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BACKGROUND When compared with warfarin, low-molecular-weight heparin (LMWH) reduces the incidence of recurrent venous thromboembolism (VTE) in cancer. However, a survival benefit of LMWH over warfarin for the treatment of cancer-associated VTE has not been established. METHODS Using the Surveillance, Epidemiology and End Results and Medicare linked database from 2007 through 2016, we identified Medicare beneficiaries (aged ≥66 years) who were: (1) diagnosed with primary gastric, colorectal, pancreatic, lung, ovarian, or brain cancer; (2) diagnosed with cancer-associated VTE; and (3) prescribed LMWH or warfarin within 30 days. The primary outcome was overall survival (OS). Patients were matched 1:1 using exact matching for cancer stage and propensity score matching for cancer diagnosis, age, year of VTE, and time from cancer diagnosis to index VTE. Cox proportional-hazards regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS A total of 9706 patients were included. Warfarin was associated with a significant improvement in OS compared with LMWH (median OS, 9.8 months [95% CI, 9.1-10.4] vs. 7.2 months [95% CI, 6.8-7.8]; HR, 0.86; 95% CI 0.83-0.90; p

This narrative on multiple myeloma in a clinical setting reflects on how medical jargon may confuse patients and their families.

ROS1-rearranged (also known as ROS1 fusion-positive) non-small-cell lung cancer is an uncommon but distinct molecular subgroup seen in approximately 1-2% of cases. Oncogene addiction due to constitutive ROS1 tyrosine kinase activation has allowed development of molecularly targeted therapies with remarkable anti-tumor activity. Both crizotinib and entrectinib, multitargeted tyrosine kinase inhibitors (TKIs) have now received approval by the FDA for treatment of patients with advanced ROS1-rearranged lung cancers; however, the clinical efficacy and safety of these drugs have been derived from expansion cohorts of single-arm phase I or basket clinical trials with relatively small populations of this clinically and molecularly distinct subgroup. Both drugs lead to high objective response rates (approximately 70-80%) and have manageable side effects, although only entrectinib has potent intracranial efficacy. Lorlatinib is an oral brain-penetrant ALK/ROS1 TKI with activity in both TKI-naive and some crizotinib-resistant settings (albeit with limited potency against the crizotinib/entrectinib-resistant ROS1-G2032R mutation). We describe cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. The next generation ROS1 TKIs (repotrectinib and DS-6051b), owing to their broad activity against kinase mutations including ROS1-G2032R in preclinical studies, hold promise to transform the current treatment paradigm and permit even further gains with regards to long-term outcomes in this subset of patients.

4039 Background: Despite potentially curative surgery, long-term survival from OGC remains poor due to high relapse rate. Neoadjuvant (naFLOT) and adjuvant (aFLOT) FLOT is currently standard treatment for resectable OGC based on data from the FLOT-4 trial. We explored whether TRG was associated with FLOT-outcome using RWD. Methods: Pts with OGC treated with naFLOT +/- aFLOT at a tertiary UK centre were identified following institutional board approval. Clinical and laboratory data were extracted from the patient record. TRG was evaluated by a histopathologist. Median overall survival (OS) and median progression-free survival (PFS) were evaluated using Kaplan-Meier and Log-rank tests; time taken from start of naFLOT, and associations between factors with Fisher’s exact (FE) test. Results: 171 pts were identified, median FU 30 mths. 144 (84%) male; median age 66 (32-84); oesophagus 66 (38%), junctional (GOJ) 73 (43%), gastric 32 (19%); stage IB 3 (2%), stage IIB 26 (15%), stage III 91 (53%), stage IVA 47 (28%) and unknown 4 (2%). Pts had median of 2 comorbidities (range 0-6); performance status (PS) 0: 95 (56%), PS 1: 71 (41%), PS 2: 3 (2%) and PS unknown 2 (1%). 132/171 pts completed 4 cycles of naFLOT and this was significantly associated with undergoing surgery (p = 0.02). Those who had surgery (140/171) had significantly improved PFS (not reached (NR) vs. 6 mths; 95% CI 2-10; p < 0.001) and OS (NR vs. 12 mths; 95% CI 6-18; p < 0.001). TRG was reported for 126/140 patients who underwent surgery. TRG 1/2 (42/126) vs. TRG ≥3 was significantly associated with improved PFS (NR vs. 35 mths; 95% CI NR; p < 0.001) and OS (median NR either group; p < 0.001). Pts with TRG 1/2 who commenced aFLOT (≥1 cycle; n = 31/42) or completed 4 cycles of aFLOT (17/31) did not have improved PFS or OS vs. those who did not. Those with TRG ≥3 who commenced aFLOT (≥1 cycle; n = 62/85) had improved PFS (median NR vs. 22 mths; 95% CI 13-31 p = 0.006) and OS (median NR vs. 25 mths; 95% CI 18-32 p = 0.019). Those with TRG ≥3 who completed 4 cycles of aFLOT (n = 38/62) had significantly improved PFS (median NR vs. 25 mths; 95% CI 14-36 p = 0.016) and OS (median NR vs. 36 mths; 95% CI 16-55 p = 0.012). There was no difference in PFS or OS in pts with TRG ≥3 who had a dose reduction at any time during aFLOT. Conclusions: TRG is a predictor of outcome following naFLOT + surgery with superior outcomes in those with TRG 1/2. Our analyses suggest that only pts with TRG >3 following naFLOT + surgery benefit from adjuvant FLOT. Prospective randomised studies are required to confirm whether pts with TRG 1/2 require treatment with aFLOT.

