Yost, Kathleen J.

Abstract Background Age has long been recognized as a poor prognostic factor in diffuse large B-cell lymphoma (DLBCL) and more recently, a lower baseline quality of life (QOL) in patients with aggressive lymphomas has been associated with an inferior overall survival (OS) (Thompson et al, 2018). Older patients with DLBCL are a heterogeneous population and commonly have comorbid conditions. A concerted effort to identify prognostic factors specific to this population is needed, including QOL. Event free survival at 24 months (EFS24) is a well validated endpoint in DLBCL (Maurer et al, 2014) and is clinically relevant in older patients. We hypothesized that baseline clinical factors and QOL would be associated with EFS24 this patient group. Methods Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis into the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Patients ≥70 years of age with DLBCL were utilized in this study. All pathology was reviewed by a lymphoma hematopathologist. Clinical variables were abstracted from the medical record. QOL was assessed at enrollment using a single item Linear Analogue Self-Assessment (LASA) and the 27-item Functional Assessment of Cancer Treatment-General questionnaire (FACT-G), which includes physical, social, emotional, and functional well-being domains. QOL scores were converted to a 0-100 scale to facilitate modeling. QOL was analyzed in patients who completed 80% of the FACT-G questions. Characteristics of the study population were compared using the Wilcoxon rank sum test. Odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the associations of clinical and continuous QOL variables with failure to achieve EFS24 using logistic regression models, with a stepwise approach to identify parsimonious multivariate models. Results A total of 389 patients ≥70 years were identified with DLBCL in the MER from 2002-2015; patient characteristics are described in the Table. In the entire study population, univariate predictors of EFS24 failure included age (OR per 10 years=1.85, 95% CI: 1.26-2.71), ECOG PS ≥2 (OR=4.78, 95% CI: 2.92-7.83), elevated LDH (OR=3.59, 95% CI: 2.27-5.65), stage III-IV (OR=1.94, 1.25-3.02), bulky disease (OR=2.86, 95% CI: 1.43-5.72), international prognostic index (OR=8.71 for IPI 5 vs IPI 0, 95% CI: 3.04-24.9), and receipt of an anthracycline (OR=0.25, 95% CI: 0.12-0.51), while none of the other variables in the Table, including the QOL variables, were statistically significant. In a stepwise multivariate analysis, only ECOG PS ≥2 (OR= 3.56, 95% CI: 2.09-6.06) and elevated LDH (OR=2.86, 95% CI: 1.78-4.60) remained significant predictors of EFS24 failure. QOL data were available on 220 patients, with 120 completing QOL questionnaires prior to receipt of chemotherapy. Compared to participants who completed their FACT-G before the initiation of chemotherapy, the median FACT-G physical (85.7 v. 71.4, p=0.005) and functional (71.4 vs 57.1, p=0.008) scores were lower in participants completing FACT-G after initiation of therapy, were higher on FACT-G emotional (79.2 vs 83.3, p=0.03), and showed no differences on FACT-G social (89.3 vs 91.7, p=0.60) or FACT-G total score (78.2 vs 74.1, p=0.17). Given these differences, we restricted the QOL analysis to those with pre-treatment data. In univariate analysis, the LASA score (OR= 0.98, 95% CI: 0.84-1.14), the FACT-G total (OR=0.99, 95% CI: 0.96-1.01), physical (OR=0.98, 95% CI: 0.97-1.00), social (OR=1.00, 95% CI: 0.98-1.03), emotional (OR= 1.00, 95% CI: 0.98-1.02), and functional (OR=0.99, 95% CI: 0.98-1.01) scores were not associated with EFS24 failure. In a stepwise multivariate analysis of clinical variables in patients with pretreatment QOL scores, only ECOG PS ≥2 (OR=3.56, 95% CI: 1.30-9.72) and female sex (OR=0.37, 95% CI: 0.16-0.85) were associated with failure to achieve EFS24. Conclusions In patients aged 70 years and older, ECOG PS and LDH were the strongest independent predictors of failure to achieve EFS24. As expected, physical and functional scores were lower in patients who completed their QOL after initiation of treatment. Restricting the analysis to patients with pre-treatment data, QOL was not associated with failure to achieve EFS24. Additional studies are needed to identify the most robust clinical predictors of EFS24, while QOL does not appear to be an important predictor of EFS24. Disclosures Reagan: Seattle Genetics: Research Funding. Maurer:Morphosys: Research Funding; Celgene: Research Funding; Nanostring: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

Abstract Purpose: The purpose of this study was to examine whether quality of life (QOL) scores at diagnosis predict survival among patients with aggressive lymphoma, controlling for clinical variables and histological subtype. Patients and Methods: Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource. Eligibility criteria included age ≥18 years; exclusion criteria included HIV-positive, non-US residency, and inability to participate in an interview conducted in the English language. All pathology was reviewed by a lymphoma hematopathologist. For purposes of this analysis, we considered “aggressive lymphoma” to include the histological subtypes diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) grade III, mantle cell lymphoma, T-cell lymphoma excluding mycosis fungoides and cutaneous types, and other (Burkitt lymphoma, high grade B-cell lymphoma NOS, grey zone, etc). Baseline QOL was measured at time of registry enrollment with the Functional Assessment of Cancer Treatment-General scale (FACT-G), which measures 4 QOL domains: physical, social/family, emotional, and functional well-being (WB); a single item Linear Analogue Self Assessment (LASA) for measuring overall QOL; and a LASA measuring spiritual WB. Patients who did not complete ≥80% of FACT-G QOL questions were excluded. Clinical data were abstracted and patients were systematically followed for event-free and overall survival (EFS, OS). QOL scores were transformed to a 0-100 scale for modeling. Generalized additive models were used to account for timing of QOL assessment in relation to treatment and diagnosis; residuals from these models were then used to assess association between QOL measures and outcome via univariate and multivariable (adjusted for IPI and subtype) Cox proportional hazards models. Results: From September 2002 to December 2009, 701 patients with aggressive lymphoma who completed baseline QOL questionnaires were enrolled and eligible for this analysis. ; Subtype was 60% DLBCL, 14% mantle cell, 11% FL grade III, 13% T-cell, and 1% other subtypes. The median age was 62 years (range 18-92), and 58% were male. At a median follow-up of 71 months (range 6-128), 316 patients (45%) had an event and 228 patients (33%) died. Patient-reported QOL was prior to therapy in 330 patients (47%) and after initiation of therapy in 371 (53%). The median overall FACT-G total score was 83 (IQR 70-93), and the median scores on the functional WB, physical WB, emotional WB, and social/family WB were 18 (13-23), 22 (17-26), 18 (16-21), and 25 (22-27), respectively. 42 patients (6%) reported a clinically deficient QOL score on the FACT-G (score ≤50 on 0-100 scale). When comparing QOL scores between those who were on active therapy versus those who were not yet treated, physical WB (p<0.0001) functional WB (p=0.00014), and total FACT-G (p=0.0013) were lower in those on active treatment. All QOL measures but emotional WB were significantly associated with OS (all p<0.04), and all but LASA spiritual WB remained significant after adjusting for IPI and NHL subtype. Associations were stronger for OS than EFS. For OS, the strongest associations were with total FACT-G (adjusted HR=0.86, 95% CI: 0.79-0.94, p=0.00062) and functional WB (adjusted HR=0.88, 95% CI: 0.83-0.93, p<0.0001). The one-question QOL LASA was also associated with OS (adjusted HR=0.92, 95% CI: 0.87-0.97, p=0.0041). The strongest association with EFS was with functional WB (adjusted HR=0.92, 95% CI: 0.88-0.97, p=0.0015). Patients with a clinically deficient QOL (baseline overall QOL ≤50) had a median OS of 59 months compared to 121 months for patients with baseline QOL >50, p=0.0002, figure 1. In a sensitivity analysis, raw QOL was modeled for OS and EFS in the subset of patients with QOL assessed prior to treatment; hazard ratios were consistent with the adjusted QOL HR in all patients. Conclusions: In this large sample of patients with aggressive lymphoma, baseline QOL is predictive of OS and EFS, even after adjustment for known factors related to survival (IPI and histological subtype). This provides evidence that patient-reported outcomes are as important as other more objective previously confirmed IPI measures. QOL should be assessed at diagnosis as a prognostic factor in patients with aggressive lymphoma. Figure 1 Association of QOL with overall survival. Figure 1. Association of QOL with overall survival. Disclosures No relevant conflicts of interest to declare.

PURPOSE: The Consumer Assessment of Healthcare Providers and Systems (CAHPS) Cancer Care Survey is a systematic assessment of health care experiences of patients with cancer. It supports comparisons among all cancer treatment settings and modalities. METHODS: Formative research included 16 focus groups with patients receiving treatment and family members; advice from a panel of oncology and quality improvement experts; and interviews with stakeholders representing oncology associations, accredited cancer centers, and community oncology practices. We conducted cognitive tests of the instrument and field tests at six cancer centers and four community oncology practices, after which the survey was finalized and obtained the CAHPS trademark. RESULTS: The survey includes 56 questions that form six core composite measures (Getting Timely Care; Supporting Patient Self-Management; Available to Provide Care and Information; Provider Communication; Care Coordination; and Courteous Office Staff); two single-item measures of family participation in care and interpreter services; and two global ratings of cancer care and the treatment team. Sixteen additional items form three supplemental composite measures: Shared Decision-Making, Keeping Patients Informed, and Access to Care. CONCLUSION: Mail-only, mail-telephone mixed-mode, and Web-mail mixed-mode data collection methods are recommended. The questionnaires and instructions for use are free and available in English and Spanish on the CAHPS Website ( www.ahrq.gov/cahps ).

AbstractBackgroundReflecting (“stop‐and‐think”) before rating may help patients consider the quality of shared decision making (SDM) and mitigate ceiling/halo effects that limit the performance of self‐reported SDM measures.MethodsWe asked a diverse patient sample from the United States to reflect on their care before completing the 3‐item CollaboRATE SDM measure. Study 1 focused on rephrasing CollaboRATE items to promote reflection before each item. Study 2 used 5 open‐ended questions (about what went well and what could be improved upon, signs that the clinician understood the patient's situation, how the situation will be addressed, and why this treatment plan makes sense) to invite reflection before using the whole scale. A linear analogue scale assessed the extent to which the plan of care made sense to the patient.ResultsIn Study 1, 107 participants completed surveys (84% response rate), 43 (40%) rated a clinical decision of which 27 (63%) after responding to reflection questions. Adding reflection lowered CollaboRATE scores (“less” SDM) and reduced the proportion of patients giving maximum (ceiling) scores (not statistically significant). In Study 2, 103 of 212 responders (49%) fully completed the version containing reflection questions. Reflection did not significantly change the distribution of CollaboRATE scores or of top scores. Participants indicated high scores on the sense of their care plan (mean 9.7 out of 10, SD 0.79). This rating was weakly correlated with total CollaboRATE scores (rho = .4, P = .0001).ConclusionReflection‐before‐quantification interventions may not improve the performance of patient‐reported measures of SDM with substantial ceiling/halo effects.

AbstractBackgroundAntifungal prophylaxis strategies for lung transplant recipients vary without consensus or standard of care. Our current study aims to identify antifungal prophylaxis practices in the United States.MethodsFrom November 29, 2018, to February 15, 2019, we emailed surveys to medical directors of adult lung transplant centers. An alternate physician representative was approached if continued non‐response after three survey attempts. Descriptive statistics were used to report findings.ResultsForty‐four of 62 (71.0%) eligible centers responded. All Organ Procurement and Transplantation Networks were represented. Only four (9.1%) centers used pre‐transplant prophylaxis for prevention of tracheobronchitis (3 of 4) and invasive fungal disease (4 of 4). Thirty‐nine of forty (97.5%) centers used post‐transplant prophylaxis: 36 (90.0%) universal and 3 (7.5%) pre‐emptive/selective prophylaxis. Most centers used nebulized amphotericin with a systemic agent (26 of 36, 72.2%). Thirty‐two of thirty‐six (88.9%) centers continued universal prophylaxis beyond the hospital setting. Duration of prophylaxis ranged from the post‐transplant hospitalization to lifelong with most centers (25 of 36, 69.4%) discontinuing prophylaxis 6 months or less post‐transplant.ConclusionMost United States' lung transplant centers utilize a universal prophylaxis with nebulized amphotericin and a systemic triazole for 6 months or less post‐transplant. Very few centers use pre‐transplant antifungal prophylaxis.

6594 Background: Given the significant short-term adverse effects of CAR-T cell therapy, it is important to evaluate its impact on QOL of patients in addition to efficacy, compared with established forms of cellular therapy like SCT. Methods: QOL was evaluated prospectively in patients undergoing CAR-T therapy, autoSCT & alloSCT for hematologic malignancies. QOL was assessed with FACT-G at baseline, 2 weeks and monthly for 6 months thereafter. Functional well-being (FWB), physical WB (PWB) emotional WB (EWB) & social WB (SWB) and change over time were compared across groups. Results: 45 patients were recruited (CAR-T: 10; Auto SCT: 22; Allo SCT: 13) with follow up for 2 weeks & 1 month available for 23 &15 patients, respectively (Table). There was no statistically significant difference in baseline total QOL scores (p=0.13), though scores were lower in the alloSCT group (85,84,68). EWB &FWB were numerically higher in the CAR-T group, followed by autoSCT group. At 2 weeks, overall QOL decreased by only 2 points in CAR-T group vs. 22 & 18 points in auto & alloSCT groups (p=0.09). Change in PWB vs. baseline was less pronounced in the CAR-T group (-1, -9, -13, p=0.03). At 1 month, overall QOL was 6 points lower than baseline in CAR-T group vs. 3 and 14 points lower in auto & alloSCT groups, respectively (p=0.34). Importantly, PWB had at least returned to baseline in the CAR-T group. Conclusions: Preliminary data show that patients undergoing CAR-T cell therapy do not experience a more significant decline in QOL compared with auto & allo SCT, and may experience fewer physical side effects in the short-term. Accrual & follow-up are ongoing. [Table: see text]

Abstract Background Little is known about how complementary and alternative medicine (CAM) is discussed in cancer care across varied settings in the U.S. Methods In two practices affiliated with one academic medical center in southern California (SoCal), and one in the upper Midwest (UM), we audio-recorded patient-clinician interactions in medical oncology outpatient practices. We counted the frequency and duration of CAM-related conversations. We coded recordings using the Roter Interaction Analysis System. We used chi-square tests for bivariate analysis of categorical variables and generalized linear models for continuous variables to examine associations between dialogue characteristics, practice setting, and population characteristics with the occurrence of CAM discussion in each setting followed by multivariate models adjusting for clinician clustering. Results Sixty-one clinicians and 529 patients participated. Sixty-two of 529 (12%) interactions included CAM discussions, with significantly more observed in the SoCal university practice than in the other settings. Visits that included CAM were on average 6 minutes longer, with CAM content lasting an average of 78 seconds. In bivariate tests of association, conversations containing CAM included more psychosocial statements from both clinicians and patients, higher patient-centeredness, more positive patient and clinician affect, and greater patient engagement. In a multivariable model including significant bivariate terms, conversations containing CAM were independently associated with higher patient-centeredness, slightly longer visits, and being at the SoCal university site. Conclusion The frequency of CAM-related discussion in oncology varied substantially across sites. Visits that included CAM discussion were longer and more patient centered. Implications for Practice The Institute of Medicine and the American Society of Clinical Oncology have called for more open discussions of complementary and alternative medicine (CAM). But little is known about the role population characteristics and care contexts may play in the frequency and nature of those discussions. The present data characterizing actual conversations in practice complements a much larger literature based on patient and clinician self-report about CAM disclosure and use. It was found that CAM discussions in academic oncology visits varied significantly by practice context, that the majority were initiated by the patient, and that they may occur more when visit time exists for lifestyle, self-care, and psychosocial concerns.

Background: Patient reported measures are fundamental to patient centered research and are often collected by questionnaires. Low participation can compromise the validity of the results; transparent reporting and comparing characteristics of participants to nonparticipants is important to assess the generalizability of survey results. We analyzed participation in a survey of social determinants of health among a population-based sample of patients with heart failure (HF). Methods: A total of 7920 residents from 11 Minnesota counties were identified with a first-ever code for HF (ICD-9 428 and ICD-10 I50) between 1/1/2013 and 12/31/2016. Participants completed a battery of 12 questionnaires by mail or telephone. Characteristics and outcomes data were extracted from medical records and compared between participants and nonparticipants. Response rate (RR) was calculated using guidelines of the American Association for Public Opinion Research (AAPOR). The association between nonparticipation and outcomes was examined by Cox proportional hazards regression for death and Andersen-Gill modeling for hospitalizations. Results: Among 7920 patients, 3438 responded to the survey (AAPOR RR#2= 43%). Numerous clinical and demographic differences between participants and non-participants were noted (Table), particularly for education, marital status, and neuropsychiatric conditions. After a mean (±SD) of 1.5±1 years after survey administration, 1,577 deaths and 5,873 hospitalizations had occurred. Nonparticipation was associated with a two-fold increased risk of death (HR: 2.30; 95% CI: 2.06-2.57; p<0.001) and a 10% increased risk of hospitalizations (HR: 1.10; 95% CI: 1.01-1.21; p=0.03) after adjusting for age, sex, marital status, coronary disease, arrhythmia, hyperlipidemia, cancer, chronic kidney disease, depression and anxiety. Conclusions: In a large survey of patients with HF, participation was associated with large differences in clinical and demographic characteristics and outcomes. Examining the impact of participation is critical to draw inference from studies of patient reported measures.