Mortality in Radiation Oncology: A 16-Year Departmental Review

Volume 96  Number 2S  Supplement 2016

ePoster Sessions S235

potential to reduce stress on physics and dosimetry staff; there may also be cost savings by reducing the need for re-milling of additional treatment devices. Author Disclosure: W.F. Hartsell: Employee; Cadence Health. Partner; Radiation Oncology Consultants, Ltd. Partnership; CPTI, Illinois CyberKnife, Elk Grove Radiosurgery. Oversight of group; National Association for Proton Therapy. Leadership; Proton Collaborative Group. V. Gondi: Partner; Radiation Oncology Consultants, Ltd. L.A. McGee: None. S.M. Niles: None. S. Schmidt: None. J.H. Chang: Partner; Radiation Oncology Consultants, Ltd. Partnership; CPTI, Illinois CyberKnife, Elk Grove Radiosurgery. M. Pankuch: None.

several key components of cancer patients’ care, supports the efforts of institutions to integrate EMRs, and encourages others to pursue this. Author Disclosure: A.A. Solanki: None. M. Surucu: Research Grant; Varian Medical Systems. B. Kazczmarz: None. T.F. McCoo: None. J.C. Roeske: Research Grant; Varian Medical Systems. W. Small: Research Grant; Varian Medical Systems.

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Purpose/Objective(s): Rushed treatment planning has been associated with decreased patient safety; however, monitoring and controlling the planning process is challenging in a busy practice. We hypothesized that providing real-time feedback to clinicians would improve the interval from treatment plan approval to treatment delivery. Materials/Methods: We developed a system that calculated the interval between plan approval and patient treatment, excluding the day of treatment. Only modulated plans requiring patient specific quality assurance were considered. The system evaluated new plans daily and for each plan having an interval that did not meet department guidelines the system sent an email to the radiation oncologist requesting an explanation for the deviation. The primary purpose of the email was to prompt the physician to be aware of incidents of rushed planning, but also served the secondary purpose of providing a data stream describing reasons for last minute plan approvals. The system was implemented at our main center and subsequently at our satellite. The fraction of plans approved after noon two days before treatment (F1) and approved after noon on the day before treatment (F2) were calculated. Results: Prior to implementation at the main center on Apr 1, 2015 and at the satellite center on September 13, 2015, retrospective data were analyzed from July 1, 2014 to the implementation date. At the main (satellite) center, 475 (259) plans were analyzed having F1 Z 31% (48%) and F2 Z 8% (17%). Based on the retrospective analysis of the main center data and discussion between key physicians and physicists, department goals were set at F1 <25% and F2 Z 0%. Subsequent to initiation of notification, 718 (98) plans were monitored having F1 Z 25% (28%) and F2 Z 5% (13%). The cumulative distribution functions of plan approval to treatment times before and after implementation of notification were compared using the twosample Kolmogorov-Smirnov test. The distributions demonstrated improvement for both sites with P value < 0.005. The physician responsible for the most cases missing the F2 goal, 19% and 31% at the main and satellite centers, respectively, was the same for both sites. Conclusion: Real-time monitoring and feedback of plan approval to treatment time reduced the number of last-minute plan approvals. At the main center, the F1 goal was achieved and the number of plans violating F2 was significantly reduced. At the satellite center, the number violating F1 and F2 goals were significantly reduced, however, F2 remained significantly above the target value. The differences in practice between the two sites are under investigation to determine factors limiting compliance at the satellite facility. Author Disclosure: R.A. Popple: Research Grant; Varian Medical Systems. Honoraria; Varian Medical Systems. R.A. Cardan: Research Grant; Varian Medical Systems. Honoraria; Varian Medical Systems. J.B. Fiveash: Research Grant; Varian Medical Systems. Consultant; Varian Medical Systems. S.A. Spencer: None. J.A. Bonner: President of University of Alabama faculty practice; University of Alabama Health Services Foundation. Department chair; University of Alabama at Birmingham.

Improving Communication of Patient Care through Integration of Hospital and Radiation Oncology Electronic Medical Records A.A. Solanki,1 M. Surucu,1 B. Kazczmarz,2 T.F. McCoo,2 J.C. Roeske,1 and W. Small, Jr1; 1Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 2Loyola University Medical Center, Maywood, IL Purpose/Objective(s): Radiation therapy (RT)-specific aspects of a patient’s cancer care are commonly documented and scheduled using an RTspecific electronic medical record (rEMR). However, patients receiving RT also receive multidisciplinary care from providers only using the hospital EMR (hEMR). We implemented an electronic interface integrating our hEMR and rEMR to improve communication of RT aspects of care between our department and the rest of the care team. The objective of this study was to assess the impact of rEMR and hEMR integration on the accessibility of RT-specific aspects of patient care to other providers. Materials/Methods: We performed a survey of 175 staff members at our academic cancer center, including physicians, nurses, and support staff. The survey asked participants to rate how important and how accessible several commonly scheduled RT encounters and documents were communicated using a Likert scale. Responses were stratified into binary groups (slightly important vs. moderately important and slightly inaccessible vs. moderately accessible). A scheduling and document interface between rEMR and hEMR was developed and implemented. We sent a follow-up survey after completion of EMR integration asking about the accessibility of the same items. Descriptive statistics and the chisquared test were performed to evaluate the importance of different items based on the provider’s role and improvement in accessibility. Results: There were 32 responses to the baseline survey. Most respondents were physicians (56%) or nurses (25%). The rEMR items that were most commonly reported to be moderately important were the dates of first treatment (n Z 29; 91%), last treatment (n Z 29; 91%), brachytherapy procedure (n Z 22; 69%), radiosurgery (n Z 22; 69%), and CT simulation (n Z 21; 66%). There were 19 responses to the post-integration survey, with no difference in the distribution of the role in the care team (P Z 0.616) or disease-site focus (P Z 0.552). As described in Table 1, the proportion of respondents who reported that the date of first treatment, brachytherapy procedure, radiosurgery, and CT simulation were moderately accessible improved significantly after EMR integration. Conclusion: Our study describes the aspects of the rEMR that are important to other members of the patient care team, and demonstrates that integrating the rEMR and hEMR leads to improved communication of