400 Background: Bladder cancer is marked by racial disparities in stage at presentation, treatment, and survival. It is unknown how somatic tumor genomes differ by race. Tumor aneuploidy, defined as aberrant counts of chromosome arms, is pervasive in tumors including bladder cancer. Its associations with race are incompletely understood. We sought here to characterize the relation of race with aneuploidy in high-grade muscle-invasive bladder cancer. Methods: To quantify how aneuploidy differs by race, we leveraged the cohort of patients with high-grade, muscle-invasive bladder cancer from The Cancer Genome Atlas. Chromosome arm gains and losses were identified based on Affymetrix SNP 6.0 arrays (Taylor 2018). We focused on aneuploidy burden defined as the count of chromosome arms altered by gains and losses per tumor, which was based on both p and q chromosome arms of all autosomes except for acrocentric autosomes (q arms only) and ranged from 0 to 34 altered chromosome arms. We used multivariable linear regression to obtain mean differences and 95% confidence intervals (CIs) in the number of altered chromosome arms between self-reported racial groups, adjusting for demographics (sex, age at diagnosis, smoking status) and tumor characteristics (grade, histology). We also evaluated associations between race and number of altered chromosome arms stratified by papillary/non-papillary histology and sex. Results: Of 362 participants, 315 self-identified as White (87%), 25 as Asian (7%), and 22 as Black (6%). 73% were men, 21% were current smokers, and 52% former smokers. Median age at diagnosis was 69 years (interquartile range [IQR]: 61 to 76). Asians and Blacks tended to be younger at diagnosis than Whites, with more never-smokers among Asians. More profiled tumors were of papillary histology among Asians (44%), and fewer among Blacks (18%), than among Whites (30%). Aneuploidy burden was high overall (median, 14 altered chromosome arms; IQR: 8 to 19); only 17% of tumors had five or fewer altered chromosome arms. Compared to Whites, aneuploidy burden overall was similar in tumors from Asians (adjusted mean difference, –2.3 fewer altered chromosome arms; 95% CI: –5.4 to 0.9) and Blacks (–1.7; 95% CI: –5.1 to 1.7). Asian race appeared more strongly associated with lower aneuploidy burden in non-papillary tumors (–3.9 altered chromosome arms; 95% CI: –7.7 to –0.1) than in papillary tumors (–0.3; 95% CI: –5.6 to 5.0), and in men (–3.5; 95% CI: –7.0 to 0.1) than in women (–0.8; 95% CI: –6.8 to 5.2). Conclusions: These findings suggest potential differences in aneuploidy burden between Asians and Whites among high-grade muscle-invasive bladder cancers. They also highlight a need for validation in cohorts that are more racially diverse and have a well-defined source population (study base) with detailed data on cancer risk factors and histopathology.

