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The transition from pediatric to adult health care is critical to the care of young adults with sickle cell disease (SCD). Young adults with SCD, compared with children with SCD, are at risk for a marked increase in disease severity, frequency of acute complications, healthcare utilization, and mortality. 1-4 Professional societies and healthcare experts recommend that young adults with chronic health conditions should transfer to adult-centered healthcare within 6 months of their last pediatric visit. 5-8 However, the effect of a 6-month transfer interval on healthcare utilization in SCD has not been studied. Given the complex health care needs of young adults with SCD, 9-15 it remains unclear whether the recommended 6-month transfer interval 5 is optimal. We hypothesized that longer gaps between pediatric and adult care would be associated with greater healthcare utilization in the first 2 to 6 years of adult care. This study included patients with SCD who were followed by a pediatric sickle cell program in the mid-southern US, participated in a transition to adult care program, 16 and fulfilled an initial adult visit to a partner adult SCD facility during the years 2011-2017. Participants were retrospectively followed from their first adult visit through December 31, 2017. Transfer gap was defined as the time (in months) between the last pediatric and the first adult sickle cell clinic visit. We estimated the association between varying transfer gaps from pediatric to adult care and the rate of healthcare utilization (inpatient, emergency department, and outpatient visits) in the first 2 to 6 years of adult care using negative binomial regression. Transfer gaps were evaluated at 6 vs ≤6) to evaluate the current recommendation to complete transfer of patients to adult care within 6 months. 6,7 Healthcare resource utilization was analyzed for the complete follow-up (up to 6 years) and for the first 2 years of adult care to assess the immediate effects of delayed transfer. In total, 172 young adults with SCD (52% male, 63% HbSS/HbSβ 0-thalassemia) transferred to adult care at a median age of 18 years during the years 2011-2017 (Table 1). Approximately 83% of the included participants transferred to adult care within the recommended 6 months. young adults with transfer gaps ≥9 months had 2.86 (95%CI: 1.32, 6.20) times the rate of acute healthcare visits (inpatient and emergency department combined) compared to those with 6 months had 2.27 (95%CI: 1.18, 4.40) times the rate of acute care visits compared to those with ≤6 months transfer gap (Table 3). The incidence rate ratio increased slightly (IRR: 2.37; 95%CI: 1.29, 4.37) when evaluating the first 2 years of adult care only. There were no apparent associations between transfer gap duration and outpatient visits during the first 6 years in adult care; however, when restricted to the first 2 years of adult care, those with gaps >6 months had 1.32 (95%CI: 1.01, 1.72) times the rate of outpatient visits compared to those with gaps ≤6 months. Consistent with current guidelines, transfer gaps between pediatric and adult-centered care of greater than 6 months were found to be associated with increased acute healthcare resource utilization. Therefore, SCD transition programs would be well-served to consider policies for young adults that initiate adult care within 6 months of leaving pediatric care. Future studies should continue to investigate duration of transfer gaps from pediatric to adult care for their long-term clinical effects and explore interventions to reduce the transfer gap in the SCD population. Figure 1 Figure 1. Disclosures Shah: Novartis: Consultancy, Research Funding, Speakers Bureau; GBT: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Guidepoint Global: Consultancy; GLG: Consultancy; Emmaus: Consultancy. Hankins: Bluebird Bio: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Global Blood Therapeutics: Consultancy.

254 Background: Quality improvement (QI) in cancer care delivery requires understanding the setting, clearly defining problem(s), and identifying targeted solutions. The Association of Community Cancer Centers (ACCC) conducted a national project to identify and provide guidance on key issues in care for patients with stage III/IV non-small cell lung cancer (NSCLC). We report the problems and solutions identified after a mixed-methods baseline data evaluation. Methods: The multi-phase ACCC QI initiative was guided by an expert steering committee. A request for applications was advertised to all ACCC programs, with committee members ranking each site in pre-specified categories (ex., replicability, practice champion engagement). After selection of sites, baseline data assessed programs’ patient populations, current care delivery practices, processes of care, and biomarker testing rates. A full-day workshop was conducted with multidisciplinary team members and expert faculty to review baseline data, refine problem statements, and identify site-specific QI solutions. Results: The 6 participating US sites were regionally diverse with a rural/urban mix. In baseline data, median patient ages were 65-72 years and patients treated were 50% stage III/50% stage IV. Biomarker testing practices, use of multidisciplinary tumor board, and clinical care pathways varied across sites. Five key QI areas were identified: 1.Management of immune related adverse events (irAE), 2.Biomarker testing, 3.Emergency visit management (EVM), 4.Access to clinical trials, and 5.Smoking cessation. Two sites identified problems with irAE management during immunotherapy (IT). The first identified needs for proactive symptom identification, assessment, and management. Solutions included: 1. a patient questionnaire to identify early signs of irAEs and 2. pilot testing a nurse-administered questionnaire. A second site identified that front-line clinicians may not be properly identifying possible irAEs. Solutions included: 1. form an IT toxicity working group and 2. educate front-line clinicians about irAEs. Two sites focused on biomarker testing. The first problem identified was inefficient tracking of testing results. Solutions were: 1. assign a nurse navigator to track, enter, and communicate test results and 2. proactively coordinate appointments for patients with positive test results. The second site identified delayed care when inadequate tissue was obtained. Solutions included: 1. pathology-driven reflex testing and 2. liquid biopsy order at diagnosis. Similar problems/solutions were developed for EVM, clinical trial access, and smoking cessation. Conclusions: Challenges in lung cancer care delivery can be identified and addressed using an intentional QI approach. Clearly defining the problem and identifying potential solution(s) are critical steps and should occur before implementation.

251 Background: Lung cancer care is complex, but, for quality improvement, can be simplified into five ‘nodal points’: lesion detection, diagnostic biopsy, radiologic staging, invasive staging, and treatment. We previously demonstrated great heterogeneity in passage through these nodal points in patients who received surgical resection for lung cancer in our healthcare system. However, examining only surgical patients may underestimate the enormity of the opportunity for quality improvement. With the aim of identifying quality gaps in pre-treatment evaluation for lung cancer, we evaluated the flow of care through these nodal points within a community-based healthcare system. Methods: We classified lung cancer care procedures received by all suspected lung cancer patients treated within the Multidisciplinary Thoracic Oncology Program at Baptist Cancer Center, Memphis TN between 2014 and 2019, into five nodal points. We compared the frequency of, and time intervals between, nodal points among patients receiving surgical, nonsurgical (chemotherapy/radiation), or no definitive treatment, using Chi-square or Kruskal Wallis tests, where appropriate. Results: Of 1304 eligible patients: 11% had no pre-treatment diagnostic procedure, 20% no PET/CT, and 39% no invasive staging. 39% of patients underwent surgical resection, 51% received non-surgical treatment, and 10% received no treatment. Patients who had surgery were less likely than those who had non-surgical treatment to get a diagnostic test, radiologic staging, and invasive staging (Table). Patients who had non-surgical treatment were more likely to pass through all five nodal points (50% v 68%, p

200 Background: Few existing studies examined lung cancer patients and caregivers’ satisfaction with the team-based multidisciplinary care (MD) in comparison to the usual serial care (SC). We hypothesized that MD, by providing early and concurrent input from key specialists collaborating as a team with patients and caregivers to develop a consensus care plan, can improve patients and caregivers’ satisfaction with care, compared to SC, in which multiple specialists independently screen, diagnose, and treat patients through a fragmented sequence of referrals. Methods: Data on newly diagnosed lung cancer patients, enrolled in a prospective matched cohort comparative effectiveness trial of MD or SC between Oct. 9th, 2014 and July 5th, 2017 in a Mid-South community hospital system, were collected at baseline, 3- and 6-month periods to assess patient and caregiver’s satisfaction with these two care-delivery models. Measures of satisfaction were adapted from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Multivariate mixed linear models were used to examine the cross-group differences, the time-related variances, and how the interaction between groups and time-periods influenced patients’ and caregivers’ satisfaction. Results: Compared with SC (N = 297), patients in MD (N = 159) were older (66 vs. 69 years), more in an early cancer stage (33% vs. 41% in stage I or II), and lower in performance score (35% vs. 45% asymptomatic). Demographic and social-economic characteristics of caregivers in MD (N = 97) and SC (N = 122) were not significantly different. Patients and caregivers in MD were more likely than those in SC to perceive their care to be better than that received by other patients (p =.003 and p