Abstract 1168; Table 1. Proportion of Respondents Reporting  Moderate Accessibility at Baseline and Post-EMR Integration Baseline (n [ 32) First treatment Last treatment Brachytherapy procedure date Radiosurgery date CT simulation date

12 12 11 12 13

(38%) (38%) (34%) (38%) (41%)

Post-integration (n [ 19) 14 12 14 15 19

(74%) (63%) (74%) (79%) (84%)

P-value 0.012 0.076 0.007 0.004 0.002

1169 Reducing Last-Minute Plan Approvals Using Automated Real-Time Monitoring and Feedback R.A. Popple, R.A. Cardan, J.B. Fiveash, S.A. Spencer, and J.A. Bonner; University of Alabama at Birmingham, Birmingham, AL

1170 Mortality in Radiation Oncology: A 16-Year Departmental Review B.A. Dyer, X. Zhao, D. Hoffman, L. Kahn, M. Hodges, J.T. Hayes, A.L. Michaud, C.B. Hess, C. Kumaran Nair, R.C. Fragoso, R.K. Valicenti, and J.S. Mayadev; University of California Davis Comprehensive Cancer Center, Sacramento, CA

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International Journal of Radiation Oncology  Biology  Physics

Purpose/Objective(s): Patient-centric education in radiation oncology reviews the therapeutic ratio of risks and benefits. Part of this discussion covers the risk of mortality caused by radiation, and the measures that are taken to prevent this outcome. We analyzed 16 years of radiation oncology mortality to investigate trends in patient outcomes and to determine patient factors associated with mortality to identify potential opportunities for quality improvement. Materials/Methods: After IRB approval, we retrospectively collected morbidity and mortality (M&M) data from all consecutively treated patients in our department from January 2000 to January 2016. Collected patient characteristics included: age, sex, date of event, disease site and subsite, tumor histology, TMN stage, and anatomic stage/prognostic group. Treatment details collected included: intent of therapy (curative or palliative radiotherapy [RT]), timing of RT (neoadjuvant/adjuvant), RT modality (3D or IMRT), use, and timing of systemic therapy and surgery, prescribed and completed radiation dose and use of brachytherapy (BT). M&M, preventable/possibly preventable outcome, and outcome related to RT were determined only from departmentally required M&M reporting to the institutional Clinical Quality Improvement & Patient Safety office using a hospital-wide standardized reporting form. Statistical analyses were conducted using multivariate regression and t-test. Results: Over 16 years, 14,189 patients were treated with RT (887 patients/year average). There were 78 reported patient deaths (0.55%) with 63 patients dying on treatment. The range of annual mortality was 2-12 patients (median 4). T-test analysis of independent variable revealed that of patients who died, sex (P Z 0.005), stage IV disease (P Z 0.001), RT given with curative intent (P Z 0.0001), use of concurrent systemic therapy (P Z 0.0029), mean dose (Gy) (P Z 0.001), and completion of RT (P 0.0001) were all strongly predictive of mortality. However, on multivariate analysis the factor most strongly correlated with increased mortality was age (P Z 0.00066). Furthermore, RT was the leading cause of death in patients who died of a preventable cause (P Z 0.00181). Conclusion: Our study is the first in the literature to investigate mortality while on radiation treatment and investigate preventable causes. Our data shows a low overall rate of mortality during RT. Patients who die while receiving RT are more likely be older and have advanced disease and are being treated aggressively with systemic therapy and with curative intent. Age was the strongest predictor of mortality and preventable deaths were strongly correlated with RT, suggesting that RT may have caused harm. These findings reinforce the need for patient acuity of care stratification metrics to better identify and support those patients most likely to suffer from potentially preventable RT-induced morbidity or mortality. Author Disclosure: B.A. Dyer: None. X. Zhao: None. D. Hoffman: None. L. Kahn: None. M. Hodges: None. J.T. Hayes: None. A.L. Michaud: None. C.B. Hess: None. C. Kumaran Nair: None. R.C. Fragoso: None. R.K. Valicenti: Oversight of all departmental decisions; University of California Davis. J.S. Mayadev: None.

