Prognostic Factors in Patients with Renal Cell Carcinoma and Brain Metastases

Volume 99  Number 2S  Supplement 2017

ePoster Sessions S169

ePoster Sessions 1000

1001

Post-treatment Neutrophil-to-Lymphocyte Ratio as a Predictor of Overall Survival in Melanoma Brain Metastases treated with Stereotactic Radiosurgery M. Chowdhary,1,2 J. Switchenko,3 G. Marwaha,4 R.A. Abrams,4 J. Jhaveri,2 J.J. Olson,5 H.K.G. Shu,2 W.J. Curran Jr2 M.K. Khan,2 and K. Patel2; 1Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, 2Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 3 Department of Biostatistics & Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, GA, 4Rush University Medical Center, Chicago, IL, 5Winship Cancer Institute of Emory University, Atlanta, GA

Prognostic Factors in Patients with Renal Cell Carcinoma and Brain Metastases P.W. Sperduto,1,2 B.J. Deegan,3 J. Li,4 K.R. Jethwa,5 P.D. Brown,5 N.A. Lockney,6 K. Beal,6 N.G. Rana,7 A. Attia,8 R. Shanley,9 E. Lou,10 A. Zahra,11 J. Buatti,12 J.K. Molitoris Jr13 J.B. Yu,14 V.L. Chiang,15 G.L. Masucci,16 D. Roberge,17 A.C. Olson,18 J.P. Kirkpatrick,18 S.E. Braunstein,19 P.K. Sneed,19 D.D. Shi,20 H.A. Shih,20 and M.P. Mehta21; 1Minneapolis Radiation Oncology PA, Minneapolis, MN, 2Gamma Knife Center, University of Minnesota Medical Center, Minneapolis, MN, 3Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 6 Memorial Sloan Kettering Cancer Center, New York, NY, 7Vanderbilt University, Nashville, TN, 8Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 9University of Minnesota Biostatistics, Minneapolis, MN, 10University of Minnesota Medical Center, Minneapolis, MN, 11University of Iowa Hospitals & Clinics, Iowa City, IA, 12 Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, 13University of Maryland Medical Center, Baltimore, MD, 14Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 15Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, 16Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, 17Centre Hospitalier de l’Universite de Montreal (CHUM), Montreal, QC, Canada, 18Duke University Medical Center, Durham, NC, 19University of California, San Francisco, San Francisco, CA, 20Massachusetts General Hospital, Boston, MA, 21Miami Cancer Institute, Baptist Health South Florida, Miami, FL

