Citations

1564 Background: Adolescent and young adult (AYA) females with early-stage ER-negative and/or HER2-positive breast cancer commonly receive chemotherapy to reduce risk of recurrence. Fertility concerns, counseling, and preservation may influence chemotherapy decisions and time to chemotherapy (TTC) initiation. Methods: We surveyed AYA survivors of stage I–III premenopausal ER-negative and/or HER2-positive breast cancer treated at Kaiser Permanente Northern and Southern California (2013-2022). Fertility concerns were defined as not having completed desired family size or being unsure about having completed desired family size at diagnosis. We summarized receipt of fertility counseling, receipt of chemotherapy, and use of oocyte/embryo cryopreservation for fertility preservation (FP). Among fertility-concerned patients who received chemotherapy, TTC (days from diagnosis) was assessed separately for neoadjuvant chemotherapy (NAC) vs for adjuvant chemotherapy (AdjC). Time to NAC was natural log–transformed and modeled with multivariable log-linear regression to estimate relative differences in TTC, adjusting for stage, study site, ER, HER2, age, and diagnosis year. Results: Of 363 respondents, 197 (54%) had fertility concerns at diagnosis; 183/197 (93%) received chemotherapy, similar to 153/166 (92%) among those without concerns (p=0.7). Of the concerned chemotherapy recipients, 45 (25%) saw a fertility specialist but did not pursue FP while 55 (30%) underwent FP. For the 112 fertility-concerned NAC recipients, FP was associated with longer TTC than no fertility specialist counseling (mean=41 vs. 30 days; adjusted ratio=1.39; 95% CI 1.15–1.69), whereas fertility specialist counseling without FP was not (mean= 31 vs. 30 days, adjusted ratio=1.04; 95% CI 0.86–1.25). For the 71 fertility-concerned AdjC recipients, TTC was similar for patients who did not see a fertility specialist (mean=63 days), those who froze oocytes/embryos (mean=65 days), and those who saw a fertility specialist but did not pursue FP (mean=69 days). Conclusions: In this AYA breast cancer cohort, there was no evidence that fertility concerns led patients to decline chemotherapy. FP was associated with a modest delay in NAC initiation (<2 weeks on average). Time to chemotherapy (TTC) among 183 AYA patients with ER− and/or HER2+ breast cancer and fertility concerns. Fertility-focused care N (n=183) Neoadjuvant chemotherapy (n=112) Mean TTC, days Relative difference in TTC, adjusted ratio (95%CI) Adjuvant chemotherapy (n=71) Mean TTC, days No fertility counseling from a specialist 83 (45%) 55 (49%) 29.6 Reference 28 (39%) 62.6 Received fertility counseling from a specialist No fertility preservation 45 (25%) 28 (25%) 30.7 1.04 (0.86,1.25) 17 (24%) 68.6 Fertility preservation 55 (30%) 29 (26%) 41.2 1.39 (1.15,1.69) 26 (37%) 64.6

PURPOSE For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. METHODS NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes. RESULTS Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms. CONCLUSION Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

ABSTRACT Objective To evaluate intracochlear electrocochleography (ECochG) amplitude parameters during cochlear implantation (CI) using a novel multi‐frequency ECochG algorithm. Methods A multi‐institutional, prospective cohort study was performed at 18 high‐volume CI centers. The inclusion criteria were adults with sensorineural hearing loss and audiometric thresholds of ≤ 90 dB hearing level at 500 Hz undergoing CI with Advanced Bionics (Valencia, CA) Ultra 3D devices between 2024 and 2025. ECochG recordings were performed with simultaneous multi‐frequency stimulation of four frequencies between 125 and 4000 Hz during cochlear implant insertion. Concurrent multi‐frequency recording allowed extraction of amplitude and phase of each frequency individually. Post hoc analysis was performed to determine the difference in the number of drop alarms between single‐ and multi‐frequency ECochG. An ECochG amplitude drop of 6 dB was defined as a drop alarm. Insertion track patterns were compared between single‐ and multi‐frequency ECochG. Results One hundred ninety‐five ears were included. Mean number of drop alarms for the single‐frequency algorithm was 1.72 (95% CI: 1.52, 1.92; median 1) compared to 0.42 (95% CI: 0.31, 0.53; median 0) for multi‐frequency; p < 0.001. The number of Type C patterns (rise in amplitude during insertion followed by a drop) decreased with the multi‐frequency ECochG algorithm compared to the single‐frequency ECochG algorithm. The number of Type D patterns (no‐response) decreased, indicating that multi‐frequency ECochG generated more responses across the cochlea than single‐frequency ECochG. Conclusions A novel multi‐frequency ECochG algorithm during CI is associated with fewer drop alarms and altered insertion track patterns, which may provide a more accurate assessment of the cochlear microenvironment. Level of Evidence 3.

