Impact of Preexisting Heart Failure on Treatment and Outcomes in Older Patients With Hodgkin Lymphoma.

Background: Older patients with Hodgkin lymphoma (HL) often have comorbid cardiovascular disease; however, the impact of pre-existing heart failure (HF) on the management and outcomes of HL is unknown. Objectives: The aim of this study was to assess the prevalence of pre-existing HF in older patients with HL and its impact on treatment and outcomes. Methods: Linked Surveillance, Epidemiology, and End Results (SEER) and Medicare data from 1999 to 2016 were used to identify patients 65 years and older with newly diagnosed HL. Pre-existing HF, comorbidities, and cancer treatment were ascertained from billing codes and cause-specific mortality from SEER. The associations between pre-existing HF and cancer treatment were estimated using multivariable logistic regression. Cause-specific Cox proportional hazards models adjusted for comorbidities and cancer treatment were used to estimate the association between pre-existing HF and cause-specific mortality. Results: Among 3,348 patients (mean age 76 ± 7 years, 48.6% women) with newly diagnosed HL, pre-existing HF was present in 437 (13.1%). Pre-existing HF was associated with a lower likelihood of using anthracycline-based chemotherapy regimens (OR: 0.42; 95% CI: 0.29-0.60) and a higher likelihood of lymphoma mortality (HR: 1.25; 95% CI: 1.06-1.46) and cardiovascular mortality (HR: 2.57; 95% CI: 1.96-3.36) in models adjusted for comorbidities. One-year lymphoma mortality cumulative incidence was 37.4% (95% CI: 35.5%-39.5%) with pre-existing HF and 26.3% (95% CI: 25.0%-27.6%) without pre-existing HF. The cardioprotective medications dexrazoxane and liposomal doxorubicin were used in only 4.2% of patients. Conclusions: Pre-existing HF in older patients with newly diagnosed HL is common and associated with higher 1-year mortality. Strategies are needed to improve lymphoma and cardiovascular outcomes in this high-risk population.

The clinical effectiveness of Fidaxomicin compared to Vancomycin in the treatment of Clostridioides difficile infection, a single center real-world experience.

BACKGROUND: The use of fidaxomicin is recommended as first line therapy for all patients with Clostridioides difficile infection (CDI). However, real-world studies have shown conflicting evidence of superiority. METHODS: We conducted a retrospective single center study of patients diagnosed with CDI between 2011-2021. A primary composite outcome of clinical failure, 30-day relapse or CDI-related death was used. A multivariable cause specific Cox proportional hazards model was used to evaluate fidaxomicin compared to vancomycin in preventing the composite outcome. A separate model was fit on a subset of patients with C. difficile ribotypes adjusting for ribotype. RESULTS: There were 598 patients included, of whom 84 received fidaxomicin. The primary outcome occurred in 8 (9.5%) in the fidaxomicin group compared to 111 (21.6%) in the vancomycin group. The adjusted multivariable model showed fidaxomicin was associated with 63% reduction in the risk of the composite outcome compared to vancomycin (HR = 0.37, 95% CI 0.17-0.80). In the 337 patients with ribotype data after adjusting for ribotype 027, the results showing superiority of fidaxomicin were maintained (HR = 0.19, 95% CI 0.05-0.77). CONCLUSION: In the treatment of CDI, we showed that real-world use of fidaxomicin is associated with lower risk of a composite endpoint of treatment failure.

Characteristics of Maine and Massachusetts nurses interested in advanced nursing degrees.

BACKGROUND: Maine (ME) and Massachusetts (MA) nursing programs aim to develop collaborative training programs, but need to identify which nurses have interest in such programs. PURPOSE: We sought to determine sociodemographics of nurses seeking advanced nursing degrees nationally, and in ME and MA using the 2018 publicly available, National Sample Survey of Registered Nurses (NSSRN). METHODS: Weighted multivariable logistic regression for advanced degree-seeking, adjusted for sociodemographics. RESULTS: Of the n = 47,274 nurses (weighted n [Wn] = 3,608,633), 90.7 % were female, 74.1 % were white, and 15.8 % sought an advanced nursing degree on average 12.7 (SD 0.2) years after their first. Females vs. males had lower odds (OR 0.63, 95%CI [0.44-0.90]) and Black vs. White race had higher odds (OR 1.30, 95%CI [1.05-1.60]) of seeking doctorates. In Maine (Wn = 20,389), age 24-29 had higher odds (OR 2.98 (95%CI [1.06-3.74]), but in Massachusetts (Wn = 101,984), age 30+ had lower odds (OR 0.32, 95%CI [0.13-0.78]) of degree-seeking vs. <24 years. Initial nursing degrees earned between 1980 and 1989 had higher odds (OR 1.99, 95%CI [1.06-3.74]) in Maine, but between 2010 and 2014 had lower odds (OR 0.32, 95%CI [0.14-0.72]) in Massachusetts of degree-seeking, vs. before 1980. CONCLUSIONS: Targets for advanced nursing training programs may vary by state and sociodemographic profile.

Harnessing multi-source data for individualized care in Hodgkin Lymphoma.

Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably. Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy. In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to estimate risks of late effects, based on cumulative exposure from frontline and salvage treatment. The resultant database and tools employed are dynamic with the expectation that they will be updated as better and more complete information becomes available.

Comparative Effectiveness of Fidaxomicin vs Vancomycin in Populations With Immunocompromising Conditions for the Treatment of Clostridioides difficile Infection: A Single-Center Study.

Background: Clostridioides difficile infection (CDI) is a leading cause of morbidity in immunocompromised hosts with increased risk of complications and recurrences. In this study, we examined the clinical effectiveness of fidaxomicin vs vancomycin in treating CDI in this patient population. Methods: This single-center retrospective study evaluated patients with CDI between 2011 and 2021. The primary outcome was a composite of clinical failure, relapse at 30 days, or CDI-related death. A multivariable cause-specific Cox proportional hazards model was used to test the relationship between treatment and the composite outcome, adjusting for confounders and treating death from other causes as a competing risk. Results: This study analyzed 238 patients who were immunocompromised and treated for CDI with oral fidaxomicin (n = 38) or vancomycin (n = 200). There were 42 composite outcomes: 4 (10.5%) in the fidaxomicin arm and 38 (19.0%) in the vancomycin arm. After adjustment for sex, number of antecedent antibiotics, CDI severity and type of immunosuppression, fidaxomicin use significantly decreased the risk of the composite outcome as compared with vancomycin (10.5% vs 19.0%; hazard ratio, 0.28; 95% CI, .08-.93). Furthermore, fidaxomicin was associated with 70% reduction in the combined risk of 30- and 90-day relapse following adjustment (hazard ratio, 0.27; 95% CI, .08-.91). Conclusions: The findings of this study suggest that the use of fidaxomicin for treatment of CDI reduces poor outcomes in patients who are immunocompromised.

Performance of the FACT-GOG-Ntx to assess chemotherapy-induced peripheral neuropathy (CIPN) in pediatric high risk Hodgkin lymphoma: report from the Children's Oncology Group AHOD 1331 study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is an under-recognized complication of several chemotherapy agents used as part of curative-intent therapy for Hodgkin Lymphoma (HL). In the absence of validated self- or proxy-report measures for children and adolescents, CIPN reporting has relied on clinician rating, with grading scales often restricted to severe manifestations. In a proof-of-concept study, we assessed the feasibility and psychometric performance of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx), a unidimensional CIPN symptom scale widely used adults with CIPN, in pediatric HL at risk for CIPN. METHODS: Youth (11+ years) and parents of all children (5-17.9 years) with newly diagnosed high-risk HL enrolled on Children's Oncology Group AHOD1331 (NCT02166463) were invited to complete the FACT-GOG-Ntx and a health-related quality of life (HRQL) measure at pre-treatment (Time 1), and during cycles 2 (Time 2) and 5 (Time 3) of chemotherapy during the first half of study accrual. Clinical grading of CIPN by providers was also assessed using the Balis Pediatric Neuropathy Scale. We evaluated Cronbach's alpha, construct validity, and agreement between raters. Change in FACT-GOG-Ntx scores over time was assessed using a repeated measures model. RESULTS: 306 patients had at least one completed FACT-GOG-Ntx with time-specific completion rates of > 90% for both raters. Cronbach's alpha was > 0.7 for youth and parent-proxy report at all time points. Correlations between FACT-GOG-Ntx and HRQL scores were moderate (0.41-0.48) for youth and parent-proxy raters across all times. Youth and parent-proxy raters both reported worse FACT-GOG-Ntx scores at Time 3 for those who had clinically-reported CIPN compared to those who did not. Agreement between raters was moderate to high. Compared to baseline scores, those at Time 3 were significantly lower for youth (ß = - 2.83, p < 0.001) and parent-proxy raters (ß = - 1.99, p < 0.001). CONCLUSIONS: High completion rates at all time points indicated feasibility of eliciting youth and parent report. Psychometric performance of the FACT-GOG-Ntx revealed acceptable reliability, evidence of validity, and strong inter-rater agreement, supporting the use of this self- or proxy-reported measure of CIPN in youth with high-risk HL exposed to tubulin inhibitors, as part of a Phase 3 clinical trial. CLINICAL TRIAL INFORMATION: Clinical Trials Registry, NCT02166463. Registered 18 June 2014, https://clinicaltrials.gov/ct2/show/study/NCT02166463.

Compared with conventional insemination, intracytoplasmic sperm injection provides no benefit in cases of nonmale factor infertility as evidenced by comparable euploidy rate.

OBJECTIVE: To evaluate whether differences in euploidy rates exist between intracytoplasmic sperm injection (ICSI) and conventional insemination (CI) in nonmale factor infertility cases. DESIGN: Retrospective cohort study. SETTING: A single, academically affiliated infertility center in the United States. PATIENTS: A total of 3554 patients who underwent in vitro fertilization cycles from January 2014 to December 2021. All cycles that had preimplantation testing for aneuploidy (PGT-A) performed by trophectoderm biopsy and had a postpreparation sperm concentration >4 million total motile sperm per milliliter were included. MAIN OUTCOME MEASURES: The primary outcome was the embryo euploidy rate per embryo biopsied in the ICSI vs. CI group. Secondary outcomes included the fertilization rate and number of embryos biopsied. Generalized estimating equations with a Poisson distribution were used to estimate the euploid rate ratio (with total embryos biopsied as an offset), while accounting for multiple retrievals per patient. To adjust for confounding, a propensity score model was fit for ICSI using 14 baseline female and male characteristics. RESULTS: Oocytes retrieved and the number of embryos biopsied were similar in both groups, while the fertilization rate per oocyte retrieved was significantly lower with ICSI (0.64 vs. 0.66). The proportion of euploid embryos in the ICSI group was significantly lower when compared with CI (0.47 vs. 0.52), with a euploid rate ratio of 0.89. Interestingly, when accounting for the variation in PGT reference laboratories over the study time period, adjusting for the date of procedure did not change the relationship between ICSI and euploid rate (rate ratio = 0.89); however, after adjusting for the PGT reference laboratory, the relationship between ICSI and euploid rate was no longer significant (rate ratio = 0.97). CONCLUSIONS: In the setting of nonmale factor infertility, ICSI resulted in a lower fertilization rate and an 11% lower embryo euploid rate compared with CI. Although the data are not statistically significant when adjusted for the PGT reference laboratory, we still can conclude that ICSI does not provide any benefit. These data support the recommendation that CI should be the preferred methodology for fertilization in nonmale factor infertility cases.

Association of Preexisting Heart Failure With Outcomes in Older Patients With Diffuse Large B-Cell Lymphoma.

Importance: Anthracycline-containing regimens are highly effective for diffuse large B-cell lymphoma (DLBCL); however, patients with preexisting heart failure (HF) may be less likely to receive anthracyclines and may be at higher risk of lymphoma mortality. Objective: To assess the prevalence of preexisting HF in older patients with DLBCL and its association with treatment patterns and outcomes. Design, Setting, and Participants: This longitudinal cohort study used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2016. The SEER registry is a system of population-based cancer registries, capturing more than 25% of the US population. Linkage to Medicare offers additional information from billing claims. This study included individuals 65 years and older with newly diagnosed DLBCL from 2000 to 2015 with Medicare Part A or B continuously in the year prior to lymphoma diagnosis. Data were analyzed from September 2020 to December 2022. Exposures: Preexisting HF in the year prior to DLBCL diagnosis ascertained from billing codes required one of the following: (1) 1 primary inpatient discharge diagnosis, (2) 2 outpatient diagnoses, (3) 3 secondary inpatient discharge diagnoses, (4) 3 emergency department diagnoses, or (5) 2 secondary inpatient discharge diagnoses plus 1 outpatient diagnosis. Main Outcomes and Measures: The primary outcome was anthracycline-based treatment. The secondary outcomes were (1) cardioprotective medications and (2) cause-specific mortality. The associations between preexisting HF and cancer treatment were estimated using multivariable logistic regression. The associations between preexisting HF and cause-specific mortality were evaluated using cause-specific Cox proportional hazards models with adjustment for comorbidities and cancer treatment. Results: Of 30 728 included patients with DLBCL, 15 474 (50.4%) were female, and the mean (SD) age was 77.8 (7.2) years. Preexisting HF at lymphoma diagnosis was present in 4266 patients (13.9%). Patients with preexisting HF were less likely to be treated with an anthracycline (odds ratio, 0.55; 95% CI, 0.49-0.61). Among patients with preexisting HF who received an anthracycline, dexrazoxane or liposomal doxorubicin were used in 78 of 1119 patients (7.0%). One-year lymphoma mortality was 41.8% (95% CI, 40.5-43.2) with preexisting HF and 29.6% (95% CI, 29.0%-30.1%) without preexisting HF. Preexisting HF was associated with higher lymphoma mortality in models adjusting for baseline and time-varying treatment factors (hazard ratio, 1.24; 95% CI, 1.18-1.31). Conclusions and Relevance: In this study, preexisting HF in patients with newly diagnosed DLBCL was common and was associated with lower use of anthracyclines and lower use of any chemotherapy. Trials are needed for this high-risk population.

The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium.

PURPOSE: The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model. METHODS: Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. RESULTS: The median age in the development cohort was 33 (18-65) years; nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. CONCLUSION: We rigorously developed and externally validated a clinical prediction model in > 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for individualized point-of-care use.

Evaluating the role of financial navigation in alleviating financial distress among young adults with a history of blood cancer: A hybrid type 2 randomized effectiveness-implementation design.

BACKGROUND: Young adulthood (YA) is a complex phase of life, marked by key developmental goals, including educational and vocational attainment, housing independence, maintenance of social relationships, and financial stability. A cancer diagnosis during, or prior to, this phase of life can compromise the achievement of these milestones. Studies of adults with cancer have demonstrated that >70% report experiencing financial side-effects, which are associated with increased mortality, diminished health-related quality of life, and forgone medical care. The goal of this project is to evaluate financial distress of YA-aged survivors of blood cancers, and the impact of financial navigation on alleviating this distress. METHODS: This three-arm, multi-site, hybrid type 2 randomized effectiveness-implementation design (EID) study will be conducted through remote consent, remote data capture and telephone-based/virtual financial navigation. Participants will be aged 18-39, and more than three years from their blood cancer diagnosis. In this six-month intervention, the study will compare the primary outcome of financial distress in three arms: (1) usual care (2) participant-initiated, ad hoc navigation, and (3) study-directed proactive navigation. The study will be evaluated via the five-component Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) outcome strategy with a mixed-methods approach through quantitative assessment of participant-reported financial distress using the Personal Financial Wellness Scale™, as the primary outcome measure, and qualitative assessment through interviews. CONCLUSION: The study will address many unanswered questions regarding financial navigation within the YA survivor population and will inform the most successful strategies to mitigate financial distress in this vulnerable population.

Effecting the culture: Impact of changing urinalysis with reflex to culture criteria on culture rates and outcomes.

