Comparative effectiveness of treatment approaches for early invasive breast cancer.

BACKGROUND: Randomized controlled trials (RCTs) suggested breast conserving therapy (BCT) and mastectomy have similar survival for early-stage breast cancer, whereas observational studies reported survival advantage for BCT. We aimed to address biases in observational studies to compare the effect of BCT and mastectomy on survival. METHODS: We emulated a target trial using institutional cancer registry. We included adult women diagnosed with early invasive first primary breast tumors ≤ 5 cm between July 2011 and December 2017. We used cloning, censoring, and weighting to estimate risk differences (RDs) and risk ratios (RRs) for all-cause mortality and recurrence or all-cause mortality between BCT and mastectomy (reference). RESULTS: Our study population comprised 534 observations with breast cancer. Median age was 56 years and 65 % were racial/ethnic minorities. The 8-year RD was 1.5 % (95 % confidence limits [CL]: -7.0 %, 9.8 %) and RR was 1.1 (95 % CL: 0.57, 2.2) for all-cause mortality. Results for recurrence or mortality were similar. CONCLUSIONS: Our results suggest that target trial emulation to mitigate selection and immortal-time biases in observational studies may generate estimates that are more compatible with RCTs when comparing the effects of BCT and mastectomy on survival. Studies with longer follow-up and more events are needed to confirm our findings.

Effectiveness of provider communication training for increasing human papillomavirus vaccine initiation at a safety-net health system.

Background: Strong provider recommendation can increase uptake of human papillomavirus (HPV) vaccination. Therefore, we developed and implemented a provider education intervention on communication strategies for recommending HPV vaccination with clinic-level audit and feedback (HPV: Communicating about HPV to Adults and Teens [HPV CHAT]). We aimed to evaluate the effect of HPV CHAT on HPV vaccine uptake in seven family medicine and pediatric clinics in a large urban health system (USA). Methods: We used a quasi-experimental design, where the eligible population included people aged 9-26 years with at least one encounter in June 2020-February 2023 at one of the participating community health clinics. We used interrupted time-series analysis to assess changes in the prevalence of HPV vaccine uptake. We used segmented Poisson regression with a log link function to estimate prevalence ratios (PR) and 95% confidence limits (CL) for level (immediate) and slope (over time) changes with adjustment for seasonality using Fourier transformation. Results: Our study population comprised 60,328 observations in which the median age was 17 years (interquartile range: 13-21). A majority (58%) were female and 87% were racial/ethnic minorities. Overall, we observed no sizeable effect of the intervention on HPV vaccination uptake. Nonetheless, heterogeneity was observed by age group with modest increases in individuals aged 9-12 and 13-17 years. Conclusion: Our provider feedback intervention had minimal effect on increasing prevalence of HPV vaccination in seven family medicine and pediatric clinics. Novel strategies are needed to address provider barriers related to HPV vaccination.

Evaluation of a human papillomavirus vaccination training implementation in clinical and community settings across different clinical roles.

Improving human papillomavirus (HPV) vaccination is a national priority but uptake declined following the coronavirus pandemic. A strong predictor of HPV vaccination in the USA is a strong provider recommendation. Therefore, we developed a brief, asynchronous training on HPV vaccine recommendations in clinical and community settings as part of a multisite quality improvement initiative. This paper aims to describe the implementation and initial outcomes of the training provided. A 20-minute training on HPV vaccine bundled recommendations, motivational interviewing, and brief responses to patient concerns (Communicating about HPV vaccination to Adults and Teens; HPV CHAT) was implemented at seven safety-net clinics, two practice-based research network clinics, and nine county immunization clinics. We integrated training with clinical care teams; thus, we assessed immediate training outcomes across their different clinical roles compared to pre-training. In April-May 2022, HPV CHAT training was launched. One hundred eighty-seven people participated in the training and completed the pre-/postevaluation surveys. Knowledge about the HPV vaccine guidelines improved with notable changes in correctly reporting vaccine eligibility (P < .05). A significant change in participants' confidence when addressing safety concerns and answering questions about the HPV vaccine (clinicians, 26.8% and 17.1%; nurses, 29.0% and 23.2%, and clinical staff, 18.2% and 37.7%) was observed. At post-test, more than 85% of clinicians and nurses reported their plan to routinely recommend the HPV vaccine. This quality improvement initiative demonstrated implementation feasibility of a brief HPV vaccine training that improved provider and clinical staff knowledge, confidence, and intention to routinely recommend HPV vaccination.

The human papillomavirus (HPV) vaccine is key to cancer prevention. Despite this fact, HPV vaccination is not widely accepted. Studies have shown that a strong recommendation can lead to HPV vaccination. Therefore, virtual educational training (Communicating about HPV vaccination to Adults and Teens; HPV CHAT) was developed to equip clinicians, nurses, and clinical staff with communication tools to support HPV recommendation and respond to patient concerns. HPV CHAT, a quality improvement initiative, was launched across numerous community and county clinical teams. To capture HPV CHAT training impact, pre- and post-evaluation surveys were disseminated alongside the training to capture training impact. After HPV CHAT implementation, training participants reported a positive impact on confidence and knowledge items; these findings were observed across all clinical roles in varying degrees. Overall, this quality improvement initiative successfully improved communication skill self-efficacy and knowledge across different clinical roles. This paper discusses training implementation strategies and the changes in knowledge and confidence after participating in the training.

Survival After Implementation of a Decision Support Tool to Facilitate Evidence-Based Cancer Treatment.

PURPOSE: Decision support tools (DSTs) to facilitate evidence-based cancer treatment are increasingly common in care delivery organizations. Implementation of these tools may improve process outcomes, but little is known about effects on patient outcomes such as survival. We aimed to evaluate the effect of implementing a DST for cancer treatment on overall survival (OS) among patients with breast, colorectal, and lung cancer. METHODS: We used institutional cancer registry data to identify adults treated for first primary breast, colorectal, or lung cancer between December 2013 and December 2017. Our intervention of interest was implementation of a commercial DST for cancer treatment, and outcome of interest was OS. We emulated a single-arm trial with historical comparison and used a flexible parametric model to estimate standardized 3-year restricted mean survival time (RMST) difference and mortality risk ratio (RR) with 95% confidence limits (CLs). RESULTS: Our study population comprised 1,059 patients with cancer (323 breast, 318 colorectal, and 418 lung). Depending on cancer type, median age was 55-60 years, 45%-67% were racial/ethnic minorities, and 49%-69% were uninsured. DST implementation had little effect on survival at 3 years. The largest effect was observed among patients with lung cancer (RMST difference, 1.7 months; 95% CL, -0.26 to 3.7; mortality RR, 0.95; 95% CL, 0.88 to 1.0). Adherence with tool-based treatment recommendations was >70% before and >90% across cancers. CONCLUSION: Our results suggest that implementation of a DST for cancer treatment has nominal effect on OS, which may be partially attributable to high adherence with evidence-based treatment recommendations before tool implementation in our setting. Our results raise awareness that improved process outcomes may not translate to improved patient outcomes in some care delivery settings.

Cardiotoxicity among socioeconomically marginalized breast cancer patients.

PURPOSE: Evidence of cardiotoxicity risk related to anthracycline or trastuzumab exposure is largely derived from breast cancer cohorts that under-represent socioeconomically marginalized women, who may be at increased risk of cardiotoxicity because of high prevalence of cardiovascular disease risk factors. Therefore, we aimed to estimate cardiotoxicity risk among socioeconomically marginalized breast cancer patients treated with anthracyclines or trastuzumab and describe clinical consequences of cardiotoxicity. METHODS: We linked electronic health records with institutional registry data from a Comprehensive Community Cancer Program within a safety-net health system. Eligible patients were adult females, diagnosed with first primary invasive breast cancer between 2013 and 2017, and initiated anthracyclines or trastuzumab as part of first-line therapy. We estimated cumulative incidence (risk) of cardiotoxicity with corresponding 95% confidence limits (CL) using the Aalen-Johansen estimator with death as competing risk. RESULTS: Our study population comprised 169 women with breast cancer (103 initiated anthracyclines and 66 initiated trastuzumab). Cumulative incidence of cardiotoxicity was 21% (95% CL: 12%, 32%) at one year and 25% (95% CL: 15%, 35%) at three years among women who initiated trastuzumab, whereas cumulative incidence was 3.9% (95% CL: 1.3%, 8.9%) at one year and 5.9% (95% CL: 2.4%, 12%) at three years among women who initiated anthracyclines. More than half of patients with cardiotoxicity experienced interruption of cancer treatment. CONCLUSION: Our findings suggest high risk of cardiotoxicity among socioeconomically marginalized breast cancer patients after initiation of anthracyclines or trastuzumab. Strategies are needed for optimizing cancer treatment effectiveness while minimizing cardiotoxicity in this population.

Timing of adjuvant chemotherapy initiation and mortality among colon cancer patients at a safety-net health system.

BACKGROUND: Prior studies reported survival benefits from early initiation of adjuvant chemotherapy for stage III colon cancer, but this evidence was derived from studies that may be sensitive to time-related biases. Therefore, we aimed to estimate the effect of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks on overall and disease-free survival among stage III colon cancer patients using a study design that helps address time-related biases. METHODS: We used institutional registry data from JPS Oncology and Infusion Center, a Comprehensive Community Cancer Program. Eligible patients were adults aged < 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2017, and received surgical resection with curative intent. We emulated a target trial with sequential eligibility. We subsequently pooled the trials and estimated risk ratios (RRs) along with 95% confidence limits (CL) for all-cause mortality and recurrence or death at 5-years between initiators and non-initiators of adjuvant chemotherapy ≤8 or ≤ 12 weeks using pseudo-observations and a marginal structural model with stabilized inverse probability of treatment weights. RESULTS: Our study population comprised 222 (for assessing initiation ≤8 weeks) and 310 (for assessing initiation ≤12 weeks) observations, of whom the majority were racial/ethnic minorities (64-65%), or uninsured with or without enrollment in our hospital-based medical assistance program (68-71%). Initiation of adjuvant chemotherapy ≤8 weeks of surgical resection did not improve overall survival (RR for all-cause mortality = 1.04, 95% CL: 0.57, 1.92) or disease-free survival (RR for recurrence or death = 1.07, 95% CL: 0.61, 1.88). The results were similar for initiation of adjuvant chemotherapy ≤12 weeks of surgical resection. CONCLUSIONS: Our results suggest that the overall and disease-free survival benefits of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks of surgical resection may be overestimated in prior studies, which may be attributable to time-related biases. Nevertheless, our estimates were imprecise and differences in population characteristics are an alternate explanation. Additional studies that address time-related biases are needed to clarify our findings.

Impact of prognostic factor distributions on mortality disparities for socioeconomically disadvantaged cancer patients.

PURPOSE: We aimed to assess whether differences in the distributions of prognostic factors explain reported mortality disparities between urban safety-net and Surveillance, Epidemiology, and End Results (SEER) cancer populations. METHODS: We used data from SEER and a safety-net cancer center in Texas. Eligible patients were adults aged ≤64 years and diagnosed with first primary female breast, colorectal, or lung cancer between 2008 and 2016. We estimated crude and adjusted risk differences (RD) in 3- and 5-year all-cause mortality (1- and 3-year for lung cancer), where adjustment was based on entropy balancing weights that standardized the distribution of sociodemographic and tumor characteristics between the two populations. RESULTS: Our study populations comprised 1914 safety-net patients and 389,709 SEER patients. For breast cancer, the crude 3- and 5-year mortality RDs between safety-net and SEER populations were 7.7% (95% confidence limits [CL]: 4.3%, 11%) and 11% (95% CL: 6.7%, 16%). Adjustment for measured prognostic factors reduced the mortality RDs (3-year adjusted RD = 0.049%, 95% CL: -2.6%, 2.6%; 5-year adjusted RD = 5.6%, 95% CL: -0.83%, 12%). We observed similar patterns for colorectal and lung cancer albeit less magnitude. CONCLUSIONS: Sociodemographic and tumor characteristics may largely explain early mortality disparities between safety-net and SEER populations but not late mortality disparities.

Smoking cessation and survival among people diagnosed with non-metastatic cancer.

BACKGROUND: We aimed to estimate the effects of smoking cessation on survival among people diagnosed with cancer. METHODS: We used data from a Comprehensive Community Cancer Program that is part of a large urban safety-net hospital system. Eligible patients were diagnosed with primary invasive solid tumors between 2013 and 2015, and were current smokers at time of diagnosis. Our exposure of interest was initiation of smoking cessation within 6 months of cancer diagnosis. We estimated inverse probability weighted restricted mean survival time (RMST) differences and risk ratio (RR) for all cause 3-year mortality. RESULTS: Our study population comprised 369 patients, of whom 42% were aged < 55 years, 59% were male, 44% were racial/ethnic minorities, and 59% were uninsured. The 3-year RMST was 1.8 (95% CL: - 1.5, 5.1) months longer for individuals who initiated smoking cessation within 6 months of cancer diagnosis. The point estimate for risk of 3-year mortality was lower for initiation of smoking cessation within 6 months of diagnosis compared with no initiation within 6 months (RR = 0.72, 95% CL: 0.37, 1.4). CONCLUSIONS: Our point estimates suggest longer 3-year survival, but the results are compatible with 1.5 month shorter or 5.1 longer 3-year overall survival after smoking cessation within 6 months of cancer diagnosis. Future studies with larger sample sizes that test the comparative effectiveness of different smoking cessation strategies are needed for more detailed evidence to inform decision-making about the effect of smoking cessation on survival among cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: The benefits of smoking cessation after cancer diagnosis may include longer survival, but the magnitude of benefit is unclear.

Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research.

BACKGROUND: Limited information is available about the representativeness of survivors engaging in patient-centered research, despite the potential for threats to generalizability. We thus aimed to assess the representativeness of survivors engaged or interested in research development. METHODS: We used data from the Health Information National Trends Survey, a nationally representative survey, to identify survivors of adult cancers. Our outcomes of interest were based on responses to questions about engagement or interest in developing patient-centered research. We estimated the ratio of relative frequencies (RRF) and corresponding 95% confidence limits (CL) of sociodemographic and survivorship characteristics between survivors engaged or interested in patient-centered research and the overall survivor population. RESULTS: Our study population comprised 934 survivors, of whom 5% reported being engaged in patient-centered research and 26% reported an interest in participating. Relative frequencies of characteristics were discordant for engaged survivors but largely similar for interested survivors compared with all survivors. In particular, engaged survivors had a higher relative frequency of individuals ages 50 to 64 years (RRF = 1.7; 95% CL, 1.1-2.5), Hispanic (RRF = 2.9; 95% CL, 1.2-6.9), non-Hispanic Black (RRF = 2.9; 95% CL, 1.1-2.5), and unemployment (RRF = 4.7; 95% CL, 1.4-16). CONCLUSIONS: We observed several meaningful differences in the characteristics of survivors engaged in patient-centered research compared with all survivors, which raises concerns about the generalizability of findings from such studies. IMPACT: Patient-centered research may not benefit the broader survivor community if survivors engaging in research development are not representative of all survivors. Greater attention to recruiting mechanisms is necessary to avoid creating disparities.

Affordable Care Act and cancer stage at diagnosis in an underserved population.

The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.