bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933
Authors: Bovi Joseph , Pugh Stephanie , Sabesevitz David , Robinson Clifford , Paulson Eric , Mehta Minesh , Gondi Vinai , Kundapur Vijayananda , Pinover Wayne , Chao Samuel , Machtay Mitchell , DeNittis Albert , Laack Nadia , Greenspoon Jeffrey , Mannel Robert , Huang Jiayi , Dominello Michael , Kachnic Lisa 
Published: August 2019

Abstract
PURPOSE: RTOG 0933 demonstrated benefits to memory following HA-WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity playing a role. WMI has been implicated in RT-induced cognitive decline. This secondary analysis explored the relationship between pre-treatment WMI and memory following HA-WBRT. METHODS AND MATERIALS: 113 patients received HA-WBRT. Standardized cognitive assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was Hopkins Verbal Learning Test Delayed Recall (HVLT-DR) at 4 mos. Secondary endpoints included HVLT Total Recall (HVLT-TR) and Recognition (HVLT-Recog). Of 113 patients, 34 underwent pre-treatment and 4-month post-treatment HVLT testing and pre-treatment post-contrast volumetric T1 and axial T2/FLAIR MRI. Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pre-treatment MRI. Correlational analyses were performed examining the relationship between pre-treatment WMI and HVLT outcomes following HA-WBRT. RESULTS: Correlation was found between larger volumes of pre-treatment WMI and decline in HVLT-Recog (r=.54, p&lt; .05) and a correlational trend was observed between larger volume of pre-treatment WMI and decline in HVLT-DR (r=.31, p=.08). Patients with higher pre-treatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-recall and –delayed recall following HA-WBRT. (r=-.36 and r=-.36, p’s &lt; .05), compared to the magnitude of stability/positive shift in those with lesser disease burden. CONCLUSION: In patients receiving HA-WBRT, pre-treatment-WMI predicts memory decline, suggesting white matter integrity pre-treatment contributes to the pathogenesis of post-WBRT cognitive toxicity independent of hippocampal stem cell radiosensitivity. Less decline or improvement in HVLT following HA-WBRT for patients with higher pre-treatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on cognition. These imaging biomarkers for cognitive toxicity will be further explored on NRG CC001 and CC003, phase III trials of WBRT with or without HA.
RADI-05. FRACTIONATED TREATMENT OF BRAIN METASTASES WITH GAMMA KNIFE ICON
Authors: Mendel Jameson , Patel Ankur , Patel Toral , Timmerman Robert , Dan Tu , Nedzi Lucien , Wardak Zabi 
Published: August 2019

Abstract
PURPOSE/OBJECTIVE(S): Stereotactic radiosurgery with Gamma Knife is a common treatment modality for patients with brain metastasis. The Gamma Knife ICON allows for immobilization with an aquaplast mask, permitting fractionated treatments. We describe one of the first experiences utilizing this technique with brain metastasis and evaluate outcomes. MATERIALS/METHODS: From June 2017 to November 2018, 29 patients with 43 separate intracranial lesions were treated with fractionated stereotactic radiotherapy using the gamma knife ICON at a single institution. Patients received between 20–30 Gy in 3–5 fractions with no margin over the course of 5 to 23 days. Local control was physician assessed. Local failure over time was modeled using cumulative incidence; lesions were censored at last radiographic follow up. RESULTS: Median tumor volume and prescription isodose was 7.7 cm3 (range 0.3–43.9) and 50% (range 40–65), respectively. Median radiographic follow-up was 7 months and median survival was 9 months. Radiation necrosis occurred in 3/3 patients treated with 27 Gy in 3 fractions, one requiring therapeutic resection. Incidence of local failure for all treated lesions was 9% at 1 year. Tumor volume &gt;7 cm3 was associated with local failure on univariate analysis (p=0.025). 100% (2/2) lesions treated with 20 Gy in 5 fractions developed local recurrence. CONCLUSION: Fractionated stereotactic radiotherapy with the Gamma Knife ICON provides excellent local control for small and large brain metastases with minimal toxicity. Tumors &gt;7 cm3 should receive at least 30 Gy in 5 fractions for optimal control. Treatment with 27 Gy in 3 fractions appears to have high rates of treatment related toxicity and should be avoided.
RADI-09. DEFINING PROGRESSION IN PATIENTS TREATED WITH TEN OR MORE BRAIN METASTASES FOLLOWING STEREOTACTIC RADIOSURGERY
Authors: Viswanatha Sirisha Devi , Rana Zaker , Ehrlich Matthew , Schulder Michael , Goenka Anuj 
Published: August 2019

Abstract
BACKGROUND: An increasing trend has been to elect for Stereotactic Radiosurgery (SRS) for the treatment of brain metastases. Progression following treatment is typically defined as a 20% increase in the initial lesion volume treated. Challenges in defining progression can arise as the reported incidence of pseudoprogression or radiation necrosis following treatment ranges from 5%-30%. The purpose of this study was to assess patterns of failure in patients treated with 10 or more brain metastases. METHODS: From March 2014 to April 2018, fifty-five patients with 10 or more total brain metastases were retrospectively reviewed following frame-based radiosurgery to a dose of 12–20 Gy. Post-treatment MRI scans were used to assess tumor response in 3 month intervals. Tumor control was defined as tumor volume ≤ 1.2 times the baseline tumor volume at each measured interval. RESULTS: Fifty-five patients received 75 total radiosurgery treatments to 692 tumors. Forty patients received synchronous treatment, while 15 received metachronous treatment. 20 patients (36%) and 72 tumors (10%) experienced progression following treatment. 46 tumors were larger after first MRI in 15 patients (28%). Of these 15 patients, eight had complete resolution in 15 tumors on subsequent scan. Of the eight patients who had resolution, six patients received immunotherapy during and after treatment and all but one patient saw an initial increase &gt;100% of their initial tumor volume. Median overall survival was 11 months. Univariate analysis revealed an association between larger brain volumes irradiated with 12 Gy and decreased overall survival (p &lt; 0.05). CONCLUSION: It is important to consider tumor growth velocity and concurrent therapy when assessing true progression after SRS treatment of brain metastases.
RADI-13. IMPACT OF CITV AND BRAF MUTATION ON MELANOMA METASTASIS RESPONSE TO STEREOTACTIC RADIOSURGERY
Authors: Alattar Ali , Joshi Rushikesh , HIrshman Brian , Carroll Kate , Nagano Osamu , Aiyama Hitoshi , Serizawa Toru , Yamamoto Masaaki , Chen Clark 
Published: August 2019

Abstract
INTRODUCTION: Survival prognostication is an important aspect of personalizing oncologic care for patients with melanoma brain metastasis (BM). We previous demonstrated the utility of a cumulative intracranial tumor volume modified diagnosis-specific graded prognostic assessment scale (CITV-dsGPA) for SRS-treated melanoma BM patients. Pertinent prognostic variables in this model included age, Karnofsky performance status (KPS), and CITV. Here we determined whether the incorporation of BRAF mutation status into this CITV-modified scale further enhanced its prognostic accuracy. METHODS: We collated the survival pattern of 331 melanoma BM patients with known BRAF mutation status treated with stereotactic radiosurgery (SRS) and validated our findings in an independent cohort of 174 patients. All patients with BRAF mutation were treated with BRAF inhibitors. The prognostic utility of the model with and without BRAF mutation information was compared using the net reclassification index (NRI &gt; 0) and integrated discrimination improvement (IDI) metric. RESULTS: Presence of the BRAF mutation was associated with a reduced hazard of death in univariate Cox proportional hazards survival analysis (hazard ratio (HR) 0.74, p&lt; 0.001). This effect persisted in a multivariate model that controlled for age, KPS, and CITV (HR 0.72, p&lt; 0.001). Addition of BRAF mutation status to the CITV-ds-GPA model for melanoma significantly improved its prognostic value, with NRI &gt;0 of 0.294 (p=0.01) and IDI of 0.017 (p=0.02). We validated these findings in an independent cohort of 174 melanoma patients. CONCLUSIONS: Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of age, KPS, CITV, and BRAF mutation status.
RADI-15. CLUSTERING AND GROUPING OF BRAIN METS IN RADIOSURGERY TREATMENTS
Authors: Salah Khaled , Mckenna John , Jozsef Gabor , Knisely Jonathan 
Published: August 2019

Abstract
INTRODUCTION: Radiosurgical treatment of numerous lesions in the brain with ‘single-isocenter’ radiosurgery on a linac often requires using multiple isocenters. With our TPS (Elements, Brainlab) multiple plans need to be generated for each set of lesions, and a sum plan calculated. We investigated how to distribute multiple lesions into two groups for two isocenters to achieve a good summed dose distribution. METHODS: The DICOM RS file is exported and the PTV data is extracted by a MATLAB program that calculates the convex hulls, estimated radii, and the centers of mass for each PTV. Two approaches were tried: (1) Lesions close to each other (closer than a certain limit) are put in different groups and (2) Create clusters by kMeans clustering, which allows close lesions but the groups are distant from each other. MATLAB programs were written for all approaches. Treatment plans were generated for three patients (20, 13, 15 lesions) using each method and compared with the actual treatment plan used to treat the patient based on the intuitive grouping of lesions by the planners. Dose maximums outside the lesions, and volumes in the normal tissue exceeding 75, 50 and 25% of the prescription dose were evaluated. RESULTS AND DISCUSSION: The coverage of all lesions for all plans were 95% of the prescription dose. The first approach allowed lowering the maximum dose between lesions, but with summing dose distributions this advantage disappeared. The maximum dose and the 75, 50 and 25% dose volumes were also all worse than in plans generated by experienced planners and higher normal brain doses are delivered if closely spaced lesions are separated into different isocenters for treatment. However, the clustering approach resulted in the same or better values of these same parameters, i.e. improved dose distributions over the dosimetrist’s intuitively chosen separation.
RADI-21. STEREOTACTIC RADIOSURGERY FOR 10 OR MORE BRAIN METASTASES PROVIDES EXCELLENT RATES OF INTRACRANIAL DISEASE CONTROL WITH SUPERIOR HIPPOCAMPAL SPARING
Authors: Susko Matthew , Garcia Michael , Ma Lijun , Nakamura Jean , Raleigh David , Fogh Shannon , Golden Encouse , Theodosopoulos Philip , McDermott Michael , Sneed Penny , Braunstein Steve 
Published: August 2019

Abstract
BACKGROUND: Recent evidence supports hippocampal sparing during whole brain radiotherapy (HS-WBRT) to improve neurocognitive outcomes in patients with brain metastases (BM). This study sought to quantify the hippocampal dosimetry and treatment efficacy of stereotactic radiosurgery (SRS) to 10 or greater BM to clarify the roles of SRS and WBRT. METHODS: Patients at a single institution treated with SRS to 10 or more BM without WBRT from 1999 to 2016 were retrospectively reviewed. Treatment-related outcomes including overall survival (OS), freedom from progression (FFP), freedom from new metastases (FFNM), and adverse radiation effect (ARE) were quantified. Hippocampal volumes were retrospectively delineated and dosimetry was evaluated in patients treated with upfront SRS. RESULTS: 143 patients with a total of 2198 lesions met criteria for inclusion with 75 patients treated with upfront SRS and 68 treated as salvage from prior WBRT. Median age was 57 (IQR: 46–65) and median KPS 80 (IQR: 70–90). Histologies included breast (n=52), lung (n=49), melanoma (n=30), and other (n=12). Median number of lesions per patient was 13 (IQR 11–17) with median total volume of treatment of 4.1 cc (IQR 2.0–9.9). 12-month FFP per lesion for upfront and salvage treatment was 96.8% (95% CI: 95.5–98.1) and 83.6% (95% CI: 79.9–87.5) respectively (p &lt; 0.001). 12-month FFNM for upfront and salvage FFSRS was 18.8% (95% CI: 10.9–32.3) versus 19.2% (95% CI: 9.7–37.8) respectively (p = 0.90). Mean hippocampal dose was 150 cGy (IQR 100–202). Symptomatic ARE was observed in 2% of patients or 1% of treated lesions. CONCLUSIONS: High rates of local control can be achieved when treating patients with greater than 10 BM with hippocampal doses that are dramatically lower than for HS-WBRT. Hippocampal sparing is readily achievable with expected rates of new metastatic lesions developing in treated patients with low rates of symptomatic ARE.
RADI-22. CHARACTERIZING CLINICAL SURVIVAL PATTERNS USING MACHINE LEARNING: AN ANALYSIS OF BRAIN METASTASIS PATIENTS TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Alattar Ali , Joshi Rushikesh , HIrshman Brian , Carroll Kate , Nagano Osamu , Aiyama Hitoshi , Serizawa Toru , Yamamoto Masaaki , Chen Clark 
Published: August 2019

Abstract
INTRODUCTION: Increased sophistication in machine-learning algorithms and artificial intelligence have begun to unveil patterns that would be otherwise unappreciated in clinical medicine. Here we applied one such algorithm, Iterative Factorial Analysis of Mixed Data (IFAMD), to better understanding combinations of clinical variables that influence clinical survival of brain metastasis (BM) patients treated with stereotactic radiosurgery (SRS). METHODS: A dataset of 6,326 BM patients was collated from four SRS centers (University of California, San Diego, Katsuta Hospital Mito GammaHouse, Tsukiji Neurological Clinic, and Melanoma Institute of Australia). IFAMD was applied to the analysis of the following clinical variables: age, Karnofsky Performance Status (KPS), cumulative intracranial tumor volume (CITV), total number of metastases, histology (breast, gastrointestinal (GI) cancer, renal cell carcinoma (RCC), melanoma, and lung cancer), systemic disease control, and survival in months. RESULTS: Our machine learning algorithm defined three groups of patients who exhibited differential survival. The group who is most likely to die within 3 months of SRS included patients with lower KPS, poor systemic disease control, higher CITV, higher number of metastasis, and who carried a diagnosis of GI cancer. Patients who are most likely to survive beyond twelve months of SRS fall into two distinct categories. The first consisted of subsets of lung and breast cancer patients with higher KPS, controlled systemic disease, and lower CITV. The second consisted of young breast cancer patients with systemic disease control, independent of KPS, CITV, and the number of metastases. CONCLUSION: Clinical survival after SRS for BM is defined by combinations of known prognostic factors. A prognostic factor critical for survival prognosis in one sub-population of BM patients may bear little relevance in another patient sub-population.
RADI-25. REPEAT STEREOTACTIC RADIOSURGERY FOR RECURRENT BRAIN METASTASES
Authors: Krivosheya Daria , Borghei-Razavi Hamid , Grabowski Matthew , Angelov Lilyana , Barnett Gene , Vogelbaum Michael , Chao Samuel , Murphy Erin , Yu Jennifer , Ahluwalia Manmeet , Suh John , Mohammadi Alireza 
Published: August 2019

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.
RADI-32. INTRACRANIAL CONTROL AND RADIONECROSIS IN MELANOMA PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Tjong Michael , Moraes Fabio , Shultz David 
Published: August 2019

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.
RADI-39. EFFECT OF RIND-BASED DOSIMETRIC TECHNIQUES FOR SCALP DOSE REDUCTION IN BRAIN IRRADIATION
Authors: No Diana , Julie Diana , Knisely Jonathan 
Published: August 2019

Abstract
OBJECTIVE: Radiation-induced alopecia is an unwanted side effect causing permanent cosmetic distress if hair regrowth does not occur. Rind-based techniques can effectively control dosimetric spread. We evaluated this technique to reduce scalp dose and alopecia while maintaining tumor coverage. METHODS: Ten consecutive brain tumor plans were retrospectively evaluated. All planning tumor volume (PTV) margins were ≤ 15.0mm from the skin surface. Departmental guidelines for fractionation were followed, with minimum 95% PTV coverage receiving 100% dose. Fractionation variation was accounted for with biologically effective dose calculation (alpha/beta=2). Rind structures encompassed 5mm depth from scalp surface; upper dose limits were customized to minimum values without PTV coverage compromise. Standard comparative plans using identical criteria, without rind structures, were calculated. Scalp dose evaluation was defined for tissue from skin to 5mm depth. Paired T-tests were used for comparative evaluation. RESULTS: Median age: 58 (range 27–85); 70% female (n=7). Histologies included gliomas (n=7) and meningiomas (n=3). Median PTV distance to skin surface: 13.5mm (range 8.0–15.0). Median PTV minimum and mean dose for rind-based plans: 88.63% (range 73.14–95.2) and 104.39% (range 102.07–107.38) of prescription and 90.90% (range 68.64–98.21) and 103.02% (range 101.91–107.04) for standard plans, respectively. Statistically significant reduction in scalp maximum and mean dose of 19.65% (p=2.72E-06) and 0.48% (p=0.007), respectively, was seen with rind-based planning. Scalp volume receiving 1000cGy-equivalent increased 6.7cc using rind-based techniques, although insignificant (p=0.33). Volume receiving 1500cGy-equivalent was significantly reduced 3.88cc (p=0.03) using rind-based techniques. With median 28.5 day follow-up, of 5 patients treated using rind-based techniques, 40% (n=2) exhibited acute alopecia compared to 100% of those treated with standard plans. CONCLUSION: Rind-based dosimetric techniques exhibit significant reduction of scalp dose in brain irradiation. 60% of patients treated using this technique experienced no alopecia, versus 0% receiving standard treatment. Further investigation is warranted to better evaluate correlation.