scholarly journals RADI-32. INTRACRANIAL CONTROL AND RADIONECROSIS IN MELANOMA PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
Michael Tjong ◽  
Fabio Moraes ◽  
David Shultz
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Brain Mri ◽  
Lesion Size ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Melanoma Patients ◽  
The Brain

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.

scholarly journals Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment

2018 ◽  
Vol 19 (9) ◽  
pp. 2653 ◽  
Author(s):  
Maike Trommer-Nestler ◽  
Simone Marnitz ◽  
Martin Kocher ◽  
Daniel Rueß ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Lesion Size ◽  
Simultaneous Treatment ◽  
Volumetric Assessment ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Melanoma Patients

Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest. We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty-six patients treated with SRS alone (n = 13; 20 lesions) or in combination with anti-PD-1 therapy (n = 13; 28 lesions) were analyzed. Lesion size was evaluated three and six months after SRS using a volumetric assessment based on cranial magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE). Local control after six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities reported were less than or equal to grade 2. One metastasis (5%) in the SRS group and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas four (14%) of the six regressed during further follow-ups. This was rated as pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be combined safely in melanoma patients with cerebral metastases. Early volumetric progression of lesions under simultaneous treatment may be related to PsP; thus, the evaluation of combined radioimmunotherapy remains challenging and requires experienced teams.

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.

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 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 Gamma knife stereotactic radiosurgery in the treatment of brainstem metastases: The MD Anderson experience

2015 ◽  
Vol 2 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Khinh Ranh Voong ◽  
Benjamin Farnia ◽  
Qianghu Wang ◽  
Dershan Luo ◽  
Mary F. McAleer ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Significant Treatment ◽  
Kaplan Meier ◽  
Treatment Dose ◽  
Md Anderson ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract Background Brainstem metastases (BSMs) represent a significant treatment challenge. Stereotactic radiosurgery (SRS) is often used to treat BSM. We report our experience in the treatment of BSM with Gamma Knife SRS (GK_SRS). Methods The records of 1962 patients with brain metastases treated with GK_SRS between 2009 and 2013 were retrospectively reviewed. Seventy-four patients with 77 BSMs and follow-up brain imaging were identified. Local control (LC), overall survival (OS), progression-free survival (PFS), and toxicity were assessed. Results Median follow-up was 5.5 months (range, 0.2–48.5 months). Median tumor volume was 0.13 cm3 (range, 0.003–5.58 cm3). Median treatment dose was 16 Gy (range, 10–20 Gy) prescribed to 50% isodose line (range, 40%–86%). Crude LC was 94% (72/77). Kaplan-Meier estimate of median OS was 8.5 months (95% CI, 5.6–9.4 months). Symptomatic lesions and larger lesions, especially size ≥2 cm3, were associated with worse LC (HR = 8.70, P = .05; HR = 14.55, P = .02; HR = 62.81, P &lt; .001) and worse OS (HR = 2.00, P = .02; HR = 2.14, P = .03; HR = 2.81, P = .008). Thirty-six percent of BSMs were symptomatic, of which 36% (10/28) resolved after SRS and 50% (14/28) had stable or improved symptoms. Actuarial median PFS was 3.9 months (95% CI, 2.7–4.9 months). Midbrain location was significant for worse PFS (HR = 2.29, P = .03). Toxicity was low (8%, 6/74), with size and midbrain location associated with increased toxicity (HR 1.57, P = .05; HR = 5.25, P = .045). Conclusions GK_SRS is associated with high LC (94%) and low toxicity (8%) for BSMs. Presence of symptoms or lesion size ≥ 2 cm3 was predictive of worse LC and OS.

scholarly journals Simultaneous stereotactic radiosurgery of multiple brain metastases using single isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

2020 ◽  
Author(s):  
Raphael Bodensohn ◽  
Anna-Lena Kaempfel ◽  
Daniel Felix Fleischmann ◽  
Indrawati Hadi ◽  
Jan Hofmaier ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Multiple Brain Metastases ◽  
Dynamic Conformal Arc Therapy ◽  
Kaplan Meier ◽  
Multiple Metastases ◽  
Magnetic Resonance Imaging Mri ◽  
Single Isocenter

