Kaiser Permanente Northern California Research Articles

Estimating dementia incidence in insured older Asian Americans and Pacific Islanders in California: an application of inverse odds of selection weights.

Literature shows heterogeneous age-standardized dementia incidence rates across US Asian American, Native Hawaiian, and Pacific Islanders (AANHPI), but no estimates of population-representative dementia incidence exist due to lack of AANHPI longitudinal probability samples. We compared harmonized characteristics between AANHPI Kaiser Permanente Northern California members (KPNC cohort) and the target population of AANHPI 60+ with private or Medicare insurance using the California Health Interview Survey. We used stabilized inverse odds of selection weights (sIOSW) to estimate ethnicity-specific crude and age-standardized dementia incidence rates and cumulative risk by age 90 in the target population. Differences between the KPNC cohort and target population varied by ethnicity. sIOSW eliminated most differences in larger ethnic groups; some differences remained in smaller groups. Estimated crude dementia incidence rates using sIOSW (versus unweighted) were similar in Chinese, Filipinos, Pacific Islanders and Vietnamese, and higher in Japanese, Koreans, and South Asians. Unweighted and weighted age-standardized incidence rates differed for South Asians. Unweighted and weighted cumulative risk were similar for all groups. We estimated the first population-representative dementia incidence rates and cumulative risk in AANHPI ethnic groups. We encountered some estimation problems and weighted estimates were imprecise, highlighting challenges using weighting to extend inferences to target populations.

Hepatocellular Carcinoma in Metabolic Dysfunction-Associated Steatotic Liver Disease

In the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC. To develop a prediction model for HCC incidence in a cohort of patients with MASLD. This prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024. Data were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD. The cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk. A total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241. This prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.

Opioid Administration Practice Patterns in Patients With Acute Respiratory Failure Who Undergo Invasive Mechanical Ventilation.

The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. Retrospective cohort study. Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. We assessed whether patients received opioid infusion and the dose of said opioid infusion. We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3-11%) and 39% (95% CI, 28-49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129-1341 µg) in the KPNC cohort and 200 µg (IQR, 0-1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1-7%) and 20% (95% CI, 15-26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals' analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.

Hydroxychloroquine and Preeclampsia in a Diverse Cohort of Women with SLE.

Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as preeclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce preeclampsia risk in lupus pregnancy. Using a cohort of pregnancies in prevalent SLE patients at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ use in early pregnancy reduced the risk of preeclampsia/eclampsia. Among SLE pregnancies from 2011-2020, we assessed HCQ use from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of use. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RR) and 95% confidence intervals of the association between HCQ and preeclampsia/eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody status was investigated through stratified analysis. There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and preeclampsia/eclampsia. The RRs were consistently lower among the nullipara pregnancies, and RRs were consistently protective but not statistically significant among the high-risk subgroup of those with history of nephritis, aPL positivity, or pregestational hypertension (both nullipara and multipara). Although this study found no reduced risk of HCQ on preeclampsia/eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data.

Evaluation of an Embedded Health Psychologist Intervention for Obstetric Patients With Adverse Childhood Experiences.

Screening for adverse childhood experiences (ACEs) and resilience in pregnancy is a promising practice for mitigating ACEs-related health complications. Yet, the best follow-up for pregnant patients with high ACEs and/or low resilience has not been established. This study evaluates referrals to and participation in an embedded health psychologist (EHP) intervention for pregnant patients with ACEs and/or low resilience. Patients in 3 Kaiser Permanente Northern California medical centers with ACEs who had also received resilience screening during standard prenatal care and who were participating in an EHP intervention were included (N = 910). The authors used multivariable logistic regression to examine whether ACEs (0, 1-2, 3+) and resilience (high vs low) were associated with referrals to and participation in EHP intervention. They also evaluated the impact of EHP intervention through clinician (N = 53) and patient (N = 51) surveys. Patients with 3+ vs 0 ACEs were more likely to receive an EHP referral (adjusted odds ratio [aOR] = 2.89, 95% confidence interval [CI]: 1.93-4.33) and were more likely to participate in EHP intervention (aOR = 2.85, 95% CI: 1.87-4.36). Those with low vs high resilience were also more likely to receive an EHP referral (aOR = 1.86, 95% CI: 1.32-2.62) and participate in EHP (aOR = 1.71, 95% CI: 1.19-2.44). When ACEs and resilience were combined, those with high ACEs and low resilience had the greatest odds of referrals and participation. Patients and clinicians reported positive experiences with EHP intervention. Patients with higher ACEs and lower resilience scores were more likely to be referred to and participate in EHP intervention, suggesting that at-risk patients can be successfully linked with a health psychologist when accessible within obstetric care.