13 Background: Early detection of lung cancer provides the best opportunity for long-term survival. In 2021 US Preventive Services Task Force (USPSTF) expanded the 2013 risk-based Low-dose CT (LDCT) screening criteria, in part to reduce unintended race and gender disparities in lung cancer detection. We evaluated the impact of the updated USPSTF criteria in a cohort of patients from an incidental lung nodule program (ILNP). Methods: We implemented an ILNP in a community healthcare system in the mid-south US. Patients with lung lesions on routinely-performed radiologic studies were triaged using evidence-based guidelines. We prospectively tracked patient demographics, clinical characteristics, procedures, complications, and health outcomes. We classified all patients in the ILNP cohort based on USPSTF 2013 and 2021 screening criteria. Statistical analysis used the chi-square test. Results: The ILNP cohort included 14,642 patients from 2015-2021. This cohort was 56% female, 65% White, 29% Black, with a median age of 64 years. Overall 1,581 (10.8%) met 2013 and 2,051 (14.0%) met 2021 USPSTF criteria. 1.9% of subjects eligible by 2013 criteria were diagnosed with lung cancer compared to 2.2% by 2021 criteria. 470 additional patients met screening criteria when we expanded from USPSTF 2013 to 2021. As expected, these patients were younger and less likely to have Medicare insurance. These additional eligible patients were significantly more likely to be female (58% v 49%, p = 0.0011) or Black (28% vs. 18%, p < 0.0001) compared to those eligible by 2013 criteria. 44 of the 470 (9%) were diagnosed with cancer: 36% adenocarcinoma, 18% squamous, and 11% small cell, 11% non-lung primary, 9% non-small cell lung cancer NOS, and 15% other or unknown histology. The median tumor size was 3 cm with an interquartile range from 1.7 to 4.2 cm. The clinical stage distribution was 34% I, 4.5% II, 15.9% III, and 31.8% IV. Conclusions: In this selective community-based cohort, USPSTF 2021 criteria identified a higher percentage of subjects with lung cancer and were more inclusive of women and minorities compared to USPSTF 2013 criteria.

Introduction We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system. Methods We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011–2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location. We categorized National Comprehensive Cancer Network guideline-concordant treatment as "preferred," or "appropriate" (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-square tests and survival using Cox regression, adjusted for multiple testing. We also performed propensity-matched and adjusted survival analyses. Results Of 6259 patients, 14% were in eMTOC, 55% metropolitan non-MTOC, and 31% regional non-MTOC cohorts. eMTOC had the highest rates of African Americans (34% versus 28% versus 22%), stages I to IIIB (63 versus 40 versus 50), urban residents (81 versus 78 versus 20), stage-preferred treatment (66 versus 57 versus 48), guideline-concordant treatment (78 versus 70 versus 63), and lowest percentage of nontreatment (6 versus 21 versus 28); all p values were less than 0.001. Compared with eMTOC, hazard for death was higher in metropolitan (1.5, 95% confidence interval: 1.4–1.7) and regional (1.7, 1.5–1.9) non-MTOC; hazards were higher in regional non-MTOC versus metropolitan (1.1, 1.0–1.2); all p values were less than 0.05 after adjustment. Results were generally similar after propensity analysis with and without adjusting for guideline-concordant treatment. Conclusions Multidisciplinary NSCLC care planning was associated with significantly higher rates of guideline-concordant care and survival, providing evidence for rigorous implementation of this model of care.

Children with acute lymphoblastic leukemia or lymphoma (ALL) undergo multiple lumbar punctures (LPs) and frequently require low-molecular-weight heparin (LMWH) for thromboembolic complications. We evaluated if withholding LMWH 24 hours before and after LPs prevented bleeding complications. Children (n=133) with ALL from who were: (1) treated at St. Jude Children's Research Hospital, (2) received LMWH (2×/day of ~1 mg/kg) between January 2004 until December 2012, and (3) underwent a LP were analyzed. Spinal hematoma was defined as a clinical suspicion leading to diagnostic imaging. Traumatic LP was defined as ≥10 red blood cells per microliter of cerebrospinal fluid. In 1708 LPs, no hematomas occurred. For each child treated with LMWH, the probability of experiencing a spinal hematoma during the entire ALL treatment course was 0% (95% confidence interval [CI], 0.0%-2.7%), and in each LP, assuming no intrapatient correlation, the probability of spinal hematoma was 0% (95% CI, 0.0%-0.2%). Traumatic LPs were more common when performed when children were not receiving LMWH therapy (odds ratio [OR], 1.5; 95% CI, 1.1-2.2) which may be explained by clinician optimization of known risk factors for traumatic cerebrospinal fluid before the procedures. Withholding LMWH for 24 hours before and after LPs in children being treated for ALL is safe.

Incomplete lung cancer resection connotes poor prognosis; the incidence varies with patient demographic, clinical, and institutional factors. We sought to develop a valid, survival impactful, facility-based surgical quality metric that adjusts for related patient demographic and clinical characteristics.Facilities performing resections for patients diagnosed with stage I to IIIA non-small cell lung cancer in the National Cancer Data Base between 2004 and 2011 were identified. Multivariate logistic regression modeling was used to estimate the expected number of margin-positive cases by adjusting for patient risk mix and calculate the observed-to-expected ratio for each facility. Facilities were categorized as outperformers (observed-to-expected ratio less than 1, p0.05), nonoutliers (p0.05), and underperformers (observed-to-expected ratio greater than 1, p0.05); and their characteristics across performance categories were compared by χA total of 96,324 patients underwent surgery at 809 facilities. The overall observed margin-positive rate was 4.4%. Sixty-one facilities (8%) were outperformers, 644 (80%) were nonoutliers, and 104 (13%) were underperformers. One third (36%) of National Cancer Institute-designated facilities, 13% of academic comprehensive cancer programs, 5% of comprehensive community cancer programs, and 13% of "other" facilities achieved outperforming status but no community cancer programs did. Interestingly, 9% of National Cancer Institute-designated facilities and 11% of academic comprehensive cancer program facilities were underperformers. Adjusting for patient demographic and clinical characteristics, outperformers had a 5-year all-cause hazard ratio of 0.88 (95% confidence interval: 0.85 to 0.91, p0.0001) compared with nonoutliers, and 0.80 (95% confidence interval: 0.77 to 0.84, p0.0001) compared with underperformers.Facility performance in lung cancer surgery can be captured by the risk-adjusted margin-positivity rate, potentially providing a valid quality improvement metric.

Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow-up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (p20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%.