Abstract Coccidioidomycosis is an invasive fungal infection that can disseminate and cause severe disease. Fosmanogepix (“gepix”), a first-in-class antifungal available via expanded access (NCT06433128), was successful in 8/11 patients (meningitis, 6/8 [75%]; nonmeningeal dissemination, 2/3 [66%]) and was well tolerated for a median treatment duration of 208 days.

Abstract Background Central precocious puberty (CPP), which is traditionally defined as the development of secondary sexual characteristics before age 8 years in girls and age 9 years in boys, results from the premature activation of the hypothalamic–pituitary–gonadal (HPG) axis. CPP can be associated with short adult stature, adverse psychosocial outcomes, and increased cardiometabolic and cancer risks in adulthood. Gonadotropin-releasing hormone (GnRH) agonists can effectively suppress premature activation of the HPG axis and have the potential to increase adult height as well as improve psychosocial and long-term health outcomes among patients with CPP. However, as secular trends have continued to shift toward earlier age of pubertal onset, some subpopulations of children with CPP, as it is currently defined, may not require the same extent of diagnostic evaluation and treatment. Objective Develop evidence-based recommendations related to the diagnosis and treatment of CPP. Methods A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to address 10 clinical questions related to the diagnosis and treatment of CPP. Systematic reviews of health-related benefits and harms were conducted for each clinical question. The guideline development panel (GDP) also used the GRADE evidence-to-decision (EtD) framework to address stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and potential impacts on health equity. Results In girls with thelarche (Tanner stage B2) between ages 7.0 and 8.0 years, the GDP suggests watchful waiting via periodic physical examinations (every 4-6 months) rather than immediately performing evaluation with laboratory testing or radiologic imaging. In addition, the GDP suggests that all girls with breast development (ie, Tanner stage B2) before age 7 years should first be observed for 4 to 6 months to differentiate unsustained or slowly progressive puberty vs rapidly progressive puberty. These recommendations are largely based on evidence that girls with slowly progressive puberty attain a normal adult height without treatment. When hormonal evaluation is performed to confirm central (GnRH-dependent) activation as the cause of precocious puberty, the GDP suggests starting the evaluation with ultrasensitive basal luteinizing hormone (LH) concentration rather than routine GnRH/GnRH agonist (GnRHa) stimulation testing for all patients. While brain magnetic resonance imaging has been a traditional part of CPP evaluation, the GDP suggests that it should not be routinely performed in girls ages 6.0 to 8.0 years and boys ages 8.0 to 9.0 years without central nervous system (eg, neuro-ophthalmologic) symptoms, largely based on a low prevalence of pathologic intracranial findings in these age groups. The GDP suggests against routine genetic testing for patients with CPP, although they judged that genetic testing (eg, MKRN3 sequencing) should be considered for patients with familial CPP through a shared decision-making process. The GDP suggests GnRHa treatment for many children with CPP, although available evidence suggests that some patient subgroups (eg, older girls with slowly progressive CPP) may be less likely to receive a net benefit with this treatment. Rather than always starting GnRHa treatment with a monthly injectable formulation, the GDP suggests that treatment should be initiated with the formulation (such as a longer-acting formulation) that is anticipated to be used long-term. The GDP suggests against routine addition of growth hormone therapy to increase adult height. They also suggest against the routine biochemical testing (eg, LH, sex steroids) to monitor pubertal suppression while receiving GnRHa, instead reserving biochemical testing to confirm clinically suspected treatment failure. Finally, the GDP suggests against routinely continuing GnRHa treatment beyond chronologic age 10.0 to 11.0 years (girls) or 11.0 to 12.0 years (boys) and/or bone age 11.0 to 12.0 years (girls) or 12.0 to 13.0 years (boys). Conclusion These clinical recommendations were developed to address important uncertainties in the diagnosis and treatment of children with CPP. They are based on the best available scientific evidence regarding clinical outcomes judged to be most important to patients and families. The GDP's overarching goal was to suggest diagnostic and therapeutic strategies that will most likely provide net clinical benefits while simultaneously considering important contextual factors such as cost and feasibility. The guideline-development process highlighted important knowledge gaps and the substantial need for additional research.

ABSTRACT Background and Aims Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease with a high risk of malignancy and limited therapeutic options. Both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend structured baseline evaluation, fibrosis staging and longitudinal surveillance. However, real‐world adherence to these practices in North America remains unclear. Methods We conducted a retrospective cohort study of 1300 patients with PSC enrolled in the Consortium for Autoimmune Liver Diseases (CALiD) registry between 2018 and 2024 across 19 centres in North America. Guideline adherence was assessed for diagnostic measures at baseline (colonoscopy to establish IBD status and noninvasive fibrosis staging) and longitudinal surveillance (colonoscopy in PSC‐IBD, abdominal imaging for hepatobiliary cancer surveillance and CA 19‐9 testing). Prescribing patterns for ursodeoxycholic acid (UDCA) were also characterised. Multivariable logistic regression was used to evaluate demographic, clinical and socioeconomic predictors of adherence. Results At diagnosis, 78.8% of eligible patients with available data underwent colonoscopy to establish IBD status, and 45% underwent noninvasive fibrosis staging. During follow‐up, only 30%–35% of patients with PSC‐IBD underwent colonoscopy annually, while abdominal imaging for hepatobiliary cancer surveillance declined from 74% at Year 1 to 51% by Year 4. CA 19‐9 testing was documented in 47% over 5‐year period. UDCA was prescribed in 51% at baseline, with median dose of 12.5 mg/kg/day. Socioeconomic factors, including lower education and household income, were associated with reduced adherence, while cirrhosis strongly predicted completion of surveillance imaging. Conclusions Adherence to guideline‐based care in PSC remains suboptimal in North America Suboptimal adherence was observed for strongly recommended practices with longstanding guideline support (colonoscopy to establish IBD status; annual CRC surveillance in PSC‐IBD) as well as practices where guideline consensus has evolved more recently or where societies differ (baseline fibrosis assessment; hepatobiliary cancer imaging). Efforts to standardise care and address socioeconomic barriers are urgently needed to improve outcomes.

Abstract STUDY QUESTION What is the fertility preservation (FP) utilization rate among transgender and gender diverse (TGD) patients at the Transgender and Intersex Specialty Care Clinic (TISCC) within the Mayo Clinic? SUMMARY ANSWER The rate of utilization of FP services by TGD patients at Mayo Clinic’s TISCC was determined to be 6.62%. WHAT IS KNOWN ALREADY TGD patients encounter several barriers when pursuing FP, which may contribute to a lower utilization rate of these services. These barriers include financial constraints and lack of insurance coverage, as well as societal and healthcare provider attitudes; TGD individuals face discrimination or lack of understanding, making it uncomfortable or difficult to discuss FP options. Additionally, there continues to be a lack of inclusive policies and support within healthcare systems that can further impede access to FP services for TGD individuals. STUDY DESIGN, SIZE, DURATION The study was executed in two phases. In the first phase, a retrospective cohort study was completed with TGD patients who provided electronic health record (EHR) research authorization from Mayo Clinic’s TISCC in Rochester, MN between 1 January 2015 and 30 July 2021. Search terms related to FP were used to determine the FP utilization rate among this patient population. In the second phase of the study, two sets of patients, (i) patients who were included in the cohort study in Phase 1, and (ii) members of JASMYN, a community organization specializing in care and wellness coordination for Lesbian, Gay, Bisexual, and Transgender (LGBT) teens and young adults in North Florida. Individuals were invited to participate in a qualitative interview exploring their cumulative healthcare experiences accessing gender-affirming care. Interviews were conducted from January 2023 to June 2023. Interviews examined participants’ perceptions of FP options, motivations for pursuing FP, and barriers to accessing both gender and fertility care. When applicable, participants also discussed their experiences pursuing FP and reflected on their satisfaction with their fertility and family planning decisions. PARTICIPANTS/MATERIALS, SETTING, METHODS In phase 1, a total of N = 1189 patients sought care from Mayo Clinic’s TISCC in Rochester, MN. Out of these patients, N = 589 patients provided research authorization and were included in the retrospective cohort study. The study team assessed whether FP terms were mentioned in each patient’s EHR, and whether patients scheduled and attended appointments with either the Department of Reproductive Endocrinology or the Department of Urology. FP search terms included sperm cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. In phase 2, N = 36 participants were interviewed, with N = 25 participants recruited from Mayo Clinic’s TISCC in Rochester, MN, and N = 11 participants recruited from JASMYN in Jacksonville, FL. Participants recruited from the Mayo Clinic participated in a video-call-based interview and those enrolled from JASMYN were interviewed in person. MAIN RESULTS AND THE ROLE OF CHANCE The study team observed a 6.62% utilization rate of FP services among N = 589 patients (median age: 28 years; age range: 8–78 years) included in the retrospective cohort study. N = 39 patients completed FP, with N = 14 receiving these services at other institutions before seeking care with the TISCC at Mayo Clinic. N = 25 patients pursued FP services within the Mayo Clinic. Patients with testes were more likely to complete FP via sperm cryopreservation when compared to the utilization of egg cryopreservation among patients with ovaries. Participants who completed an interview in Phase 2 (median age 27 years; age range: 22–80 years) reflected on their decision on whether to preserve their fertility and what factors influenced these decisions, and how their satisfaction with this decision has changed over their lifespan. The major themes reported here include the desire for biological children, planning gender care around fertility desires, conversations about FP options, physical and psychosocial barriers to pursuing FP, reflections on personal FP decisions, and reflections on having to make decisions about FP at a young age. LIMITATIONS, REASONS FOR CAUTION All participants who completed an interview have done so voluntarily; as such, there is a possibility of selection and recall bias. WIDER IMPLICATIONS OF THE FINDINGS Findings suggest that there is a need for more structured conversations around FP when TGD patients seek medical and surgical gender-affirming care. Accessibility, including financial barriers and limited insurance coverage, continues to limit the utilization of FP services among TGD patients. Increased affordability through insurance coverage may additionally improve FP utilization. STUDY FUNDING/COMPETING INTEREST(S) This project was funded by the Mayo Clinic Department of Obstetrics and Gynecology and the Mayo Clinic Center for Clinical and Translational Science (CCaTS), grant number UL1TR002377. This project was also supported by Clinical and Translational Science Award (CTSA) Grant Number TL1TR002380 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Felicity Enders reports grants from the National Institutes of Health and the Agency for Healthcare Research and Quality paid to her institution; speakers’ fees for lectures or presentations from Mount Sinai, University of Washington, University of Minnesota, University of Rochester, Cincinnati University, the National Institutes of Health, Duke University, Wake Forest University, the Patient Centered Outcomes Research Institute, Johns Hopkins University; travel support from the Association for Clinical and Translational Science and Cold Spring Harbor Laboratory; and an unpaid leadership role on the Board of Directors of the Association for Clinical and Translational Science. All other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Introduction Preoperative testosterone exposure has been associated with various health outcomes, but its impact on postoperative complications in patients undergoing total shoulder arthroplasty (TSA) has not been fully explored. This study aims to evaluate the association between preoperative testosterone exposure and postoperative medical and surgical complications in patients undergoing TSA. Methods A retrospective cohort study was conducted using the PearlDiver database. Patients who underwent TSA and used preoperative testosterone within 3 months of the index procedure were identified and matched 1:4 to controls without testosterone use using propensity score matching. Matching was performed based on age, gender, comorbidities, Charlson comorbidity index, obesity, tobacco use, and hypogonadism to balance the groups. Postoperative complications were assessed at 90 days and five years. Statistical comparisons were made using odds ratios (ORs) with 95% confidence intervals (CIs), and a p -value of <0.05 was considered statistically significant. Results The matched cohort included 677 testosterone users and 2554 controls. There were no statistically significant differences between the testosterone and control groups in 90-day complications such as myocardial infarction (OR 2.52, P = 0.31), pneumonia (OR 0.86, P = 0.70), and deep vein thrombosis (no cases in the testosterone group). Over five years, the testosterone group had a significantly higher risk of periprosthetic joint infection (4.1% vs. 2.4%, OR 1.76, 95% CI 1.10–2.75, P = 0.015), but no differences in revision rates, dislocation, aseptic loosening, or stiffness were observed. Conclusion Preoperative testosterone exposure was associated with a higher risk of periprosthetic joint infection following TSA, but no significant differences were found in major medical complications or revision rates.

Abstract Breast cancer (BC) is the most common cancer among female adolescents and young adults (AYAs; 15-39 years). While advances in treatment have improved survival, cardiovascular disease (CVD) can result from systemic therapies, and CVD is a leading cause of death in AYA cancer survivors. AYAs with BC face nearly a four-fold increased risk of CVD compared to their peers without cancer. However, data on the effects of systemic treatment on CVD in this population remains limited. We estimated risk of CVD in AYAs diagnosed with invasive BC (2006-2020), who survived ≥2 years, and were diagnosed and treated in the Kaiser Permanente (KP) Northern and Southern California. Patients were categorized by receipt of anthracycline-, alkylating-, HER2-, platinum-, and taxane-based therapies within 2 years of diagnosis. We examined the cumulative incidence of CVD starting 2 years post-diagnosis and used Cox proportional hazards regression to determine factors associated with CVD. Among 3,071 AYAs, 35.1% were non-Hispanic (NH) White, 31.6% were Hispanic, 18.3% were NH Asian, and 8.2% were NH Black. Most received systemic therapy (90.6%), including anthracycline- and alkylator without HER2-targeted therapy (41.9%) and HER2-targeted therapy without anthracycline (20.9%). Fewer AYAs received a taxane and alkylator (13.0%) or anthracycline with alkylator and taxane along with a HER2-targeting agent (6.4%). Mean follow-up after cancer diagnosis was 7.2 years (range: 2.0-17.5). The 10-year cumulative incidence of CVD was highest among AYAs who received anthracycline/alkylator/taxane/HER2-targeting therapy (19.6%), intermediate for those with anthracycline/alkylator without HER2-targeting therapy (13.0%) and those who received HER2-targeted therapy without anthracycline (14.6%), and lowest for those who received taxane/alkylator (7.3%). In the multivariable model adjusted for demographic factors and radiation, compared to taxane/alkylator, anthracycline/alkylator/taxane/HER2-targeting therapy (hazard ratio (HR)=2.63, 95% confidence interval (CI) 1.56-4.43); anthracycline/alkylator without HER2-targeting therapy (HR=1.75, CI 1.13-2.71); and HER2-targeting therapy without anthracycline (HR=2.13, CI 1.11-4.09) were associated with an increased risk of CVD. CVD risk was similar for taxane/alkylator and no systemic therapy. Other factors associated with higher risk of CVD included NH Black race/ethnicity (HR=1.90, CI 1.32-2.73 vs. NH White) and public health insurance (HR=1.67, CI 1.00-2.78 vs private). This study identifies AYA BC survivors at higher risk of CVD based on treatment regimens received, with highest risks found for those receiving anthracycline/alkylator/taxane/HER2 treatment combinations. In addition, AYAs of Black race/ethnicity and those with public health insurance experienced more CVD, underscoring the need for targeted interventions to mitigate these disparities. Citation Format: Theresa H. M. Keegan, Candice A. Sauder, Ann M. Brunson, Renata Abrahao, Anne C. Kirchhoff, Eric Haupt, Mallory Casperson, Ted Wun, Chun R. Chao, Andrew B. Smitherman, Hazel B. Nichols, Jessica Chubak, Erin E. Hahn, Lawrence H. Kushi, Kathryn J. Ruddy. Systemic therapy and cardiovascular disease in adolescent and young adult breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5219.

