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The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.

Objectives We sought to determine if implementation of low dose computed tomography (LDCT) screening for lung cancer in the United States had led to changes in patients being diagnosed with metastatic lung cancer over time. Materials Methods The Surveillance, Epidemiology, and End Result (SEER) database was utilized to determine the proportion of lung cancers diagnosed as stage I-III and stage IV from 2009-2018. Changes in lung cancer stage distribution were compared in the overall population and by race. Results From 2009 to 2018, the proportion of stage I-III lung cancers increased from 52% (51.3%-53.2%) in 2009 to 56% (54.0%-55.8%) in 2018 (p Conclusion Since the implementation of LDCT screening, the proportion of early-stage lung cancers increased in the general population. These changes in stage distribution were not present in black patients. Micro Abstract The SEER database was utilized to assess the impact of CT screening on lung cancer stage distribution from 2009-2018. The percentage of patients diagnosed with metastatic disease decreased overall, but there were no significant changes for black patients. These results associate CT screening to changes in lung cancer stage distribution, but potential racial disparities exist.

Purpose:Low-dose CT screening can reduce lung cancer–related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation–based detection of non–small cell lung cancer (NSCLC).Experimental Design:This nested case–control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation–specific real-time PCR for cancer-specific genes (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42).Results:DNA methylation at cancer-specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively.Conclusions:DNA methylation–based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.

Univariate logistic regression analysis for risk of having NSCLC.

Figure S4

Background Lung cancer is the leading cause of cancer death in women in the United States. Prospective randomized lung screening trials suggest a greater lung cancer mortality benefit from screening women compared with men. Research Question Do the United States Preventative Services Task Force (USPSTF) lung screening guidelines that are based solely on age and smoking history contribute to sex disparities in eligibility, and if so, does the use of the PLCOm2012 risk prediction model that is based on 11 predictors of lung cancer reduce sex disparities? Study Design and Methods This retrospective analysis of 883 lung cancer cases in the Chicago Race Eligibility for Screening Cohort (CREST) determined the sensitivity of USPSTF vs PLCOm2012 eligibility criteria, stratified according to sex. For comparisons vs the USPSTF 2013 and the recently published USPSTF 2021 (released March 9, 2021) eligibility criteria, the PLCOm2012 model was used with risk thresholds of ≥ 1.7%/6 years (6y) and ≥ 1.0%/6y, respectively. Results The sensitivities for screening by the USPSTF 2013 were 46.7% for women and 64.6% for men (P = .003) and by the USPSTF 2021 were 56.8% and 71.8%, respectively (P = .02). In contrast, the PLCOm2012 ≥ 1.7%/6y sensitivities were 64.6% and 70.4%, and the PLCOm2012 ≥ 1.0%/6y sensitivities were 77.4% and 82.4%. The PLCOm2012 differences in sensitivity using ≥ 1.7%/6y and ≥ 1.0%/6y thresholds between women and men were nonsignificant (both, P = .07). Compared with men, women were more likely to be ineligible according to the USPSTF 2021 criteria because their smoking exposures were Interpretation Although the USPSTF 2021 eligibility criteria are more sensitive than the USPSTF 2013 guidelines, sex disparities in eligibility remain. Adding the PLCOm2012 risk prediction model to the USPSTF guidelines would improve sensitivity and attenuate sex disparities.

Background STK11 mutation (STK11m ) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown. Methods Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w ) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival. Results 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11m . 5/16 with STK11 m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were not statistically different (STK11m vs. STK11w ): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11 w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49). Conclusions In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w . Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.

Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents., It has been proposed that resistance to targeted therapies in non-small cell lung carcinoma (NSCLC) is due to a nonhomogeneous cell population. Here the authors analyse preclinical NSCLC models using single-cell RNA-seq and identify drug tolerant cell states and subpopulations, as well as associated genes.

Disparities exist in lung cancer outcomes between African American and white people. The current United States Preventive Services Task Force (USPSTF) lung cancer screening eligibility criteria, which is based solely on age and smoking history, may exacerbate racial disparities. We evaluated whether the PLCOm2012 risk prediction model more effectively selects African American ever-smokers for screening.Lung cancer cases diagnosed between 2010 and 2019 at an urban medical center serving a racially and ethnically diverse population were retrospectively reviewed for lung cancer screening eligibility based on the USPSTF criteria versus the PLCOm2012 model.This cohort of 883 ever-smokers comprised the following racial and ethnic makeup: 258 white (29.2%), 497 African American (56.3%), 69 Hispanic (7.8%), 24 Asian (2.7%), and 35 other (4.0%). Compared with the USPSTF criteria, the PLCOm2012 model increased the sensitivity for the African American cohort at lung cancer risk thresholds of 1.51%, 1.70%, and 2.00% per 6 years (p0.0001). For example, at the 1.70% risk threshold, the PLCOm2012 model identified 71.3% African American cases, whereas the USPSTF criteria only identified 50.3% (p0.0001). In contrast, in case of whites there was no difference (66.0% versus 62.4%, respectively [p = 0.203]). Of the African American ever-smokers who were PLCO1.7%-positive and USPSTF-negative, the criteria missed from the USPSTF were those with pack-years less than 30 (67.7%), quit time of greater than 15 years (22.5%), and age less than 55 years (13.0%).The PLCOm2012 model was found to be preferable over the USPSTF criteria at identifying African American ever-smokers for lung cancer screening. The broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes.

BACKGROUND Social media in healthcare has many benefits, including the dissemination of health information,1 health promotion, and recruitment of clinical study participants.2 The COVID-19 pandemic has highlighted the benefits of the Internet and social media as tools through which individuals can exchange health information. While little is known about oncology patient preferences for social media platforms, particularly among minority populations, some studies have shown its use to be linked to the alleviation of patient stress and loneliness, increased feelings of self-efficacy and control of care, and efficient delivery of health information from health practitioners.3 OBJECTIVE The aim of this study is to assess cancer patient access to and use of social media platforms and technology. METHODS Between March 2021 to June 2021, we administered a 16-item survey adapted from the National Cancer Institute’s (NCI) Health Information National Trends Survey (HINTS)4 to patients scheduled for a visit in the oncology department at the Outpatient Care Center (OCC) at UI Health. The survey was delivered by e-mail and administered in person. Respondents were asked to identify all sources used to learn about their diagnosis, their preferred information source, social media usage and preferences, and demographics. We used Chi-square to assess associations between categorical variables. This study was approved by the Office for the Protection of Research Subjects (OPRS) at the University of Illinois at Chicago. RESULTS Demographics of our sample can be found in Table 1. Respondents use several forms of information sources. The top three include: their doctor or healthcare provider (89.3%), Internet search engine (71%), and brochures and pamphlets (40.7%). However, when directed to choose just one source, 67.4% chose their doctor or health care provider, while 21.8% chose Internet search engine. The majority of respondents use a smartphone with Internet (77.2%), a home desktop or laptop with Internet (62.5%), or a tablet with Internet (61.2%). However, approximately one-quarter of respondents indicated that they use a mobile phone without Internet or a data plan. In exploring social media use and preferences, we found the majority of respondents have a social media platform (64.7%). Having a social media platform was associated with age (X2=18.7, p CONCLUSIONS Understanding how patients exchange health information is important to ensure access to accurate information and promote engagement with the healthcare team. We found that despite having social media platforms, our patient population does not predominantly use it as an avenue to engage with their healthcare providers, but rather to find health related information. Recent trends from the HINTS survey show an increased use of social media to exchange health information with healthcare providers.5 As social media engagement is linked to positive patient outcomes, employing social media interventions can help us improve the illness experience of oncology patients. While both cancer care providers and patients are increasingly using social media as a learning and sharing tool6, the exact information-seeking behavior of cancer patients has yet to be fully examined. In the current climate where medical misinformation is rampant on the Internet, healthcare workers should find innovative ways to disseminate evidence-based patient facing information utilizing the platforms most accessed by oncology patients. Our study highlights the need to further explore communication preferences to inform the development of tailored communication strategies to support oncology patients and their families.

Recommending video-assisted thoracic surgery (VATS) over open thoracotomy to patients with early-stage non-small-cell lung cancer (NSCLC) is controversial. Accordingly, we reviewed randomized comparative studies to determine the risks and benefits of VATS lobectomy. Electronic searches on PubMed with standard search terms revealed 97 comparative studies published between 1990 and 2022. Of those, only 5 were randomized controlled clinical trials (RCT) and 1 is still ongoing although initial data has been published as an abstract form. A total of 918 patients were evaluated in 5 RCT's. All studies included patients with known or suspected primary lung cancer randomized in a 1:1 ratio to VATS or thoracotomy. Between 2 studies, reports of 1-year, 3-year and 5-year overall survival were found to be similar across surgical modalities. Additionally, no differences were found in the rates of locoregional and distant recurrence. Three studies reported no statistical differences in the number of hilar and mediastinal lymph nodes sampled. Two studies found decreased length of stay following VATS (4 days v 5 days, P = 0.027 and P = 0.008), while 2 found no difference. Increased in-hospital complications were seen in 2 studies (P = 0.008 and P = 0.039). VATS was associated with decreased pain scores, better self-reported QOL at 52 weeks (P = 0.014). Few randomized clinical trials comparing VATS lobectomy to open thoracotomy and lobectomy in early stage NSCLC have been reported. These studies suggest that VATS lobectomy offers similar outcomes with decreased in-hospital complications, pain, length of stay, and improved physical functioning when compared to thoracotomy.

Objectives Adjuvant chemotherapy is routinely offered post-surgical resection for early stage non-small-cell lung cancer (NSCLC) ≥4 cm; however, its role following definitive stereotactic body radiotherapy (SBRT) has not been well defined. We investigated the association between receipt of adjuvant chemotherapy post-SBRT and overall survival (OS) for patients with T1-T3N0M0 NSCLC in the National Cancer Database (NCDB). Materials and Methods The NCDB was queried for patients with T1-T3N0M0 NSCLC treated with definitive SBRT from 2004 to 2014. The association between non-randomized receipt of adjuvant chemotherapy and OS was analyzed for all patients (n = 24,011) and a propensity-matched cohort (n = 608) using Kaplan-Meier methods and Cox proportional hazard models. A subset analysis was performed for patients with tumors ≥4 cm (n = 2,323). Results There were 24,011 patients in the cohort with a median follow-up of 32.5 months. Of these, 322 (1.3%) received adjuvant chemotherapy. Three-year OS was 41.3% with adjuvant chemotherapy compared to 50.6% without adjuvant chemotherapy (p = 0.001). On multivariate analysis, adjuvant chemotherapy was independently associated with higher overall mortality (hazard ratio:1.22, 95% confidence interval:1.06–1.40, p = 0.005). For tumors ≥4 cm, 3-year OS was 38.2% with adjuvant chemotherapy (n = 80) compared to 33.0% without adjuvant chemotherapy (p = 0.81). After propensity-score matching, there was a persistent association between lower OS and adjuvant chemotherapy with those receiving adjuvant chemotherapy (n = 322) having 3-year OS of 41.3% compared to 60.9% without adjuvant chemotherapy (p Conclusion Adjuvant chemotherapy following definitive SBRT for T1-3N0M0 NSCLC is associated with lower OS and is not associated with a survival benefit for patients with tumors ≥4 cm.

1542 Background: The 4R Oncology model was proposed within the NCI ASCO Teams Project as an approach to facilitate patient-facing care planning, team-based delivery and patient self-management. 4R (Right Info/Care/Patient/Time) enables care teams and patients to manage complex care with a novel 4R Care Sequence plan. We previously reported that 4R significantly improved patient self-management, namely patients’ ability to organize and manage their care (Trosman JCO OP 2021). Here we report the impact of 4R on effectiveness of clinicians to plan and deliver complex multidisciplinary care. Methods: We surveyed clinicians (physicians and nurses) from 8 cancer centers (4 academic, 4 community) participating in a 4R adoption program. The survey was conducted Mar 2019 to Sep 2019 prior to 4R launch (Baseline cohort), and Nov 2021 to Jan 2022 post-4R launch (4R cohort). Baseline cohort included clinicians conducting care planning with patients. 4R cohort included clinicians who used 4R in care planning with new patients. The survey focused on clinicians’ self-reported effectiveness in planning and management of guideline-based care. Descriptive statistics and Fisher’s 2-sided test were used in analyses. Results: Baseline cohort’s response rate was 79% (66/83); 4R cohort’s response rate was 86% (62/72). 4R implementation was associated with significant improvement in all 5 metrics of effective care planning between the baseline and 4R cohorts (Table). Within the 4R cohort, 87% (54/62) clinicians found 4R Care Sequences useful or very useful for care planning and management. The majority, 79% (49/62), spent 10 minutes or less on average developing and administering 4R Care Sequence to a new patient, and 58% (36/62) reported decreased overall volume of post-visit inquiries about care plan from patients who received 4R. When asked about 4R delivery format, 65% (40/62) preferred paper, 23% (14/62) electronic delivery and 12% (8/62) had no preference. Conclusions: The 4R Oncology model is a promising approach to improving clinicians’ effectiveness in patient-facing care planning and reducing the workload associated with patient inquiries. An ongoing 4R research and implementation program continues efforts to identify optimal implementation methods and integrate 4R into clinical practice across the U.S. [Table: see text]

BACKGROUND: STK11 mutation (STK11(m)) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11(m) in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown. METHODS: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11(m) pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11(w)) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival. RESULTS: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11(m). 5/16 with STK11 (m) did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11(m) and 59 STK11(w) pts were not statistically different (STK11(m) vs. STK11(w)): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11(m) pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3–17) vs. 6 (range, 1–25) in the 17 pts with STK11(w) who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11(m) pts was significantly worse than STK11(w) pts (HR =2.25; 95% CI, 1.03–4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11(m) vs. STK11(w) patients (HR 1.47, 95% CI, 0.49–4.38, P=0.49). CONCLUSIONS: In stage III NSCLC patients who received CCRT, STK11(m) was associated with worse PFS compared to STK11(w). Larger studies are needed to further explore the prognostic implications of STK11(m) in stage III NSCLC and whether ICI impacts survival for this subgroup.

Introduction: Allostatic load (AL) is a multi-system measure of chronic stress shown to be an emerging framework for understanding disparities in cancer outcomes, but there have been no AL studies in lung cancer. Methods: We conducted a retrospective review of patients diagnosed with stage IV lung adenocarcinoma from 2016 - 2020 at the University of Illinois Hospital and Health System. An AL index included 9 biomarkers (systolic blood pressure, diastolic blood pressure, resting heart rate, BMI, albumin, eGFR, creatinine, glucose, and use of medications for hypertension, diabetes, or hypocholesteremia) with 1 point assigned for each biomarker meeting a pre-determined cutoff. AL was dichotomized between AL-high (5-9) and AL-low (0-4) with median progression-free survival of first-line therapy (mPFS1) and median overall survival (mOS) estimated for both groups with Kaplan-Meier curves. Rates of clinically actionable driver mutations (driver-POS), including EGFR, ALK, ROS1, BRAF V600e, RET, MET, NTRK, and KRAS G12C, were compared for both groups using chi-squared test. Mean AL was compared between those who were driver-POS and those who did not have a clinically actionable driver mutation (driver-NEG) using independent samples t-test. Results: A total of 61 patients were identified with 56% female and 74% former or current tobacco users. The cohort was 49% Black, 21% White, and 13% Hispanic or Latino. Mean AL at diagnosis was 3.3 (+/- 1.4). AL-high patients comprised 20% (12) of the cohort compared with 80% (49) AL-low. Between AL-high and AL-low cohorts, there was no statistically significant difference in mPFS1 (15 vs. 13 months, P = 0.98) and mOS (34 vs. 18 months, P = 0.33). Rates of driver-POS were lower in AL-high compared with AL-low (25% vs 69%, P Conclusions: Patients whose tumors did not have a clinically actionable driver mutation were associated with a higher AL, suggestive of higher chronic stress playing a role in more aggressive tumor biology. No statistically significant survival difference was observed in AL-high versus AL-low populations for mPFS1 and mOS. Larger, prospective trials are planned to correlate AL at diagnosis with clinical and biomarker data. AL, which serves as a measure of physiological dysfunction due to chronic stress associated with social disadvantage, may have implications for tumor biology and clinical outcomes in lung cancer. Citation Format: Ryan H. Nguyen, Michael Weinfeld, Mary Pasquinelli, Frank Weinberg, Natalie Reizine, Lawrence Feldman, Vijayakrishna K. Gadi. Allostatic load, tumor genomics, and outcomes in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3663.

3138 Background: TMB is routinely reported in cancer patients tested with broad-panel next generation sequencing and has become a predictive biomarker associated with response to checkpoint inhibitor (CPI) therapy. Sequencing of paired tumor and normal specimens allows correction of TMB estimates with patient-specific germline variants. When a paired normal specimen is unavailable, TMB estimates are corrected using germline variant annotations derived from population-scale germline variant surveys. Germline variants do not generate neoantigens, which is the putative target of the immune response in CPI treated patients. To evaluate TMB differences in paired sequencing (PS) and tumor-only sequencing (TOS), we compared TMB assessments—stratified by race—in two common malignancies. Methods: Using de identified records from the Tempus clinico-genomic database, cohorts of patients with non-small cell lung cancer (NSCLC) and breast cancer sequenced using the Tempus xT NGS platform (DNA-seq of 595-648 genes at 500x coverage, whole exome capture RNA-seq) and noted to not have microsatellite instability, were identified for analyses. The Kruskall-Wallis test was used to compare TMB distributions. Results: Among 4,817 NSCLC patients with race information (13% Black (B), 5% Asian (A), 82% White (W), 3,052 had PS, and 1,765 had TOS performed. Median TMB for B, A, and W patients was 5.8, 2.6, and 4.7 (within group p < 0.0001), respectively in patients with PS, and 9.5, 6, and 7.4 (within group p < 0.0001), in patients with TOS. Comparisons across PS and TOS were highly significant (p < 0.0001). The absolute difference in median TMB was 3.7, 3.4, and 2.5, respectively. Among 3,191 patients with breast cancer (17% B, 4% A, 78% W), 2,220 had PS, and 971 had TOS. Median TMB for B, A, and W patients was 2.6, 2.1, and 2.6 (within group p = 0.11), respectively, in patients with PS, and 6.3, 5.8, and 4.7 (within group p < 0.0001) in patients with TOS. Comparisons across PS and TOS were highly significant (p < 0.0001). The absolute difference in median TMB was 3.7, 3.7, and 2.1, respectively. Conclusions: PS reduces estimated TMB compared to TOS across all racial groups with a pronounced difference in Black and Asian racial groups. This is expected as population databases of germline variation are based on cohorts predominantly from individuals of European ancestry, leading to artifactually high TMB in minorities tested with TOS. As a result, artifactually elevated TMB estimates from TOS may promote treatment with CPI in patients with a low probability of response which could exacerbate known race-based outcome disparities. PS provides a more accurate estimate of TMB regardless of race and could reduce the use of CPI in patients with a low likelihood of response.

e14595 Background: Management of cancer-related pain with opioids is hypothesized to decrease efficacy of immune checkpoint inhibitors (ICIs) through immunosuppressive effects of opioids, such as down-regulation of major histocompatibility complex class II. There is limited evidence on how opioids affect outcomes in patients receiving ICIs. Methods: We identified 212 patients at the University of Illinois Hospital and Health Sciences System who received an ICI between January 1, 2015 and July 31, 2021. Overall survival (OS) and progression-free survival (PFS) were compared in patients who were not treated with opioids, patients treated with low-dose opioids (defined as less than 60 morphine milliequivalents per day), and patients treated with high-dose opioids (defined as at least 60 morphine milliequivalents per day). Results: Out of 212 patients who received an ICI, 98 (46.2%) received no opioids, 69 (32.6%) received low-dose opioids, and 45 (21.2%) received high-dose opioids. Among all patients, 105 (49.5%) died during the study duration. The overall median survival time was 23 (95% CI = 16, 38) months for the entire sample. Patients who received opioids at any dose had a median OS of 17 months compared to 37 months in those who received no opioids (HR = 1.53, p = 0.0385). When patients receiving opioids were further divided by dose, survival time was highest in those receiving no opioids, next highest in those receiving low-dose opioids, and lowest in those receiving high-dose opioids (37 months vs 18 months vs 10 months, p = 0.0515). Among all 212 patients, progression of disease occurred in 84 (39.6%) patients. The overall median time-to-progression was 24 months. There was no significant difference in median PFS between those treated with opioids (36 months) versus not (23 months, p = 0.156). Conclusions: We observed an association between opioid therapy, especially at higher doses, and decreased median OS in patients receiving ICIs. On the other hand, there was no statistical association between opioid therapy and median PFS. These data highlight a potential drug interaction in oncology care, and further analysis looking at duration of opioid use and ECOG PS is planned.[Table: see text]

Purpose: Low-dose CT screening can reduce lung cancer–related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation–based detection of non–small cell lung cancer (NSCLC). Experimental Design: This nested case–control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation–specific real-time PCR for cancer-specific genes (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42). Results: DNA methylation at cancer-specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively. Conclusions: DNA methylation–based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.

e21157 Background: Standard of care testing prior to first-line therapy for advanced lung non-small cell lung cancer (NSCLC) includes EGFR mutations, ALK rearrangements, and PD-L1 expression. There is limited real-world evidence on NSCLC molecular testing patterns in underrepresented racial and ethnic populations. Methods: We identified adult patients newly diagnosed with stage IV lung adenocarcinoma at the University of Illinois Hospital & Health Sciences System between January 1, 2015 and October 1, 2019. Rates of biomarker testing for EGFR, ALK, and PD-L1 were determined, as well as the median time from tissue biopsy to each result. Data were stratified by race and ethnicity. Timelines of molecular testing were studied in relation to cancer therapy initiation. Results: Among 80 patients diagnosed with advanced NSCLC, 70 (87.5%) received EGFR testing, 69 (86.3%) received ALK testing, and 40 (50%) received PD-L1 testing from 2015-2019. Thirty-one (81.6%) patients diagnosed from 2017-2019 had PD-L1 testing. Median time from biopsy to molecular test result in the overall population was 3.0 weeks for EGFR, 3.0 weeks for ALK, and 2.0 weeks for PD-L1. There was no significant difference in EGFR and ALK testing rates between Black and non-Black patients. PD-L1 testing was decreased in Black patients compared to non-Black patients ( p = 0.02) from 2015-2019, but there was no significant difference from 2017-2019. All three biomarkers had similar testing rates between White and non-White patients and between Hispanic and non-Hispanic patients. Median time from biopsy to PD-L1 result decreased from over 12 weeks in 2015 and 2016 to 2 weeks in 2018 and 2019. Six (7.5%) patients received first-line treatment before results were available. Two (2.5%) required treatment changes based on results. Conclusions: In an urban, academic center we found similar EGFR and ALK testing rates among race and ethnicity subgroups. PD-L1 testing was lower in Black patients from 2015-2019 but not after national guidelines recommended PD-L1 testing in 2017. Treatment was initiated without full biomarker data in multiple cases, sometimes leading to changes in therapy after results were obtained. Further studies are indicated to determine strategies for comprehensive, timely, and equitable biomarker testing in advanced NSCLC.[Table: see text]

Introduction: Eligibility criteria for lung cancer screening based solely on age and smoking history are less sensitive than validated risk prediction models. The U.S. Preventive Services Task Force (USPSTF) has proposed new guidelines to improve the sensitivity for selecting high-risk individuals and to decrease race disparity. In this retrospective study, termed the Chicago Race Eligibility for Screening Cohort, we compare the sensitivity of the proposed USPSTF2020 criteria versus the PLCOm2012 risk prediction model for selecting a racially diverse lung cancer population with a smoking history for lung cancer screening. Methods: This Chicago Race Eligibility for Screening Cohort study applies the PLCOm2012 model with a risk threshold of 1.0%/6 years and the USPSTF2020 criteria (age 50–80 y, pack-years ≥ 20 y, quit-years ≤ 15 y) to 883 individuals with a smoking history diagnosed with having lung cancer. Results: The PLCOm2012 was more sensitive than the USPSTF2020 overall (79.1% versus 68.6%, p < 0.0001) in White (81.5% versus 75.4%, p = 0.029) and in African American (82.8% versus 70.6% p < 0.0001) individuals. Of the total cohort, 254 (28.8%) would not have qualified owing to less than 20 pack-years, quit-time of more than 15 years, and age less than 50 years. Of these 254 cases, 40% would have qualified by the PLCOm2012 model. For the 20 pack-year criterion, of the 497 African American individuals, 19.3% did not meet this criterion, and of these, an additional 31.3% would have qualified by the PLCOm2012 model (p = 0.002). Conclusions: Although more sensitive than USPSTF2013, the proposed USPSTF2020 draft guidelines still have a race disparity in eligibility for screening. This study provides “real world” evidence that use of the PLCOm2012 risk prediction model eliminates this race disparity.

9033 Background: STK11 mutation ( STK11m) in patients with stage IV NSCLC is associated with inferior survival and poor response to immune check point inhibitors (ICI). The significance of STK11m in patients (pts) with stage III NSCLC treated with concurrent chemoradiation (CCRT) with and without consolidation ICI is unknown. Methods: Patient demographics, disease characteristics, treatment received and outcomes in pts with stage III NSCLC that harbor STK11m were retrospectively reviewed from 4 cancer centers. A cohort of pts with stage III NSCLC and wild type STK11 (STK11w) from the University of Iowa served as a comparison group. SPSS version 25 was used for data analysis. Results: 75 pts with stage III NSCLC who had gene sequencing were included. 16/75 (21%) had STK11m. The clinical characteristics for the 16 STK11m and 59 STK11w pts showed ( STK11m vs. STK11w): mean age: 58 vs. 64 yrs, non-squamous histology: 11/16 (69%) vs. 37/59 (63%), KRAS co-mutation: 6/16 (38%) vs. 11/59 (19%), TP53 co-mutation: 9/16 (56%) vs. 15/59 (25%), PD-L1 ≥ 50%: 2/16 (13%) vs. 10/59 (17%), received CCRT 11/16 (69%) vs. 59/59 (100%) and consolidation ICI 6/16 (38%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 7 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). Progression free survival (PFS) for the STK11m vs. STK11w pts who received CCRT but not ICI was (4.2 vs. 34.3 months, respectively. P = 0.168), for the STK11m vs. STK11w pts who received CCRT and ICI was (11.3 vs. 17.5 months, respectively. P = 0.174), and for the STK11m vs. STK11w pts who received CCRT regardless of receiving ICI (11.3 vs. 32.9 months, respectively. P = 0.021). The median overall survival for STK11m pts (16 pts) was 25.5 months (95% CI, 13.7 to 37.2) while not yet reached for the STK11w group. Conclusions: In stage III NSCLC, STK11m was associated with inferior clinical outcomes. Larger studies are needed to identify the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.

e24051 Background: CSOC conducts quality improvements (QI) for cancer patients that facilitate delivery of appropriate health maintenance and supportive cancer care at diagnosis and during treatment. CSOC is implementing a care planning QI starting at diagnosis using the 4R oncology model (Right Info / Care / Patient / Time), which provides patients a formal personalized care plan called Patient Care Sequence. Each Care Sequence includes health maintenance, cancer treatments and supportive care. As part of CSOC, we conducted provider surveys as a pre-intervention baseline to inform QI opportunities. Methods: Online survey of cancer providers from 8 cancer centers (4 academic, 4 community) conducted July 2018 - October 2019, prior to 4R implementation. The survey focused on current care planning practices and inclusion of guideline recommended health maintenance in care plans. Results: Survey response rate: 80% (180/225); respondents were 53% physicians, 20% advanced practice, 27% nurses. Only 59% (107/180) of respondents give patients care plans at diagnosis: 61% (65/107) verbally, 22% (24/107) written, 17% (18/107) using a printed form. Providers reported considerable gaps in including guideline-based health maintenance and promotion activities in care plans given to patients (Table). Additionally, 61% of providers reported concerns that it is challenging for their patients to manage their own health maintenance activities. Providers who are concerned about patients’ challenges in managing their own health maintenance are significantly more likely to give their patients a written or printed plan (76%, 32/42) compared to those providing care plans to patients verbally or not at all (56%, 77/138), p = .02. Conclusions: Guideline based health promotion activities are not consistently included in care plans, and care planning is not sufficiently conducted at cancer diagnosis. The CSOC 4R Oncology Model, which implements Patient Care Sequences at diagnosis, will address these gaps and examine the impact of formal care planning on improving utilization of health maintenance and promotion activities. [Table: see text]

This population-based study assesses demographic characteristics, CT scan findings, and lung cancer detection in minority populations compared with outcomes from the National Lung Screening Trial.

199 Background: The Commission on Cancer (CoC) Standard 3.2 requires distress screening and indicated action for cancer patients. NCCN and ASCO supportive care and age-related guidelines include patient reported concerns beyond distress. This study compares PHQ4 scores to other patient reported concerns. Methods: The Coleman Supportive Oncology Collaborative aggregated “best of” screening tools to assess patient reported needs and concerns aligned with CoC, NCCN and ASCO guidance. This supportive care screening tool was implemented at 8 sites from July 2015 thru July 2018. Analysis used chi squared test. Results: Most patients, 86% (10,635/12,295), reported one plus concerns and/or above threshold scores on PHQ4, PROMIS Pain, Fatigue or Physical Function. A chi squared comparison of patients with at least mild distress on PHQ4 to patients with no distress resulted in p values < .0001 for every screening category. Conclusions: Patients with a PHQ4 distress score of mild, moderate or severe also reported statistically significant levels of practical, family, physical, nutrition and treatment concerns. These patients also scored threshold levels for PROMIS Pain, Fatigue, and Physical Function. Screening only for distress without screening for other patient concerns may direct patients to services that do not address or focus on the underlying cause of the distress. [Table: see text]

33 Background: The Institute of Medicine and Commission on Cancer recommend systematic delivery of supportive oncology care for cancer patients. The CSOC is focused on quality improvement (QI) of supportive care across Chicago cancer centers (Weldon ASCO ’17). Supportive oncology includes distress, practical, family, physical, nutrition, pain, fatigue and care concerns. To support QI, cross-institution teams developed unique, relevant tools, methods, care delivery processes, patient handouts and online training. Methods: Ten centers (5 academic, 1 VA, 1 public, 2 safety net, 1 community) implemented supportive oncology screening and care delivery quality improvements. Centers collected data for relevant Quality Oncology Practice Initiative (QOPI) metrics. Analyses used simple frequencies and Fishers exact test. Results: Five of six QOPI measures were improved at statistically significant levels from 2014 to 2017, p < .00001. Improvements are more modest in 2016 & 2017 as 4 of the centers started this QI in 2017. Conclusions: The CSOC achieved significant improvements in supportive oncology screening and identifying and addressing patients’ needs and concerns. Additional work is needed to improve these measures to achieve the best quality of cancer care possible for every patient based on their needs and concerns. [Table: see text]

198 Background: The Institute of Medicine (IOM) 2013 Report recommends that supportive oncology care start at cancer diagnosis; the Commission on Cancer (CoC) Standard 3.2 requires distress screening and indicated action. The Supportive Oncology Collaborative, collaborative of 100+ clinicians funded by The Coleman Foundation, developed a patient-centric screening tool (CSOC-ST) adapted from ASCO Distress, NCCN Distress Problem List, IOM report and CoC standards, and other validated sub-tools (Weldon, ASCO-Q 2017). The Collaborative revised the CSOC-ST tool to align with ASCO geriatric guidelines. Methods: Literature and guidelines review of geriatric screening, added items to CSOC-ST, and piloted at 4 sites. Descriptive statistics and Fisher’s exact test used. Results: 473 patients screened with added geriatric relevant items to CSOC-ST: self-care concerns (PROMIS Instrumental Support), living alone (ASCO Distress 2014), and memory / cognition (PROMIS item bank). Treatment/care concern items were revised to identify health care power of attorney and advance directive interest. Geriatric related items endorsed by patients, see Table. PHQ4, Anxiety and Depression, average score 2.4 (mild > 3). Higher scores on the PHQ-4 were significantly associated with each of the following: self-care concerns, memory/cognition concerns and specific treatment/care concerns (p < .0001). Conclusions: Pilot results and comparison to ASCO geriatric guidelines identified important items to support geriatric patient reported outcomes screening. After pilot, added 3 items for falls/frailty. Eight sites implementing this CSOC-ST.[Table: see text]

59 Background: A challenge in supportive oncology is training the HCP workforce. The Coleman Supportive Oncology Collaborative clinicians (faculty) from 25 institutions (academic, community & safety net) developed a unique and easily accessible supportive oncology training curriculum (Trosman JR JNCCN 2017). Methods: Using data provided by The National Comprehensive Cancer Network (NCCN) Continuing Education team, we evaluated completion rates of survivorship and supportive oncology education courses using simple frequencies. Results: Over 4748 on-line courses were completed (pretest, course, post-test, evaluation) of 7184 accessed. Of 4748 courses, nurses completed 45%, physicians 17%, advance practice clinicians 16%, and others 22% (social workers, chaplains, MAs). Course completion improved from 65% to 69% after articles describing collaborative work were published in Cure and Oncology Nursing News, p = 0.0014. Conclusions: A variety of HCPs successfully completed supportive oncology guideline education via the NCCN’s education portal. These on-line courses are an efficient way to train HCPs in supportive oncology. Curriculum advertising improves course completion.[Table: see text]

e18909Background: The goal of incorporating lung cancer screening programs into health systems is to identify cases of early stage lung cancer and thereby reduce mortality. However, there is limite...

19 Background: A challenge in supportive oncology, integral to patient care, is training the health professional workforce. A collaborative funded by The Coleman Foundation of 30+ clinicians (faculty) from 25 institutions (academic, community & safety net) developed a unique fundamental survivorship care (Weldon JCO 2017) and supportive oncology training curriculum (Trosman JNCCN 2017). Methods: Using data from The National Comprehensive Cancer Network Continuing Education team, we analyzed utilization of survivorship and supportive oncology education courses using simple frequencies. Results: Over 3200 courses were completed (pretest, course, post-test, evaluation) and 4850 accessed. Nurses completed 56%, physicians 15%, social workers/psychologists/support staff 14%, advance practice clinicians 8%, and various roles for the rest. Courses in table. Conclusions: NCCN’s education portal achieved strong utilization from a variety of healthcare professionals in these courses. The Coleman Supportive Oncology Collaborative supports improvement in supportive care with tools, processes and training and will continue to update/offer courses through this portal.[Table: see text]