Abstract Background Single-isocenter dynamic conformal arc (SIDCA) therapy is an efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of SRS with SIDCA for patients with multiple brain metastases.Methods All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial, were included. The patients were irradiated using a VersaHD® linear accelerator (LINAC) from Elekta (Stockholm, Sweden). Follow-up was performed every three months, including a clinical and radiological examination with cranial magnetic resonance imaging (MRI). The data were analyzed using descriptive statistics and the Kaplan-Meier method.Results 65 patients with 254 lesions (range 2–12) were included in this analysis. Median beam on time was 23 minutes. The median follow-up at the time of analysis was 13 months (95% CI 11.1–14.9). Median overall survival and median progression-free survival was 15 months (95% CI 7.7–22.3) and 18 months (95% CI 11.1–24.9), respectively. Intracranial and local control after 6 months was 73.0% and 97.5%, respectively. During follow-up, CTCAE grade 1 adverse effects (AE) were experienced by 29 (44.6%) patients (18 of them therapy-related (27.7%)), CTCAE grade 2 AEs by 4 (6.2%) patients (one of them therapy-related (1.5%)) and CTCAE grade 3 by 3 patients (4.6%) (none of them therapy-related). 2 lesions (0.8%) in 2 patients (3.1%) were proven as radiation necrosis. Conclusions Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple metastases.

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin

2006 ◽  
Vol 104 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
Lilyana Angelov ◽  
Shih-Yuan Lee ◽  
Liang Li ◽  
Gene H. Barnett ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Local Control ◽  
Patient Survival ◽  
Radiation Therapy Oncology Group ◽  
Local Control Rate ◽  
Tumor Diameter ◽  
Tumor Margin ◽  
The Relationship

Object The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Methods Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3–83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134–0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78–92%) in tumors treated with 24 Gy, compared with 49% (CI 30–68%) in tumors treated with 18 Gy and 45% (CI 23–67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Conclusions Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

scholarly journals RADT-13. EARLY CONCURRENT IMMUNOTHERAPY WITH STEREOTACTIC RADIOSURGERY IS ASSOCIATED WITH PROLONGED SURVIVAL AND DECREASED DISTANT BRAIN FAILURE IN PATIENTS WITH NEWLY DIAGNOSED MELANOMA BRAIN METASTASES (MBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii184-ii184
Author(s):  
Alexander Augustyn ◽  
Roshal Patel ◽  
Ethan Ludmir ◽  
Lauren Haydu ◽  
Nandita Guha-Thakurta ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Continuous Variable ◽  
Additional Patient ◽  
Newly Diagnosed ◽  
Treatment Delivery ◽  
Kaplan Meier ◽  
Brain Failure ◽  
Melanoma Patients ◽  
Distant Brain Failure

Abstract INTRODUCTION We evaluated outcomes of patients with newly diagnosed MBM treated with concurrent immune checkpoint inhibition (ICI) and stereotactic radiosurgery (SRS) (concurrentTx), defined as treatment delivery within 30 days of each other. METHODS Screening of 2,617 melanoma patients who received ICI (anti-CTLA4/anti-PD1/both) between 2011-2019 identified 151 pts who received concurrentTx for MBM. Among these, 51 had newly-diagnosed MBM and received no prior ICI or SRS, and were included in the current study. Overall survival (OS) and distant brain failure (DBF) were estimated using the Kaplan-Meier method. Incidence of radiation necrosis (RN) was captured. RESULTS Median follow up from treatment initiation (either ICI or SRS, whichever occurred first) was 37 months. Median OS was 30 months. Median interval between ICI/SRS was 12 days (range: 1-29). Twenty-two patients received ICI first and 29 received SRS first, without differences in OS (p=0.22), DBF (p=0.91), or development of RN (p=0.86). However, the interval between ICI and SRS was significant. Patients who received concurrentTx 1-11 days apart (n=25, “early”) experienced a significant improvement in OS and DBF compared to 12-29 days apart (n=26, “delayed”) (p=0.01, HR 2.8; 95%CI 1.3-6.2 for OS and p=0.02, HR 2.5; 95%CI 1.2-5.6 for DBF). OS and DBF at 36 months were 67% vs. 26% and 60% vs. 27%, respectively, for the early vs. delayed groups. Time to concurrentTx as a continuous variable was significantly associated with DBF (p=0.02), but not OS (p=0.06). Although not significant, more patients developed RN in the early (26.0%) versus delayed (3.8%) group (p=0.07). No additional patient or treatment differences were identified. CONCLUSIONS Early concurrentTx was associated with prolonged OS and improved DBF in newly diagnosed MBM patients who did not receive prior CNS-directed therapy. This finding suggests therapeutic synergism related to combined early treatment and should be validated in a prospective clinical trial.

scholarly journals Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jana Schaule ◽  
Stephanie G. C. Kroeze ◽  
Oliver Blanck ◽  
Susanne Stera ◽  
Klaus H. Kahl ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Stereotactic Radiotherapy ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
Kaplan Meier ◽  
Mixed Treatment ◽  
Melanoma Patients

Abstract Background Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT). Methods This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS. Results One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03). Conclusion The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.

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