Abstract Introduction: Lung cancer rates differ across rural and urban areas, but few studies have evaluated rural-urban differences across the risk-screening continuum. We examined smoking, cessation interventions, and lung cancer screening patterns across the rural-urban continuum in a geographically defined area over 10 years. Materials and Methods: A retrospective cohort study (2014-2023) was conducted using clinical data from the Rochester Epidemiology Project, derived from healthcare encounters in a 27-county region of the midwestern United States. Patients ages 40-80 were included. We used Rural-Urban Commuting Area codes to assign residence as urban, rural, or highly rural. We examined yearly smoking prevalence, cessation intervention (pharmacotherapy, counseling), and low-dose computed tomography (LDCT) lung cancer screening. Results: Over the 10-year study period, the sample size ranged from 305,530 to 340,411 people annually with 36-38% urban, 56-57% rural, and 6-7% highly rural. Current smoking prevalence declined from 14 to 12% over the 10-year period (range=12-16%; p=0.06) and was consistently lower in urban areas (range=10-14%) than rural (range=12-17.0%) and highly rural areas (range=12-18%; p=&lt;0.001). Among individuals who currently smoked with no history of lung cancer, yearly smoking cessation intervention ranged from 16% to 23%, increasing over the 10-year period (p=&lt;0.001). Cessation medication (varenicline, bupropion, or nicotine replacement) prescription consistently increased overall over time but remained higher in urban than rural and highly rural areas (p=&lt;0.001). Cessation counseling rates also increased overall over time and were similar between urban and rural areas and lower in highly rural areas (p=&lt;0.001). Among people who had ever-smoked aged 50-80 years with no diagnosis of lung cancer, LDCT screening increased from 0.0% to 3.1% over the study period. Increases were higher in urban areas (0.0-3.6%) and similar in rural and highly rural areas (0.0-2.8% and 0.0-2.9%, respectively; p=&lt;0.001). Among people who currently smoked, LDCT screening also increased over the study period (0.0-6.4%), with higher increases in urban (0.1-8.0%) than rural (0.0-5.7%) or highly rural (0.1-6.1%) areas (p=&lt;0.001). After the new screening guidelines in 2021, rates in all areas increased year-on-year. Conclusion: In this cohort, we found that smoking prevalence, cessation interventions, and lung cancer screening improved from 2014-2023 across the rural-urban continuum. Unfortunately, smoking prevalence remained higher and cessation interventions and screening rates lower in rural compared to urban areas. The persistent patterns underscore the need for strategies to overcome barriers for rural residents and improve lung cancer prevention and early detection in all areas. Citation Format: Brianna Tranby, Paul A. Decker, Jiang Ruoxiang, David Midthun, Lori C. Sakoda, Melinda C. Aldrich, Debra Friedman, Adoma Manful, Oindrila Bhattacharyya, Christi Patten, Chyke A. Doubeni. Patterns of tobacco use, cessation interventions, and lung cancer screening in rural vs. urban areas over time; a 10-year retrospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5045.