OBJECTIVE: To evaluate the impact of changes to urinalysis with reflex to culture (UARC) reflex criteria on culture performance and clinical decision outcomes. DESIGN: Retrospective study utilizing interrupted time series analysis from December 2018 to November 2020. Primary outcomes were measures of culture performance. Secondary outcomes were rates of antimicrobial prescription for suspected urinary tract infection (UTI) and catheter-associated urinary tract infection (CAUTI). We also assessed harmful events related to antimicrobial prescription for all causes and UTI, UTI symptoms, and sepsis. SETTING: A 415-bed, academic, tertiary-care, medical center. PATIENTS: Hospitalized adult patients with urine testing performed. INTERVENTION: UARC reflex criteria were changed on October 22, 2019, from ≥5×109/L white blood cells (WBCs) or trace leukocyte esterase or positive nitrite units on urinalysis to only ≥15×109/L WBCs. RESULTS: The study included 11,322 unique UARC tests. We detected a significant decrease in the rate of urine cultures performed from UARC after the intervention (32.5-8.7 cultures per 1,000 patient days; P < .001), with improved diagnostic efficacy (ie, culture positivity increased from 34.8% to 62.1%). CAUTI rates did not change. We detected a significant decrease in antimicrobial prescription rates (P = .05), this was primarily driven by preintervention changes. One case of sepsis occurred secondary to a missed UTI, and UTIs were rarely missed after the intervention. CONCLUSIONS: Implementation of a stricter UARC reflex criterion was associated with a decrease in culture rates with improved diagnostic efficacy without significant adverse events. Continued education is needed to change antimicrobial prescribing practices.

Impact of provider-selected indication requirement on urine test utilization and positivity.

Objective: To evaluate the impact of the addition of an indication specification requirement to isolated urine-culture ordering on testing utilization. Design: Retrospective study utilizing interrupted time series analysis with negative binomial regression. The preintervention period was October 1, 2018-November 11, 2019, and the postintervention period was November 12, 2019-October 31, 2020. The primary outcome was isolated culture rate per 1,000 patient days. Secondary outcomes were the proportion of all urine tests ordered as isolated urine culture and culture positivity. An exploratory analysis assessed the appropriateness of selected testing indications. Setting: A 415-bed, urban, academic medical center. Patients: Adult patients with urine testing performed during hospital admission. In total, 1,494 unique isolated urine-culture orders were included in the analysis. Interventions: On November 12, 2019, the laboratory order interface was changed to require the ordering provider to select an indication for isolated urine culture. Results: Isolated urine-culture rates did not significantly change after the intervention (11.2-7.8 cultures per 1,000 patient days; P = .17) nor did culture positivity (26.9% vs 26.8%). Most ordering providers left the indication for testing blank, and of those charts reviewed, 67% did not have a documented condition for which isolated urine culture was the most appropriate initial test. Conclusions: The addition of an order-specification requirement for isolated urine-culture testing did not significantly affect ordering practices. The test remains overused as the initial diagnostic evaluation for a suspected urinary tract infection. Further provider education and continued changes in provider workflow are needed to achieve lasting change in practice.

Hematopoietic Stem-Cell Transplant Utilization in Relapsed/Refractory Hodgkin Lymphoma: A Population-Level Analysis of Statewide Claims Data.

PURPOSE: Although hematologic malignancies affect adults of all ages, few data exist on the real-world patterns of care for patients younger than 65 years in the United States. Understanding patterns of care from diagnosis through relapsed disease may provide insight about care across community and academic centers. We used a large statewide claims database to describe the path of Hodgkin lymphoma (HL) treatment among adults age < 65 years at diagnosis. METHODS: We defined a cohort of commercially insured patients with HL who underwent hematopoietic stem-cell transplantation (HSCT) from 2009 to 2013 in the Massachusetts All-Payer Claims Database (APCD). The primary goals of our study were to accurately identify patients and their treatment patterns who had relapsed/refractory HL and underwent HSCT. We also characterized time to treatment failure and overall survival. RESULTS: A total of 7,613 patients had International Classification of Diseases, Ninth Revision, diagnostic codes for HL. From our algorithm, we identified 117 patients as part of the final cohort who underwent autologous and/or allogeneic HSCT. Median age was 39.0 years and 50.4% were female. Initial therapy was identified for 68 of the 117 patients (58.1%). Most (> 74.4%) of the identified transplants were autologous, and 19 patients (16.2%) underwent allogeneic transplant, with or without prior autologous transplant. Of the 68 patients with initial therapy data, the median time to HSCT after completion of initial treatment was 223.5 days (Q1 = 151.5, Q3 = 414.5). CONCLUSION: We used the Massachusetts APCD to create a cohort of patients age < 65 years with relapsed/refractory HL. Our findings support the use of APCD for the large-scale analysis of patient characteristics, treatment patterns, and outcomes for young adult patients with hematologic malignancies.

Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant.

Allogeneic stem cell transplantation (AlloSCT) represents the only curative therapy for sickle cell disease (SCD). However, limited availability of matched related donors and suboptimal outcomes following AlloSCT with unrelated donors has led to investigation of alternative donors. Among children with high-risk SCD, we evaluated health-related quality of life (HRQoL) impact in the two years following familial haploidentical SCT. HRQoL was collected from parent and child raters, using the Child Health Ratings Inventories Generic measure and haploidentical SCT-specific module. Repeated measures models were fit to assess HRQoL changes over time and by rater. Nineteen children (mean age 12.9 yrs [standard deviation, 5.3]; 63% male) and their parents were included. There were no differences in the 2-yr trajectories of child physical or emotional functioning (EF) by rater. Child physical functioning and EF scores were significantly lower at day +45 than baseline, but scores recovered by day +180. There was significant improvement in EF (p = 0.03) at 2 yrs vs baseline. A similar pattern of scores over time was seen for parent ratings of child's global HRQoL. Despite treatment intensity in the initial months following AlloSCT, patient scores recovered or exceeded baseline scores at two years. This trial is registered at clinicaltrials.gov (NCT01461837).

Treatment patterns for relapsed and refractory Hodgkin lymphoma in a community oncology setting.

There is little data about treatment practices for relapsed/refractory Hodgkin Lymphoma (HL) in nonacademic settings. We describe sequential treatments and outcomes among HL patients who experienced treatment failure in an integrated community-oncology setting. We performed a retrospective cohort study among patients ≥12 years diagnosed with Stage II-IV HL from 2007 to 2012 at Kaiser Permanente Southern California (KPSC). Of 463 HL patients, 75 (16.1%) experienced treatment failure. Patients with failure received between 1 and 8 salvage therapies; 28% received ≥4 lines of therapy. Fifty-nine of 75 (79%) were initially salvaged with ifosfamide-based therapy, 44 of whom underwent hematopoietic cell transplant. Ultimately, 47% of patients died, with most deaths due to HL. Survival was shorter with increasing age at diagnosis (p = 0.02) and with greater number of lines of therapy (p = 0.02). In a community oncology setting, HL patients received multiple lines of salvage. Despite extensive treatment, nearly half of patients died of HL following relapsed/refractory disease.

Association of Treatment Intensity With Survival in Older Patients With Hodgkin Lymphoma.

Importance: Hodgkin lymphoma is an aggressive blood cancer that is highly curable in younger patients who receive multiagent chemotherapy. Worse survival in older patients may reflect less-aggressive treatment, competing risks of death, or different disease biological factors. Objective: To examine the association between treatment intensity and cause-specific mortality among older adults with Hodgkin lymphoma. Design, Setting, and Participants: This was a population-based cohort study of patients aged 65 years or older with Medicare Part A and B fee-for-service coverage who received a diagnosis of Hodgkin lymphoma from 2000 to 2013. The association between treatment intensity and cause-specific mortality was estimated separately for early-stage and advanced-stage disease with Cox proportional hazards models. Multivariable adjustment and propensity score weighting helped control for confounding. Data are from the 1999 to 2016 Surveillance, Epidemiology, and End Results Medicare database. Data analysis was performed from April 2020 to June 2021. Exposures: First-line treatment categorized as (1) full chemotherapy regimen, (2) partial chemotherapy regimen, (3) single chemotherapy agent or radiotherapy, or (4) no treatment. Main Outcomes and Measures: The main outcome was 3-year Hodgkin lymphoma-specific and other-cause mortality. Results: Among 2686 patients (mean [SD] age, 75.7 [6.9] years; 1333 men [50%]), 1307 had early-stage disease and 1379 had advanced-stage disease. For Hodgkin lymphoma-specific mortality in patients with early-stage disease, hazard ratios (HRs) were higher for partial regimens (HR, 1.77; 95% CI, 1.22-2.57) or no treatment (HR, 1.91; 95% CI, 1.31-2.79) than for full regimens; there was no difference between single-agent chemotherapy or radiotherapy and full regimens. For other-cause mortality in patients with early-stage disease, HRs were higher for partial regimens (HR, 1.69; 95% CI, 1.18-2.44), single-agent chemotherapy or radiotherapy (HR, 1.62; 95% CI, 1.13-2.33), or no treatment (HR, 2.71; 95% CI, 1.95-3.78) than for full regimens. For Hodgkin lymphoma-specific mortality in patients with advanced-stage disease, HRs were higher for partial regimens (HR, 3.26; 95% CI, 2.44-4.35), single-agent chemotherapy or radiotherapy (HR, 2.85; 95% CI, 1.98-4.11), or no treatment (HR, 4.06; 95% CI, 3.06-5.37) than for full regimens. For other-cause mortality in patients with advanced-stage disease, HRs were higher for partial regimens (HR, 1.76; 95% CI, 1.32-2.33), single-agent chemotherapy or radiotherapy (HR, 1.65; 95% CI, 1.15-2.37), or no treatment (HR, 2.24; 95% CI, 1.71-2.94) than for full regimens. Conclusions and Relevance: This cohort study found variability in the magnitude of the association between treatment intensity and mortality by stage and cause-specific mortality, possibly reflecting competing risks of death. However, full chemotherapy regimens were associated with lower mortality and could be considered for older adults who can tolerate them.

Development and validation of a prediction model for 1-year mortality among older adults with Hodgkin Lymphoma who receive dose-intense chemotherapy.

BACKGROUND: Older adults with Hodgkin Lymphoma (HL) have poorer outcomes than younger patients. There are little data about which baseline patient and disease factors inform prognosis among older patients. We sought to create a prediction model for 1-year mortality among older patients with new HL who received dose-intense chemotherapy. METHODS: We included adults ≥65 years old with a new diagnosis of classical HL between 2000-2013 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset who received full-regimen chemotherapy. Through a non-random 2:1 split, we created development and validation cohorts. Multiple imputation was used for missing data. Using stepwise selection and logistic regression, we identified predictive variables for 1-year mortality. The model was applied to the validation cohort. A final model was then fit in the full cohort. RESULTS: We included 1315 patients. In the development cohort (n = 813), we identified significant predictors of 1-year mortality including age, Charlson comorbidity index (CCI), B symptoms at diagnosis, and advanced stage at diagnosis. The c-statistic was 0.70. When this model was applied to the validation cohort (n = 502), the c-statistic was 0.65. Predictors of 1-year mortality in the final model were CCI (OR = 1.41), B symptoms (OR = 1.54), advanced stage (OR = 1.44), and older age at diagnosis (OR = 1.33). CONCLUSION: We present a prediction model for use among older adults with HL who receive intensive chemotherapy. We identify risk factors for death within 1 year of diagnosis. Future work will build upon prognostication and shared decision-making after diagnosis for this population.

Assessment of patients' understanding of and adherence to oral anticancer medication (OAM): Results of a cross-sectional institutional pilot study.

BACKGROUND: Although oral anticancer medications (OAM) provide opportunity for treatment at home, challenges include prescription filling, monitoring side effects, safe handling, and adherence. We assessed understanding of and adherence to OAM in vulnerable patients. METHODS: This 2018 pilot study defined vulnerable patients based on Chinese language, older age (≥65 years), and subsidized insurance. All participants had a cancer diagnosis and were taking an OAM filled through the hospital's specialty pharmacy. Participants reported on OAM taking (days per week, times per day, special instructions) and handling (handling, storage, disposal). The specialty pharmacist classified patient-reported responses about OAM taking and handling as adequate or inadequate. OAM regimens were classified by complexity. RESULTS: Of 61 eligible patients, 55 participated. Mean age was 68 years (standard deviation [SD] = 12) and 53% were female. Patient subgroups were: 27% Chinese, 64% ≥65 years, and 9% subsidized insurance. Forty-nine percent were on frontline therapy and median time on OAM was 1 year (Quartile 1 = 0.4, Quartile 3 = 1.7). Adequacy of OAM taking (30%) and handling (15%) were low; 15% had adequacy in both. Adequacy of OAM taking and handling did not vary by patient subgroup or regimen complexity. Mean patient-reported adherence was high (5.4, SD = 1, possible range 1-6) and did not vary by adequacy of OAM taking or handling. CONCLUSIONS: Understanding of OAM taking and handling in this group of vulnerable patients was low and did not align with patient-reported adherence. Future interventions should ensure that patients understand how to safely take and handle OAM, thereby optimizing their therapeutic potential.