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Objective: We examined whether cardiovascular vital signs (VS) were prognostic for overall survival (OS) in newly diagnosed adult cancer outpatients. Methods: Electronic medical records data for patients with a solid tumor diagnosis and ≥2 consecutive weight measurements were analysed. BP (mmHg) and RHR (beats/minute) were identified at diagnosis (T1) and final visit (T2; >=7 days after T1). Systolic blood pressure (SBP) categories: 100) categories. Results: N=5819; 59% men; mean age 61 (±12) years; 77% Caucasians; 9% African Americans. The most common tumor sites: prostate (19%), lung (15%), breast (14%). 18% had metastatic disease. Median OS after diagnosis was 27 months (range 25-28). Tachycardia had 2 to 3-fold increase in mortality. Survival time decreased by 8-10 months with lower SBP. RHR and SBP remained independently prognostic after adjusting clinically relevant characteristics at both timepoints. Conclusion: Elevated RHR and lower SBP independently predicted greater mortality in newly diagnosed cancer outpatients. These associations remained statistically significant longitudinally, and the differences observed were clinically important.

BackgroundHepatocellular carcinoma (HCC) is a major cause of cancer-related death. It is a highly vascular tumour with multiple angiogenic factors, most importantly vascular endothelial growth factor (VEGF), involved in HCC progression. Tivozanib is an oral inhibitor of VEGFR-1/2/3 with promising activity against HCC in vivo.MethodsWe conducted a phase 1b/2 study of tivozanib in patients with advanced HCC. The safety, dosing, pharmacokinetics, pharmacodynamics, and preliminary antineoplastic efficacy of tivozanib were evaluated.ResultsTwenty-seven patients received at least one dose of tivozanib. Using a 3+3 design, the recommended phase 2 dose (RP2D) of tivozanib was determined to be 1 mg per os once daily, 21 days on–7 days off. The median progression-free and overall survival were 24 weeks and 9 months, respectively, for patients treated at RP2D. The overall response rate was 21%. Treatment was well tolerated. A significant decrease in soluble plasma VEGFR-2 was noted, assuring adequate target engagement.ConclusionsAlthough this study did not proceed to stage 2, there was an early efficacy signal with a very favourable toxicity profile. A phase 1/2 trial of tivozanib in combination with durvalumab is currently underway.Trial registrationClinicalTrials.gov NCT01835223, registered on 15 April 2013.

Purpose Precision oncology is widely discussed, but cohort studies are limited. We previously reported our prospective experience of precision oncology in solid tumors, and here we report our longitudinal experience, focusing on therapeutic impact. Patients and Methods We conducted a retrospective review of 600 consecutive patients seen at Cleveland Clinic from 2013 to 2016 for treatment of incurable solid tumor malignancies for whom tumor genomic profiling was ordered using FoundationOne (Cambridge, MA). Results were discussed at our multidisciplinary genomics tumor board. Data analyzed included subsequent therapy and overall survival (OS). Results Median age was 59 years (range, 18 to 94 years), 308 (51.3%) were female, and 533 (88.8%) were white. Targeted therapy was recommended in 310 patients (51.7%). After results, 313 patients (52.2%) started any subsequent therapy; of these, 95 (30%; 15.8% overall) received genomics-driven therapy (G), and 218 (70%) received non–genomics-driven treatment (NG). For the G versus NG group, the on-label, off-label, and clinical trial therapy breakdowns were 23% versus 88%, 47% versus 3%, and 30% versus 9%, respectively. Median OS for patients receiving no therapy after tumor genomic profiling was 5.5 months; for the G and NG groups, it was 18 ( P < .001) and 14.4 ( P < .001) months, respectively ( P = NS for G v NG). The use of G increased from 10% in the first 250-patient cohort (reported earlier) to 20% in the subsequent 350-patient cohort. Conclusion Tumor genomic profiling influenced treatment in 15.8% of patients. More patients received treatment via clinical trials in the G cohort, and although not statistically significant, there was a trend toward increased OS in the G ( v NG) group. These data can further guide real-world applications of precision oncology.

Background The clinical impact of addressing potential germline alterations from tumor-only next-generation sequencing (NGS) is not well characterized. Current guidelines for cancer genetic testing may miss clinically actionable germline changes, which may have important implications for cancer screening, treatment, and prevention. We examined whether increasing involvement of the clinical genetics service during somatic tumor-only NGS review at Molecular Tumor Board (MTB) increases the detection of germline findings. Methods In a retrospective evaluation of patients who underwent tumor-only NGS and were reviewed at MTB, we quantified genetic counseling (GC) referrals as well as germline testing uptake and results across three cohorts: before (C1) and after (C2) the addition of tumor-only NGS review and after (C3) instituting a formal process to coordinate NGS-based genetics referrals to preexisting oncology appointments. All statistical tests were two-sided. Results From 2013 to 2017, 907 tumor-only NGS reports were reviewed at MTB (nC1 = 281, nC2 = 493, nC3 = 133); gastrointestinal (22.5%), lung (19.7%), genitourinary (14.8%), and breast (14.1%) were the most common index cancers. GC visits due to MTB increased with each successive cohort (C1 = 1.1%, C2 = 6.9%, C3 = 13.5%; P for trend [Ptrend] < .001), as did germline testing (C1 = 0.7%, C2 = 3.2%, C3 = 11.3%; Ptrend < .001). Diagnosis of germline pathogenic variants increased with each successive cohort (C1 = 1.4%, C2 = 2.0%, C3 = 7.5%; Ptrend = .003) and with germline pathogenic variants found by MTB review (C1 = 0.4%, C2 = 0.4%, C3 = 2.3%; Ptrend = .12). Conclusions Both review of tumor-only NGS by genetics and the institution of a process coordinating GC with oncology appointments increased the discovery of germline pathogenic variants from tumor-only NGS testing. Furthermore, this process identified germline pathogenic variant carriers who would not have otherwise met standard criteria for germline testing.