BACKGROUND Sickle cell disease (SCD) is an inherited blood disorder causing acute complications and chronic progressive end organ damage. SCD is associated with significant morbidity, early mortality, impaired health-related quality of life, and increased acute health care utilization. Hydroxyurea is a US Food and Drug Administration–approved medication that reduces disease complications, acute health care utilization, and costs. However, adherence to hydroxyurea is suboptimal. Mobile health (mHealth) interventions have the potential to improve hydroxyurea adherence, but few examples exist that are specific to the SCD population. OBJECTIVE This study aimed to design a mHealth intervention for individuals with SCD to improve adherence to hydroxyurea, using a user-centered design that was informed by specific barriers to hydroxyurea adherence and utilization in this population. METHODS This study consisted of 4 phases. In phase 1, individuals with SCD and health care providers participated in an optimization digital workshop. In phase 2, patients completed surveys pertaining to their interest in mHealth use, barriers and facilitators to hydroxyurea use, and health literacy. Phases 3 and 4 involved semistructured interviews and focus groups, respectively, and used the Health Belief Model (HBM) as the framework to investigate drivers of poor hydroxyurea adherence and to inform the development of an app prototype. In addition, in phase 4, we have incorporated the patients’ feedback on the preliminary app prototype and its features. RESULTS Barriers to hydroxyurea adherence were consistent with the literature and included forgetfulness and several specific thoughts and emotions associated with hydroxyurea use (eg, fear of side effects, depression, stigma, and hopelessness). In addition, more than half of the participants reported potentially low health literacy. Preferred patient app features included 7 key components, namely (1) medication reminders and tracker, (2) disease education, (3) communication, (4) personalization, (5) motivation, (6) support during pain episodes, and (7) social support. Utilizing a user-centered design approach, data obtained from patients and providers were translated into features within the app, mapping to components of the HBM and the specific drivers of hydroxyurea adherence and matching the literacy level of the population, resulting in the development of a novel mobile app called InCharge Health. CONCLUSIONS The InCharge Health app is an mHealth intervention developed with substantial input from users and by mapping the HBM as the framework that guided the choice for its components. InCharge Health is a customized product for the SCD population aimed at optimizing medication adherence, with the end goal of improving quality of life and health outcomes among patients with SCD. The efficacy and implementation of the InCharge Health app as an mHealth intervention to promote hydroxyurea adherence will be tested in a future stepped-wedge multicenter trial for adolescents and adults with SCD.

A large body of in vivo and in vitro evidence indicates that Manuka honey resolves inflammation and promotes healing when applied topically to a wound. In this study, the effect of two different concentrations (0.5% and 3% v/v) of Manuka honey on the release of cytokines, chemokines, and matrix-degrading enzymes from neutrophils was examined using a differentiated HL-60 cell line model in the presence of inflammatory stimuli. The results indicate that 0.5% honey decreased TNF-α, IL-1β, MIP-1α, MIP-1β, IL-12 p70, MMP-9, MMP-1, FGF-13, IL-1ra, and IL-4 release, but increased MIP-3α, Proteinase 3, VEGF, and IL-8 levels. In contrast, 3% honey reduced the release of all analytes except TNF-α, whose release was increased. Together, these results demonstrate a dose-dependent ability of Manuka honey to modify the release of cytokines, chemokines, and matrix-degrading enzymes that promote or inhibit inflammation and/or healing within a wound. The findings of this study provide further guidance for the future use of Manuka honey in wounds or tissue engineering templates. Future in vivo investigation is warranted to validate the in vitro results and translate these results to physiologically relevant environments.

Surgical resection is the main curative modality for non-small cell lung cancer (NSCLC), but variation in the quality of care contributes to suboptimal survival rates. Improving surgical outcomes by eliminating quality deficits is a key strategy for improving population-level lung cancer survival. We evaluated the long-term survival effect of providing direct feedback on institutional performance in a population-based cohort.The Mid-South Quality of Surgical Resection cohort includes all NSCLC resections at 11 hospitals in four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee. We evaluated resections from 2004 to 2013, before and after onset of a benchmarked performance feedback campaign to surgery and pathology teams in 2009.We evaluated 2,206 patients: 56% preintervention (pre-era) and 44% postintervention (post-era). Preoperative positron emission tomography/computed tomography (46% vs 82%, p0.0001), brain scans (6% vs 21%, p0.0001), and bronchoscopy (8% vs 27%, p0.0001) were more frequently used in the post-era. Patients had 5-year survival of 47% (44% to 50%) in the pre-era compared with 53% (50% to 56%) in the post-era (p = 0.0028). The post-era had an adjusted hazard ratio of 0.85 (95% confidence interval [CI], 0.75 to 0.97; p = 0.0158) compared with the pre-era. This differed by extent of resection (p = 0.0113): compared with the pre-era, the post-era adjusted hazard ratio was 0.49 (95% CI, 0.33 to 0.72) in pneumonectomy, 0.91 (95% CI, 0.79 to 1.05) in lobectomy/bilobectomy, and 0.85 (95% CI, 0.63 to 1.15) in segmentectomy/wedge resections.Overall survival after surgical resection improved significantly in a high lung cancer mortality region of the United States. Reasons may include better selection of patients for pneumonectomy and more thorough staging.

8553 Background: Lung cancer early detection improves survival, but risk-based low-dose CT screening (LDCT) only identifies a minority of patients. We implemented an ILNP in a community healthcare system, and evaluated its risks and benefits. Methods: Patients with lung lesions on routinely-performed radiologic studies were flagged by radiologists and triaged using evidence-based guidelines. We tracked demographics, clinical characteristics, procedures, complications, and health outcomes. We analyzed ILNP subjects’ eligibility for LDCT by National Lung Screening Trial (NLST), Center for Medicaid Services (CMS), NEderlands Leuvens Screening ONderzoek (NELSON), National Comprehensive Cancer Network (NCCN) Risk Groups 1 and 2 (screening recommended), NCCN Risk Group 3 (screening not currently recommended), and US Preventive Services Task Force (USPSTF) criteria from 2013 and 2020. Statistical analysis used the chi-square test and Kaplan Meier method. Results: From 2015-2020, 13,710 patients were evaluated in the ILNP program: median age, 64 years; 42% male; 65% White, 29% Black; 667 (4.9%) were diagnosed with lung cancer. Lung cancers diagnosed from ILNP were 39% adenocarcinoma / 20% Squamous Cell with clinical stage distribution 49% I, 8% II, 17% III, and 16% IV. 832 (6.1%) had invasive diagnostic testing- CT-guided biopsy (50%), bronchoscopy (30%), and/or EBUS (26%); 11% of the 832 had >1 invasive diagnostic test. The most common complications from invasive testing were pneumothorax and chest tube placement. Only 11%-20% of all ILNP patients would have been eligible for LDCT. In ILNP patients diagnosed with lung cancer, only 33% were eligible for screening by NLST criteria; the proportion increased substantially when USPSTF 2020 or NCCN Group 2 criteria were applied (Table). Compared to NLST, NCCN Group 2 criteria increased screening eligibility among cancer patients by 22% (from 33% to 55%), while only increasing screening eligibility by 6% (from 8% to 14%) in non-cancer patients. Aggregate 1-year and 3-year survival rates for lung cancer patient diagnosed through ILNP were 76% (95% CI: 73, 80) and 64% (95% CI: 59, 69). Conclusions: The ILNP identified early-stage lung cancer more frequently than most LDCT programs, with promising survival rates. The majority of subjects with lung cancer were not eligible for LDCT, we still need to optimize risk-based screening criteria. Even with new, expanded criteria for LDCT, structured ILNP is necessary to expand early detection of lung cancer.[Table: see text]

Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC.We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias.Five studies published between 2010 and 2014 were eligible for this systematic review with meta-analysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports.LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC.

Background Accurate quantification of the regional burden of sickle cell disease (SCD) is vital to allocating health-related resources. Shelby County, TN, which includes the city of Memphis and the regional pediatric SCD treatment center at St. Jude Children's Research Hospital, is home to a large population of African Americans. Procedure We postulated that the regional birth prevalence of SCD in Shelby County, TN, would differ from national rates. Using data from 2002 to 2012, we estimated the birth prevalence of SCD and sickle cell trait (SCT) in Shelby County and evaluated the distribution of SCD cases by ZIP code of residence with geographic information systems (GIS). Results The prevalence of SCD in African Americans was 1/287 (95% confidence interval [CI]: 1/323, 1/256) live births, significantly higher than the nationally reported 1/350 –1/500. The prevalence of SCT in African Americans was 1/14.7 (95% CI: 1/15.0, 1/14.3) live births, significantly lower than the nationally reported 1/12. We found that 48% of the SCD cases resided in only six of the 37 residential ZIP codes, and using GIS mapping there were two clusters composed of two and four adjacent urban ZIP codes. SCT cases were also centered predominantly in the same two clusters, but slightly more dispersed. Conclusions Recent Shelby County birth prevalence estimates differ substantially from national estimates with higher SCD and lower SCT than expected. Preliminary evidence suggests substantial clustering in two small geographic urban areas within Shelby County that may provide target areas for educational and outreach services.