e16545 Background: Purpose: The aim of this retrospective study was to assess the efficacy and toxicity of irinotecan +/- capecitabine for patients with metastatic esophago-gastric (EG) adenocarcinomas previously treated with at least two chemotherapy regimens including platinum-based, fluoropyramidines and taxanes. Introduction: Treatment for metastatic EG cancer beyond 2nd line remains controversial. Recently, the TAGS phase III trial (Shitara et al., 2018) showed overall survival benefit with Trifluridine/tipiracil of 2.1 months compared to placebo as a third line. Apatinib is also approved for use as third line in China (Li et al., 2013). Based on minimal evidence (Kang et al., 2013), irinotecan in combination with capecitabine is used in the UK. We performed a retrospective study to assess the efficacy and toxicity of irinotecan as a beyond 2nd line regime in metastatic EG adenocarcinomas in one of Europe’s largest cancer centres, The Christie. Methods: Data was collected retrospectively from all metastatic EG adenocarcinoma patients who were treated with irinotecan +/- capecitabine as a beyond 2nd line palliative treatment at the Christie Hospital from January 2014 to December 2019. Irinotecan was either given 2 or 3 weekly at dose of 180 mg/m² with or without capecitabine 800 mg/m². Response rate (RR) was calculated according to RECIST version 1.1, overall survival measured and toxicity data collected. Results: Fifty-six patients received irinotecan as beyond 2nd line palliative chemotherapy. Out of the thirty-seven patients with measurable disease on their scans, the overall response rate was 8.1% and the disease control rate was 51.4% as per RECIST 1.1. Median overall survival was 5 months (95% CI 4.2-5.8). The presence of grade 3-4 toxicities was 16% (9 patients) and included neutropenia, fatigue, nausea and diarrhea. On average, 3.7 cycles were administered, 32% (18 patients) required dose reductions, mainly secondary to grade 2 diarrhea and fatigue. Conclusions: Irinotecan in combination with capecitabine is efficacious as a beyond 2nd line regime in metastatic EG with an acceptable toxicity profile with a limited role in patients with resistant disease to first line platinum-based chemotherapies with fluoropyramidines.

Background: Digital and surveillance epidemiology via internet search engine analysis has allowed for new insights into patients' and laypersons' health concerns and awareness. Google Trends in particular has become an increasingly well-published data resource as it automatically compiles all Google searches from 2004 to the present from internet users worldwide into an aggregated, passively-collected, and publicly viewable data site. Over the past few years, cancer awareness campaigns in the United States have greatly increased awareness of specific malignancies, such as breast and prostate. However, the hematologic malignancies have not had the same level of awareness, despite rising incidence rates for leukemia, lymphoma, and myeloma from 2004 to 2015. This study sought to examine patients' and laypersons' internet searches for terms related to the three major hematologic malignancies. Methods: Google Trends (www.google.com/trends) was accessed to obtain the relative search engine traffic values for terms related to the three major blood cancers (leukemia, lymphoma, and myeloma) from January 2004 to December 2015. These values are defined as search volume indices (SVIs) and are directly obtainable from Google Trends. For comparison, SVIs for the term "cancer" were also collected during the same time frame. Using standard Boolean operators, searches for "cancer" were operationalized as CANCER + CANCERS + MALIGNANCY + MALIGNANCIES + MALIGNANT, searches for "leukemia" as LEUKEMIA + LEUKEMIAS, searches for "lymphoma" as LYMPHOMA + LYMPHOMAS + "NON HODGKIN" + NON HODGKIN + "HODGKIN DISEASE" + "HODGKIN'S DISEASE", and searches for "myeloma" as MYELOMA + MYELOMAS. Trends in the respective SVIs were analyzed with Mann-Kendall trend tests and Sen's slope estimators in R (V3.3.1), similar to previously published Google Trends analyses. Results: Individual inspection of each search term revealed the average SVI for "cancer" was 76.4, for "leukemia" was 68.0, for "lymphoma" was 75.5, and for "myeloma" was 30.4 during the time frame 2004 to 2015. Simultaneous inspection across search terms revealed the SVIs for "cancer" far outweighed searches for "leukemia," "lymphoma," and "myeloma" combined (mean SVIs 76 vs. 4, 4, and 1 respectively). Mann-Kendall trend tests showed a statistically significant decrease in searches for "leukemia" (S = -6460.0, p < 0.001) and "lymphoma" (S = -6338, p < 0.001) over time. "Myeloma" searches (S = -1321, p = 0.02) and "cancer" searches (S = -2389.0, p < 0.005) also showed a statistically significant decrease. Sen's slope estimators showed the greatest decline for "leukemia" (Q = -0.18, 95% CI: -0.19 to -0.17) and "lymphoma" (Q = -0.21, 95% CI: -0.22 to -0.20) and lowest decline for "cancer" (Q = -0.05, 95% CI: -0.06 to -0.04) and "myeloma" (Q = -0.01, 95% CI: -0.02 to 0.00). Discussion: Searches for "leukemia" and "lymphoma" have sharply declined over the time period 2004 to 2015 in the United States. Searches for "myeloma" have remained stably low over time with marginal decrease. Overall, internet searches for the hematologic malignancies represent a very small fraction of total searches for "cancer." These data suggest a declining awareness for the major hematologic malignancies despite their rising incidences in the United States. Patient awareness may be increased with greater efforts toward disease-specific advocacy campaigns and public health endeavors. Figure 1 Individual Google Trends searches for terms (in clockwise order) "cancer," "leukemia," "lymphoma," and "myeloma" in the United States from 2004 to 2015. Figure 1. Individual Google Trends searches for terms (in clockwise order) "cancer," "leukemia," "lymphoma," and "myeloma" in the United States from 2004 to 2015. Figure 2 Simultaneous Google Trends search for "cancer," "leukemia," "lymphoma," and "myeloma" in the United States from 2004 to 2015. Figure 2. Simultaneous Google Trends search for "cancer," "leukemia," "lymphoma," and "myeloma" in the United States from 2004 to 2015. Disclosures Khorana: Halozyme: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen Scientific Affairs, LLC: Consultancy, Honoraria, Research Funding.

6037Background: Definitive chemoradiation (CRT) has become an established organ preservation treatment for patients (pts) with locoregionally advanced laryngeal cancer. Although most pts will exper...

Background: Analysis of internet search traffic has provided a new proxy measure into the trends and patterns of patients' diseases and their information-seeking behaviors. In recent years, Google Trends has become a data resource of interest given its status as the largest internet search provider in the world with publicly-viewable, passively-collected, and expansive data on any searchable term or combination of terms. For instance, search terms related to influenza (e.g. fever) predicted influenza spread faster than standard surveillance as shown by Ginsberg et al in Nature 2009. The true outpatient burden and incidence of venous thromboembolism (VTE) has long been debated. Extant VTE data are limited to cases that present to medical attention, thus missing any cases that do not come to an emergency department or clinic. We hypothesized that Google Trends analysis offers potential insight into the general populations' blood clot burden and awareness. This study aimed to explore general trends of VTE-related terms and seasonal variation in searches. Methods: Google Trends was utilized to obtain relative search engine traffic values (defined as search volume indices, SVIs) for terms related to DVT in the United States from summer 2004 - winter 2015. Terms related to LEG SWELLING, CALF PAIN, VARICOSE VEINS, and LEG CLOT were used and combined with Boolean operators to combine similar terms. A separate search occurred for BLOOD CLOT and related terms to investigate awareness of VTEs. Analysis was performed in R (V3.1.1) in accordance with previously published Google Trends investigations. Results: The average relative volume of searches was highest for VARICOSE VEINS and lowest for LEG SWELLING by approximately 3.2 fold. A seasonal pattern was seen with summer months (May-Aug) having higher SVIs than winter months (Nov-Feb) for all terms in the 11 year study period except for BLOOD CLOT. Using a Wilcoxon signed rank test, mean SVI difference comparing summer to winter for LEG SWELLING showed W = 66 (p = 0.004), for CALF PAIN W = 66 (p = 0.003), for VARICOSE VEINS W = 67 (p = 0.004), and for LEG CLOT W = 65 (p = 0.005). For BLOOD CLOT, a gradual increase in SVIs was seen and characterized by a Mann-Kendall test as having a significant positive trend, S = 898, p = 0.024. Conclusions: Search terms related to VTE in the United States show a strong seasonal pattern with greater search activity in summer months compared to winters months. These data suggest a higher incidence and burden of VTE in the summer. This challenges previous notions of a weakly higher incidence of VTE in winter months, calculated as a relative risk of 1.143 by Dentali et al in 2011. The gradual increase in relative search traffic for BLOOD CLOT terms reflects a likely rising awareness and/or true rise in the incidence of VTEs in the United States from 2004-2015. Further studies should investigate whether internet search traffic correlates directly with total yearly DVT incidence rates. Keywords: Population, venous thromboembolism, incidence Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Khorana: Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria.