Bartley, Adam C.

Abstract Background: Over 10,000 new cases of myelodysplastic syndrome (MDS) are diagnosed in the US annually (MA X, Cancer 2007). Hypomethylating agents (azacitidine and decitabine), immunomodulating drugs (lenalidomide) and erythropoietin stimulating agents (epoetin α and darbepoetin) have been approved for more than a decade for the treatment of MDS. However, changes in overall outcome after the approval of these treatments are unknown. We used the National Cancer Data Base (NCDB), a nationwide oncology registry covering 70% of the US cancer population to answer these questions. Methods: We identified patients with MDS diagnosed from 2004-2013 using ICD-O-3 codes 9980-9983 and 9985-99912. Overall survival (OS) was estimated using the Kaplan-Meier method. We compared OS using the log-rank test according to demographic subgroups (sex, age [<40, 41-65, and ≥65 years], race [White, Black, Native American, Asian/Pacific Islander, and other], and ethnicity) across years of diagnosis (Period 1: 2004-2006, Period 2: 2007-2009, and Period 3: 2010-2013). Results: i) Characteristics: There were 54,953 MDS patients in our study. The median age at diagnosis was 76 years (78.7% older than 65) and 44% were females. White race (88.9%) was the most common, followed by black (7%). Four percent were Hispanics. A third (30.8%) of all patients were treated in academic centers. Three quarters (75.8%) had either Medicaid or Medicare insurance. ii) MDS Subtypes: 5q Syndrome was seen in 2008 cases (3.7%) while the most common subtype was MDS-Unclassifiable (U) (55.6%). Therapy related MDS (t-MDS) was seen in 1125 cases (2%), however coding for t-MDS was discontinued in 2009. Refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), and refractory anemia with excess blasts were seen in 9%, 7.6%, 6%, and15.6%, respectively. iii) OS: Compared to their counterparts, patients who were male, older, had a diagnosis of RAEB, covered by Medicare insurance, and treated at non-academic centers had the worse OS (all P <0.001). Across Periods 1-3, we did not see improvement in OS among demographic subgroups except for those who were <40 years old (P=0.03). Conclusions: In the past decade, the overall outcome of MDS did not improve despite the advent of new therapies. More than half of the cases were classified as MDS-U reflecting the difficulty of subtyping MDS based on World Health Organization classification. We found disparity in outcomes by demographics and type of treatment facility. This is the largest study of MDS outcome to-date and should help in understanding the gaps and areas that need future research. Figure Figure. Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

Abstract Background: Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and socioeconomic burden. Though male sex is a known risk factor for recurrent VTE, there is a paucity of literature regarding sex-based sociodemographic differences as well as differences in VTE outcomes including hospital length of stay and mortality rates. Methods: We conducted a retrospective analysis from the National Inpatient Sample (NIS) database from 2012-2013. Inclusion criteria were age 18 years and older and primary discharge diagnosis of VTE Sociodemographic features and medical comorbidities were analyzed, as were hospital length of stay and in-hospital mortality rates. Results: 107,896 patients in the NIS, representing a national estimate of 539,480 patients hospitalized for VTE between 2012 and 2013, met inclusion criteria. 53% were female and 47% were male. Mean age was 63 years and on average women were older than men (65 years versus 62 years, p<0.001). There were significant differences between men and women with respect to race, primary insurance payor, and VTE location as well as medical comorbidities (Table 1). Median overall length of stay (LOS) was 4 days and in-hospital mortality rates were 2.1%. Female sex was associated with a small but significantly longer hospital LOS (RR 1.04, CI 1.03-1.05, p<0.001) which was also seen in subgroup analyses of lower extremity DVT (RR 1.05, CI 1.03-1.06, p<0.001) and pulmonary embolism (RR 1.03, CI 1.02-1.05, p<0.001) but not upper extremity (RR 1.04, CI 0.96-1.12, p=0.36). There were no significant sex-based differences in in-hospital mortality (2.2% in women versus 2.1% in men, p=0.15). In a multivariate model correcting for sociodemographic differences and medical comorbidities, there were no significant differences between women and men with respect to hospital LOS or in-hospital mortality (Table 2). Conclusion: We used data from the NIS to study a large number of patients hospitalized for VTE, and identified several sex-based disparities in sociodemographic factors and location of VTE. However, in a multivariable analysis correcting for these factors, sex was not associated with significant differences in hospital LOS or inpatient mortality rates. Disclosures Kapoor: Celgene: Research Funding; Takeda: Research Funding; Amgen: Research Funding.

Abstract Introduction Isolated myeloid sarcoma is a rare form (<1%) of acute myeloid leukemia presenting as extramedullary tumor. Contemporary clinical data are mostly limited to institutional case series. Using the National Cancer Database, the largest public cancer registry covering >70% of all newly diagnosed cancers in the United States, we determined the patterns of anatomical presentation and clinical outcome of myeloid sarcoma. Methods We identified patients with a histologically confirmed diagnosis of isolated myeloid sarcoma from 2004-2013 using International Classification of Diseases for Oncology version 3 (ICD-O-3) code: 9930. To allow at least 1 year of follow-up, only patients diagnosed from 2004-2012 were included in the survival analysis using Kaplan-Meier estimates. Results A total of 746 patients were included in the study. The median age of patients was 59 years (range, 41 to 73) and 56% were males. The anatomical distribution and median overall survival of patients are depicted in the Table. The top 3 most common sites of presentation were connective/soft tissues (31.3%), skin/breast (12.3%), and digestive system (10.3%). Compared to other races, Blacks were more likely to have presentation in bones/joints (11.8% vs 6.3% in others), lymph nodes/spleen (22.1% vs. 9%), and less likely in skin/breast (4.4% vs. 13.8%). Asians were more likely to present with cardiopulmonary/mediastinal disease as compared to other races (13.6% vs. 4.2%). According to outcomes, we can categorize the patients into 3 groups: good (median overall survival >30 months: reproductive and digestive systems), intermediate (median overall survival 15-30 months: head/neck and kidney/bladder/retroperitoneum/adrenal), and poor (median overall survival <15 months: nervous system, connective/soft tissue, and bones/joints). There was no significant difference in overall survival between males and females (P =0.06). Among the races, Blacks had the worst overall survival (P =0.02; Figure). Conclusions This is the largest registry-based study on isolated myeloid sarcoma in the United States. Isolated myeloid sarcoma has a diverse anatomic clinical presentation and the overall survival varied significantly according to sites of presentation and racial subgroups. The results of our study may aid the prognostication of patients for treatment decision making and in the understanding of the biological differences by anatomic sites of presentation. Table Anatomical distribution and median overall survival of isolated myeloid sarcoma Table. Anatomical distribution and median overall survival of isolated myeloid sarcoma Figure Overall survival by sex and race in isolated myeloid sarcoma Figure. Overall survival by sex and race in isolated myeloid sarcoma Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

Abstract Background: Unlike acute lymphoblastic leukemia, data on acute myelogenous leukemia (AML) in the adolescents and young adults (AYA) are limited and generally derived from clinical trials, which are mostly conducted in academic centers. It is unclear whether the choice of treatment facility influences clinical outcome independent of disease biology and socio-demographic factors. This study used the National Cancer Data Base, a nationwide oncology database covering 70% of the US cancer population, to address this question. Methods: We identified 11,712 AYA patients who were diagnosed with AML from 2003-2011. We excluded patients who were: a) 15-17 years of age (n = 3,104) as treatment facility data were not available for age <18 years; b) not treated at the reporting facilities (n = 415) as follow-up might be incomplete; c) treated at treatment facilities with ≤100 new cancer cases/year (n = 18); and d) those without follow-up data (n = 47). Treatment facilities were classified as academic, comprehensive community (>500 new cancer cases/year), or community (101-500 new cancer cases/year) cancer programs. AMLs harboring t(15;17), inv(16), or t(8;21) were defined as good-risk, while the rest were considered non-good risk. Overall survival from the time of AML diagnosis was the primary outcome. We used multivariate imputation by chained equation to impute missing values, weighted Cox regression to obtain average hazard ratios (HRs), and pooled Wald c2 statistics to detect interaction. Results: We included 8,128 AYA patients with AML in the study and 25.2% were good risk. Among the good risk AMLs, 11.6%, 12.3%, and 76.1% had t(8;21), inv16, and t(15;17), respectively. The distribution of patients by treatment facility were academic (64.1%), comprehensive community (32.9%), and community (3.0%). After detecting an interaction between AML risk and type of treatment facility (P=0.038), we stratified treatment facility by AML risk and found significant differences in overall survival among good risk (P=0.02) but not non-good risk AML (P=0.19). This survival difference persisted even after adjusting for demographic (age, sex, race/ethnicity), socioeconomic (income, education, medical insurance), geographic (area of residence, travel distance), co-morbidities (Charlson-Deyo score), and treatment (receipt of chemotherapy) factors. Patients with good risk AML treated in comprehensive community cancer programs had a higher risk of death compared to those treated in academic programs (adjusted HR: 1.41, 95% CI: 1.11-1.79). For community cancer programs, the risk of death was also higher but did not reach statistical significance (adjusted HR: 1.22, 95% CI: 0.68-2.21). ). Subset analysis showed that the survival difference among those with good risk AML was observed in t(15;17) or acute promyelocytic leukemia (APL; P=0.02) but not in t(8;21) or inv16 (P=0.79). The disparity occurred primarily during the first month of APL diagnosis, wherein the risk of death was two-fold higher in community programs (Figure). Conclusions: Among AYA patients with AML, treatment at academic cancer programs was associated with a better survival, but only for the APL subgroup. Because APL comprises a fifth of all AMLs in the AYA and is a highly curable cancer, health care delivery research in APL should become a priority in this age group. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background: Approximately 1,000 acute promyelocytic leukemia (APL) patients are diagnosed in the US annually. APL has the highest cure and early mortality rates of all acute leukemias. The availability of all trans-retinoic acid (ATRA) in 1995 and arsenic trioxide in 2000 has further improved the overall survival (OS). However, whether there is uniform improvement in OS across demographic subgroups and if sooner time-to-treatment (TTT) reduces early mortality are unknown. We used the National Cancer Data Base (NCDB), a nationwide oncology registry covering 70% of the US cancer population to answer these questions. Methods: We identified patients with APL diagnosed from 1998-2011 using ICD-O-3 code 9866. Survival functions were estimated using the Kaplan-Meier method and 30-day mortality was estimated as 1-survival at 30 days. We compared OS according to demographic subgroups (gender, age [18-40, 41-64, and >65 years], race [White, Black, Native American, Asian/Pacific Islander, and other], and ethnicity) across years of diagnosis (Period [P] 1: 1998-2001, P2: 2002-2006, and P3: 2007-2011). For 30-day mortality, we compared the rates according to demographic subgroups and time periods and determined the effect of TTT (days from APL diagnosis to ATRA and/or chemotherapy). For this analysis we included only patients treated within 30 days of diagnosis and those diagnosed from 2003 to 2011. TTT was grouped as 0, 1, 2, or >3 days. We used mixed-effects logistic regression model to obtain odds ratio comparing treatment delays. Our model accounted for multiple subjects per facility with a random intercept and was adjusted for gender, Charlson-Deyo score, and year of diagnosis. Results: Characteristics: There were 8,084 APL patients in our study. The median age at diagnosis was 51 (24% were older than 65) years and 50% were females. White race (85%) was the most common, followed by black (11%) and Asian (3%). Twelve percent were Hispanic in origin. Slightly more patients (54.8%) were treated in academic centers. Thirty seven percent had either Medicaid or Medicare insurance. OS: Race had no impact on OS, although Asians had a trend towards improved OS (P=0.06). Both females and young age affected OS favorably (P <0.0001). In general, OS improved over the three time periods (P=0.002). Across Periods 1-3, we observed significant improvement in OS among the males (P=0.03), 18-40 (P=0.035) and 41-64 (P=0.005) age groups, Whites (P=0.012), and non-Spanish/Hispanics (P=0.002), but not among their counterparts. 30-day mortality rate: Age above 65 years was associated with highest 30-day mortality (33%). Similarly male gender had statistically significant higher 30-day mortality (shown in the Figure). There was no statistically significant difference among Periods 1-3. As expected, untreated patients had an increased risk of death versus treated (HR=1.9, confidence interval 1.7-2.1). TTT: A third (33.5%) of the patients was treated within two days of APL diagnosis. TTT was not independently associated with lower 30-day mortality rate (shown in the Table). Presence of disseminated intravascular coagulopathy (DIC) data was not available to analyze. Conclusions: From 1998-2011, the OS of APL continued to improve but not uniformly across demographic subgroups. In contrast, the 30-day mortality did not improve in the same time period. Both Age above 65 and male gender predicted worse 30-day mortality and OS. Our study did not find a favorable association between shorter TTT and lower 30-day mortality rate. Our study was not able to study these findings among different risk groups. Disclosures Al-Kali: Celgene: Research Funding. Tibes:TetraLogic Pharmaceuticals: Research Funding.