Purpose/Objective(s): Systemic inflammation is known to play an important role in the progression of cancer. Specifically, an increase in the neutrophil-to-lymphocyte ratio (NLR) has been associated with shorter survival in patients with various malignancies; however, this effect has yet to be elucidated for patients with melanoma brain metastases (MBM). Pathology reviews have shown that stereotactic radiosurgery (SRS) results in a leukocyte predominant inflammatory response. The aim of this study is to investigate if NLR is associated with outcomes of patients with MBM treated with SRS. Materials/Methods: After IRB approval, patients with MBM treated with SRS from 2005-2013 were retrospectively identified. NLR was calculated from full blood counts obtained from the most proximal follow-up examination following SRS. Overall survival and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. Multivariable Cox models were applied to adjust for confounders. Results: Seventy-seven consecutive patients with 138 MBM received SRS for which post-treatment NLR could be calculated. Of these, 50 patients (64.9%) with 90 MBM (65.2%) had a NLR <5. The cutoff point of 5 was chosen for NLR based on results from prior studies. Baseline patient characteristics, including active systemic disease and controlled primary, were well balanced, with only lower rates of prior immune therapy (48% vs. 22%, P Z 0.002) in the NLR 5 cohort being different. SRS treatment parameters, including number of fractions, total dose, margin size, and treatment volume (GTV and PTV), were similarly well balanced. The median time to death or last imaging follow-up was 9.12 months overall (6.8 vs. 10.2 months for NLR 5 vs. NLR <5). A statistically significant (P Z 0.004) survival advantage was seen in patients with a NLR <5 at 6 (81.4% vs. 61.3%), 12 (54.2% vs. 26.3%), and 24 months (35.7% vs. 11.7%). Post-SRS NLR (P Z 0.005) and prior immune therapy (P Z 0.014) were significant on univariate analysis. Multivariable analysis confirmed that post-SRS NLR 5 predicted for worse survival (Hazard Ratio: 2.02; 95% confidence interval, 1.16-3.54, P Z 0.013), while prior immune therapy was no longer significant. No statistically significant differences were noted in 1-year local failure (8.1% vs. 11.2%), distal failure (66.3% vs. 72.9%), or radiation necrosis (9.3% vs. 16.0%) between NLR <5 and 5. Conclusion: The post-treatment NLR value, a potential marker for postSRS inflammatory response, is inversely associated with survival for MBM treated with SRS. If prospectively validated, NLR could be deployed as a predictive biomarker and as a stratification and/or eligibility variable in clinical research. Author Disclosure: M. Chowdhary: None. J. Switchenko: None. G. Marwaha: None. R.A. Abrams: None. J. Jhaveri: None. J.J. Olson: None. H.K.G. Shu: None. W.J. Curran; ASCO. M.K. Khan: None. K. Patel: None.

Purpose/Objective(s): Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published prognostic factors and a prognostic index, the Graded Prognostic Assessment (GPA) for RCC based on 286 patients diagnosed from 1985-2005. Significant therapeutic advances (targeted therapies) have been made since then. The purpose of this analysis is to identify prognostic factors for RCC patients with newly diagnosed brain metastases in a larger contemporary cohort. Materials/Methods: A multi-institutional retrospective IRB-approved database of 626 RCC patients with new brain metastases diagnosed from 1/ 1/2006-12/31/2015 was created using the REDCap interactive software. Demographic data, clinical parameters and treatment were correlated with survival, time from primary diagnosis to brain metastases (TPDBM) and cause of death. Kaplan-Meier median survival estimates were calculated and compared with log-rank tests. Results: The median overall survival (OS) for the prior and current cohorts were 9.6 and 12 months, respectively (P < 0.01). Five prognostic factors (age, KPS, extracranial metastases (ECM), number of brain metastases and Hgb at the time of brain met diagnosis) were found to be statistically significant for survival, in contrast to only two (KPS and number of brain metastases) in the prior cohort. LDH was not significant. Median TPDBM Abstract 1001; Table 1 Factor Overall GPA

Range

N

OS (mo)

P-value

662 12 85 / 161 / 210 / 105 5 / 9 / 14 / 28 < 0.01

0-1 / 1.5-2 / 2.5-3 / 3.5-4 < 80 / 80-90 / 100 217 / 307 / 52 > 3 / 2-3 / 1 97 / 185 / 327

KPS # Brain Mets ECM present / absent 508 / 73 Hgb <11 / 11-14 / >14 118 / 239 / 113 Age >68 / 55-68 / <55 162 / 300 / 163

5 / 15 / 36 7 / 11 / 15

< 0.01 < 0.01

11 / 30 5 / 13 / 20 10 / 12 / 16

< 0.01 < 0.01 0.04

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International Journal of Radiation Oncology  Biology  Physics