105 Background: Medicaid patients with lung cancer have poorer outcomes than non-Medicaid patients, partly because of suboptimal care quality. The Association of Community Cancer Centers (ACCC) launched a project to develop, test, and refine an OCCM. Methods: The OCCM comprised 13 areas, spanning care access to supportive care/survivorship. Using the OCCM, 7 cancer programs in 6 US states conducted self-assessments of care delivery systems and implemented quality improvement projects. Sites worked with ACCC to conduct data benchmarked projects. Data collection and analysis were centralized. Statistical analyses used Kruskal−Wallis and chi-squared tests. Results: There were 926 patients (257 Medicaid/dual eligible; 669 non-Medicaid) across 7 sites. Medicaid/dual eligible patients were 52% male, 69% Caucasian, 48% active smokers, and 45% clinical stage III/IV. Prospective multidisciplinary case planning (PMCP), patient care access, and tobacco cessation were commonly selected for projects. PMCP evaluation used fortnightly tumor board (FTB), virtual tumor board (VTB), and multidisciplinary team huddle (MTH). Presentation of eligible patients was higher for VTB and MTH (FTB: 23%, VTB: 100%, MTH: 100%, p < 0.0001). While FTB and MTH discussed all cases prospectively, VTB achieved 80%. Median days (d) from diagnosis to presentation were 18 (FTB), 14 (VTB), and 9 (MTH, p = 0.14). Patient care access was evaluated with timeliness metrics at 2 sites. Site 1: Medicaid patients had a median of 13 d from lesion discovery to diagnosis and 21 d from diagnosis to treatment (not different from non-Medicaid; p = 0.96 and 0.38). 94% met the goal of treatment initiation within 45 d. Site 2: Medicaid patients had a median of 16 d from discovery to diagnosis and 27 d from diagnosis to treatment (not different from non-Medicaid; p = 0.68 and 0.83). Similar benchmarks were collected and compared for other assessment areas. Sites identified enhanced collaboration and improved programming (e.g., patient navigation) as successes. Challenges at project start included inadequate staffing and lack of centralized data collection and benchmarking. Importance of lung cancer–dedicated navigation, PMCP, and Medicaid patient needs were key transferable lessons. Conclusions: The OCCM is useful for cancer programs’ self-assessment of care delivery to Medicaid patients across 13 high-impact areas. Dissemination can advance multidisciplinary coordinated care delivery, but sites may need additional resources to evaluate outcomes.

55 Background: Lung cancer care delivery is complex, with disparate quality and outcomes. Prospective multidisciplinary case planning is a recommended but poorly validated solution. We conducted a prospective comparative effectiveness trial to evaluate the impact of multidisciplinary care on care processes and long-term survival in a large community-based healthcare system. Methods: We previously reported primary objective results comparing patients in the multidisciplinary clinic (MDC) with those not cared for in the MDC i.e. usual, SC. However, a subset of the SC subjects (and all MDC subjects) were discussed at a weekly MTOC. In this secondary analysis, we compare all subjects who were prospectively discussed at MTOC (with or without MDC) with ‘true’ SC (TSC). Subjects were frequency matched by age range, race, insurance, performance status, and initial clinical stage. We compared the thoroughness of staging, use of guideline-concordant treatment, and survival. Models were stratified by frequency matched variables and adjusted for age, sex, and histology as covariates. Statistical methods included chi-square, logistic regression with adjusted Odds Ratios (aOR), and Proportional Hazards models with adjusted Hazard Ratios (aHR); both with 95% confidence intervals. Results: Of 526 subjects enrolled, 246 (47%) were discussed at MTOC. MTOC patients were older (median age 68 v 66, p = 0.03), less intense smokers (p = 0.03), and more commercially insured (p = 0.02). Fewer MTOC subjects were clinical stage IV (33% v 45%, p = 0.01). The MTOC patients had significantly greater odds of bimodal staging (aOR: 2.2 [1.3, 3.8]), trimodal staging (2.6 [1.8, 3.8]), invasive stage confirmation (2.6 [1.7, 3.9]), and mediastinal stage confirmation (2.4 [1.6, 3.6]; all p < 0.01). The additional stage confirmation resulted in more patients who were up- or down-staged in MTOC (44% v 33%, p = 0.03). MTOC patients were twice as likely to receive National Comprehensive Cancer Network guideline-concordant treatment (aOR: 2.0 [1.3, 3.2]). Despite more thorough care, time from initial lesion detection to treatment was similar (mean: 2.86 vs. 2.83 months, p = 0.71). Health-related quality of life measures did not differ between the two arms (P = 0.07 to 0.99). We found no difference in overall (aHR: 1.1 [0.9, 1.4]) or disease free survival (aHR: 1.1 [0.9, 1.3]) between MTOC and TSC. Conclusions: MTOC improved the thoroughness of care and delivery of appropriate treatment, without delays in treatment initiation or survival improvement.

36 Background: The Multidisciplinary Thoracic Oncology Conference (MTOC) model is easier to implement than the Multidisciplinary Clinic (MDC) model, but does not directly involve patients in decision-making. We compared the processes and outcomes of lung cancer care between patients discussed in a weekly MTOC versus those seen in a MDC. Methods: Prospective observational study of thoroughness of staging, stage confirmation (defined as biopsy of the stage-defining lesion), National Comprehensive Cancer Network guideline-concordant treatment, overall (OS) and event-free (EFS) survival of lung cancer patients in a community healthcare system’s MDC and MTOC from 2014-2019. We used the chi-square test and multivariable logistic regression to evaluate guideline-concordant treatment and stage confirmation; Kaplan-Meier curves and multivariable Cox regression were used to evaluate OS and EFS. We adjusted models for age, sex, race, insurance, smoking status, and histology. Results: 614 patients received care in MDC; 571 in MTOC. MDC patients were older (median age: 69 vs. 67); less likely to be active smokers (44% vs. 47%; p=0.03); more likely to have bimodal (98% v 95%, p=0.02) and trimodal staging (60% v 46%, p

104 Background: In 2016, the Association of Community Cancer Centers (ACCC) launched a 3-year initiative to design, test, and refine an OCCM for Medicaid patients with lung cancer. The aim was to help cancer programs identify and reduce the barriers experienced by Medicaid patients by strengthening lung cancer care delivery systems. Methods: Phase I included Model development. Phases II and III included selection of 7 community-based cancer programs as testing sites to implement quality improvement projects, utilizing qualitative and quantitative assessments. Beta testing demonstrated the Model’s ability to offer practical guidance on improving care coordination to achievable target levels in high-impact areas such as patient access to care, prospective multidisciplinary case planning, and tobacco cessation. Opportunities were identified to improve care coordination beyond lung cancer to other tumor sites. Refinements for clarity of intent, ease of use, specificity, and uniformity across assessment areas were implemented, based on feedback from testing sites. Members of the Technical Expert Panel and the Advisory Committee, ACCC staff, and consultants revised the Model using consensus decision-making. Results: The final OCCM is composed of 12 inter-related assessment areas: patient entry into lung cancer program; multidisciplinary treatment planning; clinical trials; supportive care; survivorship care; financial, transportation, and housing needs; tobacco education; navigation; treatment team integration; physician engagement; electronic health records and patient access to information; and quality measurement and improvement. Each assessment area has 5 levels and corresponding metrics—level 1 represents the most basic provision of care, and level 5 represents optimal care coordination, which may be attainable for some cancer programs and aspirational for others. Progress implies cumulative and sustained fulfillment of lower level criteria. The OCCM can be deployed by cancer programs, regardless of size, setting, resource level, or cancer type. Dissemination to promote wider use is planned through an online benchmarking tool, blogs, a brochure, podcasts, and other resources. Conclusions: The OCCM can be utilized by cancer programs for objective self assessments of care delivery capabilities across 12 high-impact areas. Dissemination can advance multidisciplinary coordinated care delivery and improve clinical outcomes for patients nationwide, regardless of cancer type.