Abstract Background: The incidence for acute myelogenous leukemia (AML) is on the rise in the United States (US). Roughly 20,000 new AML patients are expected to occur in 2016 in the US (data from Surveillance Epidemiology and End Results Program). It is mainly a disease of older individuals with median age of 67 years. Unfortunately, most patients are not cured. Recent data suggest that early referral for hematopoietic stem cell transplant (HSCT) leads to more favorable outcomes, particularly those with non-good risk cytogenetics compared to alternate therapies. The objective of our study was to assess the use of upfront HSCT among AML patients with a focus on patients with non-good risk cytogenetics and determine disparity in its access based on sociodemographic and regional considerations. Methods: We analyzed data obtained from National Cancer Data Base (NCDB) Participant User Files for patients diagnosed with AML between 2004 and 2013 using the International Classification of Diseases for Oncology version 3 (ICD-O-3) codes 9840-9861, 9865-9874, 9891-9931. The data is collected prospectively by joint program of Commission on Cancer (CoC) and American Cancer Society. It covers nationwide oncology outcome from more than 1,500 CoC-accredited hospitals. Over 70% of all newly diagnosed cancer cases in the US are captured by NCDB. Since unique ICD-O-3 codes exist for the good-risk but not for intermediate- or poor-risk AML, we categorized the AML subtypes as good risk or non-good risk for analytic purposes. We considered patients with t(15;17), inv(16) and t(8;21) with corresponding ICD-O codes of 9871, 9896, and 9866, as good-risk patients. All others were considered non-good risk. Proportion of HSCT usage was estimated in various subgroups with 95% confidence intervals calculated using robust estimates of standard error. Results: We identified 80,087 patients who were diagnosed with AML between 2004 and 2013. Majority of these patients were Whites (85.9%), males (53.8%) and between the ages of 40 and 79 years (71.5%). The overall use of upfront HSCT increased consistently over time. This occurred predominantly among the non-good risk AML from a rate of 6.5% in 2004 to 12.5% in 2013 (Figure). Non-good risk patients who were Black, had Medicare insurance, with lower annual household income, and treated at facilities located in the East, South and Central parts of US ( AL, KY, MS, TN) had less access to HSCT (Table). Conclusion: The use of upfront HSCT in AML has almost doubled in the past decade, predominantly among those with non-good risk cytogenetics. Nevertheless, we found substantial disparity among sociodemographic and geographic subgroups. Future studies should try to understand and address how to bridge this gap. Disclosures No relevant conflicts of interest to declare.

