Radiomics for Survival Analysis and Prediction in Glioblastoma (GBM)—A Preliminary Study

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International Journal of Radiation Oncology  Biology  Physics

implemented by executing XML scripts in a medical linear accelerator developer mode. Patient specific TMAT QA was also performed. Results: Both TMAT and VMAT plans met the target coverage goal. TMAT significantly decreased the dose deposition in the anterior-to-posterior direction surrounding PTV. The mean doses on brainstem, optic nerves, eyes and lens were reduced by 45.6215.49%, 29.719.26%, 75.938.07% and 66.5517.82% in TMAT compared with VMAT respectively (P0.01). Maximum point doses in eyes and lens were reduced by 76.0315.91% and 70.8016.76% respectively in TMAT versus VMAT (P0.01). An XML script for a representative TMAT pituitary case was implemented in medical linear accelerator developer mode. Patient specific QA showed good agreement between measured and the calculated dose distribution. All dose points passed the Gamma criterion for a 3%/3-mm threshold. Conclusion: TMAT compared favorably with VMAT in terms of significant OARs dose reduction for both pituitary adenoma and cavernous sinus meningioma cases, and hence implicates the improvement of quality of life in patients with benign brain tumors after treatment. Deliverable TMAT plans were achieved in developer mode in medical linear accelerator via custom XML scripts allowing confirmation of dosimetric accuracy. Author Disclosure: J. Liang: None. D.H. Hristov: None. K. Otto: None. S. Kim: None.

and required NICU hospitalization with eventual improvement following steroids and bevacizumab. 3 additional patients developed asymptomatic imaging changes at a median 9.8 months (range: 4.6-16.2) with small areas of new parenchymal enhancement followed with surveillance MR imaging. Conclusion: Overall, acute effects from PRT for adult diffuse gliomas appear well tolerated. Radiographic findings suggest RN may be related to increased periventricular white matter sensitivity to RT injury. Strategies to further reduce dose and the development of imaging and molecular biomarkers to identify patients at higher risk are warranted. Author Disclosure: M. Meeks: None. S. Acharya: None. J. Huang: None. C.G. Robinson: Research Grant; Elekta. Consultant; Radialogica. Speaker’s Bureau; ViewRay. Grant funding, speaker’s bureau, travel; Varian Medical Systems. S.M. Perkins: None. J. Campian: None. G. Ansstas: None. A. Kim: None. G. Dunn: None. T. Zhao: None. B. Sun: None. K. Rich: None. C.I. Tsien: Honoraria; Merck. Vice Chair; RSNA.

2259 Imaging Changes Following Proton Radiation Therapy in Adult Diffuse Gliomas M. Meeks,1 S. Acharya,1 J. Huang,1 C.G. Robinson,1 S.M. Perkins,1 J. Campian,2 G. Ansstas,2 A. Kim,3 G. Dunn,3 T. Zhao,1 B. Sun,1 K. Rich,3 and C.I. Tsien1; 1Washington University in St. Louis, Department of Radiation Oncology, St. Louis, MO, 2Washington University in St. Louis, Department of Medical Oncology, Saint Louis, MO, 3Washington University in St. Louis, Department of Neurological Surgery, St. Louis, MO Purpose/Objective(s): There is growing interest in treating adult diffuse gliomas with proton radiation therapy (PRT) to limit onset of late neurocognitive deficits through improved sparing of normal tissue. Here, we report our experience of the incidence of imaging changes following PRT for adult diffuse gliomas. Materials/Methods: Imaging data sets of 28 consecutive adults diagnosed with primary grade 2 or 3 diffuse glioma treated with a single gantry superconducting proton accelerator treatment system was reviewed. All patients had at least six months of follow-up and none received prior cranial RT. Image data sets were reviewed for radiation-related imaging changes. Pseudo-progression (PP) was defined as radiographic worsening of a pre-existing lesion that remained stable or decreased on subsequent MRI without intervention. Radiation necrosis (RN) was defined as new areas of enhancement distant from the surgical site but in the PRT field and unrelated to tumor progression. MR perfusion, spectroscopy, PET, or histology was available for confirmation of treatment effect vs radiation related imaging changes in some cases. Results: Median patient age was 41.8 years (range: 20.7-71.2 years) and median follow-up was 13.1 months (range: 6.5-21.4 months). Median RT dose was 59.4 GyE (range: 50.4-60.0). Median GTV was 44.8 cm3 (range: 10.1-210.5 cm3). 11 patients (39.3%) received concurrent temozolomide chemotherapy. 15 patients (53.5%) received adjuvant temozolomide and 10 (35.7%) received adjuvant or neoadjuvant PCV. Lesions were located in the frontal (60.7%), parietal (14.3%), temporal (21.5%), and thalamic area (3.5%). 9 patients (32.1%) developed treatment related imaging changes. 2 patients developed pseudo-progression at 4.9 and 8.5 months, respectively. 4 patients developed symptomatic RN with periventricular enhancement remote from the surgical site; one patient developed CTCAE Grade 2 RN at 10.9 months treated with steroids, two patients with Grade 3 RN at 8.1 and 13.2 months treated with laser ablation followed by bevacizumab, and the other treated with steroids, pentoxifylline and Vitamin E with partial resolution of symptoms. One patient developed Grade 4 RN at 13.8 months

2260 Radiomics for Survival Analysis and Prediction in Glioblastoma (GBM)dA Preliminary Study H.H. Zhang,1 J.K. Molitoris,1 S. Tan,2 I. Giacomelli,3 D. Scartoni,3 C. Gzell,4 N. Bhooshan,1 W. Choi,1 W. Lu,1 W.D. D’Souza,1 and M.P. Mehta5; 1University of Maryland School of Medicine, Baltimore, MD, 2Huazhong University of Science and Technology, Wuhan, China, 3 University of Florence, Florence, Italy, 4Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, Australia, 5Miami Cancer Institute, Baptist Health South Florida, Miami, FL Purpose/Objective(s): To evaluate the value of radiomics for survival analysis and prediction of glioblastoma (GBM) patients treated with chemoradiation therapy (CRT). Materials/Methods: Twenty-eight newly diagnosed GBM patients who received CRT at our institution between 2008 and 2014 were retrospectively studied. In addition to demographics (age, race, gender) and clinical parameters (KPS, extent of resection, radiation therapy type, dose and status, whether concurrent temozolomide was adjusted/stopped), 255 imaging features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at post-operation, 1-month and 3-month post-CRT. For the radiomics approach, imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property, and their spatial-temporal changes for the 2 ROIs. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate analysis. Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to evaluate the survival prediction capability of algorithmically selected features. The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: For univariate survival analysis, 28 features (1 demographic, 2 clinical and 25 imaging) were statistically significant (P<0.05) for both OS and PFS. The types of imaging features were volumetric, intensity, geometry, texture and their spatial-temporal changes. For multivariate survival analysis, 14 of the features remained statistically significant (P<0.05) for OS and 20 features remained statistically significant (P<0.01) for PFS. When all the features were used by machine learning models to predict the survival, 24 features were algorithmically selected. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC Z 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC Z 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC Z 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC Z 0.92).

Volume 96  Number 2S  Supplement 2016 Conclusion: In this preliminary study, radiomics approach combined with patients’ demographics and clinical parameters are promising (even MGMT status was not available) for survival analysis and prediction in GBM patients treated with CRT. To achieve more accurate predictions, advanced machine learning models should be considered. Author Disclosure: H.H. Zhang: Research Grant; Varian Medical Systems. J.K. Molitoris: None. S. Tan: None. I. Giacomelli: None. D. Scartoni: None. C. Gzell: None. N. Bhooshan: None. W. Choi: None. W. Lu: None. W.D. D’Souza: None. M.P. Mehta: None.

2261 Risk Factors Associated With Interval Time Between Breast Cancer Diagnosis and Development of Brain Metastasis A. Saraf,1 C. Grubb,1 C.H. Tai,1 C.C. Wu,1 A. Jani,1 H.J. Saadatmand,1 M.E. Lapa,1 J.I.S. Andrews,1 S.D. Vanderkelen,2 S.R. Isaacson,1 S.A. Sheth,3 G.M. McKhann,4 M.B. Sisti,3 J.N. Bruce,4 S.K. Cheng,1 E.P. Connolly,1 and T.J.C. Wang1,4; 1Department of Radiation Oncology, Columbia University Medical Center, New York, NY, 2Department of Radiation Oncology, Columbia University, New York, NY, 3Department of Neurological Surgery, Columbia University Medical Center, New York, NY, 4 Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY Purpose/Objective(s): Breast cancer (BC) is a common cause of brain metastases (BM) associated with poor prognosis. At this time, the standard work up for BC does not include radiographic work up to rule out BM. We hypothesize that risk factors associated with BC may be associated with a shorter time interval for the development of BM in patients with primary breast cancer. Our goal is to identify potential BC risk factors associated with increased risk for BM. Materials/Methods: We retrospectively reviewed all BC patients with BM treated with radiation therapy at Columbia University Medical Center from 1997 to 2015. Interval time (IT) to developing BM was defined as pathological diagnosis of BC to radiographic diagnosis of BM. Kaplan-Meier (KM) curves were used to analyze the timing for developing of BM. Patients were stratified by breast cancer subtype (Her2, Luminal A/B, and triple negative) and initial BC staging. For KM analysis with BC staging, patients with stage IV disease with initial presentation of BM were excluded from the analysis. Cox proportion hazard models were used to evaluate the associated BC risk factors for development BM. Results: A cohort of 128 BC patients with BM had known BC subtype and was used in this cohort. The median IT for the entire cohort was 46 months. KM curves showed a significant difference in median IT for Her2 subtype (57 months), Luminal A/B (50 months), and triple negative (28 months) with P Z 0.005. When stratified by initial tumor staging, KM curves showed a significant difference in IT for Stage I (70 months), II (54 months), III (23 months), and IV (24 months) with P Z 0.001. Univariate analysis was performed to determine factors associated with shorter interval to the development of brain metastasis. Those included BC subtype, initial BC staging, no surgical intervention for initial BC, positive nodal status, late age of first birth, history of hormone replacement therapy (HRT), and ethnicity. Conclusion: BC subtype and initial BC staging is associated with IT to the development of BM. Additional factors including absence of primary BC surgical intervention, positive nodal status, late age of first birth, HRT and ethnicity might be related to shorter IT to BM. These results support the notion that there may be a subset of breast cancer patients in which brain MRI for staging work up can be beneficial. Author Disclosure: A. Saraf: None. C. Grubb: None. C. Tai: None. C. Wu: None. A. Jani: None. H.J. Saadatmand: None. M.E. Lapa: None. J.I. Andrews: None. S.D. Vanderkelen: None. S.R. Isaacson: None. S.A. Sheth: None. G.M. McKhann: None. M.B. Sisti: None. J.N. Bruce: None. S.K. Cheng: None. E.P. Connolly: None. T.J. Wang: None.

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2262 Hypofractionated Versus Standard Radiation Therapy in Combination With Concurrent Chemotherapy for Elderly Glioblastoma Patients: A Review of the National Cancer Data Base J. Huang,1 P. Samson,2 S.M. Perkins,1 T.A. DeWees,3 and C.G. Robinson1; 1 Washington University in St. Louis, Department of Radiation Oncology, St. Louis, MO, 2Washington University in St. Louis, Department of Surgery, St. Louis, MO, 3Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): To evaluate the effectiveness of two radiation therapies (RT) fractionation schedules when administered with concurrent chemotherapy for elderly patients with newly diagnosed glioblastoma (GBM). Materials/Methods: Elderly patients (age  60) with supratentorial and nonmetastatic GBM who underwent surgery followed by adjuvant RT of 1.8-60 Gy in combination with concurrent chemotherapy during 20102012 were identified from the National Cancer Data Base (NCDB). Concurrent chemotherapy (either single-agent or multi-agent) was specified to be within 14 days from the start of RT. Hypofractionated RT (HFRT) was defined as those who received  45 Gy with fraction size between 2.5-4 Gy. Standard-fractionated RT (SFRT) was defined as those who completed at least 45 Gy (with any fraction size) or  45 Gy but with fraction size between 1.8-2 Gy. Prognostic factors affecting OS were evaluated using Kaplan Meier method and Cox proportional hazards. Propensity score matching (PSM) was performed to adjust for potential selection bias between SFRT and HFRT groups using all available variables. Conditional inference tree regression analysis (CITRA) was performed to identify subsets of patients with comparable OS when treated with either RT schedule. Results: A total of 5265 evaluable patients were identified: 5048 received SFRT; 217 received HFRT. During the study period, HFRT use remained consistently low at < 5% per year. Older age, higher Charlson/Deyo comorbidity index (CDCI), Medicare insurance, and subtotal resection (STR) were associated with HFRT use. Median follow-up time was 10.3 months. HFRT had inferior OS compared to SFRT (median: 6.4 vs 11.2 months, P<0.001). On multivariate analysis, HFRT (hazard ratio 1.28, 95% confidence interval 1.10-1.49, P Z 0.001) was independently associated with decreased OS along with older age, male sex, higher CDCI, non-academic facility, STR, and single-agent chemotherapy . Two hundred and four pairs of HFRT and SFRT patients were matched 1:1 using PSM, and adjusted analysis also showed inferior OS for HFRT as compared to SFRT (median: 6.1 vs 9.9 months, P Z 0.005). CITRA of the entire cohort showed that two subset of patients appeared to have similar OS independent of use of HFRT or SFRT: age >70 with CDCI >0 (median: 6.9 vs 6.7 months, P Z 0.89); age >70 with CDCI of 0 and gross-total resection (median: 10.7 vs 10.6 months, P Z 0.37). Conclusion: HFRT is associated with worse OS than SFRT when administered with concurrent chemotherapy for elderly GBM patients in routine clinical practice. Age, CDCI, and surgical extent may be factors that can be used to guide selection of HFRT. Author Disclosure: J. Huang: Travel Expenses; Viewray. P. Samson: None. S.M. Perkins: None. T.A. DeWees: None. C.G. Robinson: Research Grant; Elekta. Advisory Board; Radialogica. Travel expenses and speaker’s bureau; Varian Medical Systems. Stock Options; Radialogica.

2263 Feasibility of Simultaneous Integrated Boost (SIB) to Gross Disease in Spine Radiosurgery O. Padilla,1 T. Botticello,2 B. Winey,3 A. Niemierko,2 J. Shin,4 and K.S. Oh3; 1Tufts University School of Medicine, Boston, MA, 2 Massachusetts General Hospital, Boston, MA, 3Massachusetts General Hospital, Harvard Medical School, Boston, MA, 4Harvard Medical School, Boston, MA