Evaluation of an Embedded Health Psychologist Intervention for Obstetric Patients With Adverse Childhood Experiences.

Screening for adverse childhood experiences (ACEs) and resilience in pregnancy is a promising practice for mitigating ACEs-related health complications. Yet, the best follow-up for pregnant patients with high ACEs and/or low resilience has not been established. This study evaluates referrals to and participation in an embedded health psychologist (EHP) intervention for pregnant patients with ACEs and/or low resilience. Patients in 3 Kaiser Permanente Northern California medical centers with ACEs who had also received resilience screening during standard prenatal care and who were participating in an EHP intervention were included (N = 910). The authors used multivariable logistic regression to examine whether ACEs (0, 1-2, 3+) and resilience (high vs low) were associated with referrals to and participation in EHP intervention. They also evaluated the impact of EHP intervention through clinician (N = 53) and patient (N = 51) surveys. Patients with 3+ vs 0 ACEs were more likely to receive an EHP referral (adjusted odds ratio [aOR] = 2.89, 95% confidence interval [CI]: 1.93-4.33) and were more likely to participate in EHP intervention (aOR = 2.85, 95% CI: 1.87-4.36). Those with low vs high resilience were also more likely to receive an EHP referral (aOR = 1.86, 95% CI: 1.32-2.62) and participate in EHP (aOR = 1.71, 95% CI: 1.19-2.44). When ACEs and resilience were combined, those with high ACEs and low resilience had the greatest odds of referrals and participation. Patients and clinicians reported positive experiences with EHP intervention. Patients with higher ACEs and lower resilience scores were more likely to be referred to and participate in EHP intervention, suggesting that at-risk patients can be successfully linked with a health psychologist when accessible within obstetric care.

Representativeness of Patients With Lung Cancer in an Integrated Health Care Delivery System.

Observational research is important for understanding the real-world benefits of advancements in lung cancer care. Integrated health care systems, such as Kaiser Permanente Northern California, have extensive electronic health records suitable for such research, but the generalizability of their populations is often questioned. Leveraging data from the California Cancer Registry, the authors compared distributions of demographic and clinical characteristics, in addition to neighborhood and environmental conditions, between patients diagnosed with lung cancer from 2015 through 2019 at Kaiser Permanente Northern California, National Cancer Institute-designated cancer centers (NCICCs), and all other non-NCICC hospitals within the same catchment area. Of 20,178 included patients, 30% were from Kaiser Permanente Northern California, 8% from NCICCs, and 62% from other non-NCICC hospitals. Compared to NCICC patients, Kaiser Permanente Northern California patients were more similar to other non-NCICC patients on most characteristics. Compared to other non-NCICC patients, Kaiser Permanente Northern California patients were slightly older, more likely to be female, and less likely to be Hispanic or Asian/Pacific Islander and to reside in lower socioeconomic status (SES) neighborhoods. In contrast, NCICC patients were younger, less likely to be female or from non-Asian/Pacific Islander minoritized racial groups, and more likely to present with early-stage disease and adenocarcinoma and to reside in neighborhoods with higher SES and lower air pollution than Kaiser Permanente Northern California or other non-NCICC patients. Patients from Kaiser Permanente Northern California, compared to NCICCs, are more broadly representative of the underlying patient population with lung cancer. Research using electronic health record data from integrated health care systems can contribute generalizable real-world evidence to benchmark and improve lung cancer care.

Representativeness of Patients With Lung Cancer in an Integrated Health Care Delivery System.

Observational research is important for understanding the real-world benefits of advancements in lung cancer care. Integrated health care systems, such as Kaiser Permanente Northern California, have extensive electronic health records suitable for such research, but the generalizability of their populations is often questioned. Leveraging data from the California Cancer Registry, the authors compared distributions of demographic and clinical characteristics, in addition to neighborhood and environmental conditions, between patients diagnosed with lung cancer from 2015 through 2019 at Kaiser Permanente Northern California, National Cancer Institute-designated cancer centers (NCICCs), and all other non-NCICC hospitals within the same catchment area. Of 20,178 included patients, 30% were from Kaiser Permanente Northern California, 8% from NCICCs, and 62% from other non-NCICC hospitals. Compared to NCICC patients, Kaiser Permanente Northern California patients were more similar to other non-NCICC patients on most characteristics. Compared to other non-NCICC patients, Kaiser Permanente Northern California patients were slightly older, more likely to be female, and less likely to be Hispanic or Asian/Pacific Islander and to reside in lower socioeconomic status (SES) neighborhoods. In contrast, NCICC patients were younger, less likely to be female or from non-Asian/Pacific Islander minoritized racial groups, and more likely to present with early-stage disease and adenocarcinoma and to reside in neighborhoods with higher SES and lower air pollution than Kaiser Permanente Northern California or other non-NCICC patients. Patients from Kaiser Permanente Northern California, compared to NCICCs, are more broadly representative of the underlying patient population with lung cancer. Research using electronic health record data from integrated health care systems can contribute generalizable real-world evidence to benchmark and improve lung cancer care.

Rationale and design of the KP ENRICH trial: A food is medicine intervention in low-income high-risk adults with diabetes within Kaiser Permanente

BackgroundFood insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D. MethodsThe Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy. ConclusionsThe results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D.

Predicting Self-Reported Social Risk in Medically Complex Adults Using Electronic Health Data.

Social barriers to health care, such as food insecurity, financial distress, and housing instability, may impede effective clinical management for individuals with chronic illness. Systematic strategies are needed to more efficiently identify at-risk individuals who may benefit from proactive outreach by health care systems for screening and referral to available social resources. To create a predictive model to identify a higher likelihood of food insecurity, financial distress, and/or housing instability among adults with multiple chronic medical conditions. We developed and validated a predictive model in adults with 2 or more chronic conditions who were receiving care within Kaiser Permanente Northern California (KPNC) between January 2017 and February 2020. The model was developed to predict the likelihood of a "yes" response to any of 3 validated self-reported survey questions related to current concerns about food insecurity, financial distress, and/or housing instability. External model validation was conducted in a separate cohort of adult non-Medicaid KPNC members aged 35-85 who completed a survey administered to a random sample of health plan members between April and June 2021 (n = 2820). We examined the performance of multiple model iterations by comparing areas under the receiver operating characteristic curves (AUCs). We also assessed algorithmic bias related to race/ethnicity and calculated model performance at defined risk thresholds for screening implementation. Patients in the primary modeling cohort (n = 11,999) had a mean age of 53.8 (±19.3) years, 64.7% were women, and 63.9% were of non-White race/ethnicity. The final, simplified model with 30 predictors (including utilization, diagnosis, behavior, insurance, neighborhood, and pharmacy-based variables) had an AUC of 0.68. The model remained robust within different race/ethnic strata. Our results demonstrated that a predictive model developed using information gleaned from the medical record and from public census tract data can be used to identify patients who may benefit from proactive social needs assessment. Depending on the prevalence of social needs in the target population, different risk output thresholds could be set to optimize positive predictive value for successful outreach. This predictive model-based strategy provides a pathway for prioritizing more intensive social risk outreach and screening efforts to the patients who may be in greatest need.

Diet quality and cardiometabolic risk factors among breast cancer survivors in the Pathways Study.

11039 Background: Women with breast cancer (BC) have higher risk of developing cardiometabolic conditions compared to women without BC. However, the relationship between healthy eating and onset of cardiometabolic conditions in BC survivors remains unknown. We set out to determine if diet quality at BC diagnosis was related to subsequent development of hypertension, diabetes, and dyslipidemia. Methods: This analysis included 3,415 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive BC (stages I-IV) at Kaiser Permanente Northern California (KPNC) between 2005 and 2013. Food frequency questionnaires were administered at or around the time of BC diagnosis and five diet quality indices (DQI) aligned with healthy eating were evaluated: Dietary Approaches to Stop Hypertension (DASH), a healthy plant-based dietary index (hPDI), 2020 Healthy Eating Index (HEI), American Cancer Society nutrition guidelines (ACS), and the alternate Mediterranean Diet (aMED). Incident hypertension, diabetes, and dyslipidemia were ascertained through electronic health records and participants were followed through first indication of these conditions, disenrollment from KPNC, death, or December 31, 2021. Scores were categorized into ascending quartiles of concordance for each DQI, and multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated. Results: There were 554 (16.2%) incident cases of hypertension, 362 (10.6%) of diabetes, and 652 (19.1%) of dyslipidemia over 39,263 person-years of follow-up. Participants in the highest compared to lowest HEI quartile had lower risks of hypertension (HR=0.70, 95% CI 0.53-0.92, Ptrend<0.01), diabetes (HR=0.56, 95% CI 0.40-0.77, Ptrend<0.001), and dyslipidemia (HR=0.76, 95% CI 0.59-0.99, Ptrend=0.03). Participants in the highest vs lowest hPDI quartile had lower risks of hypertension (HR=0.74, 95% CI 0.55-0.98, Ptrend<0.05) and diabetes (HR=0.65, 95% CI 0.46-0.93, Ptrend=0.02), but not dyslipidemia. Women in the highest vs lowest DASH and ACS quartiles had lower risks of diabetes (DASH:HR=0.56, 95% CI 0.39-0.79, Ptrend<0.001; ACS:HR=0.57, 95% CI 0.40-0.79, Ptrend<0.001), but not hypertension or dyslipidemia. No statistically significant differences for aMED were observed between those in the highest vs lowest quartiles. Overall, HRs were similar across DQIs for hypertension and diabetes, except for aMED, which slightly attenuated for diabetes. Conclusions: Diets concordant with HEI may provide the most overall benefit for preventing cardiometabolic conditions after a BC diagnosis. The benefit of diets aligned with hPDI, DASH, ACS, and aMED appear to vary by cardiometabolic condition. Future analyses will examine how these benefits may be modified by BC treatments. Consuming a healthful diet should be recommended to BC survivors for long-term cardiovascular health.

JAAD Game Changers: Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

JAAD Game Changers: Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

Beyond the pain: Decoding opioid use in advanced cancer ED visits.

e24034 Background: Patients with advanced cancer often turn to the emergency department (ED) for pain treatment, impacting their quality of life and escalating healthcare costs. A crucial step in reducing avoidable ED visits is to identify the characteristics of this patient group and explore potential intervention points. This study aims to characterize the use of narcotics in the ED among patients with advanced cancer. Methods: This retrospective cross-sectional study involved adults aged 18 and older diagnosed with Stage IV solid cancers who passed away within one year of diagnosis (excluding those who died within 30 days). Participants had at least one ED visit within that year at one of 21 cancer centers within Kaiser Permanente Northern California from 2018 to 2020. Demographics, clinical variables, frequencies, and trends in ED visits were collected and compared based on opioid utilization. Pain management details for those receiving opioids during ED visits were also recorded. Results: The study encompassed 2,554 patients with 6,406 ED visits in their final year of life. Sixty-one percent of these patients received opioids during their ED visits, with a median of three visits per patient. In 56% of visits, patients had filled an opioid prescription within the last 30 days. Morphine (39%) and hydromorphone (29%) were the most commonly administered opioids, primarily intravenously (66%). The prevalent cancer subtypes receiving opioids during ED visits were breast, head and neck, and upper GI. Among patients in treatment with chemo, radiation, or both, 65% received opioids during ED visits, a higher rate compared to the 55% of patients not in treatment. For treated patients, chemotherapy was associated with increased ED visits requiring opioid pain management. Median survival did not differ significantly between those who received opioids during ED visits (130 days) and those who did not (123 days). Conclusions: This study emphasizes the dynamic pain needs of this patient population throughout their final year, leading them to seek pain management from the ED when their pain exceeds their home regimen. Factors influencing these needs include cancer subtype and current treatment status, particularly chemotherapy. Further studies are essential to understanding the variations in pain needs over the final year, enabling providers to better recognize and address changes in patients' pain requirements outside the ED.

Evaluating the utility of routine survivorship exams in breast cancer: Modality of detection of recurrence in a prospective cohort study.

1629 Background: National Comprehensive Cancer Network surveillance guidelines for invasive breast cancer recommend a history and physical exam every 3-12 months for the first 5 years, followed by annually, and mammography every 12 months. However, frequent in-office visits create time toxicity for breast cancer survivors, may have low utility in recurrence detection, and can create false reassurance. This study evaluates the modality of breast cancer recurrence in an integrated health system with access to primary and specialty care. Methods: We investigated mode of detection of recurrent breast cancer in the Pathways Study, a prospective cohort study of adult women diagnosed with and treated for invasive breast cancer in Kaiser Permanente Northern California, with enrollment from 2006 to 2013, and follow-up through December 2021. In this analysis, we included 4,431 women diagnosed at Stages I-III. Cohort members were followed for recurrences, deaths, and other outcomes. Of primary interest was modality of detection of recurrence, categorized as patient-driven symptoms, surveillance mammogram, diagnostic testing (i.e., other surveillance imaging for recurrence such as PET CT or MRI), routine clinical breast exam, or incidental finding. Results: A total of 617 (13.9%) women were identified as having breast cancer recurrence. Patients with recurrence shared similar demographic characteristics to those without recurrence. The recurrence population had median age of 59.2 years, BMI of 28.2 kg/m2, and racial/ethnic composition of 63% white,13% Hispanic,12% Asian, and 10% black. The median time from diagnosis to recurrence was 4 years. Seventy percent of recurrences were found to have distant metastatic disease, of which only 6.7% had concurrent local nodal and/or breast involvement. For those without metastases, 17.7% had recurrence localized in the ipsilateral breast, 2.8% in both the breast and locoregional nodes, and 9.3% only in locoregional nodes. Most recurrences were detected by patient driven symptoms (69.4%). Among the total cases, 8.1% of patients were diagnosed by routine mammogram, 10.9% with diagnostic testing and 4.5% by incidental finding. Recurrences in 6.8% of patients were detected by routine physician exam. Overall survival for those with recurrence was 31.1% and most deaths were attributed to breast cancer (89%). Conclusions: Our study, the largest investigation of breast cancer recurrence modality of detection in a US community oncology setting with comprehensive care, revealed the majority of recurrences were identified through patient self-detection with only 6.8% detected by physician exam. Most recurrences were distant, underscoring the need for alternative screening modalities to detect metastatic recurrences earlier, especially in the context of emerging treatments and improved survival rates for oligometastatic disease.

Patient factors associated with chemotherapy modifications: Results from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.

520 Background: Understanding patient factors associated with an increased likelihood of receiving chemotherapy modifications is important for treatment planning and anticipating which patient groups might require extra support through the course of treatment. Methods: We have evaluated patient and tumor factors associated with chemotherapy modifications in a cohort of 9700 women receiving adjuvant chemotherapy for breast cancer at Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA) in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study diagnosed between 2005-2019. The outcome variable, receipt of a ‘chemotherapy modification’ is defined as a composite representing any of the following deviations from the intended regimen: dose reduction >10% (first cycle or overall), extensive delay (any single delay >14 days), regimen change, or receipt of fewer cycles of any given drug than intended in the original chemotherapy plan. Multivariable-adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Several factors were associated with chemotherapy modifications. Notably, older age was associated with an increased likelihood of modifications (p-trend<0.001), with adults aged 80+ years at diagnosis 1.93-fold more likely to experience modification than adults 18-39 years (95% CI: 1.50-2.50). Increased comorbidity and BMI were also associated with increased likelihood of modification (p-trend for both:<0.001), with patients with a Charlson Comorbidity Index of 3+ (vs 0) having an PR of 1.33 (95% CI: 1.19-1.48) and those with a BMI of 35+ kg/m2 (vs <25 kg/m2) having an PR of 1.53 (95% CI: 1.41-1.65). HER2+ status (PR HER2+ vs HER2-: 1.99 95% CI: 1.89-2.10) and higher stage of disease (PR IIIA vs I:1.24; 95% CI: 1.13-1.35; p-trend<0.001) were associated with increased likelihood of chemotherapy modification, while hormone receptor positivity was associated with lower likelihood of modification (PR ER+ and/or PR+ vs ER-/PR-: 0.93; 95% CI: 0.88-0.99). Diagnosis in more recent years was also associated with decreased likelihood of modification (PR 2015-2019 vs 2004-2009: 0.70; 95% CI: 0.66-0.75), as was higher neighborhood income (PR Q4 vs Q1: 0.78; 95% CI: 0.72-0.84). Conclusions: Several patient-level and clinical factors were associated with chemotherapy modifications, including age, comorbidity, BMI, and ER/PR/HER2 status. Future research might focus on the groups noted to have increased risk of treatment modification to better understand the factors underlying these changes, as well as the impact on patient outcomes.

Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.

10502 Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k, and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]

Revisiting the Association of ECOG Performance Status With Clinical Outcomes in Diverse Patients With Cancer.

The ECOG performance status (PS) scale was developed to support national clinical trials, but the degree to which ECOG PS predicts clinical outcomes in patient subgroups outside of clinical trials is relatively unknown. This study examined associations between ECOG PS and adverse outcomes in a diverse community oncology population. In this retrospective cohort study, demographic and clinical characteristics, including the most recent ECOG PS between January 1, 2017, and December 31, 2019, were examined for patients receiving cancer treatment within Kaiser Permanente Northern California (KPNC). Proportional hazard models were used to evaluate the effect of ECOG PS on adverse outcomes. A total of 21,730 patients were identified. Overall, most patients had an ECOG PS of 0 (42.5%) or 1 (42.5%). In multivariable analysis, an ECOG PS of 3 or 4 was associated with higher risk of 30-day emergency department visits (adjusted hazard ratio [aHR], 3.85; 95% CI, 3.47-4.26), 30-day hospitalizations (aHR, 4.70; 95% CI, 4.12-5.36), and 6-month mortality (aHR, 7.34; 95% CI, 6.64-8.11) compared with an ECOG PS of 0. Additionally, we found that upper gastrointestinal and stage IV cancers were associated with a higher risk of adverse outcomes compared with breast and stage I cancers, respectively. When adjusted for ECOG PS, African American race, Asian race, and female sex were associated with a lower risk of mortality than White race and male sex. An ECOG PS of 3 or 4 was more predictive of mortality in younger patients and those with breast cancer (P<.001). ECOG PS and upper gastrointestinal and stage IV cancers were independently associated with increased risk of emergency department visits, hospitalizations, and mortality, whereas African American and Asian race and female sex were associated with decreased risk of mortality. An ECOG PS of 3 or 4 was more predictive of an increased risk of mortality in younger patients and patients with breast cancer. These findings can enhance the use of ECOG PS for clinical decision-making and defining eligibility for clinical trials.

Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL).

11158 Background: Zanubrutinib (zanu) is a next-generation selective Bruton’s tyrosine kinase inhibitor (BTKi) with superior efficacy over first generation ibrutinib (ibru) in CLL/SLL patients (pts). Herein we present real-world treatment patterns based on a formulary change from ibrutinib to zanubrutinib in pts with CLL/SLL in an integrated community oncology practice. Methods: We retrospectively analyzed CLL/SLL pts 18 years and older who received at least 3 months of zanubrutinib from October 1, 2018 to September 15, 2023 at Kaiser Permanente Northern California. Treatment patterns, treatment-emergent adverse events (TEAEs: AEs reported during BTKi use), treatment-limiting adverse events (TLAEs: AEs leading to BTKi discontinuation), and mortality were reported. Results: A total of 281 pts received zanu (median age: 71 years; 64% male); 190 pts switched from ibru (ibru-zanu), and 91 pts received zanu only. Most pts were White (75%) followed by Black (10%). Compared with ibru-zanu pts, zanu-only pts were older (median age 74 vs 69 years) and had more comorbidities but were comparable in sex, race, and insurance type. The primary reasons for switching to zanu were formulary change (73%) and progression (15%). Median follow-up time after initiation of first BTKi was longer in the ibru-zanu group (Table). Similar TEAE rates were seen with use of both BTKi therapies, with lower TLAE rates with zanu (Table). Most common TLAE were atrial fibrillation and fatigue for ibru, and cytopenias and rash/bruising for zanu. Cardiac TLAE and non-TLAE rates overall were higher with ibru than zanu, and the rates decreased while on zanu after switching from ibru (Table). Dose modification occurred in 34 pts on ibru and 50 pts on zanu (18 ibru-zanu pts, 32 zanu-only pts), with reductions primarily for grade 1-2 AEs. Of the 281 pts who received zanu, 79% remain on treatment at the end of data collection; 13 pts died (8 from infection, including 5 from COVID), with no reports of treatment-related deaths. Conclusions: In the real-world setting post-formulary change, zanu is effective and safe in pts with or without prior ibru use. Zanu use had lower cardiotoxicity and TLAE rates than ibru though data was limited by a difference in follow-up time. Similar results were seen in zanu-only pts despite being older and having more comorbidities, with discontinuation most often due to grade &lt;3 AEs. [Table: see text]

Patient characteristics associated with primary prophylactic granulocyte colony-stimulating factor (G-CSF) use among women treated for early-stage breast cancer.

e12605 Background: The National Comprehensive Cancer Network (NCCN) recommends several chemotherapy regimens for early-stage breast cancer that have elevated risk of neutropenia (&gt;20%). In these regimens, primary prophylactic use of granulocyte colony-stimulating factor (G-CSF) is recommended. Little is known about how patient-level factors relate to receipt of prophylactic G-CSF among women receiving these regimens. Methods: In the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study, we examined use of G-CSF among women with stage I-IIIA breast cancer between 2005-2019 in Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA). We evaluated the patient-level factors associated with primary prophylactic G-CSF use (≤7 days before to ≤3 days after first day of chemotherapy) among women receiving chemotherapy regimens with high risk of neutropenia, for which the NCCN guidelines recommend prophylactic G-CSF use. Multivariable-adjusted prevalence ratios (PR) and their corresponding 95% Confidence Intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Overall, while all 3,083 women receiving these regimens ultimately received G-CSF, 2412 (79%) received primary prophylactic G-CSF within the period 7 days prior to 3 days post first cycle. Younger women had higher prevalence of prophylactic G-CSF receipt (82.7% in ages 18-39 years vs. 58.1% in 70+ years). Black women had higher prevalence of receipt compared to white women (82.7% in non-Hispanic Black women vs 76.1% in White women). Women with a higher body mass index (BMI) had lower prevalence of receipt compared to normal weight women (73.3% in 35+ kg/m2 group vs 81.5% in 18.5-&lt;25 kg/m2 group). In multivariable models, older women were less likely to receive prophylactic G-CSF (PR70+ vs 18-39: 0.69; 95% CI: 0.57-0.84; p-trend&lt;0.001), as were those with a higher BMI (PRBMI 35+ vs 18.5-&lt;25: 0.92; 95% CI: 0.85, 0.97; p-trend=0.006), and a later year of diagnosis (PR2016-19 vs 2005-07: 0.81; 95% CI: 0.77, 0.85; p-trend&lt;0.001). Although race/ethnicity was not significantly associated with receipt of prophylactic G-CSF use overall in multivariable models, we observed Non-Hispanic Black women to experience slightly higher likelihood of G-CSF receipt than Non-Hispanic White women (PR: 1.08; 95% CI: 1.02, 1.15). Conclusions: Women of older age and those with higher BMI were less likely to receive primary prophylactic G-CSF, as were women treated in later years. Further research looking at timing of G-CSF use is warranted, as are studies examining provider/facility-level factors in relation to patterns of G-CSF use, G-CSF’s impact on survival outcomes, and the real-world impact of decisions around G-CSF use across age, BMI, and racial/ethnic groups.

Population-Level Identification of Patients With Lynch Syndrome for Clinical Care, Quality Improvement, and Research.

Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system. Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively. Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS. It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.