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    • dub inhibitor br Material and methods The study population w

    2019-05-30


    Material and methods The study population was selected from the National Cancer Institute’s SEER database. The SEER database collects data from 18 geographic registries, covering approximately 28% of the U.S. population [17]. The SEER⁎Stat software (Version 8.0.4; NCI; Bethesda, MD) was used to identify 997 adult patients diagnosed with primary lymphoma of bone during a 15-year dub inhibitor from 1989 to 2003. Histology was selected by using ICD-O-3 codes 9590/3, 9591/3, 9670/3, 19671/3, 9675/3, 9680/3, and 9684/3. Primary site was selected as C40.0, C40.1, C40.2, C40.3, C40.8, C40.9, C41.2, C41.3, C41.4, and C41.9. Exclusion criteria included lesions of the skull and face, T-cell lymphoma, and cases without follow up data, yielding a final study population of 692 patients. Tumor location was dichotomized as either appendicular or axial. The scapula was considered to be part of the appendicular skeleton, while the pelvic bones were considered to be part of the axial skeleton. Marital status was categorized as single, married, or other (including separated, divorced or widowed). Rural–urban continuum code was collapsed into a binary variable: Metro county or non-metro county, using guidelines by SEER and the Economic Research Service [18,19]. SEER registry region was aggregated into regions (Northeast, South, Southwest, Midwest, and West). Race was categorized as White, Black or Asian/Other. Age was considered as a categorical variable (<30 years, 30–59 years, ≥60 years). Statistical analysis was performed in SAS version 9.3 (SAS Institute, Cary, NC). The effects of categorical variables on survival were assessed by computing Kaplan–Meier product limit curves and compared using the log-rank test. The effects of continuous variables were analyzed using Cox proportional hazards regression. The Bonferroni method was applied when performing multiple comparisons. Factors that appeared to be significantly associated with survival in the univariate analysis were considered for inclusion in the final multivariable Cox proportional hazards regression model. A result was considered statistically significant with a p-value <0.05. Efron’s method was used to adjust for tied failure times.
    Results The final analysis included 692 patients, whose demographic and clinical characteristics are presented in Table 1. The majority of patients were white (89.0%), non-Hispanic (91.3%), and lived in metropolitan counties (87.4%). The majority of patients were over the age of 60 years (55.6%), and diffuse large B-cell lymphoma was the most common histologic classification (71.2%). The western region of the United States contributed the largest proportion of patients to the study population (56.5%). The estimated overall survival of patients for all patients in this study was 49.6% at 5-years, and 30.2% at 10-years (Fig. 1). The incidence of PLB during the 15-year study period ranged from 0.1/100,000 to 0.3/100,000 (Fig. 2). The annual percent change for this time period was non-significant, suggesting a stable incidence over the study period. In univariate analysis, significant factors for overall survival included age (p<0.0001), marital status (p<0.0001), anatomic location of tumor (p<0.0001), geographic region (p=0.02), and tumor grade (p=0.01). After Bonferroni adjustment, tumor grade was no longer a significant prognostic indicator for overall survival. Furthermore, after Bonferroni adjustment for multiple comparisons, tumor grade and geographic region were not statistically significantly associated with overall survival. Univariate analysis results for categorical variables are presented in Table 2. Kaplan–Meier product limit curves are provided for age (Fig. 3), marital status (Fig. 4), and tumor location (Fig. 5). The final multivariable model demonstrated that age (p<0.0001), marital status (p=0.02), and appendicular or axial tumor location (p=0.004) remained significant independent prognostic variables for overall survival (Table 3). A survival advantage was demonstrated for younger patients. The mortality rate for PLB patients in the 30–59 age group is estimated to be 4.4 times that for those patients in the <30 age group, after adjusting for marital status and tumor location (CI: 1.7–11.2; p=0.002). Furthermore, patients aged 60 or older are estimated to have a mortality rate 12.8 times that for <30 year-old patients, after adjusting for tumor location and marital status (CI: 5.1–32.3; p<0.0001), though this finding is potentially influenced by medical comorbidities.