BM lesions, and 22 surgical cavities). 43 (66%) patients were ECOG 0–1. 35 (54%) patients had solitary BM. 41 (63%) had symptomatic BM. Half of the patients had primary lung cancer. Median follow-up was 4.8 months (range:0.1–39 months). 10 LF were observed at a median of 3.5 month post-SRS, with 6- and 12-month LF cumulative incidence of 14% and 24% respectively. 30 DF were observed at a median of 3.3 months, with 6- and 12-month DF cumulative incidence of 38% and 63% respectively. The 12- and 24-month OS were 39% and 26% respectively. In multivariate analyses, better ECOG status, solitary BM lesion, resection of BM pre-SRS, and use of subsequent systemic therapy were independently associated with improved OS. CONCLUSION This is one of the few Australian series reporting on outcomes following SRS for limited BM, with comparable outcomes to published international series.

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