compounds. Cell lines tested included MCF7 (breast cancer), PC3 (prostate cancer), HL60 (leukemia) and SKMEL5 (melanoma). Every treatment against a small molecule was defined relative to a control consisting of cells grown in the same plate and tested with vehicle alone. Genome-wise mRNA expression data were collected by means of Affymetrix GeneChip microarrays. The previously tested RSI 10 gene assay was calculated before and after exposure to each small molecule using the previously published algorithm. RSI is modeled after the surviving fraction of cells at 2 Gy (SF2) (range Z 0-1) with a lower RSI indicating greater radiosensitivity. A change in the RSI value of 0.15 in either direction was used as a cut-point of clinical applicability. Results: We identified 20 small molecules meeting criteria as potential clinically applicable radiosensitizers and one potential radioprotective small molecule. The potential radiosensitizers included: camptothecin, cephaeline, emetine, alsterpaullone, cicloheximide, anisomycin, cantharidin, tyrphostin, terfenadine, daunorubicin, and doxorubicin among others. Several of these small molecules including camptothecin derivatives irinotecan and topotecan as well as doxorubicin have been previously identified in the literature as radiosensitizers. Furthermore, the identified radiosensitizing small molecules target DNA repair, cell cycle inhibition, apoptosis and tyrosine kinase signaling, all methods proven to be involved in modulating RT response. In contrast, sulindac sulfide, a non-steroidal anti-inflammatory drug (NSAID), was the sole compound identified as a potential radioprotector. Conclusion: In this robust analysis, we present a novel RSI based approach to screen small molecules to combine with RTas radiosensitizers. Initial validation confirms several of the identified molecules to be known radiosensitizers and mechanisms identified are involved in radiosensitization. This method may provide a systematic approach to screen small molecules as radiosensitizers. Author Disclosure: K.A. Ahmed: None. T. Strom: None. J.G. Scott: None. E.A. Welsh: None. H.L. McLeod: None. L.B. Harrison: None. S.A. Eschrich: Stock; CvergenX. Patent/License Fees/Copyright; RSI. J.F. Torres-Roca: Stock; CvergenX. Patent/License Fees/Copyright; RSI.

1171 The Radiosensitivity Index (RSI) and the Connectivity Map: A Genomically Guided Approach for the Identification of Novel Radiosensitizers K.A. Ahmed, T. Strom, J.G. Scott, E.A. Welsh, H.L. McLeod, L.B. Harrison, S.A. Eschrich, and J.F. Torres-Roca; Lee Moffitt Cancer Center and Research Institute, Tampa, FL Purpose/Objective(s): The development of genomically guided approaches to identify small molecule candidates to combine with radiation therapy (RT) as radiosensitizers is central to the advancement of combined modality therapy. We hypothesize the radiosensitivity index (RSI), a previously developed and extensively validated molecular signature of radiation sensitivity could be combined with data from the Connectivity Map to provide a systematic screening method for the identification of novel radiosensitizers. Materials/Methods: Gene expression profiling before and after exposure to 1309 distinct small molecules was downloaded from the Connectivity Map. Small molecules represented a broad range of activity including U.S. Food and Drug Administration (FDA) approved drugs as well nondrug bioactive tool

1172 Enhancing the Relative Biological Effectiveness of Proton Therapy Using EGFR-Targeted Gold Nanorods A. Khoo,1 N. Sahoo,2,3 S. Krishnan,3,4 and P. Diagaradjane1,3; 1 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Physics, UT MD Anderson Cancer Center, Houston, TX, 3Center for Radiation Oncology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): In recent years, proton beam radiation therapy (PBRT) has gained attention as a treatment for tumors of anatomically complex organs. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. This limitation can be overcome by artificially enhancing the RBE. While the interaction of photon beams with gold nanoparticles (GNPs) is known to enhance therapeutic efficacy, little is known about the potential of GNPs to enhance the therapeutic efficacy of PBRT. This study evaluates the radiosensitization potential of gold nanorods (GNRs) using proton beams and characterizes RBE with respect to the standard clinical 6 MV photons. To enhance intracellular delivery, these GNRs are conjugated to Cetuximab e an antibody to epidermal growth factor receptor (EGFR) that is overexpressed in most tumors. Materials/Methods: GNRs were synthesized by the seed-mediated surfactant-assisted approach and characterized by transmission electron microscopy (TEM) for uniformity of size and shape, zeta potential for positive surface charge, and absorbance spectrophotometry for characteristic plasmon resonance peaks. Cetuximab-GNR (cGNR) conjugates were made using thiol-maleimide chemistry and characterized by absorbance and zeta potential. Binding affinity of cGNRs to head and neck cancer cells (HN5) was evaluated using dark field microscopy and TEM to optimize the incubation time for subsequent clonogenic assays. The radiosensitization potential of cGNRs when irradiated with 6 MV photon and proton beams (100 and 160 MeV) at central and distal locations along the spread-out Bragg peak (SOBP) was determined using clonogenic assays. The dose enhancement