Patterns of prescription opioid use and opioid-related harms among adult patients with hematologic malignancies.

INTRODUCTION: Treatment advances for hematologic malignancies (HM) have dramatically improved life expectancy, necessitating greater focus on long-term cancer pain management. This study explored real-world patterns of opioid use among patients with HM. METHODS: This retrospective cohort study identified adults diagnosed with HM from January 1, 2013 through December 31, 2019 using the Truven MarketScan Commercial Claims and Encounters database. Across several HM types, we described rates of high-risk opioid use (based on Pharmacy Quality Alliance measures) and opioid-related harms, including incident opioid use disorder (OUD) diagnoses and opioid-related hospitalizations or emergency department (ED) visits. We used multivariable Cox regression to generate adjusted hazard ratios and 95% confidence intervals comparing the risk of opioid-related harms between patients with versus without high-risk opioid use. RESULTS: Our sample included 43,190 patients with HM. Median age at HM diagnosis was 54 years (interquartile range = 44-60). Most patients (61.9%) were diagnosed with lymphoma. Approximately half (49.2%) had an opioid dispensed in the follow-up period. Among all patients, 20.0% met criteria for high-risk opioid use, 0.9% had an OUD diagnosis, and 0.3% experienced an opioid-related hospitalization/ED visit in follow-up. High-risk opioid use increased the risk of an OUD diagnosis by 3.3 times (p < 0.0001) and an opioid-related hospitalization/ED visit 4.2 times (p < 0.0001). CONCLUSION: High-risk opioid use was prevalent among patients with HM and significantly increased the risk of opioid-related harms. However, rates of opioid-related harms were low. These findings highlight the importance of continually monitoring pain and opioid use throughout HM survivorship to provide safe, effective HM pain management.

Perceptions of prescription opioids among marginalized patients with hematologic malignancies in the context of the opioid epidemic: a qualitative study.

PURPOSE: Opioids are essential for treating pain in hematologic malignancies (HM), yet are heavily stigmatized in the era of the opioid epidemic. Stigma and negative attitudes towards opioids may contribute to poorly managed cancer pain. We aimed to understand patient attitudes towards opioids for HM pain management, particularly among historically marginalized populations. METHODS: We interviewed a convenience sample of 20 adult patients with HM during outpatient visits at an urban academic medical center. Semi-structured interviews were audio-recorded, transcribed, and qualitatively analyzed using the framework method. RESULTS: Among 20 participants, 12 were female and half were Black. Median age was 62 (interquartile range = 54-68). HM diagnoses included multiple myeloma (n = 10), leukemia (n = 5), lymphoma (n = 4), and myelofibrosis (n = 1). Eight themes emerged from interviews that seemed to influence HM-related pain self-management, including (1) fear of opioid-related harms, (2) opioid side effects and harms to health, (3) fatalism and stoicism, (4) perceived value of opioids for HM-related pain, (5) low perceived susceptibility to opioid-related harms and externalizing blame, (6) preferences for non-opioid pain management approaches, (7) trust in providers and opioid accessibility, and (8) external sources of pain management support and information. CONCLUSIONS: This qualitative study demonstrates that fears and stigmatized views of opioids can conflict with marginalized patients' needs to manage debilitating HM-related pain. Negative attitudes towards opioids were shaped by the opioid epidemic and reduced willingness to seek out or use analgesics. IMPLICATIONS FOR CANCER SURVIVORS: These findings help expose patient-level barriers to optimal HM pain management, revealing attitudes, and knowledge to be targeted by future pain management interventions in HM.

Health-related Quality of Life in Hormone Receptor-Positive Early Breast Cancer: Analyses From the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey.

This study describes health-related quality of life (HRQoL) among older Medicare beneficiaries with hormone receptor-positive (HR+) early breast cancer (eBC). Women aged ≥65 years diagnosed with stage I-III HR+ eBC between 1997 and 2014 using the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey Data Resource were included. HRQoL was measured using the Short Form Health Survey including physical/mental component summary (PCS/MCS) scores and subscales. Patient surveys ≤ 24 months post-diagnosis were matched to non-cancer controls. Mean differences in HRQoL were compared using analysis of covariance. Among 1880 HR+ eBC patients versus 5640 matched non-cancer controls, eBC patients surveyed ≤ 6 months post-diagnosis (n = 530) scored lower on component scores (PCS mean difference = 1.6 [95%CI: 0.6-2.6]; MCS mean difference = 2.0 [95%CI: 1.0-3.0]) and multiple subscales. Among women surveyed 19 to 24 months post-diagnosis (n = 402), mean differences in HRQoL were modest (PCS: 1.2 [95%CI: 0.1-2.4]; MCS: -1.5 [95%CI: -2.7 to -0.3]). Most differences in HRQoL following diagnosis of eBC did not indicate statistical significance or minimally important difference, emphasizing that preservation of HRQoL is an important and realistic goal among patients with eBC.

Physical functioning, frailty and risks of locally-advanced breast cancer among older women.

OBJECTIVE: Women with multiple comorbidities have competing health needs that may delay screening for early detection of breast cancer. Our objective was to determine associations between physical functioning and frailty with risk of locally-advanced breast cancer (BC). METHODS: We conducted a retrospective cohort study of women 65 years and older diagnosed with first primary stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Physical health-related quality of life was measured using Veterans RAND 12 Item Health Survey scales within two years before diagnosis; frailty was determined by calculating deficit-accumulation frailty index (DAFI) scores. Multivariable modified Poisson regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for risk of locally-advanced (stage III) versus early-stage (I-II) BC. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 2189 (91%) were diagnosed with incident stage I-II BC and 222 (9%) were diagnosed at stage III. Compared to women with early-stage disease, women with locally-advanced BC had lower physical component scores (37.8 vs. 41.4) and more classified as pre-frail or frail (55% vs. 50%). In multivariable models, frailty was not associated with increased risk of locally-advanced disease. However, worse physical function subscale scores (lowest vs. upper quartile; RR = 1.56, 95% CI 1.04-2.34) were associated with risk of locally-advanced BC. CONCLUSIONS: Breast cancer screening among non-frail older women should be personalized to include women with limited physical functioning if the benefits of screening and early detection outweigh the potential harms.

Impact of time to distant recurrence on breast cancer-specific mortality in hormone receptor-positive breast cancer.

Women with hormone receptor (HR)-positive early-stage breast cancer (BC) have five-year survival rates of > 90% but remain at serious risk for developing distant metastases beyond five years from diagnosis. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to examine associations between distant recurrence-free interval (DRFI) and risk of BC-specific mortality following distant relapse. The analysis includes 1,057 women with second primary stage IV BC who were initially diagnosed with AJCC stages I-III HR-positive BC between1990 and 2016. Overall, 65% of women had a preceding DRFI of ≥ 5 years. Five-year BC-specific survival following development of distant recurrence was 52% for women with DRFI ≥ 5 years compared to 31% in women with DRFI of < 5 years. In multivariable analyses, risks of cancer-specific mortality following distant recurrence were lower in women with DRFI of 5 years or more (subdistribution hazard ratio = 0.72, 95% CI 0.58-0.89, p = 0.002). The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients who develop a distant recurrence of disease.

The association between physical health-related quality of life, physical functioning, and risk of contralateral breast cancer among older women.

BACKGROUND: Physical limitations prior to cancer diagnosis may lead to suboptimal health outcomes. Our objective was to evaluate the impacts of poor physical health-related quality of life (HRQOL) and physical functioning (PF) on the risk of contralateral breast cancer (CBC). METHODS: We performed a nested case-control study of women with invasive unilateral breast cancer (UBC) who did not receive prophylactic contralateral mastectomy using the Surveillance, Epidemiology and End Results Medicare Health Outcomes Survey data resource. Among 2938 women aged ≥ 65 years diagnosed with first stage I-III UBC between 1997 and 2011, we identified 100 subsequent CBC cases and 915 matched controls without CBC using incidence density sampling without replacement. Pre-diagnosis physical HRQOL and PF were determined using Medical Outcomes Trust Short Form-36 (SF-36)/Veterans Rand 12-Item Health Survey (VR-12) responses within 2 years prior to first UBC diagnosis. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. RESULTS: Cases and controls were similar with respect to comorbidities, stage, surgery, and radiation treatments, but differed by hormone receptor status (ER/PR-negative, 23% and 11%, respectively) of first UBC. Cases had modestly lower mean pre-diagnosis physical HRQOL (- 1.8) and PF (- 2.2) scores. In multivariable models, we observed an increased CBC risk associated with low physical HRQOL (lowest vs. highest quartile, OR = 1.8; 95% CI 0.8-4.3), but CIs included 1.0. Low PF was associated with a 2.7-fold (95% CI 1.1-6.7) increased CBC risk. CONCLUSIONS: Findings indicate that low physical HRQOL, specifically poor PF, is associated with CBC risk. Efforts to understand and minimize declines in PF post-breast cancer are well motivated.

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

Associations between frailty and cancer-specific mortality among older women with breast cancer.

PURPOSE: Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between pre-diagnosis frailty and risks of BC-specific and all-cause mortality in older women. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries ages ≥ 65 years with stage I-III BC using the Surveillance, Epidemiology and End Results-Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail, or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 49.5% were categorized as robust, 29.4% were pre-frail and 21.1% were frail. Fewer frail women compared to robust women received breast-conserving surgery (52.8% vs. 61.5%, frail vs. robust, respectively) and radiation (43.5% vs. 51.8%). In multivariable analyses, degree of frailty was not associated with BC-specific mortality (frail vs robust SHR 1.47, 95% CI 0.97-2.24). However, frail women with BC had higher risks of all-cause mortality compared to robust women with BC (HR 2.32, 95% CI 1.84-2.92). CONCLUSION: Among a cohort of older women with BC, higher degrees of frailty were associated with higher risk of all-cause mortality, but not BC-specific mortality. Future study should examine if preventing progression of frailty may improve all-cause mortality.

Predicting Treatment Failure for Initiators of Hepatitis C Virus Treatment in the era of Direct-Acting Antiviral Therapy.

Introduction: Hepatitis C virus (HCV), the leading cause of advanced liver disease, has enormous economic burden. Identification of patients at risk of treatment failure could lead to interventions that improve cure rates. Objectives: Our goal was to develop and evaluate a prediction model for HCV treatment failure. Methods: We analyzed HCV patients initiating direct-acting antiviral therapy at four United States institutions. Treatment failure was determined by lack of sustained virologic response (SVR) 12 weeks after treatment completion. From 20 patient-level variables collected before treatment initiation, we identified a subset associated with treatment failure in bivariate analyses. In a derivation set, separate predictive models were developed from 100 bootstrap samples using logistic regression. From the 100 models, variables were ranked by frequency of selection as predictors to create four final candidate models, using cutoffs of ≥80%, ≥50%, ≥40%, and all variables. In a validation set, predictive performance was compared across models using area under the receiver operating characteristic curve. Results: In 1,253 HCV patients, overall SVR rate was 86.1% (95% CI = 84.1%, 88.0%). The AUCs of the four final candidate models were: ≥80% = 0.576; ≥50% = 0.605; ≥40% = 0.684; all = 0.681. The best performing model (≥40%) had significantly better predictive ability than the ≥50% (p = 0.03) and ≥80% models (p = 0.02). Strongest predictors of treatment failure were older age, history of hepatocellular carcinoma, and private (vs. government) insurance. Conclusion: This study highlighted baseline factors associated with HCV treatment failure. Treatment failure prediction may facilitate development of data-driven clinical tools to identify patients who would benefit from interventions to improve SVR rates.

Self-reported health and survival in older patients diagnosed with multiple myeloma.

PURPOSE: Patient-reported outcomes such as self-reported health (SRH) are important in understanding quality cancer care, yet little is known about links between SRH and outcomes in older patients with multiple myeloma (MM). We evaluated associations between SRH and mortality among older patients with MM. METHODS: We analyzed a retrospective cohort of patients ages ≥ 65 years diagnosed with first primary MM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data resource. Pre-diagnosis SRH was grouped as high (excellent/very good/good) or low (fair/poor). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and all-cause and MM-specific mortality. RESULTS: Of 521 MM patients with mean (SD) age at diagnosis of 76.8 (6.1) years, 32% reported low SRH. In multivariable analyses, low SRH was suggestive of modest increased risks of all-cause mortality (HR 1.32, 95% CI 1.02-1.71) and MM-specific mortality (HR 1.22, 95% CI 0.87-1.70) compared to high SRH. CONCLUSION: Findings suggest that low pre-diagnosis SRH is highly prevalent among older patients with MM and is associated with modestly increased all-cause mortality. Additional research is needed to address quality of life and modifiable factors that may accompany poor SRH in older patients with MM.

Depressive symptoms, mental health-related quality of life, and survival among older patients with multiple myeloma.

PURPOSE: To examine the impact of pre-diagnosis depressive symptoms and mental health-related quality of life (HRQOL) on survival among older patients with multiple myeloma (MM). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource. Patients aged 65 years and older diagnosed with first primary MM between 1998 and 2014 were identified, and presence of depressive symptoms was determined based on responses to 3 depression screening questions prior to MM diagnosis. Veterans RAND 12 mental component summary (MCS) scores were analyzed to evaluate mental HRQOL. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of all-cause and cancer-specific mortality. RESULTS: Of 522 patients, mean (SD) age at diagnosis was 76.9 (6.1) years and 158 (30%) reported depressive symptoms. Patients with depressive symptoms had a higher number of comorbid conditions and nearly all (84%) scored below the median MCS. Pre-diagnosis depressive symptoms were not associated with all-cause (HR = 1.01, 95% CI 0.79-1.29) or cancer-specific mortality (HR = 0.94, 95% CI 0.69-1.28). MM patients scoring in the second MCS tertile (vs the highest tertile) had a modestly increased risk of all-cause (HR = 1.19, 95% CI 0.91-1.55) and cancer-specific mortality (HR = 1.17, 95% CI 0.86-1.60), but these estimates were not statistically significant. CONCLUSION: Pre-diagnosis depressive symptoms and lower mental HRQoL did not impact survival among older MM patients. Highly prevalent depressive symptoms among older MM patients deserve clinical attention. Such efforts can inform clinicians in tailoring care for this vulnerable population.