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.

Impact of the radiosurgery prescription dose on the local control of small (2 cm or smaller) brain metastases

2017 ◽  
Vol 126 (3) ◽  
pp. 735-743 ◽  
Author(s):  
Alireza M. Mohammadi ◽  
Jason L. Schroeder ◽  
Lilyana Angelov ◽  
Samuel T. Chao ◽  
Erin S. Murphy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Local Control ◽  
Radiation Necrosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Local Progression ◽  
Prescription Dose

OBJECTIVE The impact of the stereotactic radiosurgery (SRS) prescription dose (PD) on local progression and radiation necrosis for small (≤ 2 cm) brain metastases was evaluated. METHODS An institutional review board–approved retrospective review was performed on 896 patients with brain metastases ≤ 2 cm (3034 tumors) who were treated with 1229 SRS procedures between 2000 and 2012. Local progression and/or radiation necrosis were the primary end points. Each tumor was followed from the date of radiosurgery until one of the end points was reached or the last MRI follow-up. Various criteria were used to differentiate tumor progression and radiation necrosis, including the evaluation of serial MRIs, cerebral blood volume on perfusion MR, FDG-PET scans, and, in some cases, surgical pathology. The median radiographic follow-up per lesion was 6.2 months. RESULTS The median patient age was 56 years, and 56% of the patients were female. The most common primary pathology was non–small cell lung cancer (44%), followed by breast cancer (19%), renal cell carcinoma (14%), melanoma (11%), and small cell lung cancer (5%). The median tumor volume and median largest diameter were 0.16 cm3 and 0.8 cm, respectively. In total, 1018 lesions (34%) were larger than 1 cm in maximum diameter. The PD for 2410 tumors (80%) was 24 Gy, for 408 tumors (13%) it was 19 to 23 Gy, and for 216 tumors (7%) it was 15 to 18 Gy. In total, 87 patients (10%) had local progression of 104 tumors (3%), and 148 patients (17%) had at least radiographic evidence of radiation necrosis involving 199 tumors (7%; 4% were symptomatic). Univariate and multivariate analyses were performed for local progression and radiation necrosis. For local progression, tumors less than 1 cm (subhazard ratio [SHR] 2.32; p < 0.001), PD of 24 Gy (SHR 1.84; p = 0.01), and additional whole-brain radiation therapy (SHR 2.53; p = 0.001) were independently associated with better outcome. For the development of radiographic radiation necrosis, independent prognostic factors included size greater than 1 cm (SHR 2.13; p < 0.001), location in the corpus callosum (SHR 5.72; p < 0.001), and uncommon pathologies (SHR 1.65; p = 0.05). Size (SHR 4.78; p < 0.001) and location (SHR 7.62; p < 0.001)—but not uncommon pathologies—were independent prognostic factors for the subgroup with symptomatic radiation necrosis. CONCLUSIONS A PD of 24 Gy results in significantly better local control of metastases measuring < 2 cm than lower doses. In addition, tumor size is an independent prognostic factor for both local progression and radiation necrosis. Some tumor pathologies and locations may also contribute to an increased risk of radiation necrosis.

scholarly journals Predictors of Radiation Necrosis in Long-term Survivors of Stereotactic Radiosurgery for Brain Metastases

2016 ◽  
Vol 96 (2) ◽  
pp. E104 ◽  
Author(s):  
Z.A. Siddiqui ◽  
M.D. Johnson ◽  
A.M. Baschnagel ◽  
P.Y. Chen ◽  
D.J. Krauss ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Radiation Necrosis ◽  
Long Term Survivors

scholarly journals Predictors of radiation necrosis in long-term survivors after Gamma Knife stereotactic radiosurgery for brain metastases

2019 ◽  
Vol 7 (4) ◽  
pp. 400-408
Author(s):  
Zaid A Siddiqui ◽  
Bryan S Squires ◽  
Matt D Johnson ◽  
Andrew M Baschnagel ◽  
Peter Y Chen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Radiation Necrosis ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Target Volumes ◽  
Gamma Knife Stereotactic Radiosurgery ◽  
Long Term Survivors

Abstract Background The long-term risk of necrosis after radiosurgery for brain metastases is uncertain. We aimed to investigate incidence and predictors of radiation necrosis for individuals with more than 1 year of survival after radiosurgery for brain metastases. Methods Patients who had a diagnosis of brain metastases treated between December 2006 and December 2014, who had at least 1 year of survival after first radiosurgery were retrospectively reviewed. Survival was analyzed using the Kaplan-Meier estimator, and the incidence of radiation necrosis was estimated with death or surgical resection as competing risks. Patient and treatment factors associated with radiation necrosis were also analyzed. Results A total of 198 patients with 732 lesions were analyzed. Thirty-four lesions required salvage radiosurgery and 10 required salvage surgical resection. Median follow-up was 24 months. The estimated median survival for this population was 25.4 months. The estimated per-lesion incidence of radiation necrosis at 4 years was 6.8%. Medical or surgical therapy was required for 60% of necrosis events. Tumor volume and male sex were significant factors associated with radiation necrosis. The per-lesions incidence of necrosis for patients undergoing repeat radiosurgery was 33.3% at 4 years. Conclusions In this large series of patients undergoing radiosurgery for brain metastases, patients continued to be at risk for radiation necrosis throughout their first 4 years of survival. Repeat radiosurgery of recurrent lesions greatly exacerbates the risk of radiation necrosis, whereas treatment of larger target volumes increases the risk modestly.

scholarly journals Long-Term Survivorship Following Stereotactic Radiosurgery Alone for Brain Metastases: Risk of Intracranial Failure and Implications for Surveillance and Counseling

Neurosurgery ◽  
2017 ◽  
Vol 83 (2) ◽  
pp. 203-209
Author(s):  
Emile Gogineni ◽  
John A Vargo ◽  
Scott M Glaser ◽  
John C Flickinger ◽  
Steven A Burton ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Cox Regression ◽  
Primary Study ◽  
Regression Methods ◽  
Kaplan Meier ◽  
Relapse Rates

Abstract BACKGROUND Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is &lt;2 yr; thus, limited literature on risks of recurrence exists beyond 2 yr. OBJECTIVE To investigate the possibility that for subsets of patients the risk of intracranial failure beyond 2 yr is less than the commonly quoted 50% to 60%, wherein less frequent screening may be appropriate. METHODS As a part of our institutional radiosurgery database, we identified 132 patients treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 yr of survival and follow-up from SRS. Primary study endpoints were rates of actuarial intracranial progression beyond 2 yr, calculated using the Kaplan–Meier and Cox regression methods. RESULTS The median follow-up from the first course of SRS was 3.5 yr. Significant predictors of intracranial failure beyond 2 yr included intracranial failure before 2 yr (52% vs 25%, P &lt; .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P &lt; .01). On parsimonious multivariate analysis, failure before 2 yr (HR = 2.2, 95% CI: 1.2-4.3, P = .01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = .01) remained significant predictors of intracranial relapse beyond 2 yr. CONCLUSION Relapse rates beyond 2 yr following SRS alone for brain metastases are low in patients who do not suffer intracranial relapse within the first 2 yr and with low-volume brain metastases, supporting a practice of less frequent screening beyond 2 yr. For remaining patients, frequent (every 3-4 mo) screening remains prudent, as the risk of intracranial failure after 2 yr remains high.

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 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 &gt;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.

scholarly journals RADI-25. REPEAT STEREOTACTIC RADIOSURGERY FOR RECURRENT BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i26-i26
Author(s):  
Daria Krivosheya ◽  
Hamid Borghei-Razavi ◽  
Matthew Grabowski ◽  
Lilyana Angelov ◽  
Gene Barnett ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Radiation Necrosis ◽  
Gamma Knife Radiosurgery ◽  
Post Treatment ◽  
Average Dose ◽  
Single Fraction ◽  
Perfusion Studies

Abstract INTRODUCTION: Mainstream modality of treatment of oligo-metastatic disease is stereotactic radiosurgery (SRS). While the local control rate is nearing 90%, 7% of lesions and 10 to 15% of patients develop radiation necrosis post treatment. In the face of increasing lesion size and evidence of recurrence, re-treatment of the enlarging lesion with radiosurgery can be attempted. The aim of the project is to evaluate outcomes of lesions treated with repeat SRS. METHODS: We conducted a retrospective review of all patients that were treated with Gamma Knife radiosurgery at our institution from 2000 to 2018. Fifty-one lesions in 39 patients were identified that had recurrence during follow-up period and were treated with a second single-fraction SRS. RESULTS: A combination of imaging studies, such as PET and/or perfusion studies, lesion biopsy, and clinical course were used to make the diagnosis of lesion recurrence. The average radiation dose at first treatment was 21 Gy, and the average dose at second treatment was 19 Gy. The median time between treatments was 16.8 months, ranging from 2.5 to 75.3 months, and the median follow-up after second treatment was 10.2 months. Of 51 lesions that received two SRS treatments, 49% (25 lesions) continued to progress at a median interval of 4.8 months post treatment, of which 35% (18 lesions) were diagnosed as radiation necrosis based on biopsy results or advanced brain imaging. The overall rate of radiation necrosis post second SRS treatment was determined to be 16% per lesion and 21% per patient. CONCLUSION: Recurrent brain metastases that are re-treated with single fraction SRS are associated with a higher risk of radiation necrosis. Alternative treatment strategies, including fractionation of subsequent SRS treatments, radiation dose reduction, and combination with laser ablation could be considered to ensure symptom and disease control to reduce the rate of subsequent radiation necrosis.

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