ALBERT

Description: Background: There is a well-known risk of developing multiple myeloma in plasmacytoma, especially in solitary bone tumors. However, the risk of other cancers is not clear. The aim of this study was to estimate the risk of second cancers in patients with plasmacytoma, as compared to general population, and patients with multiple myeloma. Methods: Surveillance, Epidemiology and End results (SEER) 18 dataset was queried to identify patients (age Results : With a follow-up of 13,392 person-years, 331-second cancers were diagnosed in 2046 plasmacytoma survivors (1155 SPB and 891 extraosseous plasmacytoma). The risk of subsequent solid tumors was not higher compared to age and sex matched background population with a SIR of 1.02 (95 % CI .88-1.17 AER 2.23/10,000). The risk was higher for developing multiple myeloma (SIR 30.8 25-38 AER 67/10,000), leukemia (SIR 3.4, 95% CI; 2-5.2 AER 10/10,000) and non-Hodgkin's lymphoma (NHL) (SIR 3.2, 95 % CI 2.1-4.7 AER 13.4/10,000) in "two-month" survivors of plasmacytoma as compared to general population. The risk of developing solid tumors was similar in SPB (SIR 1.07, 95% CI; .87-1.30 AER 9/10,000) and extraosseous (SIR .98, 95% CI; .77-1.19 AER -5/10,000) plasmacytoma. However the risk of transformation to multiple myeloma was 3.7 fold (hazard ratio 3.7, 95% CI; 2.2-6.3) (p

Description: Background: Therapeutic advancements have led to significant improvement in outcomes for MM patients. Revised diagnostic criteria from International Myeloma Working Group focus on initiating treatment before the onset of end-organ damage. Thus, timeliness of initial therapy can significantly improve patient morbidity and outcomes. Such an analysis has not been reported for MM. Methods: We analyzed patients diagnosed with MM between 2004-2015 from the National Cancer Database (NCDB). Patients who received systemic treatment any time within the first year of diagnosis were included; those treated later than one year were considered possibly initially diagnosed with smoldering myeloma and hence, excluded. Time to initial treatment was divided into centiles with the 4 centiles analyzed being 0-7 days, 8-18 days, 19-37 days and 〉37 days. We performed univariate and multivariate analyses to compare sociodemographic and clinical factors influencing patient distribution across these timeliness categories and trends over time. Results: A total of 53,665 patients were included with 15,282 in 0-7 days, 12,462 in 8-18 days, 12,723 in 19-37 days and 13,198 in the 〉37 days treatment categories. Distribution across these centiles over time is shown in Figure. Univariate analyses showed a significant difference in distribution across the timeliness categories by year of diagnosis, patient age, gender, race/ethnicity, education level, insurance type, comorbidity score, treatment facility type, geographical location and distance to treating facility (all p37 days to treatment) for women (p

Description: Background: Median age at diagnosis for MM is 69 years with approximately 33% of the newly diagnosed MM (NDMM) patients aged ≥80 years (elderly). Yet, outcomes data and clinical trial participation in elderly MM patients are limited due to frailty and frequent comorbidities. Moreover, elderly patients are not candidates for stem cell transplant (SCT) and age is an independent poor prognostic marker, leading to disparate outcomes. The present study evaluated trends in outcomes and predictors of survival among elderly NDMM patients in the United States (U.S.). Methods: Using Surveillance Epidemiology and End Results (SEER) database, we extracted data on age, gender, geographical regions, year of diagnosis, and vital status for elderly patients (age ≥ 80 years) with MM from 1975 to 2016. Relative survival (RS) was estimated as the ratio of observed survival to the survival expected in the general population in the absence of malignancy. This adjusted for the competing causes of mortality prevalent in elderly patients. Mortality rates were age-adjusted. To estimate trends in mortality, we estimated annual percentage change (APC) and average annual percentage change (AAPC) by fitting the data in the join point regression model using the NCI's Join point Regression Program, Version 4.5.0.1. A multivariate analysis was conducted to analyze the predictors of overall and myeloma-specific mortality among elderly patients fitting into Cox proportion hazard regression model. Results: A total of 17,265 elderly MM patients were eligible for the study. Majority were females (n=9,487, 55%), were non-Hispanic whites (NHW) (n=12,895, 74.7%) and were diagnosed in the Western region of the U.S. (n=8,541, 49.5%). The median age was 84 years (IQR 81-87). The median RS for the whole period (1975-2016) was 19.8 months with 1- and 5- year RS of 60.1% (95%CI: 58.8-61.3) and 20.9% (95%CI: 19.5-22.3) respectively. The median RS increased from 8.45 months in 1975 to 29.86 months in 2013. One and 5- year RS also increased from 42.7% (95%CI: 32.4-52.5) and 12.9% (95%CI: 5.8-22.7) in 1975 to a 1- and 5-year RS of 72.3% (95%CI: 65.4-78.1) and 31.1% (95%CI: 23.4-39.1) in 2013, respectively (Fig.1). However, the age standardized mortality rate for the whole period showed an increasing trend with an AAPC of 2.3 (0.5-4, P

Description: Background: Racial disparities in outcomes of cancer patients have been reported. Access to comprehensive cancer centers is associated with improved overall survival (OS) but racial/ethnic minorities may have a disparate access to such care. While the impact of treatment facility volume on outcomes has been evaluated, outcomes of centers with minority-predominant patient population have not been studied. We compared demographic profiles, facility level data and OS of patients treated at minority-predominant facilities to facilities that treated predominantly non-Hispanic Whites (NHW) with non-DLBCL. Methods: The National Cancer Database (NCDB) was used to identify all non-DLBCL patients diagnosed between 2004 and 2015. "Minority-treating facilities" were defined as facilities in the top decile by proportion for initial treatment of non-Hispanic African-Americans (NHAA), Hispanics and other races. We performed univariate and multivariate analyses to compare sociodemographic and clinical factors influencing outcomes between minority treating and non-minority treating facilities. A subgroup analysis stratified by race/ethnicity was also conducted to study the effect of treating facilities on the outcome of NHWs and minorities separately. Results: Of 1339 total facilities, 123 (9.1%) qualified as minority treating. Of 207,239 eligible patients in NCDB, 18,719 (9.03%) received treatment at the minority-treating facilities and of these, 11,190 (~60%) belonged to the minority races. Overall, 4.5% (6,988/156,664) NHWs and 30% (11,190/37,639) minorities received treatment at the minority-treating facilities. Several demographic and facility level characteristics were significantly different among the patients treated at minority-treating facilities as compared to non-minority treating facilities. Overall, significantly higher number of patients in minority-treating hospitals had lower income and education, had Medicaid coverage or lack of insurance. The OS of patients in minority treating facilities was significantly worse as compared to non-minority facilities (Figures). On multivariate analysis, patients who received treatment at minority-treating facilities were at 10% (HR=1.10, 95% CI: 1.06-1.14 p

Description: Background: Survival of patients with MM has improved significantly over recent years due to therapeutic advancements. Population-level data has shown that a substantial proportion of MM patients may die early after their diagnosis and real-world evidence regarding early mortality (≤6 months after MM diagnosis) has been conflicting. We evaluated the trends, causes and predictors of early mortality among newly diagnosed MM (NDMM) patients in the real world. Methods: We used Surveillance Epidemiology and End Results (SEER) database, to identify all adult patients (age ≥ 18 years) who were diagnosed of MM from 1975 to 2015. Data on age, gender, geographical regions, year of diagnosis, survival time, vital status at 6 months after diagnosis and cause of death (COD) were extracted. Ages were categorized as quartiles while period of diagnosis for multivariate analysis were categorized by running a joinpoint analysis separately for the all-cause and myeloma-specific mortality. To look at trends in early mortality, we estimated proportion of deaths for each year and plotted it as a scatterplot against the year of diagnosis and fitted it in the join point regression model by applying the NCI's Join point Regression Program, Version 4.5.0.1. By this method we identified the year(s) when a trend change was produced, calculated the annual percentage change (APC) in rates between trend-change points, and the average annual percentage change (AAPC) in the whole period studied. To correct for known errors with COD attribution, we applied a special COD variable which has been recently developed by the SEER program to indicate if the death was due to the primary cancer diagnosis or other causes. A multivariate analysis was conducted to analyze the predictors of all-cause and myeloma-specific mortality within 6 months by fitting into logistic regression model. Results: Of 90,975 NDMM patients, early mortality due to any cause was noted in 18,810 (20.7%). For the whole cohort, median age was 68 years, majority of the patients were males (53.1%), of non-Hispanic white (NHW) race/ethnicity (65.5%) and were diagnosed in SEER registries in the western region (53.9%). An overall survival (OS) of ≤6 months was seen for approximately 22% of NHW but 18% of non-Hispanic blacks (NHB) and Hispanics. OS of ≤6 months was seen in 10% of patients in the first quartile of age (

Description: Background: MM is associated with significant morbidity even at the time of presentation and there is ample data to support that MM treatment improves overall survival (OS) as well as quality of life (QoL) due to effective symptom control. Patient refusal to recommended cancer treatment is not common in clinical practice but has been reported in certain cancers. There is no data on characteristics of MM patients who refuse treatment despite physician recommendation and outcomes of such patients. Methods: We used the National Cancer Database (NCDB) from 2004-2015 to extract data on adult MM patients who refused any systemic therapy as part of their initial care despite physician recommendation. Information on patient age, gender, race/ethnicity, education, year of diagnosis, income, geographical location, comorbidities, systemic treatment, survival time and vital status was obtained. Average annual percent change (AAPC) and average percent change (APC) were calculated to analyze the trends, and periods with similar APC were compared for statistically significant changes by applying join point regression. Multivariate models were employed to identify factors predicting refusal to therapy and to assess its impact on OS. Results: Of 75,734 eligible patients who were recommended treatment for MM (chemotherapy and or immunotherapy), 2138 (2.8%) patients did not receive any treatment due to refusal. Significantly higher number of females, patients in older age groups (age groups 60-79 and ³ 80 years), Medicare recipients and with ≥2 comorbidities refused treatment recommendation. On multivariate analysis, advanced age groups 60-79 years (OR = 1.47; 95% CI 1.27-1.31 p

Description: Background: The treatment of NHL has witnessed a paradigm shift over time, with targeted immunotherapy, stem cell transplant (SCT) among others. Historically, XRT was used quite frequently for the management of NHL but with advent of better systemic therapy, its utilization has changed. Trends and patterns of care for XRT use have never been formally reported. Methods: We identified patients with NHL diagnosis in the National Cancer Database (NCDB) between years 2004 and 2015. Demographic, clinical, facility level, initial treatment and outcome data were collected. The utilization of XRT in diffuse large B-cell (DLBCL) and non-DLBCL NHL were analyzed separately by univariate and multivariate analyses. To analyze the trends in the rates of XRT, we applied segmented linear regression to calculate the average annual percent change (AAPC) and 95% confidence Interval (CI) with a 'p' value. AAPC and CIs were calculated using the segmented package in R studio v1.1.49. Rest of the analyses was conducted using StataCorp version 15.1. Results: A total of 133,182 DLBCL and 204,933 non-DLBCL patients were identified. Among patients with DLBCL, 27,895 (20.9%) patients received RT. The rate of XRT declined from 25% in 2004 to 18.4% in 2015 with estimated AAPC of -0.59% (95%CI: -0.70- -0.49), p= 0.03 (Figure 1). In a subgroup analysis, a similar decline in the rate of XRT was evident across all the age groups, combined stages I and II vs stages III and IV and nodal vs extra nodal DLBCL (Table 1). Among non DLBCL, 33,369 (16.3%) patients received XRT. There was a statistically significant decline in the rate of XRT from 18.03% in 2004 to 16.3% in 2014 with an AAPC of -0.26 (95%CI: -0.38- -0.14) p

Description: Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this. Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis. Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p

Description: Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p