bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTHR-09. IDENTIFYING EPIGENETIC SIGNATURES IN LUNG ADENOCARCINOMAS THAT PREDICT DEVELOPMENT OF BRAIN METASTASIS
Authors: Zuccato Jeffrey , Mamatjan Yasin , Aldape Kenneth , Zadeh Gelareh 
Published: August 2019

Abstract
INTRODUCTION: Metastases are the most common adult brain tumor with half spreading from lung cancers and they reduce median overall survival from 26 to 12 months. There are no robust patient-specific predictors of brain metastasis. Epigenetic signatures predict disease recurrence in other cancers and identifying brain metastasis methylation-based signatures may allow for treatment approaches to high-risk patients that prevent their development. METHODS: In 207 lung adenocarcinomas, multivariate cox time to brain metastasis analyses including clinically-relevant variables (lung tumor size and TNM nodal score) along with significant covariates on univariate analyses were performed. DNA was extracted from 142 of these tumors and profiled on the Illumina Infinium EPIC array. A generalized boosted regression classification model used differentially methylated CpG sites significantly predicting time to brain metastasis in a 70% training cohort cox analysis (p&lt; 0.05). Resulting methylation-based risk scores were compared to size and nodal status in a multivariate analysis of the independent 30% testing cohort. RESULTS: Of 207 patients with 72 brain metastatic events, tumor size (HR=1.5, 95%CI 1.1–2.0, p=0.01), N status (N3 vs. N0, HR=9.9, 95%CI 3.1–31, p=0.0001), EGFR status (HR=0.4, 95%CI 0.2–0.8, p=0.014), and age (HR=0.7, 95%CI 0.5–1.0, p=0.039) independently predicted their development. Methylation-based risk scores significantly predicted time to brain metastasis in a univariate analysis of the testing cohort (p=0.03). A multivariate analysis of testing cohort patients identified methylation score as the only independent predictor of brain metastasis (HR=4.3, 95%CI 1.1–17, p=0.038) accounting for tumor size and N score. CONCLUSIONS: Genome-wide DNA methylation signatures predict brain metastasis development in lung adenocarcinomas independent of tumor size and nodal disease. The design of a nomogram combining methylation profile other clinical factors may be used to determine patient specific brain metastasis risk values to guide patient counselling, extent of treatment, and screening.
OTHR-12. DRIVING RECOMMENDATIONS IN PATIENTS WITH NEWLY DIAGNOSED BREAST CANCER BRAIN METASTASES
Authors: Swartz Leigh , Egloff Heidi , Morikawa Aki , Van Poznak Catherine 
Published: August 2019

Abstract
BACKGROUND: Approximately 5% of all patients with breast cancer develop breast cancer brain metastases (BCBM). Medical and legal guidance on health conditions associated with driving may vary by state. The paucity of data to guide clinicians’ recommendations on driving in the setting of BCBM prompted this review of clinical practice. The primary objective is to determine the frequency of provider-documented driving recommendations with secondary objectives to define associated clinical factors. METHODS: University of Michigan’s (UM) DataDirect tool retrospectively searched records dated 11/30/2012 to 11/30/2018 using ICD 9 and 10 codes for breast cancer (C50.912, C50.911, C50.919, 174.9, 175.9) and for brain metastases (C79.31, D49.6, D43.2, 198.3, 239.6). Eligibility criteria were: age ≥ 18, BCBM, UM pathology confirmation of breast cancer, CNS imaging at time of diagnosis performed or reviewed at UM, and UM consultation with medical oncology, radiation oncology, neuro-oncology, neurosurgery, or neurology within 4 weeks of BCBM diagnosis. Chart abstraction included clinical and demographic factors for descriptive analysis. RESULTS: Only 87 of the 188 identified subjects (46%) met eligibility criteria. The most common exclusions were non-breast cancer brain lesion (n=40), neither UM imaging nor pathology (n=23) and no intra-parenchymal brain metastases (n=22). Of the 87 eligible subjects, 21 (24%) had documented recommendations against driving. Five of the 7 subjects with documented seizure history within 4 weeks of diagnosis also had documented recommendations against driving. There were 32 of 87 subjects on anti-epileptics of which 13 had documented driving recommendations. CONCLUSIONS: The minority of patients (24%) with newly diagnosed BCBM had a documented recommendation against driving. Seizure activity was strongly associated with documentation of driving recommendations. Other than seizure activity, general parameters regarding the safety of driving with newly diagnosed BCBM are not well defined. Prospective study is indicated to provide data supported recommendations regarding driving with BCBM.
RADI-02. SINGLE-SESSION VERSUS MULTISESSION GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER: RETROSPECTIVE ANALYSIS
Authors: Kim Jin Wook , Park Kawngwoo 
Published: August 2019

Abstract
PURPOSE: To evaluate the efficacy of Gamma Knife radiosurgery (GKS) in patients with large brain metastases by comparing single-session radiosurgery (S-GKS) and multisession radiosurgery (M-GKS), the authors retrospectively analyzed the clinical outcomes of the patients who underwent GKS for brain metastases from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between January 2010 and December 2016, 66 patients with 74 lesions &gt;=10 cm3 from large brain metastases from only NSCLC were included. Fifty-five patients with 60 lesions were treated with S-GKS; 11 patients with 14 lesions were treated with M-GKS. Median doses were 16 Gy (range, 11–18 Gy) for the S-GKS group and 8 Gy (range, 7–10 Gy) in three fractions for the M-GKS group. RESULTS: With a mean follow-up period of 13.1 months (range, 1.3–76.4 months), the median survival duration was 21.1 months for all patients. Median tumor volume was 14.3 cm3 (range, 10.0–58.3). The local control rate was 77.0% and the progression-free survival rate was 73.6% at the last follow-up. There were no significant between-group differences in terms of local control rate (p = 0.10). Compared with S-GKS, M-GKS did not differ significantly in radiation-induced complications (38.1% versus 45.4%, p = 0.83). While eight patients who underwent S-GKS experienced major complications of grade &gt;=3, no toxicity was observed in patients treated with M-GKS. CONCLUSIONS: M-GKS may be an effective alternative for large brain metastases from NSCLC. Specifically, severe radiation-induced toxicity (≥ grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment to preserve neurological function.
RADI-08. A SURVEY BASED STUDY OF BRAIN METASTASES MANAGEMENT FOR PATIENTS WITH NON-SMALL CELL LUNG CANCERS OR MELANOMA
Authors: Fong Chin Heng , Leighl Natasha , Butler Marcus , Doherty Mark , Kruser Timothy , Shultz David 
Published: August 2019

Abstract
INTRODUCTION: The standard of care for 1–4 brain metastases (BrM) is stereotactic radiosurgery (SRS), whereas whole brain radiation remains the standard treatment for extensive BrM, and surgical resection is appropriate in certain scenarios. Some newer systemic therapies such as tyrosine kinase inhibitors and immunotherapy have impressive CNS activity and are used by some practitioners either alone or in combination with other modalities as first-line treatment for BrM. We conducted a survey to ascertain current real-world practices for the treatment of BrM from NSCLC and melanoma. OBJECTIVES: Our study aimed to assess practice patterns of oncologists who treat BrM from NSCLC or melanoma. We also investigated the extent to which various clinical factors influence decision making. METHODOLOGY: We created 2 sets of surveys: one for Medical-/Clinical-/Neuro- oncologists and another for Radiation oncologists/Neurosurgeons. Surveys were conducted online or on-line. Following administration, data was tabulated and analyzed. Statistical analyses were performed using Fisher’s exact test. RESULTS: Of 361 respondents, 250 were Radiation oncologists/Neurosurgeons, and 111 were Medical-/Clinical-/Neuro- oncologists. For patients with 1–3 brain lesions, all &lt; 2cm, 34% of respondents recommended systemic therapy alone as first-line treatment. In contrast, only 15% recommend systemic therapy alone for &gt;9 lesions, at least one &gt; 2cm. Medical-/Clinical-/Neuro- oncologists were more likely to recommend systemic therapy alone compared to Radiation oncologists/ Neurosurgeons for 1–3 lesions, all &lt; 2cm (53% vs. 28%, p&lt; .0001). For patients with &gt; 9 BrM, one &gt;2cm diameter, Medical-/Clinical-/Neuro- oncologists were not significantly more likely to recommend systemic therapy alone (20% vs 13%, p=.11). DISCUSSION: Our results reveal that significant numbers of physicians recommend systemic therapy alone as first-line therapy in BrM and that management decisions correlate with a physician’s type of practice. These findings underscore the need for prospective clinical trials to direct appropriate BrM management.
RADI-10. THERAPEUTIC EFFECTS OF fSRS IN 44 CASES OF BRAIN METASTASES OF NSCLC WITH A MAXIMUM DIAMETER ≥ 4CM AND ANALYSIS OF ITS PROGNOSTIC FACTORS
Authors: Mingyao Lai , Zhen Junjie , Li Juan , Zhou Jiangfen , Hu Qingjun , Ye Minting , Li Shaoqun , Xiao Xiao , Wang Lichao 
Published: August 2019

Abstract
OBJECTIVE: To analyze the therapeutic effects of fSRS on brain metastases of NSCLC with a maximum diameter ≥ 4 cm, and explore the prognostic factors. METHODS: A retrospective analysis was conducted on the clinical data of 44 cases of brain metastases of NSCLC with a maximum diameter ≥ 4 cm in Guangdong Sanjiu Brain Hospital from January 2006 to December 2016. RANO criteria were adopted for imaging evaluation at 3 months after completion of radiotherapy. One- and 2-year survival rates were calculated and the differences in survival rates between groups were analyzed with Log-rank test. Kaplan-Meier method was used in univariate analysis to investigate the effects of KPS, RPA classification, number of metastases, total lesion volume, systemic treatment and surgery on prognosis; and Cox regression model in multivariate analysis. RESULTS: The postoperative imaging evaluation showed that there were 5 cases of CR, 20 of PR, 12 of SD and 7 of PD. The median PFS, OS, 1- and 2-year survival rates were 6 months, 16 months, 65.9% and 20.5%, respectively. KPS, RPA classification, number of metastases and surgery had no significant correlations with prognosis. However, systemic treatment and the maximum lesion volume ＜28.3cc were considered as favorable factors related to prognosis (P=0.046, 0.027). Moreover, the maximum lesion volume ＜28.3cc was found to be the independent prognostic factor for the survival (P=0.035). CONCLUSION: Treatment of brain metastases of NSCLC with a maximal diameter ≥4 cm with fSRS is proved to be feasible. The maximum lesion volume is related to prognosis. Systemic treatment (chemotherapy, TKI treatment, etc.) may improve prognosis, but more cases are needed to investigate the prognostic significance.
RADI-14. FRAMELESS STEREOTACTIC RADIOSURGERY ON THE GAMMA KNIFE ICON: EARLY EXPERIENCE FROM 42 PATIENTS WITH BRAIN METASTASES
Authors: Vulpe Horia , Save Akshay , Xu Yuanguang , Elliston Carl , Garrett Matthew , Wu Cheng-Chia , Cheng Simon , Jani Ashish , Bruce Jeffrey , McKhann Guy , Sisti Michael , Wang Tony 
Published: August 2019

Abstract
BACKGROUND: The Gamma Knife (GK) Icon uses a Cone-Beam CT (CBCT) scanner and an infrared camera system to support the delivery of frameless radiosurgery. There are limited data on patients treated with frameless GK radiosurgery (GKRS) for brain metastases. OBJECTIVE: To describe the early experience, process, technical details, and short-term outcomes with frameless GKRS for brain metastases at our institution. METHODS: We describe our patient selection and workflow for frameless GKRS in detail. Because of the short interval of follow-up, we provide crude rates of local control. RESULTS: 42 patients had a total of 96 brain metastases. Median age was 69. 77 intact lesions were treated definitively, 18 cavities postoperatively, and 1 had GKRS for recurrence after resection. 11 patients underwent repeat GKRS to the same area. Median dose was 20Gy in 1 fraction (range: 14–21), 24Gy in 3 fractions (range: 19.5–27), and 25Gy in 5 fractions (Range: 25–30). Median treatment time was 23.7 minutes (Range: 7.3 – 85.5). 29 patients had a follow-up MRI in our records after completing GKRS. Median follow-up time was 105 days (Range: 16 – 314). 16 local recurrences (LR) were identified in 9 patients. An additional 6 patients had distant brain recurrence without LR. Crude mean time between GKRS and LR was 101 days (range 44–161 days). There were 6 patients with grade 1, 3 with grade 2, 2 with grade 3, and 1 with grade 4 toxicity. We found an improvement in workflow and a greater number of patients eligible for GKRS due to the ability to fractionate treatments. CONCLUSION: We report a large cohort of consecutive patients with brain metastases treated with frameless GKRS. We look forward to studies with longer follow-up to provide valuable data on clinical outcomes and to further our understanding of the radiobiology of hypofractionation in the brain.
RADI-18. STEREOTACTIC RADIOSURGERY OR FRACTIONATED STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM SMALL CELL LUNG CANCER
Authors: Thomas Evan , Travis Roman , Boggs D Hunter , Marcrom Sam , Markert James , Spencer Sharon , Riley Kristen , Strickler Scott , Bredel Markus , Willey Christopher , Guthrie Bart , Fiveash John 
Published: August 2019

Abstract
BACKGROUND: Current standard of care (SOC) management of the brain differs between non-small cell lung cancer (NSCLC) & small cell lung cancer (SCLC). For SCLC, WBRT is considered SOC, even for solitary metastasis. In the setting of no-known metastases, prophylactic cranial irradiation (PCI) is considered SOC. SRS is occasionally utilized in SCLC, e.g. in setting of limited metastasis after WBRT/PCI, or limited metastasis after excellent systemic response to extracranial therapy, or if patient declines WBRT. In this study, we sought to understand more about the nature and outcomes of patients with SCLC who received intracranial SRS at our institution. METHODS: We reviewed radiosurgery treatments from 2005 thru 2019 for patients with SCLC who received SRS. Variables included were: time interval between diagnosis/SRS and death, prior WBRT/ PCI, number of targets, performance status, modality (GK or linac), prior surgery, and available follow-up. RESULTS: We identified 92 SRS treatments among 74 patients. 30 received upfront SRS, the remainder as post-WBRT/PCI salvage. Median survival after initial diagnosis was 22.0 months (min = 6.6, max 55.4). Median survival after first SRS was 6.1 months (min = 0.5, max = 40.4). Median recorded KPS was 75.6. Mean number of mets treated was 3.4 (min = 1, max = 12). Prescription dose range was 12 to 20Gy in single fraction, and 25 to 30Gy in five fraction treatment. 53 treatments were performed on Gamma Knife, 37 with linear accelerator. Four patients were treated post-operatively, one patient was treated pre-operatively. CONCLUSIONS: Survival in our cohort of SCLC patients receiving intracranial SRS compared favorably with historical SCLC controls (8-13mo after dx). Future work will seek to clarify whether there is a difference in brain metastasis velocity between patients treated with upfront PCI/WBRT or SRS, and also seek to address the minimum necessary dose to control SCLC metastases.
RADI-26. DOSIMETRIC EVALUATION OF 6 MV VERSUS 10 MV PHOTONS FOR HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIOTHERAPY
Authors: Julie Diana , Mahase Sean , No Diana , Salah Khaled , Knisely Jonathan 
Published: August 2019

Abstract
OBJECTIVE: Whole brain radiotherapy (WBRT) causes neurocognitive decline. Hippocampal avoidance WBRT (HA-WBRT) reduces hippocampal irradiation, potentially mitigating neurocognitive sequelae. We compared hippocampal and brain dosimetry with HA-WBRT with 6 megavoltage (MV) versus 10 MV photon energies. METHODS: Twenty consecutive patients treated with WBRT were retrospectively replanned with HA-WBRT techniques using 6 MV and 10 MV photons. Coplanar volumetric modulated arc therapy was employed, with a prescription dose of 3000 cGy in 10 fractions. Planning was done with Eclipse version 13.6 or 15.6. Nine patients were planned with 2.5 mm multileaf collimator leaves, with the remainder planned with 5 mm leaves. The hippocampi were contoured and a HA structure was generated using a uniform 5 mm expansion. A planning target volume (PTV) was defined as the brain parenchyma minus the HA structure. NRG-CC001 dose constraints were used. For each variable, descriptive statistics were calculated. Comparisons were made using two-tailed Wilcoxon signed rank tests or paired t-tests. RESULTS: The minimum hippocampal dose (D100%) was improved with 6 MV plans, 841 cGy compared to 914 cGy with 10 MV (p&lt; 0.005). The maximum hippocampal dose (D0.03cc) was reduced with 6 MV planning, 1614 cGy versus 1676 cGy for 10 MV (p&lt; 0.0001). With 6 MV photons, a greater number of plans met NRG-CC001 constraints without deviations. 6 MV photons improved PTV coverage by the 95% isodose line, 96.6% compared to 95.9% for 10 MV (p=0.021). 6 MV photon plans decreased the volume of PTV receiving ≥105% of the prescription, 84.2% versus 87.9% for 10 MV (p=0.006). The mean dose, hot spots, and cold spots did not differ by photon energy. PTV dose constraints were always met. CONCLUSION: 6 MV photon HA-WBRT plans are dosimetrically superior to 10 MV, reducing hippocampal radiation dose, without compromise in brain coverage and improved target dose homogeneity.
RADI-41. CLINICAL OUTCOMES FOLLOWING RAPID DELIVERY SINGLE ISOCENTER RADIOSURGERY FOR FIVE OR MORE BRAIN METASTASES: VOLUMETRIC MODULATED ARC THERAPY VS. DYNAMIC CONFORMAL ARC
Authors: Vaslow Zachary , Manning Matthew , Sintay Benjamin , Wiant David , Boyles Susan , Stern Joseph 
Published: August 2019

Abstract
BACKGROUND: Recent advances in the delivery of stereotactic radiosurgery (SRS) has led to wider availability and use of this technology. The ability to rapidly delivery radiosurgery to multiple targets utilizing single-isocenter techniques represents an additional step forward for these otherwise time-consuming therapies. The current retrospective study measures and compares clinical outcomes in patients with 5 or more brain metastases treated using a single-isocenter RapidArc (RA) volumetric-modulated arc therapy (VMAT) approach, with those treated using a single-isocenter dynamic conformal arc (DCA) approach. METHODS: We queried retrospectively a radiosurgery database registry of 680 patients from 11/2012- 3/2019. We included patients with 5 or more brain metastases who had documented SRS treatment plans utilizing a single-isocenter approach, either VMAT or DCA. Radiosurgery was delivered using a linac-based platform capable of delivering radiotherapy to multiple simultaneous targets. We obtained information on patient gender, age, number of lesions, primary cancer histology. Patients were separated by collimation plan (VMAT vs DCA); overall survival (OS) was estimated using Kaplan-Meier method. RESULTS: We found 49 patients that met our criteria for inclusion. Median age was 57 yrs. with a majority being females (n=28, 57.2%). Number of targets was between 5 and 20; median number of targets was 7. Most common primary site histology was non-small cell lung (51.0%), followed by breast (14.2%). For DCA collimation group, median OS was 20.5 weeks (95% CI: 12.4, 34.5), with a 6 month OS of 36.0% (95% CI: 19.2%, 54.9%). For VMAT collimation group, median OS was 20.0 weeks (95% CI: 10.8, 46.1), with a 6 month OS of 39.1% (95% CI: 11.3%, N/A). CONCLUSIONS: For patients with 5 or more brain metastases treated with rapid delivery single-isocenter radiosurgery, no significant difference in survival outcomes were demonstrated between DCA and VMAT collimation techniques.
RADI-44. MANAGEMENT OF MULTIPLE BRAIN METASTASES BY STAGED SRS FOCUSING ON UTMOST RISK LESIONS
Authors: Zhen Junjie , Li Shaoqun , Lai Mingyao , Wen Lei , Zhou Cheng , Cai Linbo 
Published: August 2019

Abstract
BACKGROUND: Patients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. METHODS: Patients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3 cm or a subtentorial invasion ≥ 2 cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. RESULTS: A total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2–14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17–0.83) cm and a median volume reduction was 3.22 (0.01–9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (&gt; grade 3). CONCLUSIONS: Staged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted.