bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTHR-15. PATIENTS WITH LIMITED STAGE SMALL CELL LUNG CANCER THAT RECUR WITH ISOLATED BRAIN METASTASES HAVE PROLONGED SURVIVAL
Authors: Bonder Bryan , Larijani Fatemeh Ardeshir , Dowlati Afshin , Rogers Lisa 
Published: August 2019

Abstract
INTRODUCTION: Small cell lung cancer (SCLC) frequently metastasizes to the brain. In patients with limited-stage disease (disease confined to one radiation portal), the incidence of brain metastasis after 3 years is 50–60%. We reviewed patients with SCLC and hypothesized that isolated brain recurrence has a unique natural history. METHODS: 471 adult SCLC patients seen at University Hospitals Case Medical Center from 1998 to 2014 were screened. Patients were separated by those with isolated brain metastases and those with other patterns of metastasis. Demographic data including age, race, sex, smoking history and clinical data such as TNM classification, stage, treatment, and time to relapse and death were collected. Median overall survival (mOS) and progression free survival (mPFS) were compared using log-rank tests and Kaplan-Meier plots were constructed. In a separate cohort of metastatic SCLC we examined differences in next generation sequencing (NGS) of targeted exomes between primary and metastatic sites including the brain. RESULTS: 281 extensive-stage patients and 40 limited-stage patients were included. 12% (30/281) of the extensive-stage patients and 25% (10/40) of limited-stage patients had isolated brain metastases. Patients with limited-stage disease who developed isolated brain metastases had significantly improved mOS as compared to those who developed other sites of metastasis (OS = 38.7 months vs. 20.2 months, p=0.033). Furthermore, mPFS for limited-stage patients with isolated brain metastases was improved compared to other patterns of metastases (PFS = 17.9 months vs. 10.1 months, p = 0.03). NGS demonstrated that NOTCH1 mutations were infrequent in biopsies from all metastatic sites but were common in primary lung tumors. CONCLUSION: In our single center review, patients with limited-stage SCLC who recurred only in the brain had improved survival as compared to those who had other patterns of metastases. Our initial work demonstrates differences in oncogenic gene mutations between the metastatic and primary tumors.
RADI-06. SINGLE- VERSUS MULTI-FRACTION STEREOTACTIC RADIOSURGERY FOR BRAINSTEM METASTASES
Authors: Jacobs Corbin , Woldemichael Kehali , Williamson Hannah , Abisheva Zhanerke , Howell Elizabeth , Abdelgadir Jihad , Dechant Cosette , Floyd Scott , Fecci Peter , Kirkpatrick John , Adamson Justus , Torok Jordan 
Published: August 2019

Abstract
BACKGROUND: For intracranial metastases with planning target volume (PTV) overlap of the brainstem (BSmet), the radiosurgical dose-fractionation that optimizes the therapeutic window is unknown. MATERIALS/METHODS: A retrospective review of brain metastases (BM) with/without BSmets treated with single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2–5 fractions) radiosurgery (HF-SRS) between 2012–2016 was performed. Brainstem biologically effective doses (BED) and single-fraction equivalents of brainstem V10/V12 were calculated using α/β=3. Characteristics were compared between patients with/without BSmet and between SRS/HF-SRS cohorts using Wilcoxon rank sum, chi-square, or Fisher’s exact tests. Radiographic progression (RP) was assessed in patients with post-treatment contrasted MRI and defined as BSmet enlargement regardless of etiology (progression, radionecrosis, indeterminate). Kaplan-Meier estimates were compared between cohorts using log-rank test. RESULTS: 634 SRS/HF-SRS courses were identified, of which 59 (9.3%) treated ≥1 BSmet in 55 patients. BSmets occurred more commonly in patients with &gt;4 BM (31% vs 10%, p&lt; 0.001) and intracranial recurrence (39% vs 20%, p=0.003). BSmets were treated in 1 (22/59; 37%), 2 (1/59; 2%), or 5 (36/59; 61%) fractions. Age, KPS, and primary tumor site were balanced between SRS/HF-SRS cohorts. The HF-SRS cohort had significantly larger BSmet PTV (median 1.39cc vs 0.39cc, p=0.021), marginal dose (median 25Gy vs 15Gy, p&lt; 0.001), brainstem V10 (median 1.60cc vs 0.47cc, p&lt; 0.001), brainstem V12 (median 0.78cc vs 0.06cc, p&lt; 0.001), and mean brainstem BED (median 9.27Gy3 vs 6.55Gy3, p=0.019). The SRS cohort was more likely to have prior whole brain radiotherapy (50% vs 14%, p=0.005) and restart steroids post-treatment (78% vs 41%, p=0.019). RP occurred in 6/17 vs 2/25 patients in the SRS vs HF-SRS cohorts, respectively (p=0.045). HF-SRS trended to higher freedom from RP (93% vs 74% @12mo; p=0.072). There was no overall survival difference (p=0.36). CONCLUSIONS: HF-SRS was associated with decreased RP and decreased likelihood of restarting steroids despite treating larger BSmets.
RADI-11. NRG ONCOLOGY CC001: A PHASE III TRIAL OF HIPPOCAMPAL AVOIDANCE IN ADDITION TO WHOLE-BRAIN RADIOTHERAPY (WBRT) PLUS MEMANTINE TO PRESERVE NEUROCOGNITIVE FUNCTION IN PATIENTS WITH BRAIN METASTASES (BM)
Authors: Tomé Wolfgang , Deshmukh Snehal , Gondi Vinai , Brown Paul , Wefel Jeffery , Armstrong Terri , Bruner Deborah , Bovi Joseph , Robinson Clifford , Khuntia Deepak , Grosshans David , Konski Andre , Roberge David , Kundapur Vijayananda , Devisetty Kiran , Shah Sunjay , Usuki Kenneth , Anderson Bethany Marie , Mehta Minesh , Kachnic Lisa 
Published: August 2019