was 20 months. Shorter TPDBM was seen with younger age, absent ECM and lower GPA (each P < 0.01). The cause of death was known in 262/492 (53%) and among those, 61 (23%) were neurologic and 64 (24%) were both neurologic and systemic. Conclusion: The existing Renal GPA and the prognostic factors previously identified (KPS and # brain metastases) were confirmed but additional prognostic factors (age, ECM, Hgb) were found to refine prognostication in this larger contemporary cohort. Over the past decades, median OS improved from 9.6 to 12 months (P < 0.01). The Renal GPA will be updated with these new data and made available free online at http:// brainmetgpa.com. Author Disclosure: P.W. Sperduto: Partnership; Minneapolis Radiation Oncology. B.J. Deegan: None. J. Li: None. K.R. Jethwa: None. P.D. Brown: None. N.A. Lockney: None. K. Beal: None. N.G. Rana: None. A. Attia: None. R. Shanley: None. E. Lou: None. A. Zahra: None. J. Buatti: None. J.K. Molitoris: None. J.B. Yu: None. V.L. Chiang: None. G. Masucci: None. D. Roberge: None. A.C. Olson: None. J.P. Kirkpatrick: None. S.E. Braunstein: None. P.K. Sneed: None. D.D. Shi: None. H. Shih: None. M.P. Mehta: Research Grant; Cellectar. Consultant; Novartis, Cavion, Novocure, Varian, Agenus, Insys, Remedy, IBA. Board of Directors; Pharmacyclics. DSMB; Monteris.

neurologic death (HR Z 1.07; CI 1.00-1.15 P Z 0.07) or time to WBRT (P Z 0.18). The iBMV 4 metastases/year was predictive of distant brain failure per Gray’s test (P Z 0.02). Conclusion: The iBMV is a metric that predicts for BMV and OS. A higher iBMV was associated with a worse OS and numerically higher BMV. Lung histology was associated with a higher iBMV than breast. The presence or absence of BM at time of initial cancer diagnosis was not predictive for survival, as calculated from time of first SRS to death. Author Disclosure: M. Soike: None. E. McTyre: None. M. Farris: None. R.T. Hughes: None. C.K. Cramer: None. M.C. LeCompte: None. J. Ruiz: None. J. Bourland: Travel Expenses; American Association of Physicists in Medicine. Governance and membership; Soc Directors Academic Medical Physics Programs. Governance; American Institute of Physics. Non-voting board member (as AIP board member) and active committee memberships; American Association of Physicists in Medicine. M.T. Munley: None. A. Laxton: None. S.B. Tatter: None. M.D. Chan: Honoraria; Elekta. Advisory Board; Novocure.

1002 Initial Brain Metastasis Velocity: Does the Rate at Which Cancers First Seed the Brain Affect Outcomes? M. Soike, E. McTyre, M. Farris, R.T. Hughes, C.K. Cramer, M.C. LeCompte, J. Ruiz, J.D. Bourland, M.T. Munley, A. Laxton, S.B. Tatter, and M.D. Chan; Wake Forest Baptist Medical Center, WinstonSalem, NC Purpose/Objective(s): Brain metastasis velocity (BMV) is a novel metric used to describe the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). BMV, as defined in a previous publication, is a valuable tool to help guide the decision for WBRT vs SRS for salvage therapy. A limitation in the application of BMV is that it requires the number of metastases at time of treatment failure after initial SRS. By investigating patient characteristics at time of first SRS, we developed initial brain metastasis velocity (iBMV), a new metric that takes into account factors that influence the BMV prior to treatment failure. Particularly, it incorporates the rate at which cancer seeds the brain from time of initial cancer diagnosis. Materials/Methods: We retrospectively reviewed patients with BM treated at our institution from 2000-2013 with upfront SRS without WBRT. BMV for each patient was calculated as the cumulative number of new metastases from initial SRS divided by units of years. We defined iBMV, a new metric for patients who were diagnosed with BM after their primary cancer diagnosis. iBMV was calculated as the number of BM at the time of initial SRS over the unit of years from initial diagnosis to first SRS. Thus, representing a rate that the primary cancer seeded the brain. We performed a linear regression to assess the relationship of iBMV to BMV and overall survival (OS) after first SRS to death and other oncologic outcomes. iBMV was not calculated for patients who presented with stage IV disease with BM or for patients who developed BM <2 months from initial diagnosis. Results: From 2000-2013, 736 patients were treated at our institution with upfront SRS without WBRT. Median OS was 8.6 mos (IQR 7.9-9.6). The presence or absence of BM at initial cancer diagnosis was not predictive of survival after first SRS, neurologic death, or BMV and the median number of BM at first SRS was similar (median BM Z 1.0, IQR Z 1-3, P Z 0.71). Four hundred forty-three (60%) patients developed BM 2 months after initial diagnosis. In these 443 patients, the median time to first SRS from time of initial diagnosis was 27.2 mos (IQR Z 24.7-31.4). Median iBMV was 0.73 (IQR Z 0.30-1.74). Lung histology was associated with a higher iBMV compared to breast (b Z 0.09 SE Z 0.02, P < 0.001). Renal cell, melanoma, and other histologies did not have significantly different iBMV rates compared to breast. The iBMV was predictive of both BMV after treatment (b Z 23.87, SE 6.92, P<0.001) and OS (HR Z 1.11; CI: 1.03-1.20, P Z 0.006). The iBMV was not significant for predicting

1003 Discrepancies Between Biological Markers of Primary Breast Cancer and Their Brain Metastases: An International Multicenter Study O. Kaidar - Person,1 I. Meattini,2 P. Jain,3 P. Bult,4 N.L. Simone,5 I. Kindts,6 R. Steffens,7 C.G. Weltens,8 P. Navarria,9 Y. Belkacemi,10 J. Lopez,11 L. Livi,12 B.G. Baumert,13 B. Vieites,14 D. Limon,15 N. Kurman,16 J.B. Yu,17 V.L. Chiang,18 P. Poortmans,19 and T.M. Zagar20; 1 UNC Chapel Hill, Chapel Hill, NC, 2University of Florence, Florence, Italy, 3Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 4Radboud university medical center, Nijmegen, Netherlands, 5Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, PA, 6KU Leuven University of Leuven, Department of Oncology, B-3000 Leuven, Leuven, Belgium, 7MediClin Robert-Janker-Clinic/ Clinical Cooperation Unit of Neurooncology, Bonn, Germany, 8University Hospitals Leuven, Department of Radiation Oncology, B-3000 Leuven, Belgium, 9Humanitas Cancer Center and Research Hospital, Rozzano, Italy, 10Department of Radiation Oncology, Hopitaux Universitaires Henri Mondor, INSERM U955 E7 and University of Paris-Est Creteil (UPEC)., Creteil, France, 11 Department of Radiation Oncology, University Hospital Virgen del Rocio, Seville, Spain, 12University of Florence, Department of Biomedical, Experimental and Clinical Sciences “Mario Serio,” Florence, Italy, 13 MediClin Robert-Janker-Kinik & University of Bonn Medical Centre, Bonn, Germany, 14Department of Pathology, University Hospital Virgen del Rocio, Seville, Spain, 15Duke University Medical Center, Durham, NC, 16 Oncology Institute, Davidoff Center, Rabin Medical Center, Petah-Tikva, Israel, 17Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 18Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, 19Radboud University Medical Center, Nymegen, Netherlands, 20Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC Purpose/Objective(s): Discordances between the Estrogen receptor [ER], Progesterone receptor [PR] and Human Epidermal growth factor receptor 2 [HER2] expression between the primary tumor and the brain metastasis were investigated in breast cancer (BC) patients with brain metastases (BM). Materials/Methods: Retrospective data was collected by 11 institutions from 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines pathology (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution’s ethical research committee. Results: A total of 167 BC patients with BM were included. Patients’ demographics and disease related information are listed in Table 1. Out of 119 patients (71%) that had full receptor information of both primary tumor and BM (ER, PR, and HER2), 25 patients (21%) had a change in receptor status: 7 of 26 (27%) ER/PR positive/HER2 negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR positive/HER2 positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost