ALBERT

Description: Background: PET-assisted initial staging (PET-staging) may be useful for the accurate identification of stage I and limited stage II FL patients (pts) as candidates for potentially curative radiotherapy, for guidance of biopsy, and in determining the field of radiation. However, most guidelines recommend its judicious use in FL because its impact on treatment decisions and outcomes remains unclear. We sought to identify the factors associated with the use of PET-staging in FL and its impact on survival. Methods: We used the linked Surveillance, Epidemiology, and End Results-Medicare database to identify FL patients (pts) ≥ 65 years diagnosed between 2001 and 2009. We defined PET-staging as any whole body PET scan received 3 months prior through 6 months after diagnosis, and before the receipt of any treatment. We used multivariable logistic regression models to evaluate the relationships between pt and treatment setting characteristics, and the use of PET-staging. We examined the effects of PET-staging on overall and lymphoma-related survival (OS and LRS) using standard and propensity score (PS) matched Cox proportional hazards (CPH) regression models adjusted for pt and treatment setting characteristics. We evaluated the effect of unmeasured confounders on survival advantage from PET-staging by performing an instrumental variable (IV) CPH analysis using regional patterns of PET-staging as an instrument associated with PET use but not associated with survival (Wright, J.D. et al. Cancer 2014; Hadley, J. et al. JNCI 2010). Results: Of the 4,409 eligible pts, 58% were female, 93% were white, 80% lived in metropolitan areas, 23% lived in areas where ≥ 25% of the population had not completed high school, 46% had stage III/IV FL, 18% had grade 3 FL, 6% had B-symptoms, 16% had extra-nodal involvement, 13% had ≥ 2 comorbidities, 13% had poor performance status, and 56% most frequently visited hospitals affiliated with a research network. The increasing use of PET-staging for FL by year is displayed in the figure. Pts were more likely to undergo PET-staging if they lived in metropolitan areas (ref. less urban/rural pts; odds ratio [OR] 1.30; 95% CI 1.04-1.63); in areas with higher education levels (ref. lower levels; OR 1.25; 95% CI 1.01-1.54); had grade 3 FL (ref. grade 1 or 2 FL; OR 1.56; 95% CI 1.29-1.90); and if they most frequently visited a hospital affiliated with a research network (ref. no affiliation; OR 1.29; 95% CI 1.11-1.49). PET-staging was less commonly associated with age ≥ 81 years (ref. age 66-70; OR 0.55; 95% CI 0.45-0.67), residence in the Midwest region (ref. Southern region; OR 0.49; 95% CI 0.38-0.63), African American race (ref. White race; OR 0.59; 95% CI 0.39-0.89), presence of B-symptoms (OR 0.70; 95% CI 0.53-0.91), and poor performance status (OR 0.63; 95% CI 0.51-0.77). Results from the CPH regressions are shown in the table. Even after controlling for pt demographics, comorbidities, performance status, disease characteristics, treatment, year of diagnosis, and characteristics of the most frequently visited hospital, PET-staging was associated with improved OS (hazard ratio [HR] 0.77; 95% CI 0.69-0.86) and LRS (HR 0.69; 95% CI 0.57-0.83). This survival advantage persisted after either PS or IV-based adjustments. Conclusion: PET-staging has been widely used in newly diagnosed FL patients as a baseline investigation before initiation of therapy without well-established evidence of benefits and increased substantially over the study period. Regional, institutional, and socio-demographic variability exists in the use of PET-staging. PET-staging has been more commonly used in higher grade patients, and less commonly used in the oldest patients, patients with poorer performance status, and in patients with B-symptoms, indicating that clinicians may selectively utilize PET-staging for certain subgroups. However, the apparent survival advantage associated with PET-staging may not be entirely due to selection based on observed or unobserved confounders. Further investigation is warranted into the mechanisms of the apparent survival advantage associated with the use of PET-staging in FL. Figure 1 Figure 1. Table. OS LRS Estimation method HR (95% CI) HR (95% CI) CPH 0.77 (0.69 - 0.86) 0.69 (0.57 - 0.83) Propensity score matched CPH (caliper width 0.005) 0.82 (0.70 - 0.95) 0.63 (0.50 - 0.79) Propensity score matched CPH (caliper width 0.01) 0.81 (0.69 - 0.94) 0.74 (0.59 - 0.92) IV 0.44 (0.26 - 0.78) 0.20 ( 0.09 - 0.46) Disclosures No relevant conflicts of interest to declare.

Description: Background The role of anthracyclines in the management of Grade 3 (G3) FL is unclear. Furthermore, the patterns of care and outcomes of first-line treatment strategies for G3 FL in older adults are not clearly established. We describe the patterns of use, determinants of treatment, and survival outcomes of first-line management strategies for G3 FL with emphasis on four common first-line regimens: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), rituximab (R) plus CHOP (R-CHOP), cyclophosphamide, vincristine, and prednisone (CVP), and R plus CVP (R-CVP). Methods We used the linked Surveillance, Epidemiology, and End Results -Medicare database to identify 1,308 G3 FL patients (pts) diagnosed between 1995 and 2009 and focused on pts diagnosed between 1999 and 2009 when claims with R appear. We ascertained first-line management strategies from Medicare claims made within 90 days of diagnosis. We used multiple variable logistic regression models to evaluate the relationship between pt characteristics and the use of first-line R-CHOP. We used Kaplan-Meier estimators stratified by FL stage to evaluate survival functions for first-line management strategies and performed multiple variable Cox proportional hazards regressions adjusted for pt demographics, comorbidity index, disease characteristics, and year of diagnosis to compare the impact of first-line management strategies on survival. Results Of the 1,308 G3 FL pts, 59% were female, 91% were Caucasian, 3% were African American, 44% had stage III/IV disease, 6% had B-symptoms, and 36% had extranodal involvement. The median age at diagnosis was 75 (interquartile range 70-80). Common first-line management strategies were: observation (obs), 29%; R-CHOP, 26%; CHOP, 9%; radiotherapy alone (XRT), 8%; R alone, 8%; R-CVP, 7%; and CVP, 5%. The use of R-CVP and R-CHOP increased over time (Figure 1). In the cohort of pts diagnosed between 1999 and 2009 the use of R-CHOP was less commonly associated with age 〉80 years (ref. age 66-70 years; OR 0.19; 95% CI 0.11-0.31), comorbidity index ≥ 2 (ref. index =0; OR 0.54; 95% CI 0.31-0.92), and more commonly associated with stage III/IV FL (OR 1.46; 95% CI 1.05-2.02), and year of diagnosis (ref. years 1999-2001; OR for 2002 3.68; 95% CI 1.77-7.64; steady increase thereafter). The table displays median survival and hazard ratios (HRs) for first-line management strategies. The most favorable outcomes were associated with first-line R-chemotherapy (R-Chemo). Among first-line R-chemo regimens, R-CHOP was associated with the most favorable outcomes (Figure 2). Conclusion R-CHOP is the most commonly used first-line regimen in the United States for older adult pts with FL G3. Even after controlling for disease characteristics and comorbidity, R-CHOP was associated with the most favorable survival outcome. Disclosures: No relevant conflicts of interest to declare.

Description: Context: Despite having the highest incidence of diffuse large B-cell lymphoma (DLBCL), individuals older than 80 years are rarely included in DLBCL clinical trials or epidemiological studies. We sought to better characterize DLBCL presentation, treatment, and survival patterns for this age group. Objective: We investigated demographic and clinical characteristics at diagnosis, treatment selection factors, and the impact of treatment regimen on overall survival (OS) and lymphoma-related survival (LRS) for DLBCL patients 〉80 years. We hypothesized that patients 〉80 years were more likely to undergo observation and less likely to receive standard-of-care rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We also hypothesized that patients 〉80 years who received R-CHOP would have superior OS and LRS, even after controlling for demographic and clinical factors. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine DLBCL patients diagnosed from 1999-2009 and followed through 2010. Our population-based cohort contained 5,924 DLBCL patients aged ≥66 years; 1,422 were 〉80 years. Only patients treated within 6 months of diagnosis with R-CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); rituximab plus CVP (R-CVP); or patients undergoing observation were included in order to examine factors associated with the use of anthracyclines. Chi-squared tests compared characteristics and initial treatments of DLBCL patients 〉80 years and 66-80 years. Multivariable logistic regression models examined treatment selection factors in patients 〉80 years. Standard and propensity score-adjusted multivariable Cox proportional hazards models adjusted for patient demographics, clinical characteristics, comorbidities, performance status, and year of diagnosis examined relationships between treatment regimen, treatment duration, and survival. Results: Among patients 〉80 years, 58% were female, 91% were Caucasian, 36% had stage III/IV disease, 39% had extranodal involvement, 7% had B-symptoms, 28% had poor performance status, and 14% had ≥2 comorbidities. Patients 〉80 years were less likely to receive R-CHOP (43% vs. 61%) and more likely to be observed (30% vs. 15%) or receive R-CVP (12% vs. 4%); all p80 years. The initial receipt of R-CHOP was more commonly associated with female sex (odds ratio (OR) 1.31, 95% confidence interval 1.01-1.71), being married (OR 1.69, 1.07-2.66) and a diagnosis after 2001 (OR for 2002 11.71, 6.32-21.70; persistently increased ORs thereafter). The initial receipt of R-CHOP was less commonly associated with extranodal disease (OR 0.71, 0.55-0.91), poor performance status (OR 0.57, 0.44-0.75), and residence in a census tract with 〉12% of residents living in poverty (OR 0.69, 0.50-0.96). Initial observation was more commonly associated with the same factors that were less commonly associated with R-CHOP use and was less commonly associated with stage III/IV disease (OR 0.66, 0.50-0.87). Kaplan-Meier survival curves revealed that in patients 〉80 years, R-CHOP was associated with the best OS and LRS. Multivariable Cox proportional hazards models revealed that R-CHOP for 〉4 cycles was associated with the best OS in patients 〉80 years of all stages (hazard ratio (HR) 0.48, 0.37-0.62). Among stage III/IV patients, R-CHOP for 〉4 cycles (HR 0.48, 0.31-0.72) and R-CVP for 〉4 cycles (HR 0.40, 0.21-0.76) demonstrated significantly longer OS. Conclusions:Although DLBCL patients 〉80 years were less likely to receive R-CHOP, this regimen conferred the best survival. The failure of very elderly DLBCL patients to receive R-CHOP may occur due to clinical factors such as poor performance status, but commonly varies across demographic factors such as area-level poverty, which may reflect bias in the under-utilization of R-CHOP in very elderly patients that is not based on clinical parameters. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in very elderly patients, and algorithms should be developed to help guide therapy in this population. Disclosures No relevant conflicts of interest to declare.

Description: Background Therapeutic decision making for patients with low-grade (grade 1 and 2) FL involves deciding whether to treat, when to treat, and which among the numerous treatment modalities to administer. The lack of trials comparing outcomes of these treatment modalities makes it a complex process. This study seeks to examine the evolving treatment paradigm and evaluate the outcomes of first-line management strategies for low-grade FL in adults aged ≥ 66. Methods We used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 4,233 low grade FL patients (pts) aged 66 years and older diagnosed between 1995 and 2009. We ascertained first-line management strategies from Medicare claims made within 90 days of diagnosis. We used Kaplan-Meier estimators stratified by stage to evaluate survival functions for first-line management strategies. We used multivariate Cox proportional hazards models—stratified by stage and adjusted for patient demographics, comorbidity index, and year of diagnosis—to compare the impact of first-line management strategies on overall survival (OS). Results Of the 4,233 pts, 57% were female, 3% were African American, 93% were White, 51% resided in big metropolitan areas, 70% were diagnosed after 2000, 44% had stage III/IV disease, and 38% had extranodal involvement. The median age at diagnosis was 74 years (interquartile range 70-80). Common first-line management strategies were: observation (obs), 47%; chemotherapy (chemo) plus rituximab (R), 20%; chemo alone, 12%; R alone, 9%; and radiotherapy (XRT) alone, 9%. Among pts receiving chemo plus R (R-chemo), the most commonly used regimens were: R-CHOP (R, cyclophosphamide, doxorubicin, vincristine, and prednisone; 36%), R-CVP (R, cyclophosphamide, vincristine, and prednisone; 47%), R-Fludarabine based (9%), and R-other (7%). The table displays median survival and hazard ratios (HRs) for first-line management strategies. Among stage I/II cases, most favorable outcomes were observed in cases receiving XRT alone, whereas among stage III/IV cases most favorable outcomes were observed in the group that received R-chemo. In the subset of stage III/IV pts that received R-chemo, R-CHOP was associated with the most favorable outcomes. HRs decreased steadily with increasing years of diagnosis. Conclusion First-line R-chemo is commonly used in older adults with low-grade FL in the United States and is associated with most favorable survival outcomes. XRT is associated with very favorable outcomes in stage I/II pts. Outcomes have improved steadily in the past 10 years. CVP–cyclophosphamide, vincristine, prednisone; CHOP- cyclophosphamide, doxorubicin, vincristine, prednisone Disclosures: No relevant conflicts of interest to declare.

Description: Background The treatment paradigm for FL has evolved greatly since the advent of rituximab (R) in 1997. However, a standard of care for first-line management of FL is yet to emerge (Friedberg, JCO 2009). This study seeks to describe the determinants of and temporal patterns in the use of first-line management strategies. Methods We used the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 7,931 FL patients (pts) aged ≥ 66 years diagnosed between 1995 and 2009. We ascertained first-line management strategies from Medicare claims made within 90 days of diagnosis. Pts with no FL related treatment claims were classified as observation (obs). We used multiple variable logistic regression models to evaluate the relationship between pt characteristics and the use of two common first-line management strategies—obs and immunochemotherapy with R, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Results Of the 7,931 pts, 57% were female, 3% were African American, 93% were White, 51% resided in big metropolitan areas, 52% were diagnosed after the year 2000, 44% had stage III/IV disease, 17% had grade 3 disease, and 39% had extranodal involvement. The median age at diagnosis was 75 years (interquartile range 70-80). Common first-line management strategies were: obs, 41%; chemotherapy (chemo) plus R, 26%; chemo alone, 11%; R alone, 10%; and radiotherapy (rad) alone, 9%. Among pts receiving chemo plus R the most commonly used regimens were: R-CHOP (50%), R-CVP (R, cyclophosphamide, vincristine, and prednisone, 35%), R-Fludarabine based (7%), R-Other (7%). Trends in the use of first-line management strategies are displayed in the figure. Obs was more commonly associated with age ≥81 years (ref. age 66-70 years; OR 1.41; 95% CI 1.22-1.62) and African American race (ref. White race; OR 1.77; 95% CI 1.33-2.37), and less commonly associated with stage III/IV FL (ref. stage I/II FL; OR 0.84; 95% CI 0.76-0.93); grade 3 FL (ref. grade 1/2 FL; OR 0.37; 95% CI 0.32-0.43), presence of B symptoms (ref. absent; OR 0.54; 95% CI 0.41-0.71), and year of diagnosis (ref. year 1995; OR for 2002 0.57; 95% CI 0.35-0.94; steady decrease thereafter). In the cohort of patients diagnosed between 1999 and 2000, first-line R-CHOP was more commonly associated with stage III/IV FL (ref. stage I/II; OR 1.53; 95% CI 1.27-1.83), grade 3 FL (ref. grade 1/2; OR 7.30; 95% CI 5.86-9.09), presence of B symptoms (ref. absent; OR 1.46; 95% CI 1.04-2.04), and year of diagnosis (ref. years 1999-2001; OR for 2002 3.74; 95% CI 2.38-5.87; steady increase thereafter), and less commonly associated with age 76-80 years (ref. age 66-70 years; OR 0.65; 95% CI 0.51-0.82), age ≥81 years (OR 0.20; 95% CI 0.15-0.27), African American race (ref. White race; OR 0.46; 95% CI 0.25-0.85) and comorbidity index ≥2 (ref. index 0; OR 0.55; 95% CI 0.41-0.76). Conclusions As anticipated, the use of chemo plus R and single-agent R increased steadily after the introduction of R in1997, while that of obs and chemo alone decreased over the same period. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 897 Background: Since the 1970s, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL). Beginning in 2002, published randomized, controlled clinical trials changed the standard of care by demonstrating that when rituximab is added to CHOP complete response rates and overall survival improved. However, it remains unclear how these results influenced the use of combination chemo-immunotherapy in clinical practice in the United States. We examined a national cohort of patients with DLBCL to assess clinical and demographic features of patients who receive chemo-immunotherapy and those who do not. Methods: Patients diagnosed with DLBCL (ICD-O codes 9679 and 9680) between January 1, 2001 and December 31, 2004, were selected from the National Cancer DataBase (NCDB), a hospital-based cancer registry jointly sponsored by the American Cancer Society and the American College of Surgeons that includes more than 1,400 Commission-on-Cancer-approved sites and captures ∼75% of all newly diagnosed cases of cancer in the United States. Data on patient demographics, stage at diagnosis, health insurance, area-level education status, facility characteristics, and type of treatment were collected. Multivariable log binomial models were performed to examine the association between race, insurance and the use chemo-immunotherapy compared with chemotherapy alone, adjusting for other covariates. Results: The study population included 38,002 patients with DLBCL. Overall, 27% received combination chemo-immunotherapy and 50% received chemotherapy alone. At diagnosis there were racial differences in baseline characteristics. Black pts were younger (median age 53 vs. 70 years), more likely to present with stage III/IV disease (44.5% vs. 40.9%), more likely to be uninsured (9.5% vs. 2.5%) or Medicaid insured (17.3% vs. 3.4%) and more likely to reside in a zip code where ≥29% of the population had no high school diploma (38.1% vs. 11.6%) when compared with White pts (all p

Description: Background The oldest old constitute a large proportion of the total patient (pt) population with FL. Therapeutic decision making in this group is limited by comorbidities, adverse disease and pts' characteristics, potential treatment toxicity, and limited life expectancy. Further, randomized clinical trials have rarely included this pt population. Whether current practice patterns for these pts affect their outcome remains unanswered. Therefore, we aimed to determine treatment selections, patterns of care, prognostic factors, and survival outcomes of first-line management strategies in a large United States (US) based cohort of the oldest old (pts aged 〉 80 years at diagnosis). Methods We used the linked Surveillance, Epidemiology, and End Results -Medicare database to identify 1,878 FL cases in pts 〉 80 years diagnosed between 1995 and 2009 and focused on the period when rituximab (R) claims occurred. We ascertained first-line management strategies from Medicare claims made within 90 days of diagnosis. We used multiple variable logistic regression models to evaluate the relationship between pt characteristics and the use of two common first-line management strategies—observation (obs) and treatment with R, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We used Kaplan-Meier estimators stratified by stage to evaluate survival functions for first-line management strategies and Cox proportional hazards models adjusted for pt demographics, comorbidity index, disease characteristics, and year of diagnosis to compare the impact of first-line management strategies on survival. Results Of the 1,878 oldest adult pts, 63% were female, 95% were white, 2% were African American, 52% had stage III/IV FL, 17% had grade 3 FL, 5 % had B-symptoms, 35% had extranodal involvement, and 14% had a comorbidity index ≥ 2. Common first-line management strategies were: obs, 46%; R, 17%; chemotherapy (chemo) plus R, 11%; chemo, 11%; and radiotherapy (XRT), 11%. In the cohort of pts diagnosed between 1995 and 2009, obs was more commonly associated with urban pts (ref. less urban/rural pts; OR 1.91; 95% CI 1.15-3.18), and comorbidity index of ≥ 1 (ref. index=0; OR 1.28; 95% CI 1.00-1.64). Obs was less commonly associated with stage III/IV FL (ref. stage I/II; OR 0.67; 95% CI 0.54-0.84), grade 3 FL (ref. grade 1/2; OR 0.35; 95% CI 0.26-0.47), and year of diagnosis (ref. year 1995; OR for 1997 0.23; 95% CI 0.07-0.75; steady decrease thereafter). In the cohort of pts diagnosed between 1999 and 2009, the use of R-CHOP was associated with grade3 FL (ref. grade 1/2; OR 8.20; 95% CI 3.83-17.55) and presence of B-symptoms (ref. absent; OR 4.18; 95% CI 1.81-9.62). R-CHOP use did not vary with year of diagnosis. The table displays median survival and hazard ratios (HRs) for first-line management strategies. Most favorable outcomes were associated with first-line R-Chemo. Among stage III/IV cases, the least favorable outcomes were observed in the group that received chemo without R. The HRs did not vary with more recent years of diagnosis. Conclusion In this largest retrospective analysis of the oldest old US-based FL pts, we demonstrate that first-line R-Chemo is associated with improved survival. Confirmatory prospective studies specifically designed for this pt population are warranted. CVP-cyclophosphamide, vincristine, prednisone; CHOP- cyclophosphamide, doxorubicin, vincristine, prednisone; R-CVP- rituximab, cyclophosphamide, vincristine, prednisone. Disclosures: No relevant conflicts of interest to declare.

Description: Women diagnosed with breast cancer at a relatively early age (≤45 years) or with bilateral disease at any age are at elevated risk for additional breast cancer, as are their female first-degree relatives (FDRs). We report on a randomized trial to increase adherence to mammography screening guidelines among survivors and FDRs. From the Georgia Cancer Registry, breast cancer survivors diagnosed during 2000–2009 at six Georgia cancer centers underwent phone interviews about their breast cancer screening behaviors and their FDRs. Nonadherent survivors and FDRs meeting all inclusion criteria were randomized to high-intensity (evidence-based brochure, phone counseling, mailed reminders, and communications with primary care providers) or low-intensity interventions (brochure only). Three and 12-month follow-up questionnaires were completed. Data analyses used standard statistical approaches. Among 1055 survivors and 287 FDRs who were located, contacted, and agreed to participate, 59.5% and 62.7%, respectively, reported breast cancer screening in the past 12 months and were thus ineligible. For survivors enrolled at baseline (N = 95), the proportion reporting adherence to guideline screening by 12 months post-enrollment was similar in the high and low-intensity arms (66.7% vs. 79.2%, p = 0.31). Among FDRs enrolled at baseline (N = 83), screening was significantly higher in the high-intensity arm at 12 months (60.9% vs. 32.4%, p = 0.03). Overall, about 72% of study-eligible survivors (all of whom were screening nonadherent at baseline) reported screening within 12 months of study enrollment. For enrolled FDRs receiving the high-intensity intervention, over 60% reported guideline screening by 12 months. A major conclusion is that using high-quality central cancer registries to identify high-risk breast cancer survivors and then working closely with these survivors to identify their FDRs represents a feasible and effective strategy to promote guideline cancer screening.