Cholangiocarcinoma is an aggressive malignancy with few available studies assessing incidence and mortality. In this study, we aim to investigate trends of incidence and mortality in a large nation-wide epidemiologic study.We used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.We reviewed 16,189 patients with cholangiocarcinoma, of which 64.4% were intrahepatic. Most patients were whites (78.4%), males (51.3%), and older than 65 years (63%). A total of 13,121 patients died of cholangiocarcinoma during the study period. Cholangiocarcinoma incidence and mortality were 11.977 and 10.295 and were both higher among Asians, males, and individuals older than 65 years. Incidence rates have significantly increased over the study period (APC=5.063%, P.001), while mortality increased significantly over the study period (APC=5.964%, P.001), but decreased after 2013 (APC=-25.029, P.001).The incidence and mortality of cholangiocarcinoma were increasing in the study period with significant observed disparities based on race and gender.

e16208 Background: Neuroendocrine neoplasms (NENs) are a group of biologically and clinically heterogenous malignancies of different anatomic sites, the majority of which lie within the gastrointestinal (GI) tract. Prior literature has reported on the association between NENs and other primary malignancies (OPM), but these studies are limited by small sample sizes. We aim to further analyze the association of NENs and OPM on a larger scale using a population-based cancer registry. Methods: Primary malignancies with NEN features were identified from the Surveillance Epidemiology and Ends Results registry between 1975-2017. The histology/behavior of NEN included carcinoid tumor, neuroendocrine carcinoma (NEC), pancreatic endocrine tumor, atypical carcinoid tumor, and other (insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid). First NEN observation from each patient was examined. Patients with NEN were grouped into 3 categories: NEN only, NEN first followed by OPM, and non-NEN first followed by NEN based on sequence number of primary cancer. Secondary malignancy sites were analyzed. Distribution of NEN between GI and non-GI sites was described. Demographics were compared by NEN sequence groups and between GI and non-GI sites. Results: 45,896 patients with NEN were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 yrs). 65.7% of NENs were observed in GI sites. Within the GI tract, 31.3% were small intestine, 25.1% rectum, 16.6% pancreatobiliary, and < 11% in other GI locations. Age at NEN diagnosis was younger in those with GI NENs (median 60.0 vs 65.0, p < 0.001). 71.2% of patients had NEN only, 10.4% had NEN first followed by OPM, and 18.4% had a non-NEN primary followed by NEN. Mean age was 58.9 for NEN primary only, 61.0 for NEN primary first and 68.3 for non-NEN primary first (p < 0.0001). More Caucasian patients had non-NEN primary first (82.3%) compared to NEN primary only (76.9%) and NEN primary first (75.5%). There were no gender differences amongst the three groups. Carcinoid tumor histology was more prevalent in NEN primary first (78.6%) compared to NEN primary only (67.3%) and non-NEN primary first (66.6%), while NEC histology was more prevalent in NEN only (27.4%) and non-NEN first (29.3%) compared to NEN first. Among patients with NEN first followed by a second primary malignancy (SPM), 23.6% of females had a secondary breast malignancy and 28.9% of males had a secondary prostate malignancy. Conclusions: 28.8% of patients with NENs were found to have OPM, either preceding or following their NEN diagnosis. Of those with a SPM following NEN, breast and prostate were the most common sites for women and men, respectively. It is imperative that patients with NEN undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the timeframe in which they occur in relation to the NEN.

432 Background: Pancreatic cancer is associated with poor outcomes at any stage. A very small number of patients - approximately 3% of those with metastatic disease - experience long-term survival through 5 years but the biologic mechanisms underlying the benefit observed with these “exceptional responders” are incompletely understood. We explored potential genomic differences between exceptional responders and typical responders to treatment for advanced pancreatic cancer that could confer a more favorable biology. Methods: We included consecutive exceptional responders and matched controls (MCs) with advanced pancreatic cancer in a 1:3 ratio from the Cleveland Clinic from April, 2013 – August, 2017. ERs were defined as patients with overall survival (OS) > 18 months for metastatic disease and > 24 months for locally advanced disease. Controls were matched by age, gender, stage and type of chemotherapy given and experienced OS at or below median survival for their stages. Clinical variables including demographics, comorbidities, stage, histology and treatment history were collected. Next generation sequencing (NGS) was performed for DNA sequencing of 648 genes and tumor mutation burden (TMB) on available tissue. The study population initially comprised of 14 exceptional responders and 42 MCs. However, only 4 exceptional responders and 6 MCs were included for analysis due to insufficient tissue for NGS for the remaining patients. Descriptive statistics were used for statistical analysis. Differences in survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Results: The median ages for the exceptional responders and MCs were 69 and 67.5 years, respectively. Both groups were at least 75% male and white. Of the exceptional responders, 50% had pancreatic tail primaries compared to 0% of the MCs. There were no differences between groups in first-line chemotherapy used. Exceptional responders had significantly fewer non-synonymous mutations compared to MCs (2.25 vs. 5.17, p = 0.014). Mutation count < 3 was associated with significantly better progression-free survival (PFS) and OS as shown in the Table. TMB did not differ between exceptional responders and MCs (4.88 vs. 5.70 Muts/Mb, p = 0.39). Of the exceptional responders, 50% had alterations in BAGE2 versus 0% of MCs. Conversely, 50% of MCs had alterations in LRP1B, CUL4B or APC vs. 0% of exceptional responders. Conclusions: Having a lower number of non-synonymous mutations may correlate with exceptional response to systemic therapy and therefore with improved survival in pancreatic cancer. Pancreatic tail primary may also be associated with improved outcomes. These findings, though limited by small sample size, should encourage future study into genomic signatures of exceptional response. [Table: see text]

379 Background: The median age of diagnosis of pancreatic ductal adenocarcinomas (PDAC) is 70 years. Only about 20% of patients are diagnosed prior to the age of 60. We sought to identify clinical characteristics and outcomes of patients with early-onset PDAC as compared to later-onset PDAC. Methods: We identified histologically confirmed cases of pancreatic adenocarcinoma with information about age and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using log rank test. Results: Of 321,896 patients who met inclusion criteria, 71,263 (22%) were younger than 60 years and 250,633 were 60 years of age or older at diagnosis. Median OS for younger patients was 9.5 months, compared to 5.6 months for older patients ( p< 0.0001). Younger patients were more likely to be diagnosed with stage IV disease (47.8% vs 43.4%), to be Black (16.1% vs 10.7%) or Hispanic (6.4% vs 4.5%), have a Charlson-Deyo comorbidity index of 0 (73.5% vs 63.3%), have private insurance (65.1% vs 20.5%), and receive treatment at academic centers (45.9% vs 40.9) (all p< 0.0001). Younger patients were also more likely to receive surgery (26.2% vs 19.5%), radiation (23.0% vs 15.9%), and chemotherapy (65.9% vs 46.7%) (all p< 0.0001). Conclusions: Survival for patients with early-onset PDAC is significantly better than older patients despite more patients being diagnosed with stage IV disease. This may be attributable to younger patients having less comorbidities and receiving more treatment. Concerningly, Black and Hispanic patients make up a larger proportion of younger patients with PDAC, and further work is needed to investigate these differences and underlying causes.

196 Background: While most PDAC are sporadic, up to 10% are inherited. In 2018, ASCO and NCCN guidelines were updated to recommend that all patients with PDAC be considered for genetic counseling (GC) and germline testing. Furthermore, interest in treating patients with targeted therapy, such as olaparib, for germline mutations is increasing. We implemented a quality improvement project to identify the referral rate to GC for patients with PDAC, with the goal of improving the referral rate to 60%. Methods: Barriers to GC referral were identified using quality improvement tools developed at the ASCO Quality Training Program. Three “plan, do, study, act” (PDSA) cycles were implemented: 1) updating the electronic order and tumor board template to include GC recommendation (Aug–Oct 2019), 2) physician education (Nov–Dec 2019) and 3) patient education and physician reinforcement (Jan–Feb 2020). Baseline data to evaluate impact of PDSA intervention (from April to June 2019) on documented discussions about GC and placement of the referral order was completed via chart review. Results: Between April 2019 to January 2020, 199 patients with PDAC were seen in medical oncology clinic as new patient visits. Thirteen patients had previously completed GC. For the remainder, baseline discussion and referral rates were 25% and 9%, respectively. Discussion and referral rates improved to 55% and 30% after PDSA 1, to 73% and 33% after PDSA 2, and to 95% and 58% after PDSA 3, respectively. Forty-nine patients were referred at the first visit and 23 were referred at a subsequent visit. Forty-six patients underwent GC. In patients who completed germline testing 8.9% (4/45) were found to have a pathogenic variant in BRCA2, TP53, ATM, and MUTYH. Conclusions: With increased physician and patient education, we were able to improve the GC discussion rate from 25% to 95% and referral rate from 9% to 58%. While we did not meet our aim of 60% GC referral rate, we identified obstacles and outlined an improved process for early GC referrals. Enacting processes to reinforce GC referrals for patients with PDAC is likely to increase detection of germline mutations in this population.

Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. Methods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. Results: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P 3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks. Conclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.

Introduction: Symptom and Quality of Life (QOL) data are important patient reported outcomes. Early identification of these is critical for appropriate interventions. Data collection may be helped by modern information technology. Aim: This study examined symptoms and QOL in people with solid tumors at their first visit to a medical oncologist. We also evaluated the clinical utility of tablet computers (TC) to collect this data. Methods: This was a prospective study of 105 consecutive patients in the cancer outpatient clinic of a tertiary level academic medical center. Symptom and QOL data was collected by TC with wireless database upload. Results: One-third participants had moderate to severe pain; almost half clinically significant pain that interfered with daily activities. Tiredness, anxiety, and drowsiness were common (prevalence - 79%, 63% and 50% respectively). One-third of those who had items identified from the Edmonton System Assessment System also volunteered other symptoms, mostly gastrointestinal problems. Many of those affected also reported impaired Global Wellbeing and low Overall QOL. There was a 98% completion rate, which took on average ten minutes. Direct observation and informal feedback from patients and physicians regarding the acceptability of TC in this setting was uniformly positive. Conclusions: Amongst people with newly diagnosed solid tumors clinically important psychological and physical symptoms, QOL problems and difficulties with daily activities were commonly present in the 24-hour period and in the week before a first Medical Oncology visit. Symptom and QOL data collection by TC in busy outpatient clinics showed good clinical utility.

e19012 Background: While precision oncology is becoming increasingly integrated into standard of care for most incurable solid tumor malignancies, there is paucity of data regarding the clinical significance of VUS. In this study, we aim to evaluate whether the number of VUS is associated with overall survival (OS). We also analyze racial disparities pertaining to the number of VUS present and identify which, if any, genes possess prognostic implications. Methods: This is a retrospective review of 389 consecutive patients seen at Cleveland Clinic from 2014 to 2016 with incurable solid tumor malignancies, for whom next-generation sequencing (NGS) was ordered using Foundation One™ (Cambridge, MA). Demographics, number of VUS, genes involved, and race were summarized. OS was estimated by Kaplan-Meier and compared by log rank test. Results: Median age was 60 years, 202 (52%) patients were female, 338 (86.7%) were Caucasian, and 31 (8.0%) were African American. On NGS, 376 (97%) patients had VUS reported. The median number of VUS was 9 (range 1-116). When dichotomized at the median, the number of VUS did not affect OS. Genes most commonly implicated in reported VUS were LRP1B (88, 22.6%), MLL3 (83, 21.3%), MLL2 (73, 18.8%), ARID1B (70, 18.0%), PRKDC (60, 15.4%), PREX2 (58, 18.7%), and SPTA1 (56, 14.4%). Patients found to have a variant of unknown significance in MLL2 had worse median OS as compared to those who did not (2.61 vs 3.76 years respectively; p = 0.033). When profiled by race, Caucasians had lower numbers of VUS (p = 0.002; Table). Conclusions: We did not find a clear association between the number of VUS and OS. MLL2, a gene known to predict poor prognosis as a pathogenic variant, was seen in our study to have similarly poor prognostic implications as a variant of unknown significance. Racial disparities in genomics exist as African Americans are under-represented and have greater numbers of VUS as compared to Caucasians. Further research is warranted to elucidate these disparities. [Table: see text]

42 Background: Appendiceal carcinomas (AC) account for 1-2% of colorectal cancers (CRC) and are generally treated like other CRC. However, there is limited data to guide treatment. While AC originate on the right side of the colon, it is unclear if they behave like as right-sided CRC (R-CRC). We seek to learn how AC differ from right versus left-sided CRC (L-CRC). Methods: We identified histologically confirmed cases of appendiceal and colorectal adenocarcinomas with information about stage and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database. Kaplan-Meier method and log-rank test were used to estimate and compare OS. Results: 833,939 patients met our inclusion criteria: 15,138 (1.8%) AC, 447,551 (53.7%) L-CRC, 308,794 (37.0%) R-CRC, and 62,456 (7.5%) transverse CRC (T-CRC). Median age at diagnosis of all patients was 68 years (range:18-90); AC was lowest at 61 years for stage I-III disease and 58 years for stage IV disease. Stage IV AC was more common in females 3628/5739 (63.22%). AC had the best OS among site groups in stage I-III. Median OS for stage I-III AC was 128.8 months (95% CI: 117.9-139.0), with 5-year OS rate of 0.69 (95% CI: 0.67-0.70); L-CRC median OS was 111.6 months (95% CI: 110.9-112.4), with 5-year OS rate of 0.681 (95% CI: 0.680-0.683); R-CRC median OS was 88.5 months (95% CI: 87.8-89.1), with 5-year OS rate of 0.613 (95% CI: 0.611-0.615); and T-CRC median OS was 86.2 months (95% CI: 84.7-87.6), with 5-year OS rate of 0.608 (95% CI: 0.604-0.613) (p [Table: see text]

Weight changes occur throughout the cancer trajectory. Most research has focused on changes during or after treatment, so clinical significance of change at diagnosis remains unclear. This study aimed to determine prevalence, predictors and prognostic significance of weight changes at diagnosis in outpatients with solid tumours presenting to a tertiary academic medical centre. A retrospective study of the electronic medical record was conducted (n = 6477). Those with weight recorded within 6 months of cancer diagnosis (pre-diagnosis, T0) and 2 subsequent weights (diagnosis, T1; final visit, T2) were identified (n = 4258). Percentage weight change was categorised into four bands (0.1–2.4%; 2.5–5%; 5.01–9.9%; ≥ 10%) for gain and loss. A stable category was also included. Mean age is 61 ± 12.5 years. Common tumour sites: breast (17%; n = 725), prostate (16%; n = 664), lung (14%; n = 599). 15% (n = 652) had metastatic disease at T1. 98% (n = 4159) had weight change at T1. Head & neck and upper gastrointestinal cancers were significantly associated with weight loss (p

Introduction Prognostication in cancer is challenging and inaccurate. C-Reactive Protein (CRP), a cheap and sensitive marker of inflammation may help. This study investigated the relationship between CRP and prognosis in a large cohort of solid tumors with mixed cancer diagnoses and stages. Methods Electronic medical records of 4931 adults with solid tumors who attended the Taussig Cancer Institute from 2006–2012 were reviewed. Demographic and clinical characteristics were recorded. Maximum CRP (mCRP) was identified for each individual. CRP was analysed as a time-dependent, continuous and categorical variable for association with survival. Results Two thirds of patients had a high mCRP. This was consistently associated with shorter survival, even after correction for time from diagnosis, and when analysed as a continuous or a categorical variable. When mCRP values above 10 mg/L were subcategorized, a higher mCRP was always worse. Even among those with normal values, statistically and clinically significant shorter survival was noted at mCRP levels >5 mg/L. Conclusions In a large representative cohort of consecutive solid tumor patients the risk of death was clinically and statistically significantly greater with a high mCRP. This was independent of other variables and regardless of statistical method from both dates of diagnosis and test. CRP appeared to be underutilized. Our results support the routine use of CRP as a universal cost-effective independent prognostic indicator in most solid tumors.

BACKGROUND: Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (

Purpose: Hospital transfers may affect clinical outcomes. Evaluation of admission by source of transfer, time of admission, and provider type may identify opportunities to improve inpatient outcomes. Methods: We reviewed charts of patients admitted to the solid tumor oncology service between July and December 2014 from the Cleveland Clinic Foundation (CCF) Main Campus emergency department (ED), CCF Regional EDs, outside hospital (OSH) ED, OSH inpatient services, and CCF outpatient clinics. Data collected included time of admission, mortality and severity risk scores, and provider type. Risk factors were assessed for clinical outcomes, including activations of the Adult Medical Emergency Team, intensive care unit transfers, in-hospital mortality, and length of stay (LOS). Results: Five hundred admissions were included. OSH inpatient transfers had significantly higher disease severity compared with all other origins of admission. OSH inpatient transfers demonstrated significantly longer LOS compared with all other origins of admission, and higher mortality rates compared with the outpatient direct admits and CCF Main Campus ED admits. After adjusting for disease severity and risk of mortality, OSH ED patients remained at higher risk for Adult Medical Emergency Team activation, OSH inpatient transfers had the longest LOS, and CCF Main Campus ED patients had the lowest risk of mortality. Time of admission and provider type were not associated with any of the outcomes. Conclusion: Oncology inpatients transferred from an outside health care facility are at higher risk for adverse outcomes. The magnitude of difference is lessened, but still significant, after adjustment for disease severity and risk of mortality.

Purpose: Neutropenic fever (NF) is an oncologic emergency and has resulted historically in inpatient management. The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify patients with NF at a low risk of complications who can be managed safely as outpatients. Despite established guidelines supporting outpatient management of low-risk neutropenic fever (LRNF), provider awareness is low, and inpatient admission for intravenous antibiotics continues to be standard of care. Methods: Inpatient provider algorithm implementation and education began in the second quarter of 2014. Providers calculated MASCC scores for patients with nonleukemia hematologic malignancies and solid tumors at admission. Data were collected in a prospectively maintained registry. Patients identified as low risk by MASCC score were placed under observation and started on oral antibiotics. If exclusion criteria and social barriers were not identified, discharge within 48 hours was planned. Results: Eighty-three patients with NF were admitted to the Taussig Cancer Institute inpatient oncology unit between November 2014 and June 2015. Fifty-three patients (64%) had LRNF by MASCC score. Patients with LRNF had an average length of stay of 3.3 days, compared with 6.2 days in our historical cohort. Sixteen patients (30%) were discharged within 24 hours. Only two patients with LRNF had a culture-proven infection, both Enterococcus urinary tract infections. Three patients required nonelective readmission. There were no deaths caused by NF. Conclusion: This pilot study demonstrates that a formal algorithm for LRNF management combined with provider education can improve current inpatient standard of care and length of stay without an increase in morbidity.

Purpose To compare overall survival and toxicities after yttrium-90 ( 90 Y) radioembolization and chemoembolization with drug-eluting embolics (DEE) in patients with infiltrative hepatocellular carcinoma (HCC). Materials and Methods Retrospective review of 50 patients with infiltrative HCC without main portal vein invasion who were treated with 90 Y radioembolization (n = 26) or DEE chemoembolization (n = 24) between March 2007 and August 2012 was completed. Infiltrative tumors were defined by cross-sectional imaging as masses that lacked well-demarcated boundaries, and treatment allocations were made by a multidisciplinary tumor board. Median age was 63 years; median tumor diameter was 9.0 cm; and there were no significant differences between groups in performance status, severity of liver disease, or HCC stage. Toxicities were graded by Common Terminology Criteria for Adverse Events v4.03. Overall survival from treatment was assessed by Kaplan-Meier analysis, with analysis of potential predictors of survival with log-rank test. Results There was no difference in the average number of procedures performed in each treatment group (DEE, 1.5 ± 1.1; 90 Y, 1.6 ± 0.5; P = .97), and technical success was achieved in all cases. Abdominal pain (73% vs 33%; P = .004) and fever (38% vs 8%; P = .01) were more frequent after DEE chemoembolization. There was no significant difference in median overall survival between treatment groups after treatment (DEE, 9.9 months; 90 Y, 8.1 months; P = .11). Conclusions 90 Y radioembolization and DEE chemoembolization provided similar overall survival in the treatment of infiltrative HCC without main portal vein invasion. Abdominal pain and fever were more frequent after DEE chemoembolization.

Despite advances in treatment modalities, colorectal cancer (CRC) still accounts for about half a million deaths yearly worldwide. The majority of metastatic CRC are unresectable, and of those who undergo resection, few are cured. Advances in chemotherapy and targeted therapy have improved survival, but options remain limited, making the case for incorporating novel modalities in CRC treatment paradigm. Our improved understanding of the tumor immune microenvironment had led to the development of novel immunotherapeutic agents that have been tested in clinical trials such as cancer vaccines. Cancer vaccines are designed to activate the effector immune cells in order to generate an immune response against tumors. Dendritic cell vaccines offer potential benefits for CRC patients but requires further evaluation. We reviewed the role of dendritic cells in the colorectal tumor microenvironment and dendritic cancer vaccine studies in colorectal cancer.

e18288 Background: Swallowing is a complex process with four phases. It initiates digestion and is essential for proper nutrition. Difficulty swallowing independently correlated with cancer survival. We retrospectively evaluated the prevalence and incidence of difficulty swallowing in an acute care palliative medicine unit. BMI and survival were also examined. Methods: Electronic Medical Records (EMR) 2010-2012 was reviewed. Assessment comprised of 3 steps: nurse survey on patient condition (coma, intubation, PEG/feeing tube, respiratory distress), screening questionnaire and clinical swallowing test. Change in BMI from the day of admission to discharge calculated. Survival calculated from EMR and Social Security Death Index. Results: N = 261 with cancer identified; 47% known metastases. The mean age (± SD) was 68 ± 13 years. 55% females. 71% Caucasians and 25% African Americans. It was common in lung, gastrointestinal (GI) and genitourinary (GU) cancers. Clinical swallowing test was indicated in 94%. Prevalence of difficulty swallowing = 6%. Incidence of difficulty swallowing = 21%. Change in Body Mass Index (BMI) from 26 ± 7 (Mean ± SD) to 26 ± 6 on admission to discharge respectively. Median (25th, 75th percentile) survival: 25(13, 62) days. Conclusions: Difficulty swallowing was common in lung, GI and GU cancers. The incidence of difficulty swallowing in acute care palliative medicine unit was 21% and prevalence 6%. 75% with difficulty swallowing identified by nurse’s initial survey, 19% through screening questionnaires and 6% clinical swallowing test. Pneumonia/respiratory and GI problems were common. Swallowing evaluation critical for comprehensive cancer care.

Introduction Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT. Methods A prospectively maintained LT database was retrospectively analyzed for patients with recurrent HCC following LT between 2001 and 2011–34 patients. Patients were divided into two groups based on whether they were prescribed sorafenib (n = 17) or not prescribed sorafenib (n = 17). The primary endpoint was overall survival. Results There were no significant differences between the two groups analyzed. Seventeen patients were on sorafenib for recurrent HCC, with a mean daily dose of ~444 mg. Mean duration of treatment was ~10 months. Side effects included: thrombocytopenia, diarrhea, rising transaminases, fatigue, hand–foot skin reaction, and nausea. Survival in the sorafenib vs. non-sorafenib group was greater at three-, six-, nine-, and 12-month intervals and overall survival. Conclusion Sorafenib can be well tolerated and safe in patients with recurrent HCC following LT and may be associated with a modest survival benefit. To our knowledge, this is the largest single-center retrospective analysis of patients prescribed sorafenib for recurrent HCC after LT.

Background and aim Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. Methods Search of the Cleveland Clinic's CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. Results Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn's disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35-1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54-1.4; P = 0.58) between IBD and non-IBD patients. Conclusion Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy.

Physicians can do a better job of palliating symptoms and improving the quality of life of cancer patients if they understand the principles of symptom management. We review the general principles of symptom management for fatigue, anorexia, constipation, dyspnea, nausea, and vomiting.

e18710Background: Precision oncology approaches to selecting therapies are increasingly being used, but there are limited data on benefit to patients. We expand on our initial prospective cohort da...

e16122Background: Therapeutic approaches and prognosis in cancer depend on the baseline performance status and comorbidities. The first line therapy for iHCC has been sorafenib since 2007, the only...

364 Background: Sorafenib has been the only FDA-approved medication for inoperable HCC (iHCC) as first line. Agents with better tolerability and potential to improve progression-free-survival (PFS) are needed. Tivozanib (TIVO) is an inhibitor of vascular endothelial growth factor (VEGF) tyrosine kinase, inhibiting angiogenesis critical in HCC. Methods: This is a phase 1b/2 study with HCC patients (pts) having a measurable disease, Child-Pugh class A, and no prior systemic therapy. Phase 1b portion followed a modified 3 + 3 design; phase 2 portion was a two-stage, single arm, un-blinded study. Adverse events were categorized based on CTCAE, and tumor imaging was assessed per RECIST. Results: At 3 centers with IRB approval, 21 eligible pts were enrolled. In phase 1b, 8 pts were enrolled at a starting dose of 1mg once daily q21days with one week off. Upon escalation to 1.5mg, two pts had dose limiting toxicities (DLTs, grade 3 mucositis and hypertension) and came off study without completing the DLT period. The dose of TIVO was de-escalated to 1 mg, and the accrual of remaining patients to phase 2 portion occurred at 1 mg. In a total of 19 pts, median follow up was 16.9 months (mo). The primary endpoint of median PFS was 5.5 mo. Partial response (PR) was seen in 4/19 (21%) and stable disease (SD) in 8/19 (42%): disease control rate was 63%. Overall survival (OS) at 6 and 12 mo was 58% and 25%. Median OS was 7.5 mo. Three pts have remained on TIVO for > 2 years. Viral loads of hepatitis B and C remained stable during the study. Adverse events (AEs) related to TIVO included grade 3 fatigue (15.7%), decreased appetite (5.3%), pulmonary embolism (5.3%), hand-foot syndrome (5.3%), elevated LFT (10.5%), and grade 4 hypertension (5.3%). Conclusions: TIVO is tolerable at 1 mg in iHCC. In few pts, TIVO had deep and durable responses. Biomarker driven studies of TIVO in the context of immunotherapy are warranted. Acknowledgment: We appreciate support from NCCN. Clinical trial information: NCT01835223.

399 Background: Precision oncology – the use of next-generation sequencing (NGS) to identify therapeutic options for advanced cancer patients – is being used widely, but its utility in patients with pancreatobiliary (PB) cancers has not been studied systematically. We evaluated the prevalence of actionable alterations and their impact on therapeutic decision-making in patients with PB cancers. Methods: We conducted a retrospective cohort study of consecutive patients seen at the Cleveland Clinic between 2013 and 2016 with incurable solid tumor malignancies, in whom FoundationOne™ (Cambridge, MA) NGS was ordered. All results were reviewed at a multidisciplinary genomics tumor board (GTB), which determined actionability and made therapeutic recommendations. Treatment decisions (on label, off label, or clinical trials) based on said recommendations were reviewed. Results: The study population was 600 patients, of whom 53 had PB cancers. For these 53, median age was 59.6 years; 62.2% (33/53) were female; 86.8% (46/53) were Caucasian. Eight samples (15.1%) had inadequate tissue; of 45 resulted cases, 21 (46.7%) were recommended treatment, including clinical trials (n = 19) and off-label drugs (n = 2). The most common targets for therapy were FGFR (5/21) and CDKN2 (3/21). Of 21 patients with recommendations, only two (9.5%) received genomics-driven therapy, compared with 31.7% (86/271) of patients with other solid tumor malignancies (p = 0.03). One received an IDH1 inhibitor, and one received dabrafenib and trametinib for a BRAF alteration; both on clinical trials. At time of last follow-up, best responses were unknown and partial response, respectively. Unavailability of clinical trials in the vicinity (9.5%), and clinical trial ineligibility, mainly due to poor performance status (9.5%), were common reasons for lack of actionability. Conclusions: Benefit from precision oncology in the PB population is low, with only 4.4% (2/45) of patients with NGS results eventually receiving genomics-driven therapy. Benefit to patients will not improve until access to clinical trials is enhanced and patients are evaluated for these trials earlier in the course of their disease, when their performance status is likely to be higher.

Background: Respiratory depression is the most feared opioid-related side-effect yet research on the topic is sparse. We evaluated changes in respiratory parameters during parenteral opioid titration for cancer pain to determine if opioid titration was associated with evidence of hypoventilation. The primary outcome measure was to measure changes in end-tidal CO2 (ET-CO2) during opioid titration to pain control. Methods: Subjects with severe cancer pain admitted for parenteral opioid titration for poorly controlled pain were eligible. Those who were oxygen dependent were excluded. ET-CO2, O2 saturation, respiratory rate (RR), and vital signs were monitored daily until pain control was achieved. Results: 30 patients completed the study of which 29 are reported. The mean ET-CO2 at initial evaluation was 33.39 ∓ 5.0 and 34.79 ∓ 5.7 mmHg at pain control (P =0.14, 95% CI -0.5 to 3.3). None had an ET-CO2 ≥50 mmHg. All maintained O2 saturation ≥92%. RR dropped transiently below 10/minute in two subjects. Conclusions: Parenteral opioid titration for relief of cancer pain was not associated with respiratory depression as demonstrated by significant changes in ET-CO2 or oxygen saturation in non-oxygen dependent cancer patients.

Survival after surgical resection for pancreatic cancer remains poor. A subgroup of patients die early (6 months), and understanding factors associated with early mortality may help to identify high-risk patients. The Khorana score has been shown to be associated with early mortality for patients with solid tumors. In the current study, the authors evaluated the role of this score and other prognostic variables in this setting.The current study was a cohort study of patients who underwent surgical resection for pancreatic cancer from January 2006 through June 2013. Baseline (diagnosis ±30 days) parameters were used to define patients as high risk (Khorana score ≥3). Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) were calculated.The study population comprised 334 patients. The median age was 67 years, 50% of the study population was female, and 86% of the patients were white. The pancreatic head was the primary tumor site for 73% of patients; 67% of tumors were T3 and 63% were N1. The median Khorana score was 2; 152 patients (47%) were determined to be high risk. Adjunctive treatment included chemotherapy (70%) and radiotherapy (40%). The postoperative (30-day) mortality rate was 0.9%. The 6-month mortality rate for the entire cohort was 9.4%, with significantly higher rates observed for high-risk patients (13.4% vs 5.6%; P = .02). On multivariable analyses (examining a total of 326 patients), the Khorana score (HR for high risk, 2.31; P = .039) and elevated blood urea nitrogen (HR, 4.34; P.001) were associated with early mortality.Patients at high risk of early mortality after surgical resection of pancreatic adenocarcinoma can be identified using simple baseline clinical and laboratory parameters. Future studies should address preoperative interventions in these patients at high risk of early mortality.

e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.

494 Background: The management of borderline resectable pancreatic cancer (BRPC) remains unsettled and the predictors of outcome are uncertain. We evaluated the role of neoadjuvant therapy (nRx) and outcomes in patients with BRPC. Methods: We conducted a retrospective cohort study of consecutive patients with BRPC who received nRx and were followed at the Cleveland Clinic. A histopathologic diagnosis of pancreatic carcinoma was required. Tumor anatomy was assessed by contrast-enhanced cross-sectional imaging (CT or MRI), and BRPC was defined as a tumor-vessel wall interface involving one or more of: celiac artery, superior mesenteric artery, common hepatic artery, main portal vein, superior mesenteric vein; making margin-negative resection unlikely. Baseline laparoscopy was performed to rule out occult metastatic disease. Chemotherapy (CT), radiation (RT), surgery details, and pathologic and survival outcomes were evaluated. Hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study population comprised 79 patients from 2009 to 2014. Median age was 64 years; 52% were male; 85% were Caucasian. Pancreatic head/neck were the primary site in 81%; body/tail in 19%. Vascular involvement included arterial in 32 (41%), and venous in 65 (82%) patients. nRx included RT in all patients; 77 (97%) received CT; gemcitabine (n = 50, 63%) was the most common agent. After CT/RT, 36 (46%) patients had unresectable/inoperable disease: 29 (37%) for anatomic reasons, 4 (5%) for physiologic reasons, and 3 (4%) for both. Surgical resection was performed in 43 (54%) patients; 38 (88%) had negative margins; 30 (70%) had negative nodes; 32 (74%) received adjuvant CT. There were no statistically significant predictors of resection. After median follow-up of 27 mths, there have been 45 deaths (57%); median overall survival (mOS) is 23.5 mths (95% CI: 16-28 mths). Only cancer resection was associated with survival (mOS, resected: not reached; mOS, not resected: 12.8 mths; HR: 0.30, 95% CI: 0.16-0.56, p = 0.0002). Conclusions: Surgical resection, if feasible, of BRPC is associated with improved OS. Strategies to improve the odds of resection should be evaluated in prospective studies.

148 Background: Hospitalized patients (pts) on solid tumor oncology (STO) services have palliative needs including pain management. This quality improvement project sought to establish a new STO-specific co-rounding PM consult service, evaluate the use of consult criteria for STO inpatients, assess the impact/interest in an embedded service, improve access to PM for STO pts and improve palliative education to STO teams. Methods: During October 2015 to January 2016, a new PM consult service was established for the 2 STO inpatient services at Cleveland Clinic. The PM attending physician (MD) rounded with each of the STO teams twice a week. On weekdays, the PM MD chart-screened all STO pts for palliative needs such as uncontrolled pain (2 pain scores ≥ 6 out of 10 in 24 hours), unplanned readmission within 30 days or contact with a PM MD as an outpatient. Other PM needs were assessed on rounds. PM consults were offered for pts who screened positive and were performed if approved by the STO team. STO MDs were surveyed anonymously regarding acceptance of the embedded service. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data regarding pain management during the pilot period was reviewed. Results: Average daily census for the 2 STO teams was 28 pts. There were 282 positive palliative screens in 4 months, 119 of whom were seen in consultation (42%.) The embedded service saw 42-45 new consults per month. The PM team followed 22-35% of all STO inpatients. 14-18 pts/month new to PM were referred to the outpatient PM clinic after discharge. STO MDs indicated strong acceptance of the embedded PM team for pain management, STO team education and coordination of care. All STO MDs wanted the service to continue. HCAHPS pain scores for the entire STO floor improved from a baseline 39th percentile to 98thpercentile. Conclusions: PM was integrated successfully into daily hospital care of STO pts at our institution using a co-rounding model and consult criteria. The service was busy and well received by STO MDs. Continuity with outpatient PM was provided. HCAHPS pain scores improved for the entire STO floor, including pts not directly seen by PM.

Incorporation of tablet computers (TCs) into patient assessment may facilitate safe and secure data collection. We evaluated the usefulness and acceptability of a TC as an electronic self-report symptom assessment instrument. Research Electronic Data Capture Web-based application supported data capture. Information was collected and disseminated in real time and a structured format. Completed questionnaires were printed and given to the physician before the patient visit. Most participants completed the survey without assistance. Completion rate was 100%. The median global quality of life was high for all. More than half reported pain. Based on Edmonton Symptom Assessment System, the top 3 most common symptoms were tiredness, anxiety, and decreased well-being. Patient and physician acceptability for these quick and useful TC-based surveys was excellent.