Abstract
BACKGROUND: NRG CC001, a phase III trial of WBRT+memantine (WBRT+M) with or without Hippocampal Avoidance (HA), sought to assess the neuro-protective effects of lowering the radiation dose received by the hippocampus. METHODS: Patients (pts) with brain metastases were stratified by RPA class and prior radiosurgery/surgery and randomized to either WBRT+M or HA-WBRT+M (30Gy/10 fractions). Standardized neurocognitive function (NCF) tests were performed at baseline, 2, 4, 6, and 12 months (mos.). The primary endpoint was NCF failure, defined as decline using the reliable change index on Hopkins Verbal Learning Test-Revised, Trail Making Test, or Controlled Oral Word Association. Cumulative incidence estimated NCF failure (death without NCF failure was competing risk); between-arms differences tested using Gray’s test. Deterioration at each collection time point was tested using a chi-square test. Patient-reported symptoms were assessed using the MD Anderson Symptom Inventory with Brain Tumor module and analyzed using mixed effects models and t-tests. RESULTS: From 7/2016 to 3/2018, 518 patients were randomized. Median follow-up was 7.9 mos. HA-WBRT+M was associated with lower NCF failure risk (adjusted HR=0.74, p=0.02) due to lower risk of deterioration in executive function at 4 mos. (p=0.01); and encoding (p=0.049) and consolidation (p=0.02) at 6 mos. Age≤61 predicted for lower NCF failure risk (HR=0.60, p=0.0002); non-significant test for interaction indicated independent effects of HA and age. Patient-reported fatigue (p=0.036); difficulty speaking (p=0.049); and problems remembering things (p=0.013) at 6 mos. favored the HA-WBRT+M arm. Imputation models accounting for missing data also favored the HA-WBRT+M arm for patient-reported cognition (p=0.011) and symptom interference (p=0.008) at 6 mos. Treatment arms did not significantly differ in toxicity; intracranial progression or overall survival. CONCLUSIONS: While achieving similar intracranial control and survival; Hippocampal Avoidance during WBRT+M for brain metastases better preserves NCF and patient-reported symptoms. Supported by UG1CA189867 (NCORP) and DCP from the NCI.
RADI-29. BIOLOGIC SUBTYPES OF BREAST CANCER BRAIN METS AS A PREDICTOR OF LOCAL CONTROL AFTER STEREOTACTIC RADIOSURGERY
Authors: Salgado Lucas Resende , Smith Andrew , Cohen Alexandra , Tseng Tzu-Chi , Lin Jung-Yi , Moshier Erin , Green Sheryl , Germano Isabelle 
Published: August 2019

Abstract
INTRODUCTION: Brain metastases (BM) are diagnosed in approximately 15% of breast cancer (BC) patients. Biologic subtype is predictive of loco-regional recurrence following breast conserving therapy and/or mastectomy with the highest risk in the ER-/PR-/HER2- (TN) subtype. The aim of this study is to determine whether biologic subtype is predictive of local control (LC) in BC patients with BM treated with Stereotactic Radiosurgery (SRS). MATERIALS/METHODS: All patients underwent LINAC-based SRS at our institution. Patients were subdivided into three biologic subtypes: ER+/Her2- (Luminal), Her2+, and TN (Basal). Kaplan Meier method was used to estimate the overall survival (OS). Cox proportional hazard model was used to analyze association of local failure (LF) with biologic subtypes. This is an IRB-approved single center retrospective study. RESULTS: 108 BC BM in 50 consecutive patients were included in this study with a median follow up of 11.1 months. The median disease-specific GPA was 2.0, and all patients received systemic chemotherapy and/or hormonal therapy. The 12 month LC rates for the entire cohort were 85%, 87%,49% for Luminal, Her2+ and Basal, respectively, with a significantly shorter LC for the basal sub-type (p=0.014). The 12 month OS rates were 83%, 88%, 80% for Luminal, Her2+ and Basal, respectively with a no significant difference in OS among the subgroups. 24% of the lesions were treated with salvage whole brain radiation therapy. CONCLUSIONS: This study shows that in BC patients with BM treated with SRS, biologic subtype impacts LC but not OS. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multi-center studies are necessary to corroborate our results.
RADI-31. MULTI-INSTITUTIONAL VALIDATION OF BRAIN METASTASIS VELOCITY, A RECENTLY DEFINED PREDICTOR OF OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY
Authors: Chan Michael , McTyre Emory , Soike Michael , Ayala-Peacock Diandra , Hepel Jaroslaw , Page Brandi , Contessa Joseph , Chiang Veronica , Attia Albert , Braunstein Steve , Chung Caroline , Ruiz Jimmy , Fiveash John , Chao Samuel , Farris Michael 
Published: August 2019

Abstract
INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting. METHODS: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (&lt; 4 BMV), intermediate (4–13 BMV), and high-risk groups (&gt;13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS. RESULTS: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV &lt; 4, BMV 4–13, and BMV &gt; 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p &lt; 0.0001). Compared to initial salvage with WBRT, salvage SRS was associated with improved OS following DBF for BMV &lt; 4 (p = 0.05), BMV 4–13 (p = 0.002) and BMV &gt; 13 (p = 0.0001). CONCLUSIONS: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation vs salvage SRS after DBF.
RADI-33. DISTRIBUTED FRAMELESS GAMMA KNIFE RADIOSURGERY: A NEW TREATMENT PARADIGM FOR PATIENTS WITH BRAIN METASTASES
Authors: Patel Ankur , Mendel Jameson , Plitt Aaron , Nedzi Lucien , Timmerman Robert , Dan Tu , Barnett Samuel , Mickey Bruce , Patel Toral , Wardak Zabi 
Published: August 2019

Abstract
INTRODUCTION: Stereotactic radiosurgery (SRS) has excellent efficacy for patients with limited intracranial disease. Its use in patients with &gt;10 brain metastases remains controversial. Nonetheless, cancer patients are living longer due to advancements in systemic therapeutics and avoiding the neurocognitive toxicities of whole brain radiation therapy is critical. Recent reports suggest that SRS may be effective in patients with ≥10 metastases. Treating large numbers of brain metastases in a single Gamma Knife radiosurgery (GKRS) treatment session poses several challenges. Treatment of metastases in close proximity to one another leads to an increased dose to normal brain, potentially increasing the risk of necrosis. Furthermore, single session treatment of multiple metastases may last several hours, causing significant patient discomfort. Here, we describe a novel treatment paradigm to address these issues: distributed frameless GKRS. Patients with ≥6 brain metastases undergo multi-session frameless GKRS with both temporal and spatial distribution over 2–5 sessions, decreasing treatment time per day and not treating adjacent metastases simultaneously. METHODS: We evaluated all patients with brain metastases who underwent distributed frameless SRS, using the Gamma Knife ICON, between January 2017 and November 2018. Fifty-one patients with 1097 unique lesions were included in this analysis. RESULTS: Mean patient age was 58.8 (range 29–89) years. Median follow-up was 4.1 (range: 0–20.4) months. The median number of metastases treated was 5 (range: 1–19) per treatment session and 11.5 (range: 3–82) per treatment course. The median number of treatment sessions per treatment course was 3 (range: 2–10). The median number of treatment courses, per patient, was 1 (range: 1–4). The median margin dose was 15 Gy. The median overall survival was 5.9 (range: 0.2–20.9) months. CONCLUSIONS: Distributed frameless Gamma Knife radiosurgery is technically feasible and should be considered in lieu of single session GKRS for patients with ≥6 brain metastases.
RADI-34. USE OF LOW-DOSE STEREOTACTIC RADIOSURGERY FOR ADVANCED BRAIN METASTASES
Authors: Yang Daniel , Yu James , Chiang Veronica 
Published: August 2019

Abstract
BACKGROUND: Gamma knife stereotactic radiosurgery (GKSRS) is commonly used to treat brain metastases. However, treatment time significantly increases as a function of increasing dose and number of lesions treated. In patients with large number of brain metastases, advanced disease, and poor performance status, low-dose GKSRS may be better tolerated and allows for safer re-treatment with radiotherapy should tumors recur. METHODS: We queried our institutional GKSRS database and identified patients treated with low-dose GKSRS for brain metastases as defined by a prescription of 12–15 Gy margin dose. Overall survival was measured from time of initial low-dose GKSRS to death or study exit. A composite endpoint of time to additional GKSRS, whole brain radiotherapy (WBRT), craniotomy, or death was used to examine disease progression. RESULTS: We identified 30 patients treated with low-dose GKSRS at a single institution between 2008 to 2018. A total of 428 brain metastases were treated, with a median of 12 (IQR=4–20) brain metastases per patient. Thirteen patients received immunotherapy concurrent with low-dose GKSRS, and 23 patients received mutation-targeted therapy or immunotherapy. Median overall survival was 238 (IQR 91–580) days, and median composite time to disease progression was 121 (IQR = 33–371) days. The two longest survivors in our cohort are alive at over three years. One had testicular cancer, and the other had melanoma. The metastatic melanoma patient had a BRAF V600E tumor and received mutation-targeted systemic therapy. He received standard-dose GKSRS and WBRT prior to low-dose GKSRS, as well as immunotherapy prior to and concurrent with low-dose GKSRS. CONCLUSIONS: A heterogenous population with large number of brain metastases was treated with low-dose GKSRS, with acceptable but varied results in terms of survival and tumor control. Further study with larger cohorts is warranted to optimize selection criteria and timing of low-dose GKSRS with other radiotherapy and systemic agent.
RADI-35. AN ANALYSIS OF RESPONSE ENDPOINTS FOR BRAIN METASTASIS PATIENTS TREATED WITH STEREOTACTIC RADIOSURGERY AND PD(L)-1 INHIBITORS
Authors: Kotecha Rupesh , Miller Jacob , Kim Joseph , Juloori Aditya , Chao Samuel , Murphy Erin , Peereboom David , Mohammadi Alireza , Barnett Gene , Vogelbaum Michael , Angelov Lilyana , Suh John , Ahluwalia Manmeet 
Published: August 2019

Abstract
PURPOSE: Recent trials have evaluated the role of anti-PD(L)-1 inhibitors alone in patients with newly diagnosed brain metastasis, resulting in a suggested paradigm shift. In the absence of randomized comparisons, an evaluation of outcomes for similar patients treated with radiotherapy are needed to provide baseline comparative data. METHODS: This retrospective cohort study included patients diagnosed with brain metastasis from 2010–2017 at a single tertiary care institution who received SRS and at least one anti-PD(L)-1 inhibitor. Primary endpoints included the rate of best intracranial response (either a complete [CR] or partial response [PR]), rate of intracranial benefit (percentage of patients with stable disease [SD] for at least 6 months), and overall objective response rates. RESULTS: 150 patients met the eligibility criteria for this study and the median follow-up time was 10 months (Range: 1–130 months). Only a minority of patients from this cohort would have been eligible for comparative systemic therapy alone trials: 8 (CheckMate 204, CM), 8 (ABC), and 50 patients (Yale Institutional trial, YI). Best intracranial objective response rates for these trial eligible patients were 64% (CM), 64% (ABC), and 72% (YI), respectively. The 6-month rates of intracranial benefit across patients were 75% (CM), 75% (ABC), and 93% (YI), respectively. The rates of either a CR, PR, or SD across trial eligible patients were 100% (CM), 100% (ABC), and 94% (YI), respectively. More than 50% of patients experienced out-of-field progression in each of the patient subgroups. CONCLUSIONS: Over a seven year period, very few patients treated with SRS and anti-PD(L)-1 inhibitor therapy in a busy academic practice would have been eligible for systemic therapy alone per trial eligibility criteria. In these highly favorable subgroups, patients experience high rates of objective response, best intracranial response, and intracranial benefit after SRS and anti-PD(L)-1 therapy, representing optimal brain metastasis management.
RADI-36. FRAME-BASED VERSUS FRAMELESS GAMMA KNIFE RADIOSURGERY FOR BRAIN METASTASES
Authors: Patel Ankur , Plitt Aaron , Mendel Jameson , Nedzi Lucien , Timmerman Robert , Dan Tu , Barnett Samuel , Mickey Bruce , Wardak Zabi , Patel Toral 
Published: August 2019

Abstract
INTRODUCTION: Brain metastases occur in 10 to 40% of cancer patients. In an effort to avoid the neurocognitive toxicities of whole brain radiation therapy, stereotactic radiosurgery (SRS) has become the preferred treatment option for most brain metastases. Many cancer patients will require several rounds of SRS during the course of their disease. Frame-based radiosurgery causes physical discomfort with each treatment session. We present our experience with frameless Gamma Knife radiosurgery (GKRS) and compare the clinical outcomes to frame-based treatments in the same patient cohort. METHODS: We evaluated all patients with brain metastases who underwent both frame-based and frameless SRS, using the Gamma Knife ICON, between January 2017 and November 2018. 11 patients with 110 unique lesions were included in this analysis. Clinical outcomes, including local control, were compared between the two treatment modalities. RESULTS: Mean patient age was 60.0 (range: 41 – 76) years. Median follow-up was 7.9 (range: 0 – 22.1) months. Median number of metastases treated was 4 (range: 1 – 9) per frame-based treatment and 3 (range: 1 – 10) per frameless treatment. Median number of frame-based and frameless procedures, per patient, was 1 (range: 1 – 3) and 1 (range: 1 – 2), respectively. Median tumor volume was 0.06 (range: 0.01 – 11.49) cm3 in the frame-based treatments and 0.14 (range: 0.01 – 4.22) cm3 in the frameless treatments. Median margin dose was 18 Gy for both the frame-based and frameless treatments. Local control was 86.5 and 91.5% at 6 and 9 months post-treatment, respectively in the frame-based treatments and 82.8 and 87.5% at 6 and 9 months post-treatment, respectively in the frameless treatments. CONCLUSIONS: Frameless GKRS results in similar rates of local control compared to frame-based GKRS. This treatment option should be considered in patients undergoing GKRS, as it balances clinical outcomes with patient comfort.
RADI-42. ASSOCIATION BETWEEN TUMOR LOCATION AND TOXICITY OUTCOMES AFTER STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Wang Boya , Kaidar-Person Orit , Sasaki-Adams Deanna , Jaikumar Sivakumar , Ewend Matthew , Nakamura Zev , Chen Ronald , Zagar Timothy , Tepper Joel , Marks Lawrence , Khagi Simon , Shen Colette 
Published: August 2019

Abstract
OBJECTIVE: The toxicities associated with stereotactic radiosurgery (SRS) are important factors when considering treatment options and supportive management for patients with brain metastases. We assessed the association between brain metastasis location and rates of toxicity after SRS. METHODS: We conducted a retrospective single-institution review of 170 patients treated with SRS for brain metastases from 2008–2016 with median follow-up of 8.6 months. Typical SRS doses were 18-20Gy in 1 fraction (lesions &lt; 2cm), 18-21Gy in 3 fractions (lesions 2-3cm), and 25-30Gy in 5 fractions (lesions &gt;3cm). Toxicity measures evaluated included radiation necrosis, seizure, and dexamethasone requirement. RESULTS: A total of 221 lesions were treated among frontal (29%), cerebellar (23%), parietal (16%), temporal (15%), occipital (14%), and other (brainstem, thalamus, basal ganglia) (4%) regions. The rate of SRS-related radionecrosis was 4% for all patients and significantly correlated with metastasis volume (increasing from 1% to 7% for lesions ≤1cm3 to &gt;3cm3) and prior whole brain radiotherapy (WBRT) but not with metastasis location or prior resection on multi-variable analysis (P&lt; 0.05). Post-SRS seizure occurred in 9% of all patients but was significantly higher for primary motor cortex and sensory cortex lesions, associated with 52% and 33% seizure rates, respectively (P&lt; 0.05). Of patients who initially presented with seizure and were on anti-epileptic medication during SRS, 53% had no further seizures, while 47% did have post-SRS seizures, nearly all with motor cortex lesions. Only 5% of patients had new-onset seizure after SRS, related to lesion hemorrhage or motor cortex location. Dexamethasone use &gt;3 months post-SRS was higher for motor strip lesions. CONCLUSION: Brain metastasis location in the primary motor cortex was associated with higher rates of post-SRS seizure, including new-onset seizures and breakthrough seizures on anti-epileptic medication during SRS. Rates of radionecrosis were associated with lesion volume and prior WBRT but not with metastasis location.