9044 Background: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. In this study, we aim to determine the association between the number of patients with stage IV NSCLC treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods: Using the National Cancer Database, we identified patients diagnosed with stage IV NSCLC between 2004 and 2013. We classified the facilities by quartiles (Q; mean patients with NSCLC treated per year): Q1: < 13.8; Q2: 13.8 to 23.6, Q3: 23.6 to 30.3, and Q4: > 30.3. We used sandwich variance estimators to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race), socioeconomic (insurance type), receipt of chemotherapy, and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results: There were 281,654 patients with stage IV NSCLC treated at 1,275 facilities. The median age at diagnosis was 66 years, and 55.7% were men. The median annual facility volume was 23.6 patients per year (range, 1.0 to 301.4). The distribution of patients according to facility volume was: Q1: 6.6%, Q2: 14.9%, Q3: 25.4%, and Q4: 53.1%. The unadjusted median overall survival by facility volume was: Q1: 4.4 months, Q2: 4.5 months, Q3: 4.7 months, and Q4: 5.3 months ( P< .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95% CI, 1.03 to 1.07]; Q2 HR, 1.06 [95% CI, 1.03 to 1.09]; Q1 HR, 1.09 [95% CI, 1.06 to 1.13]). Conclusions: Patients who were treated for stage IV NSCLC at lower-volume facilities had a significantly higher risk of all-cause mortality compared with those who were treated at lower-volume facilities. [Table: see text]

8050 Background: There is a lack of contemporary studies analyzing the optimum radiation dose and prognostic factors for outcomes of extramedullary plasmacytomas. In this study, we aim to answer these questions by utilizing the National Cancer Data Base (NCDB). Methods: This is a retrospective study of patients with histologically confirmed diagnosis of plasmacytoma from 2000-2011 using NCDB. Patients who had bone marrow involvement were excluded from the analysis. Hazard ratios were calculated using the Cox-proportional hazard method. In addition, we utilized survival trees as a novel tool for assessing prognostic effect of factors among four age quartiles (Q): Q1: 18-52, Q2:52-62, Q3:62-72, and Q4: ≥72 years. Results: A total of 5,056 patients were included in the study (median age 62 years; range, 52-72 years). Of these, 63% were males. Radiation therapy was received by 3,905 patients, with a median radiation dose of 45 Gy. A radiation dose of ≥40 Gy was associated with improved overall survival (OS) as compared to <40 Gy. Factors associated with worse OS included older age (≥65 years) and bone disease (Table). In survival tree analysis, radiation dose ≥44.5 Gy was associated with better OS in Q1 as compared to lower dose. For Q2 and Q3, disease location played a major role, with improved survival seen in upper aero-digestive and lymph node disease as compared to bone and soft tissue. In Q3, among the bone and soft tissue disease, radiation dose ≥ 43.5 Gy was associated with the better survival as compared to ≤43.5 Gy. In Q4, soft tissue and upper aerodigestive plasmacytomas had better outcomes as compared to bone and lymph node disease. Among the latter group, a radiation dose ≥30.3 Gy was associated with improved OS as compared to lower dose. Conclusions: This is the largest study of extramedullary plasmacytomas in the United States. This study shows that dose of radiation has a significant impact on outcomes, in addition to disease location and age. [Table: see text]

1573 Background: There are no epidemiologic studies of SWM due to lack ofICD codes specific for smoldering status. Methods: The NCDB represents ~70% of cancer cases in the US. It records the time to initial treatment or reasons for not receiving treatment. Using the 2004-2012 database, we estimated the overall proportion of new adult WM cases that are smoldering and analyzed outcomes according to socio-geo-demographic subgroups. Patients who were recommended treatment (irrespective of administration status) or died within 120 days of diagnosis were considered to have active WM while those who did not require treatment and had follow-up ≥120 days after diagnosis were considered to have SWM. Results: 2322 (28%) of 8302 patients diagnosed with WM were SWM. Median age at diagnosis was 71 (range 28-90) years. Median age did not change significantly during 2004-2012 (P = 0.83) but the proportion of smoldering disease decreased with time (P = 0.02). The proportions of SWM according to socio-geo-demographic subgroups are shown in the Table. Conditional survival (given survival to 4 months) at 5-years was 66% vs. 70% and at 10-years was 38% vs. 46% for active WM vs. SWM, respectively. The OS for SWM was significantly better among females and those who were younger, privately insured, with less co-morbidities and residing closer to a health facility. However, the OS did not differ by racial groups or era of diagnosis 2004-2008 vs 2009-2012. On multivariate analysis, sex, age group and co-morbidity index were significant factors affecting OS while race, insurance, distance from health facility and era of diagnosis were not. Conclusions: Approximately 28% of WM cases in the US are smoldering at diagnosis. The prevalence of SWM varied among socio-geo-demographic subgroups. Sex, age and co-morbidities significantly affect survival of SWM. [Table: see text]