Spending Analysis of Machine Learning-Based Communication Nudges in Oncology.

BACKGROUND: Serious illness conversations (SICs) in the outpatient setting may improve mood and quality of life among patients with cancer and decrease aggressive end-of-life care. Interventions informed by behavioral economics may increase rates of SICs between oncology clinicians and patients, but the impact of these interventions on end-of-life spending is unknown. METHODS: This study is a secondary analysis of a stepped-wedge cluster randomized, controlled trial that involved nine medical oncology practices and their high-risk patients at a large academic institution between June 2019 and April 2020. The study included 1187 patients who were identified by a machine-learning algorithm as high risk of 180-day mortality and who died by December 2020. The patients were randomly assigned to standard of care (controls) or to a behavioral intervention designed to increase clinician-initiated SICs. We abstracted spending - defined as inflation-adjusted costs for acute care (inpatient plus emergency room), office/outpatient care, intravenous systemic therapy, other therapy (e.g., radiation), long-term care, and hospice - from the institution's accounting system, and we captured spending at inpatient, outpatient, and pharmacy settings. To evaluate intervention impacts on spending, we used a two-part model, first using logistic regression to model zero versus nonzero spending and second using generalized linear mixed models with gamma distribution and log-link function to model daily mean spending in the last 180days of life. Models were adjusted for clinic and wedge fixed effects, and they were clustered at the oncologist level. For all patients with at least one SIC within 6 months of death, we also calculated their mean daily spending before and after SIC. RESULTS: Median age at death was 68years (interquartile range, 15.5), 317 patients (27%) were Black or of ethnicities other than white, and 448 patients (38%) had an SIC. The intervention was associated with lower unadjusted mean daily spending in the last 6 months of life for the intervention group versus controls ($377.96 vs. $449.92; adjusted mean difference, -$75.33; 95% confidence interval, -$136.42 to -$14.23; P=0.02), translating to $13,747 total adjusted savings per decedent and $13 million in cumulative savings across all decedents in the intervention group. Compared with controls, patients in the intervention group incurred lower mean daily spending for systemic therapy (adjusted difference, -$44.59; P=0.001), office/outpatient care (-$9.62; P=0.001), and other therapy (-$8.65; P=0.04). The intervention was not associated with differences in end-of-life spending for acute care, long-term care, or hospice. Results were consistent for spending in the last 1 and 3 months of life and after adjusting for age, race, and ethnicity. For patients with SICs, mean daily spending decreased by $37.92 following the first SIC ($329.87 vs. $291.95). CONCLUSIONS: A machine learning-based, behaviorally informed intervention to prompt SICs led to end-of-life savings among patients with cancer, driven by decreased systemic therapy and outpatient spending. (Funded by the Penn Center for Precision Medicine and the National Institutes of Health; ClinicalTrials.gov number, NCT03984773.).

Electronic Medical Record-Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non-Small Cell Lung Cancer: Results From a Prospective Clinical Trial.

PURPOSE: Less than half of the patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)-based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P = .026), and received NCCN guideline-concordant care (89.8% v 78.2%, P = .035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team-focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites.

Clinician- and Patient-Directed Communication Strategies for Patients With Cancer at High Mortality Risk: A Cluster Randomized Trial.

Importance: Serious illness conversations (SICs) that elicit patients' values, goals, and care preferences reduce anxiety and depression and improve quality of life, but occur infrequently for patients with cancer. Behavioral economic implementation strategies (nudges) directed at clinicians and/or patients may increase SIC completion. Objective: To test the independent and combined effects of clinician and patient nudges on SIC completion. Design, Setting, and Participants: A 2 × 2 factorial, cluster randomized trial was conducted from September 7, 2021, to March 11, 2022, at oncology clinics across 4 hospitals and 6 community sites within a large academic health system in Pennsylvania and New Jersey among 163 medical and gynecologic oncology clinicians and 4450 patients with cancer at high risk of mortality (≥10% risk of 180-day mortality). Interventions: Clinician clusters and patients were independently randomized to receive usual care vs nudges, resulting in 4 arms: (1) active control, operating for 2 years prior to trial start, consisting of clinician text message reminders to complete SICs for patients at high mortality risk; (2) clinician nudge only, consisting of active control plus weekly peer comparisons of clinician-level SIC completion rates; (3) patient nudge only, consisting of active control plus a preclinic electronic communication designed to prime patients for SICs; and (4) combined clinician and patient nudges. Main Outcomes and Measures: The primary outcome was a documented SIC in the electronic health record within 6 months of a participant's first clinic visit after randomization. Analysis was performed on an intent-to-treat basis at the patient level. Results: The study accrued 4450 patients (median age, 67 years [IQR, 59-75 years]; 2352 women [52.9%]) seen by 163 clinicians, randomized to active control (n = 1004), clinician nudge (n = 1179), patient nudge (n = 997), or combined nudges (n = 1270). Overall patient-level rates of 6-month SIC completion were 11.2% for the active control arm (112 of 1004), 11.5% for the clinician nudge arm (136 of 1179), 11.5% for the patient nudge arm (115 of 997), and 14.1% for the combined nudge arm (179 of 1270). Compared with active control, the combined nudges were associated with an increase in SIC rates (ratio of hazard ratios [rHR], 1.55 [95% CI, 1.00-2.40]; P = .049), whereas the clinician nudge (HR, 0.95 [95% CI, 0.64-1.41; P = .79) and patient nudge (HR, 0.99 [95% CI, 0.73-1.33]; P = .93) were not. Conclusions and Relevance: In this cluster randomized trial, nudges combining clinician peer comparisons with patient priming questionnaires were associated with a marginal increase in documented SICs compared with an active control. Combining clinician- and patient-directed nudges may help to promote SICs in routine cancer care. Trial Registration: ClinicalTrials.gov Identifier: NCT04867850.

A Framework for Integrating Telehealth Equitably across the cancer care continuum.

The COVID-19 pandemic placed a spotlight on the potential to dramatically increase the use of telehealth across the cancer care continuum, but whether and how telehealth can be implemented in practice in ways that reduce, rather than exacerbate, inequities are largely unknown. To help fill this critical gap in research and practice, we developed the Framework for Integrating Telehealth Equitably (FITE), a process and evaluation model designed to help guide equitable integration of telehealth into practice. In this manuscript, we present FITE and showcase how investigators across the National Cancer Institute's Telehealth Research Centers of Excellence are applying the framework in different ways to advance digital and health equity. By highlighting multilevel determinants of digital equity that span further than access alone, FITE highlights the complex and differential ways structural determinants restrict or enable digital equity at the individual and community level. As such, achieving digital equity will require strategies designed to not only support individual behavior but also change the broader context to ensure all patients and communities have the choice, opportunity, and resources to use telehealth across the cancer care continuum.

University of Pennsylvania Telehealth Research Center of Excellence.

Drawing from insights from communication science and behavioral economics, the University of Pennsylvania Telehealth Research Center of Excellence (Penn TRACE) is designing and testing telehealth strategies with the potential to transform access to care, care quality, outcomes, health equity, and health-care efficiency across the cancer care continuum, with an emphasis on understanding mechanisms of action. Penn TRACE uses lung cancer care as an exemplar model for telehealth across the care continuum, from screening to treatment to survivorship. We bring together a diverse and interdisciplinary team of international experts and incorporate rapid-cycle approaches and mixed methods evaluation in all center projects. Our initiatives include a pragmatic sequential multiple assignment randomized trial to compare the effectiveness of telehealth strategies to increase shared decision-making for lung cancer screening and 2 pilot projects to test the effectiveness of telehealth to improve cancer care, identify multilevel mechanisms of action, and lay the foundation for future pragmatic trials. Penn TRACE aims to produce new fundamental knowledge and advance telehealth science in cancer care at Penn and nationally.

Cancer Treatment Before and After Physician-Pharmacy Integration.

Importance: Integration of pharmacies with physician practices, also known as medically integrated dispensing, is increasing in oncology. However, little is known about how this integration affects drug use, expenditures, medication adherence, or time to treatment initiation. Objective: To examine the association of physician-pharmacy integration with oral oncology drug expenditures, use, and patient-centered measures. Design, Setting, and Participants: This cohort study used claims data from a large commercial insurer in the US to analyze changes in outcome measures among patients treated by pharmacy-integrating vs nonintegrating community oncologists in 14 states between January 1, 2011, and December 31, 2019. Commercially insured patients were aged 18 to 64 years with 1 of the following advanced-stage diagnoses: breast cancer, colorectal cancer, kidney cancer, lung cancer, melanoma, or prostate cancer. Data analysis was conducted from May 2023 to March 2024. Exposure: Treatment by a pharmacy-integrating oncologist, ascertained by the presence of an on-site pharmacy or nonpharmacy dispensing site. Main Outcomes and Measures: Oral, intravenous (IV), total, and out-of-pocket drug expenditures for a 6-month episode of care; share of patients prescribed oral drugs; days' supply of oral drugs; medication adherence measured by proportion of days covered; and time to treatment initiation. The association between an oncologist's pharmacy integration and each outcome of interest was estimated using the difference-in-differences estimator. Results: Between 2012 and 2019, 3159 oncologists (745 females [27.1%], 2002 males [72.9%]) treated 23 968 patients (66.4% female; 53.4% aged 55-64 years). Of the 3159 oncologists, 578 (18.3%) worked in practices that integrated with pharmacies (with a low rate in 2011 of 0% and a high rate in 2019 of 31.5%). In the full sample (including all cancer sites), after physician-pharmacy integration, no significant changes were found in oral drug expenditures, IV drug expenditures, or total drug expenditures. There was, however, an increase in days' supply of oral drugs (5.96 days; 95% CI, 0.64-11.28 days; P = .001). There were no significant changes in out-of-pocket expenditures, medication adherence, or time to treatment initiation of oral drugs. In the breast cancer sample, there was an increase in oral drug expenditures ($244; 95% CI, $41-$446; P = .02) and a decrease in IV drug expenditures (-$4187; 95% CI, -$8293 to -$80; P = .05). Conclusions and Relevance: Results of this cohort study indicated that the integration of oncology practices with pharmacies was not associated with significant changes in expenditures or clear patient-centered benefits.

Association of Remote Patient-Reported Outcomes and Step Counts With Hospitalization or Death Among Patients With Advanced Cancer Undergoing Chemotherapy: Secondary Analysis of the PROStep Randomized Trial.

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.

Association between oral targeted cancer drug net health benefit, uptake, and spending.

BACKGROUND: Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-out-pocket (OOP) costs. The ASCO Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. METHODS: We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide de-identified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication. RESULTS: We included 8,524 patients with incident claims for eight oral TCDs with nine first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (IQR $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10,118.79 (IQR $6,365.95-$10,600.37) for an incident 28-day TCD supply. Total spending increased $1,083.56 for each 10-point increase in NHB score (95% CI $1,050.27-$1,116.84, p < .01 for H0=$0). CONCLUSION: Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Trends in low-value cancer care during the COVID-19 pandemic.

OBJECTIVE: To assess the association between the onset of the COVID-19 pandemic and change in low-value cancer services. STUDY DESIGN: In this retrospective cohort study, we used administrative claims from the HealthCore Integrated Research Environment, a repository of medical and pharmacy data from US health plans representing more than 80 million members, between January 1, 2016, and March 31, 2021. METHODS: We used linear probability models to investigate the relation between the onset of the COVID-19 pandemic and 4 guideline-based metrics of low-value cancer care: (1) conventional fractionation radiotherapy instead of hypofractionated radiotherapy for early-stage breast cancer; (2) non-guideline-based antiemetic use for minimal-, low-, or moderate- to high-risk chemotherapies; (3) off-pathway systemic therapy; and (4) aggressive end-of-life care. We identified patients with new diagnoses of breast, colorectal, and/or lung cancer. We excluded members who did not have at least 6 months of continuous insurance coverage and members with prevalent cancers. RESULTS: Among 117,116 members (median [IQR] age, 60 [53-69] years; 72.4% women), 59,729 (51.0%) had breast cancer, 25,751 (22.0%) had colorectal cancer, and 31,862 (27.2%) had lung cancer. The payer mix was 18.7% Medicare Advantage or Medicare supplemental and 81.2% commercial non-Medicare. Rates of low-value cancer services exhibited minimal changes during the pandemic, as adjusted percentage-point differences were 3.93 (95% CI, 1.50-6.36) for conventional radiotherapy, 0.82 (95% CI, -0.62 to 2.25) for off-pathway systemic therapy, -3.62 (95% CI, -4.97 to -2.27) for non-guideline-based antiemetics, and 2.71 (95% CI, -0.59 to 6.02) for aggressive end-of-life care. CONCLUSIONS: Low-value cancer care remained prevalent throughout the pandemic. Policy makers should consider changes to payment and incentive design to turn the tide against low-value cancer care.

Applying Machine Learning Techniques to Implementation Science.

Machine learning (ML) approaches could expand the usefulness and application of implementation science methods in clinical medicine and public health settings. The aim of this viewpoint is to introduce a roadmap for applying ML techniques to address implementation science questions, such as predicting what will work best, for whom, under what circumstances, and with what predicted level of support, and what and when adaptation or deimplementation are needed. We describe how ML approaches could be used and discuss challenges that implementation scientists and methodologists will need to consider when using ML throughout the stages of implementation.

Detection of Medication Taking Using a Wrist-Worn Commercially Available Wearable Device.

PURPOSE: Medication nonadherence is a persistent and costly problem across health care. Measures of medication adherence are ineffective. Methods such as self-report, prescription claims data, or smart pill bottles have been used to monitor medication adherence, but these are subject to recall bias, lack real-time feedback, and are often expensive. METHODS: We proposed a method for monitoring medication adherence using a commercially available wearable device. Passively collected motion data were analyzed on the basis of the Movelet algorithm, a dictionary learning framework that builds person-specific chapters of movements from short frames of elemental activities within the movements. We adapted and extended the Movelet method to construct a within-patient prediction model that identifies medication-taking behaviors. RESULTS: Using 15 activity features recorded from wrist-worn wearable devices of 10 patients with breast cancer on endocrine therapy, we demonstrated that medication-taking behavior can be predicted in a controlled clinical environment with a median accuracy of 85%. CONCLUSION: These results in a patient-specific population are exemplar of the potential to measure real-time medication adherence using a wrist-worn commercially available wearable device.

Protocol for a pragmatic stepped wedge cluster randomized clinical trial testing behavioral economic implementation strategies to increase supplemental breast MRI screening among patients with extremely dense breasts.

BACKGROUND: Increased breast density augments breast cancer risk and reduces mammography sensitivity. Supplemental breast MRI screening can significantly increase cancer detection among women with dense breasts. However, few women undergo this exam, and screening is consistently lower among racially minoritized populations. Implementation strategies informed by behavioral economics ("nudges") can promote evidence-based practices by improving clinician decision-making under conditions of uncertainty. Nudges directed toward clinicians and patients may facilitate the implementation of supplemental breast MRI. METHODS: Approximately 1600 patients identified as having extremely dense breasts after non-actionable mammograms, along with about 1100 clinicians involved with their care at 32 primary care or OB/GYN clinics across a racially diverse academically based health system, will be enrolled. A 2 × 2 randomized pragmatic trial will test nudges to patients, clinicians, both, or neither to promote supplemental breast MRI screening. Before implementation, rapid cycle approaches informed by clinician and patient experiences and behavioral economics and health equity frameworks guided nudge design. Clinicians will be clustered into clinic groups based on existing administrative departments and care patterns, and these clinic groups will be randomized to have the nudge activated at different times per a stepped wedge design. Clinicians will receive nudges integrated into the routine mammographic report or sent through electronic health record (EHR) in-basket messaging once their clinic group (i.e., wedge) is randomized to receive the intervention. Independently, patients will be randomized to receive text message nudges or not. The primary outcome will be defined as ordering or scheduling supplemental breast MRI. Secondary outcomes include MRI completion, cancer detection rates, and false-positive rates. Patient sociodemographic information and clinic-level variables will be examined as moderators of nudge effectiveness. Qualitative interviews conducted at the trial's conclusion will examine barriers and facilitators to implementation. DISCUSSION: This study will add to the growing literature on the effectiveness of behavioral economics-informed implementation strategies to promote evidence-based interventions. The design will facilitate testing the relative effects of nudges to patients and clinicians and the effects of moderators of nudge effectiveness, including key indicators of health disparities. The results may inform the introduction of low-cost, scalable implementation strategies to promote early breast cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05787249. Registered on March 28, 2023.

Protocol to evaluate sequential electronic health record-based strategies to increase genetic testing for breast and ovarian cancer risk across diverse patient populations in gynecology practices.

BACKGROUND: Germline genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) for individuals including, but not limited to, those with a personal history of ovarian cancer, young-onset (< 50 years) breast cancer, and a family history of ovarian cancer or male breast cancer. Genetic testing is underused overall, and rates are consistently lower among Black and Hispanic populations. Behavioral economics-informed implementation strategies, or nudges, directed towards patients and clinicians may increase the use of this evidence-based clinical practice. METHODS: Patients meeting eligibility for germline genetic testing for breast and ovarian cancer will be identified using electronic phenotyping algorithms. A pragmatic cohort study will test three sequential strategies to promote genetic testing, two directed at patients and one directed at clinicians, deployed in the electronic health record (EHR) for patients in OB-GYN clinics across a diverse academic medical center. We will use rapid cycle approaches informed by relevant clinician and patient experiences, health equity, and behavioral economics to optimize and de-risk our strategies and methods before trial initiation. Step 1 will send patients messages through the health system patient portal. For non-responders, step 2 will reach out to patients via text message. For non-responders, Step 3 will contact patients' clinicians using a novel "pend and send" tool in the EHR. The primary implementation outcome is engagement with germline genetic testing for breast and ovarian cancer predisposition, defined as a scheduled genetic counseling appointment. Patient data collected through the EHR (e.g., race/ethnicity, geocoded address) will be examined as moderators of the impact of the strategies. DISCUSSION: This study will be one of the first to sequentially examine the effects of patient- and clinician-directed strategies informed by behavioral economics on engagement with breast and ovarian cancer genetic testing. The pragmatic and sequential design will facilitate a large and diverse patient sample, allow for the assessment of incremental gains from different implementation strategies, and permit the assessment of moderators of strategy effectiveness. The findings may help determine the impact of low-cost, highly transportable implementation strategies that can be integrated into healthcare systems to improve the use of genomic medicine. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05721326. Registered February 10, 2023. https://www. CLINICALTRIALS: gov/study/NCT05721326.

Estimating Pack-Year Eligibility for Lung Cancer Screening Using 2 Yes or No Questions.

This cross-sectional study describes the development and testing the accuracy of using 2 yes or no questions to estimate pack-year eligibility for lung cancer screening.

Cluster Randomized Pragmatic Clinical Trial Testing Behavioral Economic Implementation Strategies to Improve Tobacco Treatment for Patients With Cancer Who Smoke.

PURPOSE: Few cancer centers systematically engage patients with evidence-based tobacco treatment despite its positive effect on quality of life and survival. Implementation strategies directed at patients, clinicians, or both may increase tobacco use treatment (TUT) within oncology. METHODS: We conducted a four-arm cluster-randomized pragmatic trial across 11 clinical sites comparing the effect of strategies informed by behavioral economics on TUT engagement during oncology encounters with cancer patients. We delivered electronic health record (EHR)-based nudges promoting TUT across four nudge conditions: patient only, clinician only, patient and clinician, or usual care. Nudges were designed to counteract cognitive biases that reduce TUT engagement. The primary outcome was TUT penetration, defined as the proportion of patients with documented TUT referral or a medication prescription in the EHR. Generalized estimating equations were used to estimate the parameters of a linear model. RESULTS: From June 2021 to July 2022, we randomly assigned 246 clinicians in 95 clusters, and collected TUT penetration data from their encounters with 2,146 eligible patients who smoke receiving oncologic care. Intent-to-treat (ITT) analysis showed that the clinician nudge led to a significant increase in TUT penetration versus usual care (35.6% v 13.5%; OR = 3.64; 95% CI, 2.52 to 5.24; P < .0001). Completer-only analysis (N = 1,795) showed similar impact (37.7% clinician nudge v 13.5% usual care; OR = 3.77; 95% CI, 2.73 to 5.19; P < .0001). Clinician type affected TUT penetration, with physicians less likely to provide TUT than advanced practice providers (ITT OR = 0.67; 95% CI, 0.51 to 0.88; P = .004). CONCLUSION: EHR nudges, informed by behavioral economics and aimed at oncology clinicians, appear to substantially increase TUT penetration. Adding patient nudges to the implementation strategy did not affect TUT penetration rates.

Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.

PURPOSE: Current guidelines recommend molecular genotyping for patients newly diagnosed with metastatic nonsquamous (mNSq) non-small-cell lung cancer (NSCLC). The association between availability of molecular genotyping before first line (1L) therapy and overall survival (OS) is not known. METHODS: We conducted a real-world cohort study using electronic health records in patients newly diagnosed with mNSq NSCLC. Cox proportional-hazards multivariable regression models were constructed to examine the association between OS and test result availability before 1L therapy, adjusting for covariates. Additional analyses were conducted to assess the consistency and strength of the relationship. Multivariable logistic regression models were used to examine the association between concurrent tissue and plasma testing (v tissue alone) and result availability. RESULTS: Three hundred twenty-six patients were included, 80% (261/326) with results available before 1L (available testing group), and 20% (65/326) without results available (unavailable testing group). With 14.2-month median follow-up, patients in the available testing group had significantly longer OS relative to the unavailable testing group (adjusted hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P < .0001). The adjusted odds of availability of results before 1L therapy was higher with concurrent tissue and plasma testing (v tissue testing alone; adjusted odds ratio, 2.06; 95% CI, 1.09 to 3.90; P = .026). CONCLUSION: Among patients with mNSq NSCLC in a real-world cohort, availability of molecular genotyping results before 1L therapy was associated with significantly better OS. Concurrent tissue and plasma testing was associated with a higher odds of availability of results before 1L therapy. These findings warrant renewed attention to the completion of molecular genotyping before 1L therapy.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Behavioural economic interventions to embed palliative care in community oncology (BE-EPIC): study protocol for the BE-EPIC randomised controlled trial.

INTRODUCTION: Palliative care (PC) is a medical specialty focusing on providing relief from the symptoms and stress of serious illnesses such as cancer. Early outpatient specialty PC concurrent with cancer-directed treatment improves quality of life and symptom burden, decreases aggressive end-of-life care and is an evidence-based practice endorsed by national guidelines. However, nearly half of patients with advanced cancer do not receive specialty PC prior to dying. The objective of this study is to test the impact of an oncologist-directed default PC referral orders on rates of PC utilisation and patient quality of life. METHODS AND ANALYSIS: This single-centre two-arm pragmatic randomised trial randomises four clinician-led pods, caring for approximately 250 patients who meet guideline-based criteria for PC referral, in a 1:1 fashion into a control or intervention arm. Intervention oncologists receive a nudge consisting of an electronic health record message indicating a patient has a default pended order for PC. Intervention oncologists are given an opportunity to opt out of referral to PC. Oncologists in pods randomised to the control arm will receive no intervention beyond usual practice. The primary outcome is completed PC visits within 12 weeks. Secondary outcomes are change in quality of life and absolute quality of life scores between the two arms. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at the University of Pennsylvania. Study results will be disseminated in peer-reviewed journals and scientific conferences using methods that describe the results in ways that key stakeholders can best understand and implement. TRIAL REGISTRATION NUMBER: NCT05365997.