Key Points Question What are the barriers to care experienced by adolescents and adults living with sickle cell disease in the United States? Findings This survey study conducted by the Sickle Cell Disease Implementation Consortium enrolled 440 adolescents and adults in 7 different states and found that most respondents were pleased with their usual care physicians but had negative experiences in acute care settings. Pain and the frequency of pain episodes were associated with patient-reported self-efficacy, further emphasizing the association of severe pain with poor outcomes in this population. Meaning A negative perception of care in the emergency department setting may be a barrier for seeking care among adolescents and adults living with sickle cell disease., Importance Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, and previous studies have shown that individuals with SCD are affected by multiple health disparities, including stigmatization, inequities in funding, and worse health outcomes, which may preclude their ability to access quality health care. This needs assessment was performed as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to assess barriers to care that may be faced by individuals with SCD. Objective To assess the SCD-related medical care experience of adolescents and adults with SCD. Design, Setting, and Participants This one-time survey study evaluated pain interference, quality of health care, and self-efficacy of 440 adults and adolescents (aged 15 to 50 years) with SCD of all genotypes and assessed how these variables were associated with their perceptions of outpatient and emergency department (ED) care. The surveys were administered once during office visits by trained study coordinators at 7 of 8 SCDIC sites in 2018. Results The SCDIC sites did not report the number of individuals approached to participate in this study; thus, a response rate could not be calculated. In addition, respondents were not required to answer every question in the survey; thus, the response rate per question differed for each variable. Of 440 individuals with SCD, participants were primarily female (245 [55.7%]) and African American (428 [97.3%]) individuals, with a mean (SD) age of 27.8 (8.6) years. The majority of participants (306 of 435 [70.3%]) had hemoglobin SS or hemoglobin S β0-thalassemia. Most respondents (361 of 437 [82.6%]) reported access to nonacute (usual) SCD care, and the majority of respondents (382 of 413 [92.1%]) noted satisfaction with their usual care physician. Of 435 participants, 287 (66.0%) reported requiring an ED visit for acute pain in the previous year. Respondents were less pleased with their ED care than their usual care clinician, with approximately half (146 of 287 [50.9%]) being satisfied with or perceiving having adequate quality care in the ED. Participants also noted that when they experienced severe pain or clinician lack of empathy, this was associated with a negative quality of care. Age group was associated with ED satisfaction, with younger patients (, This survey study evaluates pain interference, quality of health care, and disease-specific self-efficacy to assess perceived barriers for seeking care among adults and adolescents with sickle cell disease..

e14010 Background: Medicaid patients with lung cancer often have less favorable outcomes than non-Medicaid patients, which, given provision of care is typically comparable, may be due to socioeconomic disparities between these populations. In 2016, the Association of Community Cancer Centers (ACCC) embarked on a 3-year initiative to develop and test the Optimal Care Coordination Model (OCCM) to improve care coordination for Medicaid patients with lung cancer. A framework of 13 independent care delivery areas, spanning access to care to survivorship and supportive care, aids cancer programs in identifying barriers to access and use of their care, with a focus on Medicaid patients, and therefore enables optimal care coordination. Methods: Seven community-based healthcare systems in 6 U.S. states were selected as OCCM beta testing sites and then supported by the ACCC via site visits and biweekly calls. Sites self-assessed the quality of their care in selected OCCM areas to identify relevant quality improvement projects and improve understanding of needs specific to Medicaid patients. Results: Total patient enrollment across all sites was 926 (257 Medicaid; 669 non-Medicaid). Each site selected 1–2 priority OCCM areas, including patient access to care, prospective multidisciplinary case planning, or tobacco cessation, for projects. Enhanced collaboration, improved programming (e.g., patient navigation and formation of lung health leadership team), and organic programmatic changes due to the OCCM work were identified as successes. Site-specific challenges included inadequate staffing at project start and lack of centralized data collection and coordination. The importance of lung cancer–dedicated navigation, multidisciplinary conference use for treatment planning, and understanding needs specific to Medicaid patients were key transferable lessons. Examples of institutional support received by sites during the project included opportunities for staff training and leadership commitment from other hospital departments to assist with care delivery improvements. Use of the existing OCCM framework; increased staffing, particularly for lung cancer navigation; and expanded community outreach were identified in the sustainability plans. Conclusions: OCCM beta testing helped sites self-assess care delivery and identify areas for improvement. Ultimately, it was apparent that Medicaid patients need to be treated differently to obtain equity of outcomes with non-Medicaid patients.

2004 Background: Much-advocated, the value and impact of multidisciplinary care and planning (MDC) needs greater evidence. We compared non-small cell lung cancer (NSCLC) patient characteristics, treatment patterns and survival in a large community healthcare system spanning 3 US states with some of the highest lung cancer incidence and mortality rates. Methods: We identified MDC patients in the Tumor Registry NSCLC data from 2011-2017. Because the MDC program was located in metropolitan Memphis, we separated non-MDC patients by location of care resulting in 3 cohorts: MDC, non-MDC metropolitan care and non-MDC regional care. Using National Comprehensive Cancer Network guidelines, we categorized treatment by stage as ‘preferred’, ‘appropriate’ (allowable under certain circumstances). We compared demographic and clinical characteristics across cohorts using chi-squared tests and compared survival using Cox regression with Bonferroni adjustment. We repeated survival analysis with propensity matched cohorts. Results: Of 6259 patients, 14% received MDC, 56% metro care and 30% regional care; MDC had the highest rates of African Americans (34% v 28% v 22%), stage I-IIIB (63 v 40 v 50), urban residents (81 v 78 v 20), stage-preferred treatment rates (66 v 57 v 48), stage-appropriate treatment rates (78 v 70 v 63;), and lowest non-treatment rates (6 v 21 v 28). All p

2028 Background: Tobacco cessation is essential to high quality oncology care. Many patients smoke when diagnosed and continue to smoke during treatment, which adversely affects treatment response and survival. Although most patients are motivated to quit, few receive effective cessation therapy. The multidisciplinary clinic (MDC), where patients, their caregivers, and key specialists coordinate care, is an ideal setting to integrate a cessation program. To assess the need for cessation services within a MDC setting, we surveyed incoming patients about their smoking status, interest in quitting, and willingness to participate in a clinic-based cessation program. Methods: The study was conducted in the Multidisciplinary Thoracic Oncology Program at Baptist Cancer Center, Memphis TN. We evaluated sociodemographic/clinical characteristics, smoking status, and tobacco dependence of consecutive new patients diagnosed with lung cancer from 2014-2019, who completed a social history questionnaire. Current smokers reported their interest in quitting and their willingness to participate in a cessation program. Chi square tests and logistic regression models were used to compare characteristics of those who would participate vs. those who would not/were unsure. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the association between willingness to participate in a cessation program and overall survival, adjusted for age, sex, race, and total pack-years of smoking. Results: Of 641 patients, the average age was 69 years (range: 32-95), 47% were men, 64% white/34% black, and 17% college graduates; 90% had ever smoked, 34% currently smoked, and 24% quit smoking within the past year. Among current smokers, 60% were very interested in quitting and 37% would participate in a clinic-based cessation program. Willingness to participate was associated with greater interest in quitting (p = 0.0010) and greater overall survival (log rank p = 0.01;HR: 0.48, 95% CI: 0.24-0.95) but was not associated with any sociodemographic, clinical, or smoking-related characteristics. Conclusions: Over half (58%) of patients in a community-based MDC program were current smokers/recent quitters. Willingness to participate in a cessation program was associated with improved survival, suggesting patients with favorable prognoses are especially interested in receiving cessation support. There is considerable need for cessation services and relapse-prevention support within a coordinated, MDC lung cancer care setting.

Invasive mediastinal nodal staging is recommended before curative-intent resection in patients with non-small cell lung cancer deemed at risk for mediastinal lymph node involvement. We evaluated the use and survival effect of preoperative invasive mediastinal nodal staging in a population-based non-small cell lung cancer cohort.We analyzed all curative-intent resections for non-small cell lung cancer from 2009 to 2018 in 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions, comparing patients who did not have invasive mediastinal nodal staging with those who did.Preoperative invasive nodal staging was used in 22% of 2916 patients, including mediastinoscopy only in 13%, minimally invasive procedures only in 6%, and both approaches in 3%. Sixty-three percent of patients at risk for nodal disease (tumor size ≥3.0 cm/T2-T4; N1-N3 by computed tomography or positron-emission tomography-computerized tomography criterion) did not undergo invasive staging; among those who did not have invasive testing, 47% had at least 1 of the 3 clinical indications. Mediastinoscopy yielded a median of 3 lymph nodes and 2 nodal stations; 17% of mediastinoscopies and 31% of endobronchial ultrasound procedures yielded no lymph node material. Patients not invasively staged were more likely to have no nodes (6% vs 2%; P .0001) and no mediastinal nodes (20% vs 11%; P .0001) examined at surgery. Invasive staging was associated with significantly better survival (P = .0157).More than a decade after the 2001 American College of Surgeons Patient Care Evaluation report, preoperative invasive nodal staging remains underused and of variable quality, but was associated with survival benefit in high-risk patients.

Avascular necrosis (AVN) is a chronic bone complication of sickle cell disease (SCD) resulting in significant morbidity. Understanding associated risk factors can facilitate risk-based screening, earlier identification, and prompt intervention. Between 1998 and 2014, 26 symptomatic cases with imaging evidence of AVN were compared 1:5 with age- and SCD genotype-matched controls (n = 128). Patients with 1-5 vaso-occlusive crisis (VOC) (OR 11.9, 95% CI, 1.4-99.9; P = 0.02) and more than 5 VOC (OR 53.6, 95% CI, 5.5-520.2; P = 0.0006) in a 5-year period were more likely to have AVN. Symptomatic patients with more than five VOC in 5 years may benefit from radiologic screening for AVN.

BACKGROUND: Accurate pathologic nodal staging improves early-stage non-small-cell lung cancer survival. In an ongoing implementation study, we measured the impact of a surgical lymph node specimen collection kit and a more thorough pathologic gross dissection method, on attainment of guideline-recommended pathologic nodal staging quality. METHODS: We prospectively collected data on curative-intent non-small cell lung cancer resections from 2009–2016 from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions. We categorized patients into 4 groups based on exposure to the two interventions in our staggered implementation study design. We used Chi-squared tests to examine the differences in demographic and disease characteristics and surgical quality criteria across implementation groups. RESULTS: Of 2,469 patients, 1,615 (65%) received neither intervention; 167 (7%) received only the pathology intervention; 264 (11%) received only the surgery intervention; 423 (17%) had both. Rates of non-examination of lymph nodes reduced sequentially in the order of no intervention, novel dissection, kit, and combined interventions, including non-examination of: any lymph nodes, hilar/intrapulmonary and mediastinal nodes (p

Background Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease-modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children's Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime. Procedures Initiated in 2014, the SCCRIP study prospectively recruits patients diagnosed with SCD and includes retrospective and longitudinal collection of clinical, neurocognitive, geospatial, psychosocial, and health outcomes data. Biological samples are banked for future genomics and proteomics studies. The organizational structure of SCCRIP is based upon organ/system-specific working groups and is opened to the research community for partnerships. Results As of August 2017, 1,044 (92.3% of eligible) patients with SCD have enrolled in the study (860 children and 184 adults), with 11,915 person-years of observation. Population demographics included mean age at last visit of 11.3 years (range 0.7-30.1), 49.8% females, 57.7% treated with hydroxyurea, 8.5% treated with monthly transfusions, and 62.9% hemoglobin (Hb) SS or HbSB0 -thalassemia, 25.7% HbSC, 8.4% HbsB+ -Thalassemia, 1.7% HbS/HPFH, and 1.2% other. Conclusions The SCCRIP cohort will provide a rich resource for the conduct of high impact multidisciplinary research in SCD.

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.

The St. Jude Children’s Research Hospital (St. Jude) comprehensive sickle cell center serves a 150 mile catchment radius around Memphis, TN, USA. Full travel expenses are provided for routine and acute care visits for sickle cell disease patients living ≥35 miles from St. Jude. We compared hospitalization rates to national estimates and assessed if driving distance was a barrier to sickle cell healthcare despite the travel reimbursement policy. We evaluated the associations between hospitalizations and routine clinic visits and distance from St. Jude using negative binomial models and we conducted bias analyses by Monte Carlo simulation. We followed 545 patients (2550 patient-years) aged ≤18 years with sickle cell disease (Hb SS only) from 2007 to 2012. The hospitalization rate per patient-year was 0.65 [95% CI (confidence interval): 0.62, 0.68), significantly lower than the national rate of 1.16 (95% CI: 1.14, 1.18). Children living 35 miles) was associated with decreased hospitalization rates, despite the travel allowances that are provided for those who live ≥35 miles from the hospital.

Among youth with sickle cell disease (SCD), morbidity and mortality substantially increase following departure from pediatric care. The purpose of this study was to investigate the efficacy of co-location transitional model by comparing the rate of health care utilization pre- and post-transfer to adult care and to evaluate the relation between disease specific knowledge and the co-location model. All patients transferring from pediatric to adult care between October 2011 and December 2013, opting for the co-location model to transition from pediatric to adult care in Memphis, TN were included in the analysis. Overall utilization, comprised of both acute care visits and hospitalizations, and health-maintenance visits were compared pre- and post-transfer. Additionally, the association between patient understanding of pain and all health care utilization were assessed. There were 59 participants who established adult care using the co-location transitional model. We found an increase in acute care visits, but a decrease in hospitalizations, that resulted in no change in overall utilization (IRR: 1.11; (95%CI: 0.76, 1.63) comparing pediatric to adult care. The overall utilization rate during adult care was below those previously reported (3.61 vs. 1.65 per person-year, p

Importance Pathologic nodal stage is the most significant prognostic factor in resectable non-small cell lung cancer (NSCLC). The International Association for the Study of Lung Cancer NSCLC staging project revealed intercontinental differences in N category-stratified survival. These differences may indicate differences not only in cancer biology but also in the thoroughness of the nodal examination. Objective To determine whether survival was affected by sequentially more stringent definitions of pN staging quality in a cohort of patients with NSCLC after resection with curative intent. Design This observational study used the Mid-South Quality of Surgical Resection cohort, a population-based database of lung cancer resections with curative intent. A total of 2047 consecutive patients who underwent surgical resection at 11 hospitals with at least 5 annual lung cancer resections in 4 contiguous US Dartmouth hospital referral regions in northern Mississippi, eastern Arkansas, and western Tennessee (>90% of the eligible population) were included. Resections were performed from January 1, 2009, through January 25, 2016. Survival was evaluated with the Kaplan-Meier method and Cox proportional hazards models. Exposures Eight sequentially more stringent pN staging quality strata included the following: all patients (group 1); those with complete resections only (group 2); those with examination of at least 1 mediastinal lymph node (group 3); those with examination of at least 10 lymph nodes (group 4); those with examination of at least 3 hilar or intrapulmonary and at least 3 mediastinal lymph nodes (group 5); those with examination of at least 10 lymph nodes, including at least 1 mediastinal lymph node (group 6); those with examination of at least 1 hilar or intrapulmonary and at least 3 mediastinal nodal stations (group 7); and those with examination of at least 1 hilar or intrapulmonary lymph node, at least 10 total lymph nodes, and at least 3 mediastinal nodal stations (group 8). Main Outcomes and Measures N category-stratified overall survival. Results Of the total 2047 patients (1046 men [51.1%] and 1001 women [48.9%]; mean [SD] age, 67.0 [9.6] years) included in the analysis, the eligible analysis population ranged from 541 to 2047, depending on stringency. Sequential improvement in the N category-stratified 5-year survival of pN0 and pN1 tumors was found from the least stringent group (0.63 [95% CI, 0.59-0.66] for pN0 vs 0.46 [95% CI, 0.38-0.54] for pN1) to the most stringent group (0.71 [95% CI, 0.60-0.79] for pN0 vs 0.60 [95% CI, 0.43-0.73] for pN1). The pN1 cohorts with 3 or more mediastinal nodal stations examined had the most striking survival improvements. More stringently defined mediastinal nodal examination was associated with better separation in survival curves between patients with pN1 and pN2 tumors. Conclusions and Relevance The prognostic value of pN stratification depends on the thoroughness of examination. Differences in thoroughness of nodal staging may explain a large proportion of intercontinental survival differences. More thorough nodal examination practice must be disseminated to improve the prognostic value of the TNM staging system. Future updates of the TNM staging system should incorporate more quality restraints.

Sickle cell disease (SCD) genetic knowledge is important when individuals make reproductive decisions. This study assessed feasibility and efficacy of delivering basic genetic information to 101 adolescents with SCD. Participants completed a questionnaire to test SCD genetic knowledge at 3 timepoints: before genetic education session (pretest), after the session (posttest), and 6 months later (follow-up). Scores at 3 timepoints were compared by Wilcoxon signed-rank tests, and group differences were compared by Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. Participants' median scores significantly increased from pretest to posttest and from pretest to follow-up. Males had a greater change in scores than females. Scores decreased slightly from posttest to follow-up. Participants with HbSS/HbSβ⁰-thal genotype and participants with more prior pain episodes exhibited a smaller increase in median scores than those with HbSC/HbSβ⁺-thal genotype and no prior pain history; however, all groups had substantial gains from pretest to posttest and follow-up tests demonstrating that adolescents with SCD can learn basic genetics. This study established that genetic education can successfully be incorporated in transition to adult care programs for adolescents with SCD. Genetic education should be included in the standard plan of care for adolescents with SCD to assist them in making informed reproductive choices.

Background In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea. Procedure All patients

Background More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function. Methods Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc99m liver–spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake

8546 Background: Early detection reduces lung cancer (LC) mortality. We prospectively evaluated LC patients diagnosed through Lung Cancer Screening (LCS) or an Incidental Lung Nodule Program (ILNP) (‘early detection’ programs) compared to routinely diagnosed LC patients in a multidisciplinary program (MDP). Methods: We compare demographics, tumor characteristics, and survival between the three groups diagnosed within the same healthcare system from 2015-2018. The ILNP prospectively tracks patients with suspicious lung lesions on routinely-performed studies flagged by radiologists using a standard macro text. LCS used Medicare eligibility criteria. Statistical methods include the chi-square test, Kruskal-Wallis test, and proportional hazards models with hazard ratios (HR) and 95% confidence intervals. Results: ILNP detected 201 lung cancers from 4713 scans (4.3%), LCS yielded 35 lung cancers from 1540 low-dose CT scans (2.3%), while MDC had 926 LC cases not detected by LCS or ILNP. Mean age at diagnosis for ILNP/LCS/MDC was 70/69/67 years (p = 0.0083); African Americans were under-represented in LCS (25%/11%/32%, p = 0.0104). LCS had the highest proportion with commercial insurance (46%/54%/43%, p = 0.3442). Early detection groups were more likely to have adenocarcinoma histology (ILNP/LCS/MDC: 61%/57%/49%, p = 0.0113). Smoking exposure was highest in LCS cohort (mean pack years: 48/64/52, p = 0.0500); 11% of ILNP, 8% MDC patients were never-smokers. Only 36% ILNP and 39% MDC patients were eligible for LCS by NLST criteria and 30%/40% by NELSON criteria. Reasons for ineligibility included smoking status in 73-90% and age in 7-27% of patients. Stage I/II distribution was (66%/58%/21%, p < 0.0001), stage IV 15%/20%/36%; surgical resection rates were (56%/55%/31%, p < 0.0001). Overall survival was longer in early detection groups (LCS HR: 0.31 [0.11,0.82]; ILNP HR: 0.51[0.33,0.81]) compared to MDC (p = 0.0011). Conclusions: The majority of LC patients were ineligible for LCS, but the ILNP identified LC in a high proportion of such patients, with similar stage re-distribution, curative-intent treatment, and survival rates. Structured ILNP complement LCS for early LC detection, such programs need to be built out.

6549 Background: LC is common and lethal; care-delivery is complex, varies in quality and outcomes, stimulating calls for multidisciplinary treatment planning (MTP) involving key specialists. This much-advocated model lacks rigorous evaluation. We conducted a prospective cohort study of MTP v Serial Care (SC) in a community healthcare system. Methods: Newly-diagnosed LC patients with performance status (PS) 0-2, and their caregivers, were enrolled from a LC multispecialty group clinic (MGC) or single-specialty general oncology clinics. A subset of general oncology clinic patients were discussed in a Multidisciplinary Thoracic Oncology Conference (MTOC), others were not (Serial Care [SC]). In this analysis, we compare MGC and MTOC patients (MTP recipients) to SC patients. Primary endpoint was overall survival (OS); secondary endpoints were measures of quality: staging practices, guideline-concordant treatment, timeliness of care, patient and caregiver satisfaction. We adjusted proportional hazards and logistic models for age, sex, histology, stage, PS, insurance, and race. Results: 254 patients received MTP v 272 SC. After a median 30 months’ follow up, there was no difference in OS (adjusted hazard ratio 1.10 [CI 0.87-1.40], p = .43). Stage-confirmatory biopsy was done in 61% MTP v 45% SC patients (adjusted odds ratio [aOR] 2.59, CI 1.74-3.86, p < .0001); 81% MTP v 68% SC patients received guideline-concordant treatment (aOR 2.04, CI 1.31-3.19, p < .002). Although the time from lesion detection to diagnostic biopsy (25 v 15 days, p = .004) or staging biopsy (29 v 20 days, p = .007) was higher with MTP, there was no difference in time to definitive treatment (60 v 57 days, p = .06). MTP patients and their caregivers reported greater satisfaction with the combined quality of care received from all team members (p < .0001) at baseline, 3 and 6 months. Conclusions: MTP for LC significantly improved the quality of care including the thoroughness of staging, use of guideline-concordant care, and patient satisfaction. Contrary to reports from retrospective analyses, timeliness of care was worse with MTP. Patient and caregiver satisfaction was superior with MTP. Despite improved quality, MTP was not associated with improved LC survival. Clinical trial information: NCT02123797.

e20052 Background: We quantified variation in stage specific, guideline concordant treatment and examined the interaction with rurality and overall survival (OS). Methods: We used tumor registry data for non-small cell lung cancer (NSCLC) patients at 5 institutions in the Mississippi Delta from 2011-2017, including patient demographics, clinical stage, treatment, and OS. We defined rurality by Rural-Urban Commuting Area codes, hospital and patient zip codes; based stage-stratified treatment on National Comprehensive Cancer Network guidelines; used Chi-squared and ANOVA F-tests to assess differences across institutions and logistic regression to assess associations between appropriate care, patient- and institution-level rurality. We used Log-rank tests to examine differences in OS and Cox proportional hazard regression to calculate hazard ratios (HR). Results: 6,259 patients were identified across 2 rural (n = 1255, 20%) and 3 metropolitan (metro) institutions (n = 5004, 80%). There were significant demographic and clinical differences between institutions: proportion of African-Americans (range: 6-37%, p < 0.001), uninsured (3-18%, p < 0.001), patient rurality (17-99%, p < 0.001), ‘no treatment’ rates (17-31%, p < 0.001). Metro patients or those treated at metro institutions were more likely to receive guideline-concordant treatment (odds ratio: 1.34, 95% CI [1.20 - 1.49]; 1.45 [1.28 - 1.65], respectively) than their rural counterparts and had improved OS (HR: 0.89; 95% CI [0.84 - 0.95]; 0.68 [0.63 - 0.72], respectively). They were also less likely to receive ‘no treatment’ (0.62 [0.55 - 0.71], p < 0.001; 0.51 [0.49 - 0.66], p < 0.001, respectively). Among patients with proper care, there were no patient-level rurality based OS differences (p = 0.2203) but those treated at metro institutions had better OS (p < 0.001). When stage-stratified, only advanced-stage patients treated at metro institutions had better survival (p < 0.001), no other differences in OS were detected for early or late-stage patients. Conclusions: Institution-level rurality had greater influence than patient-level rurality on receipt of guideline concordant care and OS. Appropriate care eliminated patient-level rurality OS disparities.

Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease-modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSβ+ -thalassemia, 28.9% in untreated HbSS/HbSβ0 -thalassemia, 34.2% in HbSS/HbSβ0 -thalassemia hydroxyurea-treated, and 57% in HbSS/HbSβ0 -thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N-terminal pro-brain natriuretic peptide (NT-pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSβ0 -thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT-pro BNP in untreated HbSS/HbSβ0 -thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSβ+ -thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.

Background Chronic transfusions help prevent primary stroke in children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities. However, the effects of transfusions on TCD velocities and brain MRI/MRA findings are incompletely described. Procedure We reviewed TCD and brain MRI/MRA results in 27 children with SCA and abnormal TCD velocities receiving transfusions to prevent primary stroke. All TCDs were performed by a single examiner, immediately prior to a scheduled transfusion. We also examined the effects of laboratory and clinical parameters on TCD responses to transfusion therapy. Results For the whole cohort, the average pre-transfusion HbS on transfusions was 31.7 ± 12.3%. The most significant decline in TCD velocities occurred within 10 months of starting transfusions. Follow-up TCD values trended upward with increasing pre-transfusion %HbS levels while on treatment. Half of the children had persistent conditional/abnormal TCD velocities despite transfusions and 28% had new/progressive stenosis on MRA, but none had primary stroke during 73 patient-years of follow-up. Conclusions For children with SCA and abnormal TCD velocities, transfusions lower TCD velocities and help prevent stroke, but do not always result in normal velocities or protect against progression of cerebral vasculopathy. Improved adherence to transfusion goals may improve on-treatment TCD velocities. Pediatr Blood Cancer 2013;60:1499–1502. © 2013 Wiley Periodicals, Inc.

Elevated foetal haemoglobin (HbF) levels are protective against some manifestations of sickle cell anaemia but the impact on retinopathy is unknown. We report on 123 children with HbSS, 10.6% of whom developed retinopathy. Independent of hydroxycarbamide, children with a HbF

The physiological basis and mechanistic requirements for a large number of functional immunoreceptor tyrosine-based activation motifs (ITAMs; high ITAM multiplicity) in the complex of the T cell antigen receptor (TCR) and the invariant signaling protein CD3 remain obscure. Here we found that whereas a low multiplicity of TCR-CD3 ITAMs was sufficient to engage canonical TCR-induced signaling events that led to cytokine secretion, a high multiplicity of TCR-CD3 ITAMs was required for TCR-driven proliferation. This was dependent on the formation of compact immunological synapses, interaction of the adaptor Vav1 with phosphorylated CD3 ITAMs to mediate the recruitment and activation of the oncogenic transcription factor Notch1 and, ultimately, proliferation induced by the cell-cycle regulator c-Myc. Analogous mechanistic events were also needed to drive proliferation in response to weak peptide agonists. Thus, the TCR-driven pathways that initiate cytokine secretion and proliferation are separable and are coordinated by the multiplicity of phosphorylated ITAMs in TCR-CD3.

Liver R2* values calculated from multi-gradient echo (mGRE) magnetic resonance images (MRI) are strongly correlated with hepatic iron concentration (HIC) as shown in several independently derived biopsy calibration studies. These calibrations were established for axial single-slice breath-hold imaging at the location of the portal vein. Scanning in multi-slice mode makes the exam more efficient, since whole-liver coverage can be achieved with two breath-holds and the optimal slice can be selected afterward. Navigator echoes remove the need for breath-holds and allow use in sedated patients.To evaluate if the existing biopsy calibrations can be applied to multi-slice and navigator-controlled mGRE imaging in children with hepatic iron overload, by testing if there is a bias-free correlation between single-slice R2* and multi-slice or multi-slice navigator controlled R2*.This study included MRI data from 71 patients with transfusional iron overload, who received an MRI exam to estimate HIC using gradient echo sequences. Patient scans contained 2 or 3 of the following imaging methods used for analysis: single-slice images (n = 71), multi-slice images (n = 69) and navigator-controlled images (n = 17). Small and large blood corrected region of interests were selected on axial images of the liver to obtain R2* values for all data sets. Bland-Altman and linear regression analysis were used to compare R2* values from single-slice images to those of multi-slice images and navigator-controlled images.Bland-Altman analysis showed that all imaging method comparisons were strongly associated with each other and had high correlation coefficients (0.98 ≤ r ≤ 1.00) with P-values ≤0.0001. Linear regression yielded slopes that were close to 1.We found that navigator-gated or breath-held multi-slice R2* MRI for HIC determination measures R2* values comparable to the biopsy-validated single-slice, single breath-hold scan. We conclude that these three R2* methods can be interchangeably used in existing R2*-HIC calibrations.

Surgery is the most important curative treatment modality for patients with early-stage non-small cell lung cancer (NSCLC). We examined the pattern of surgical resection for NSCLC in a high incidence and mortality region of the United States over a 10-year period (2004-2013) in the context of a regional surgical quality improvement initiative. We abstracted patient-level data on all resections at 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in North Mississippi, East Arkansas, and West Tennessee. Surgical quality measures focused on intraoperative practice, with emphasis on pathologic nodal staging. We used descriptive statistics and trend analyses to assess changes in practice over time. To measure the effect of an ongoing regional quality improvement intervention with a lymph node specimen collection kit, we used period effect analysis to compare trends between the preintervention and postintervention periods. Of 2566 patients, 18% had no preoperative biopsy, only 15% had a preoperative invasive staging test, and 11% underwent mediastinoscopy. The rate of resections with no mediastinal lymph nodes examined decreased from 48%-32% (P0.0001), whereas the rate of resections examining 3 or more mediastinal stations increased from 5%-49% (P0.0001). There was a significant period effect in the increase in the number of N1, mediastinal, and total lymph nodes examined (all P0.0001). A quality improvement intervention including a lymph node specimen collection kit shows early signs of having a significant positive effect on pathologic nodal examination in this population-based cohort. However, gaps in surgical quality remain.

Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non-small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them.Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology.We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone.NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection.