scholarly journals MLTI-12. TIMING OF SYSTEMIC THERAPY ADMINISTRATION RELATIVE TO STEREOTACTIC RADIOSURGERY AND DEVELOPMENT OF RADIATION NECROSIS IN PATIENTS WITH BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i16-i17
Author(s):  
Lubna Hammoudeh ◽  
Daniel Cagney ◽  
Ayal Aizer
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Radiation Necrosis ◽  
Data Set ◽  
Dana Farber Cancer Institute ◽  
Extracranial Disease ◽  
Oncologic Therapy

Abstract PURPOSE: The mainstay of oncologic therapy for patients with brain metastases involves brain-directed radiation, increasingly given via stereotactic radiosurgery (SRS), and systemic therapy for extracranial disease control. We sought to investigate the association between the timing of systemic therapy and SRS administration on development of radiation necrosis among patients with brain metastases. METHODS: We retrospectively identified 429 patients treated at Brigham and Women’s Hospital/Dana-Farber Cancer Institute with SRS for newly-diagnosed brain metastases between 2001–2015. Systemic therapy was tiered into 4 categories: chemotherapy, immunotherapy, hormonal therapy, and targeted therapy. All images were manually reviewed by two radiation oncologists specializing in brain tumors to assess the presence versus absence of radiographic necrosis. Patients with radiographic necrosis who harbored associated neurologic symptoms or were managed with steroids/bevacizumab/resection were considered to have symptomatic radiation necrosis. Data were analyzed using univariable Cox regression in SAS v9.4. The median follow-up in surviving patients was 1.79 years. RESULTS: In total, 252/429 and 361/429 patients received systemic therapy pre and/or post SRS, respectively. Patients receiving systemic therapy ≤5 days before SRS displayed higher rates of radiographic (HR 2.48, 95% CI 1.06–5.81, p=.04) and symptomatic (HR 3.74, 95% CI 1.08–12.98, p=.04) necrosis; a similar association was seen in patients receiving systemic therapy ≤5 days after SRS (HR 1.72, 95% CI 0.84–3.53, p=.14 and HR 4.42, 95% CI 1.75–11.14, p=.002, respectively). Trends towards increased necrosis risk were noted when comparing systemic therapy administration 1–5 days versus 6–10 days before/after SRS. The above 4 associations were significant when restricting the cohort to patients receiving targeted systemic therapy (HR-range 3.57–21.49, p-range 0.01–0.04). CONCLUSIONS: Our results suggest that a reasonable delay between SRS and systemic therapy administration may reduce rates of radiation necrosis, even among patients receiving targeted therapies. Validation in an independent data set would lend further support to this concept.

scholarly journals SURG-02. LASER INTERSTITIAL THERMAL THERAPY FOR BRAIN METASTASES: OUTCOMES AND PREDICTORS OF LOCAL RECURRENCE

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Dhiego Bastos ◽  
Ganesh Rao ◽  
Isabella Glitza ◽  
Jonathan Loree ◽  
Jeffrey S Weinberg2 ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Protective Factor ◽  
Progressive Disease ◽  
Cox Regression ◽  
Radiation Necrosis ◽  
Newly Diagnosed ◽  
Predicting Factors ◽  
Risk Of Treatment

Abstract BACKGROUND: LITT has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. Objectives: Evaluate the predictive factors associated with local recurrence after LITT. METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. RESULTS: 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence and 31 radiation necrosis). Freedom from local recurrence at 6 months was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 months. Incompletely ablated lesions had a shorter median time for local recurrence (p< 0.001). Larger lesions (>6cc) had shorter time for local recurrence (p=0.03). Dural based lesions showed a shorter time to local recurrence (p=0.01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (p=0.01). Patients receiving systemic therapy after LITT had longer time to local recurrence (p=0.01). In multivariate Cox-regression model the HR for incomplete ablated lesions was 4.88 (p< 0.001), 3.12 (p=0.03) for recurrent tumors, and 2.56 (p=0.02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. CONCLUSIONS: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

scholarly journals Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?

2016 ◽  
Vol 125 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Rovel J. Colaco ◽  
Pierre Martin ◽  
Harriet M. Kluger ◽  
James B. Yu ◽  
Veronica L. Chiang
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Lower Risk ◽  
Median Overall Survival ◽  
Radiation Necrosis ◽  
Cytotoxic Chemotherapy ◽  
High Dose ◽  
The Brain ◽  
Dose Radiation

OBJECT Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases. METHODS A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received. RESULTS The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06–5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18–0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT. CONCLUSIONS Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era.

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 <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 < .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P < .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.

Systemic therapy for patients with breast cancer and one to three brain metastases (BM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1090-1090
Author(s):  
Zaid A Soomro ◽  
Omar Alhalabi ◽  
Ryan Sun ◽  
Aya Albittar ◽  
Limin Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Survival Time ◽  
Systemic Therapy ◽  
Local Therapy ◽  
Extracranial Disease ◽  
The Impact ◽  
Extracranial Metastases

1090 Background: Despite advances in systemic therapies and improved overall survival of metastatic breast cancer (MBC) patients, the development of brain metastases (BMs) remains a challenging complication that affects quality of life and increases morbidity and mortality. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable systemic disease. Methods: We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) after diagnosis of the initial 1-3 BMs on the patient’s progression-free survival time (PFS), defined as time to death, to a second BMs or to extracranial metastases. All MBC patients with 1 to 3 BMs only (without extracranial disease) treated at our institution between 2002 and 2017 were identified. For each patient, full information on follow-up and administered therapies were mandatory for inclusion. Hazard ratios (HR) were calculated using the Cox proportional hazard model. We also computed the restricted mean survival time (RMST) up to 5 years of follow-up. Results: Among the 2645 patient with BM treated at our institution, 80 were included for analysis. In regards to primary BMs management in patients, 46 of 80 (57%) were treated by radiation therapy, 6 of 80 (7.5%) underwent surgical resection, and 28 of 80 (35%) were managed by a combination of surgery and radiation therapy. All patients had staging imaging documenting lack of extracranial metastases at the time of local therapy of BMs. Following the primary management of BM, we observed that providers changed systemic therapy in 32 of 80 (40%), defined as the CST group. CST included both initiation of therapy in 16 of 80 (20%) and switching of adjuvant therapy in 16 of 80 (20%). Median PFS among CST was 7.7 months vs. 7.2 months among no CST (HR = 0.855, 95% confidence interval (CI) 0.53-1.38, p = 0.52). 5-year RMST for the CST group was 16.6 months vs. 12.8 months in no CST group. The difference of 3.8 months (95% CI 4.3-11.8) was not statistically significant. Conclusions: Patients with 1-3 BMs without extracranial disease had a median PFS close to 7.5 months after local therapy. Consistent with current standard of care of maintaining the same systemic therapy approach upon developing isolated BMs, our findings did not demonstrate a significant difference in PFS between patients who experienced a change in systemic therapy compared to those who did not.

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.

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.

scholarly journals RADT-09. TYPE AND TIMING OF SYSTEMIC THERAPY USE PREDICT SURVIVAL IN PATIENTS WITH BRAIN METASTASES TREATED WITH RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Kevin Fan ◽  
Nafisha Lalani ◽  
Nathalie Levasseur ◽  
Andra Krauze ◽  
Lovedeep Gondara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Performance Status ◽  
Population Based ◽  
The Novel ◽  
Brain Radiotherapy ◽  
Prognostic Assessment ◽  
Baseline Variable ◽  
Extracranial Disease

Abstract PURPOSE We aimed to investigate whether systemic therapy (ST) use around the time of brain radiotherapy (RT) predicts overall survival for patients with brain metastases (BM). We also aimed to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) in a population-based cohort. METHODS We used provincial RT and pharmacy databases to retrospectively review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016. We used a randomly selected subset with complete baseline data to develop a multivariate analysis (MVA)-based nomogram including ST use to predict survival after RT and to validate the DS-GPA. RESULTS In our 3095-patient cohort, the median overall survival (OS) of the 999 recipients of ST after RT was 5.0 months (CI 4.1-6.0) longer than the OS of the 2096 non-recipients of ST after RT (p< 0.0001): targeted therapy (HR 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55) and cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79). The OS of patients who discontinued ST after RT was 0.9 months (CI 0.3-1.4) shorter than the OS of those who did not receive ST before nor after RT (p< 0.0001). A MVA in the 200-patient subset demonstrated that the traditional baseline variables: cancer diagnosis, age, performance status, presence of extracranial disease, and number of BMs predicted survival, as did the novel variables: ST use before RT and ST use after RT. The MVA-based nomogram had a bootstrap-corrected Harrell’s Concordance Index of 0.70. In the 179 patients within this subset with DS-GPA-compatible diagnoses, the DS-GPA overestimated OS by 6.3 months (CI 5.3- 9.8) (p= 0.0006). CONCLUSIONS The type and timing of ST use around RT predict survival for patients with BMs. A novel baseline variable “ST planned after RT” should be prospectively collected to validate these findings in other cohorts.

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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