Background:Obesity's impact on cancer treatment outcomes is poorly understood, especially in the context of immuno-oncology. This study explores how obesity and medical comorbidities are associated with overall survival in cancer patients receiving immune checkpoint inhibitors (ICIs). Additionally, considering the influence of sex on body composition in obesity, this study examines the relationship between sex, obesity, medical comorbidities, and survival. Methods:This cohort study involved 688 patients with metastatic cancer received ICIs as first- or second-line therapy. Obesity was assessed using body mass index (BMI). Cox proportional hazard models and Kaplan-Meier survival analysis were used to examine associations between predictors and overall survival. Results:Patients with higher BMI had longer overall survival, and hazard ratio (HR) for death was 0.83 (95% CI 0.73-0.95) for every 10 units increased in BMI. Additionally, patients belonged to the highest BMI group (≥ 40) had the lowest risk of death when comparing to patients with BMI 18.5 to < 30 with HR 0.58 (95% CI 0.37-0.90). In subgroup analysis, a significant association between high BMI and decreased HR for death was predominantly observed in the male cohort. In multivariate analysis, the prognostic value of BMI remained significant after adjusting for performance status, line of therapy, age-adjusted medical comorbidities, and cancer type. Conclusions:Obesity was associated with decreased mortality risk for cancer patients who had received ICIs. There could be a sex-dependent association between survival benefit and obesity.

Examine which demographic, lifestyle, and clinical risk factors differ between patients with early-onset colorectal cancers (EOCRC) compared to late-onset colorectal cancers (LOCRC). We conducted a case-case comparison of risk factors and symptoms for EOCRC and LOCRC, utilizing the Ohio Colorectal Cancer Prevention Initiative (OCCPI) data, a statewide study of newly diagnosed CRC among Ohio residents, aged 20–92 years. Unconditional logistic regression (odds ratios (OR) and 95

BACKGROUND:Banning cigarette filter ventilation has been raised by some public health researchers and organisations because it has misled people who smoke to believe they are smoking a safer cigarette. AIM:To examine the potential effects of banning ventilated filters on smoking behaviour and biomarkers of toxicant exposures. TRIAL DESIGN:Randomised controlled trial with parallel semi-blind study design. METHODS:People who smoke (n=164) ventilated cigarettes daily were randomised to smoke 'ventilated' (≈27% ventilation) or 'unventilated' (≈0.11% ventilation) study cigarettes for 6 weeks. Non-inferiority testing was conducted on the changes in urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL) and cigarettes per day (CPD) between the two cigarette groups. Superiority testing was conducted for differences in smoking intensity (amount of nicotine in cigarette butts), other exposure biomarkers and subjective responses. RESULTS:The unventilated condition was generally non-inferior to the ventilated condition for change in total NNAL (3% greater for unventilated vs ventilated, less than the non-inferiority 15% margin but with wide variability with an upper bound of 95% CI of 16%, p=0.064) and in CPD (0.22 cigarettes greater for unventilated vs ventilated, lower than the non-inferiority margin of 2, p<0.001). There were no significant differences between the two groups in other biomarkers (p>0.05). Less intensity of smoking was observed with unventilated cigarettes (difference of changes=-0.04 mg nicotine, p=0.002), aligning with higher self-reported ratings of nicotine strength (p=0.005) and aversion (p=0.028). CONCLUSIONS:Overall, banning filter ventilation is unlikely to lead to greater toxicant exposures but certain subgroups might experience greater exposures.

Advancing age and deregulated obesity are well-established risk factors for breast cancer risk. While epigenetic ageing, a measure of biological ageing, has been linked to breast cancer risk, prior studies have mainly focused on blood-based measures. We aimed to study well-established epigenetic age estimates in normal breast tissue in relation to obesity-related metabolic markers. We analysed breast tissue from 91 cancer-free women, using DNA methylation age (mAge) clocks, including first-generation clocks (Hannum, Horvath), mortality-related clocks (Grim, Pheno), and methylation-based telomere length (DNAmTL). Pearson correlations assessed relationships among the clocks. Linear regression was used to associate mAge clocks with obesity-related blood markers (leptin, adiponectin, IGF-1, IGFBP-3), adjusting for chronological age, race, body mass index (BMI), and smoking, applying a false discovery rate threshold of 0.1. We explored effect modification by menopausal status using interaction terms. In the normal breast tissue, the strongest correlation of mAge estimates was observed between Horvath-mAge and Grim-mAge (r = 0.85). BMI was positively associated with all mAge estimates except Pheno-mAge. Older Grim-mAge and longer DNAmTL were associated with higher levels of adiponectin, IGF-1, and IGFBP-3, while older Horvath-mAge was associated only with IGF-1. Associations of DNAmTL with IGF-1 and adiponectin differed statistically by menopausal status. Epigenetic age in breast tissue, particularly Grim and DNAmTL, is associated with obesity-related metabolic markers, independent of chronological age, BMI, and smoking. Although limited by a moderate sample size, our findings indicate a potential biological pathway linking mAge-related metabolic dysregulation that may provide insight into breast cancer risk.

Since the introduction of vaping with electronic cigarettes in the late 2000s, controversy has continued to exist regarding the risks and benefits. Many studies indicate that electronic cigarettes are an effective smoking-cessation tool. Now, a large database analysis by Kim et al. provides a glimpse of the risks of lung cancer for smokers who quit with versus without vaping.

The lungs harbor diverse microbial communities that may influence pulmonary health, potentially through lung aging. While accelerated lung aging can increase susceptibility to pulmonary diseases, no studies have yet linked the lung microbiome to biological aging in disease-free individuals. We assessed well-studied methylation-based biological aging (mAge) markers (Horvath, GrimAge, PhenoAge, and telomere-length) in the lungs of healthy smokers (SM), electronic cigarette (EC) users, and never-smokers (NS) (n = 26, 21–30 years). We used metatranscriptome profiling to detect live bacteria. Using XGBoost, we performed feature selection on 1016 bacterial species to predict faster or slower lung mAge, and the selected bacterial species were used as explanatory variables in a logistic regression model. Linear regression analyses examined the associations between identified bacterial species and urinary metabolites of exposure to smoking and EC use, including volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). The logistic regression models identified bacterial species that classified individuals with faster or slower lung aging based on each mAge estimate (accuracy 77

The adenosinergic pathway represents a critical immunometabolic checkpoint within the tumor microenvironment of non-small cell lung cancer (NSCLC), contributing to immune suppression and therapeutic resistance. PBF-1129, an oral, selective A2B adenosine receptor (A2BAR) antagonist, was evaluated in a phase 1, open-label, dose-escalation trial (NCT03274479) in patients with advanced/metastatic NSCLC who had progressed on standard therapies. All patients had previously received chemotherapy and immune checkpoint blockade. Twenty-one patients received escalating doses (40–320 mg once daily), with no dose-limiting toxicities observed. The most frequently reported treatment related adverse events of any grade were lymphocytopenia (n = 8, 38.1

Chronological age is the most well-established risk factor for breast cancer; 80% of women diagnosed with breast cancer are aged 45 or older. This strong association is likely the result of age-related alteration in biological processes, including cellular senescence, telomere attrition, and epigenetic alteration, including DNA methylation. DNA-methylation-based age (mAge) estimates reflect biological age, and mAge provides insights into cumulative exposure to cancer risk factors, but there is limited understanding of how epigenetic age in normal breast tissue is related to breast cancer risk factors, including biological and epidemiological risk factors. We evaluated well-established DNA methylation age (mAge) estimates in the breast tissue of 91 cancer-free women, focusing on the first-generation mAge (Hannum and Horvath), mortality-related mAge (Grim and Pheno), and methylation-based-telomere-lengths (DNAmTL). Biomarkers that are potentially related to breast cancer risks were measured in breast tissue and blood, along with self-reported risk factors, including lifestyle, reproductive history, and family cancer history. Regression models, adjusted for chronological age, race, and body mass index (BMI), were used to estimate associations with a false discovery rate (FDR) at 0.05. Higher BMI is significantly associated with older Hannum-mAge, Horvath-mAge, Grim-mAge, and longer DNAmTL. Grim-mAge and DNAmTL were positively associated with obesity biomarkers (adiponectin, IGF1, and IGFBP3 in breast tissue and blood), and reproductive-related markers (age at menarche and age at first use of oral contraceptives, age at first birth, and age at last birth). Additionally, Horvath-mAge was significantly associated with tissue Ki67, IGF1, and age at first use of oral contraceptives. A family history of breast cancer was significantly associated with shorter DNAmTL. We found associations between epigenetic age and various biological and epidemiological factors of breast cancer risk. Our findings support further studies to examine whether mAge, particularly Grim-mAge and DNAmTL, in normal breast tissue can predict the incidence of breast cancer and potentially can serve as a biomarker for personalized intervention, given that DNA methylation can be modified through lifestyle changes. Amarnath Singh, Joseph P. McElroy, Daniel Y. Weng, Sarah A. Reisinger, Cheryl Thompson, Freudenheim L. Jo, Peter G. Shields, Min-Ae Song. Epigenetic age in normal breast tissues and its association with breast cancer risk factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB307.

BACKGROUND:Cigarette smoke and electronic cigarettes (EC) contain volatile organic compounds (VOCs) that can irritate the respiratory tract and affect pulmonary health. No studies have reported relationships between VOCs from smokers and EC users and pulmonary cellular behavior, such as lung biological aging. METHODS:Using urinary total nicotine equivalent (TNE) and propylene glycol, the primarily E-liquid constituent, the tobacco use status of smokers (SM, n = 13), EC users (n = 12), and never-smokers (NS, n = 31) was confirmed. In the lungs of SM and EC, we assessed methylation age (mAge) estimates and cellular senescence-related gene expression. Ten urinary metabolites of VOCs with and without adjusting for nicotine intake, TNE, were associated with mAge estimates and gene expression. RESULTS:Compared to EC users, SM had a significantly higher level of TNE-adjusted metabolites of acrylonitrile and 1,3-butadiene, while showing a lower level of a metabolite of benzene. TNE-adjusted metabolites of 1,3 butadiene, ethylene oxide, and acrylonitrile were overall positively associated with Pheno-mAge (an epigenetic clock for lifespan/mortality), with different patterns of the associations by smoking group. IFNG and STAT1 showed an overall positive association with TNE-adjusted metabolites of propylene oxide and acrylamide, with a stronger association in SM compared to EC. Without controlling for TNE, a benzene metabolite was the only significant associated with POU5F1. CONCLUSIONS:This is the first study reporting associations between smoking/EC-related VOCs and lung biological aging with strong associations in SM, supporting the need for further research on the roles of VOCs-related epigenetic aging and cell senescence genes in pulmonary diseases.

BACKGROUND:With the highest cancer incidence and mortality rates in the country, rural Appalachia has experienced a decades-long health decline, due in part to high smoking rates. Cigarette smoking prevalence exceeds 30% in much of the region. Oral nicotine pouches (ONPs), which contain nicotine but no tobacco, present an unexplored opportunity to reduce cigarette smoking and cancer incidence. OBJECTIVES:We outline the protocol for the Appalachian Research to Impact Smoking's Effects (ARISE) study, a randomized controlled trial to determine whether ONPs affect cigarette smoking patterns short- and long-term, and to evaluate their abuse liability versus nicotine replacement therapy (NRT) in a large sample of Appalachian smokers (clinicaltrials.gov: NCT06763536). METHODS:Between 2025 and 2029, we will recruit 1,000 adult smokers living in rural Appalachian counties across 11 states. Participants will be identified via media outreach, mobile cancer screening, community events, and respondent-driven sampling, then randomized to ONP or NRT and complete four study phases: Baseline, Sampling, Switch, and Observation. In the Sampling phase, participants will receive varied flavors and nicotine strengths of their assigned product and select preferred options for use. During the Switch Phase, they will attempt to quit smoking and switch completely to their assigned product. The Observation phase will monitor tobacco use after discontinuation of study products. Study procedures will be conducted online and by mail, including surveys, expired carbon monoxide verification, and product delivery. The primary outcome is 7-day biochemically verified cigarette abstinence at the end of the Switch Phase. Secondary outcomes include switching rates, product appeal, craving, withdrawal, dependence, and purchases during the Observation phase. An intention-to-treat log-binomial regression model will estimate the effect of intervention assignment on cigarette abstinence. CONCLUSIONS:Results will inform whether and how ONPs should be regulated, approached clinically, and used in public health interventions to reduce the burdens of cigarette smoking in Appalachia.

INTRODUCTION:Cigarettes with higher levels of filter ventilation (FV) are misperceived as less harmful and may be more appealing to consumers. Setting limits on FV has been considered as a policy, but a better understanding of any potential unintended consequences is needed. METHODS:FV (0.2%-61.1%) measured for 114 subbrands was merged with Wave 1 (2012-2013) of the Population Assessment of Tobacco Use and Health (PATH) data, restricted to adults 25+ years of age who smoked daily, and examined by quartiles. Inverse probability of exposure weights were used to estimate the causal effect of FV on past 30-day smoking at subsequent waves while accounting for potential confounders including demographics, menthol, heaviness of smoking, and past quit attempts. RESULTS:Compared to those in the first (lowest) quartile of FV, those in the second, third, and fourth quartiles had 1.02 (95% confidence interval = 0.57, 1.82), 0.86 (0.42, 1.73), and 1.52 (0.90, 2.56) times the odds of no past 30-day smoking at Wave 2 (approximately 1 year later, p = .163), and 1.28 (0.80, 2.07), 1.11 (0.67, 1.83), and 1.65 (1.01, 1.24) times the odds of no past 30-day smoking at Wave 4 (3 years later, p = .238). CONCLUSIONS:This observational study found no strong evidence of a causal effect of FV on past 30-day smoking at approximately 1 and 3 years follow-up. However, our effect size estimates were not precise and thus an increase in the ability to quit smoking due to higher FV levels cannot be ruled out. IMPLICATIONS:Setting a maximum limit on FV in cigarettes could address the misperception that highly ventilated cigarettes are less harmful and the link between FV and lung adenocarcinoma. It is important to understand whether such a policy would have unintended consequences on longer-term smoking behavior. We found no strong evidence that FV affects past 30-day smoking 1-3 years later, but could not rule out the possibility that higher FV increases cessation rates. If future studies confirm these epidemiologic findings, this could mean that setting a limit on FV would not lead to reductions in the ability to quit smoking.

While electronic cigarettes (ECIG) may have lower toxicant delivery than cigarettes, ECIG-liquids and aerosols still contain toxicants that can potentially disrupt lung lipid homeostasis. Participants from two studies underwent bronchoscopy and bronchoalveolar lavage (BAL). Ninety-eight participants (21-44 years old) were included in a cross-sectional study, with 17 ECIG users, 52 non-smokers, and 29 smokers. In the four-week clinical trial, 30 non-smokers were randomly assigned to use nicotine-free, flavorless ECIG or no use. A panel of 75 quantifiable lipid species and 7 lipid classes were assessed in the BAL using two tandem mass spectrometry (MS/MS) platforms. Ten cytokines and lipid-laden macrophages (LLM) were analyzed using the V-PLEX Plus Proinflam Combo 10 panel and Oil Red O staining, respectively. In the cross-sectional study, 43 lipids were associated with smoking status at FDR<0.1, including two between ECIG and non-smokers (PC(14:0/18:1) and PC(18:0/14:0)) in pairwise follow-up analyses (Bonferroni-adjusted p<0.017). Associations between lipid species and cotinine, inflammatory markers, including IL-1β and IL-8, and LLM were also identified, as well as differences in lipid classes between smokers and the other groups. Smokers had higher saturated lipids, including ceramide (CER), sphingomyelin (SM), and diacylglycerol (DAG) than that of non-smokers and ECIG users. No significant associations were identified in the 4-week clinical trial. Smoking was associated with altered lipid levels, as compared to both non-smokers and ECIG users; the majority were downregulated and ECIG effects tend to be smaller in magnitude than smoking effects, although some were different than those in the smokers group. This is a novel study of healthy individuals examining lipidomic differences between smokers, ECIG users, and non-smokers, indicating potential roles of smoking and ECIG-related lipid alterations in pulmonary disease. The study was approved by The OSU Institutional Review Board (OSU-2015C0088) in accordance with its ethical standards, the Helsinki declaration, and the Belmont Report, and is registered on Clinicaltrials.gov (NCT02596685; 2015-11-04).

8054 Background: Adjuvant durvalumab has transformed the treatment landscape for patients with locally advanced non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (CRT). However, in the landmark PACIFIC trial, only one-third of patients achieved long-term disease-free survival, underscoring the need for additional biomarkers to guide patient selection. Lymphocytopenia, a common side effect of CRT, has been associated with poor responses to immunotherapy. In this study, we investigate the incidence, degree, and timing of CRT-induced lymphocytopenia and association with survival among patients receiving durvalumab adjuvant therapy. Methods: This retrospective study included patients with unresectable Stage III NSCLC who underwent CRT followed by at least one dose of durvalumab at The Ohio State University. Clinical data was extracted through review of electronic medical records. Absolute lymphocyte count (ALC) was collected at baseline prior to CRT initiation, the lowest ALC during CRT, and 30 days post-CRT. Lymphocytopenia was classified using the Common Terminology Criteria for Adverse Events V5. Overall survival (OS) was calculated from CRT initiation to date of death or loss to follow-up. Cox proportional hazards model was used to evaluate the associations of baseline, lowest, post-CRT ALC, as well as the percentage change in ALC from baseline to lowest (relative ALC change) with OS. Results: This study included 118 patients with a mean age of 63.9 years (SD: 9.7), who received durvalumab within 12 weeks of completing CRT. Baseline characteristics were obtained (Table 1). Median baseline ALC was 1645 cells/µL (IQR: 1340–2190), dropping to 300 cells/µL (IQR: 200–450) during CRT and 755 cells/µL (IQR: 510–1040) post-CRT. Grade ≥3 lymphocytopenia occurred in 97 patients (82.2%) during CRT. Baseline, lowest, and post-CRT ALC were not associated with OS, but the relative decline in ALC from baseline was strongly associated. A 10% decrease in ALC from baseline was associated with a 48% increased risk of death (HR = 1.48; 95% CI: 1.14–1.91; p < 0.01) after adjusting for age, ECOG performance status (PS), histology, PD-L1 expression, chemotherapy regimen, and RT duration. Conclusions: Dynamic change in ALC from pre-treatment baseline to nadir during CRT is a strong prognostic indicator for OS in patients with advanced NSCLC receiving adjuvant durvalumab. Studies are warranted to elucidate the underlying mechanisms. Additionally, this highlights lymphocytopenia as a potentially modifiable side effect, which could be addressed with myeloprotective treatment. Baseline characteristics. Characteristic No. of Patients (%) ECOG PS = 0 18 (15.4) ECOG PS = 1 80 (68.4) Positive PD-L1 expression 80 (76.9) Squamous cell vs. other 51 (43.2); 67 (56.8) Weekly carboplatin/paclitaxel vs. other 88 (74.6); 30 (25.4)

Early-onset colorectal cancer (EOCRC) has increased in the last several decades and now accounts for 10% of new CRC diagnoses in the U.S. Most EOCRC cases are sporadic, with no identified molecular causes that differ from late-onset CRC (LOCRC), suggesting that modifiable environmental factors may have an enhanced role in EOCRC. Despite observed links between supplement and medication use and overall CRC risk, few studies have examined usage in EOCRC, compared usage with LOCRC, or assessed their potential protective effects for EOCRC. To address this gap, we evaluated self-reported supplement and medication use in sporadic EOCRC, compared to LOCRC incidence. We utilized baseline data from the Ohio Colorectal Cancer Prevention Initiative (OCCPI), a statewide initiative to increase access to germline genetic testing for patients with newly diagnosed CRC. OCCPI enrolled 3310 patients from 2013-2016. The current study included 1408 individuals with germline negative CRC and completed baseline questionnaires (n=1408). Model covariates included year of cancer diagnosis, sex, race, education, marital status, employment status, insurance type, and history of other cancer. The primary exposures of interest were the supplements: vitamins A, B-complex, C, D, E, and K, beta-carotene, calcium, iron, magnesium, potassium, selenium, zinc, and fish oil, and the following medications: ACE inhibitors, beta blockers, calcium blocker, digoxin, coumadin, diuretics, anti-diabetic medication, antacids, antidepressants, acetaminophen, and nonsteroidal anti-inflammatory drugs. The outcome of interest was odds of EOCRC, with LOCRC as reference, adjusting for multiple comparisons. Among 260 EOCRC and 1148 LOCRC cases, those with EOCRC were significantly more likely to have graduated college (43.6% v. 30.4%), be single/never married (12.4% v. 6.8%), currently employed (72.3% v. 33.6%), and have private insurance (83.7% v. 40.3%). Individuals with EOCRC were more likely to report having a history of asthma (p=0.003) and less likely to report a history of comorbidities, specifically diverticulitis (p<0.001), heart attack (p<0.001), hepatitis B or C (p=0.04), high cholesterol (p<0.001), stroke (p=0.001), and other cancer(s) (p<0.001). Preliminary analyses suggest that current use of vitamin D (aOR, 0.48; 95%CI, 0.25-0.93) and metformin (aOR, 0.24; 95%CI, 0.19-0.59), was associated with lower odds of developing EOCRC, compared to LOCRC, while current (aOR, 0.39; 95%CI, 0.23-0.67) and past (aOR, 0.48; 95%CI, 0.27-0.86) use of aspirin was associated with lower odds of EOCRC. Current use of antidepressants (aOR, 2.53; 95%CI, 1.55-4.14) was associated with higher odds of developing EOCRC, compared to LOCRC. Further analyses are ongoing. In conclusion, EOCRC patients differ demographically and in supplement and medication use from those with LOCRC. These findings suggest that these exposures may influence EOCRC risk, warranting further investigation. Holli A. Loomans-Kropp, Yevgeniya Gokun, Rand Akasheh, Rachel Pearlman, Cecilia DeGraffinreid, Jo Freudenheim, Peter Shields, Electra D. Paskett. Supplement And Medication Use in Early-Onset Colorectal Cancer: An Analysis of the Ohio Colorectal Cancer Prevention Initiative [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr PR016.

BACKGROUND:Patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are at risk for severe immune-related adverse events (irAEs). Limited data exists on the association between severe irAEs requiring hospitalization (irAEh) and overall survival (OS) in patients with NSCLC who received front-line ICIs, as well as risk factors for irAEh. METHODS:Electronic medical records of consecutive patients with metastatic NSCLC treated with front-line pembrolizumab with or without chemotherapy from 2017 to 2022 were assessed retrospectively. An irAEh was defined as any severe irAE requiring hospitalization within 1 year of ICI initiation. Clinical characteristics for the entire cohort were reported descriptively. Kaplan-Meier survival analysis and the Cox proportional hazard model were used to assess the OS and HR between groups. RESULTS:Among 312 patients, 203 (65 %) were hospitalized for any reason within 1 year of initiating pembrolizumab, including 37 (12 %) for irAEs. irAEh and overall hospitalization rates did not differ for patients treated with pembrolizumab alone compared to pembrolizumab in combination with chemotherapy. The most common reasons for irAEh were pneumonitis and colitis. Patients with irAEh experienced significantly shorter median OS (8.6 months; 95 % CI: 5.0-19.9) compared to those without irAEh (22.7 months; 95 % CI: 18.2-27.4; P = 0.027). Patients who experienced early-onset irAEh (<6 months) had a significantly shorter median OS of 5.4 months (95 % CI: 2.7-8.6) compared to those with late-onset irAEh (≥6 months), median OS not reached (NR); 95 % CI: 8.6-NR; P = 0.003. Patients hospitalized for any reason during the first year of treatment had a shorter median OS (11.2 months; 95 % CI: 9.5-15.2) than those who were not (49.4 months; 95 % CI: 39.5-62.4; P < 0.001). CONCLUSIONS:Severe irAEs requiring hospitalization or hospitalization for any cause within the first year of initiating pembrolizumab among patients with NSCLC was associated with worse survival outcomes.

Immune checkpoint inhibitors (ICIs) are first line treatment for advanced lung cancer. Tobacco use is a shared risk factor for lung cancer and chronic obstructive pulmonary disease (COPD). Although many patients with COPD and lung cancer receive ICIs, the impact of ICIs on COPD is unknown. Here, we evaluated whether ICI treatment was associated with increased COPD disease burden. We conducted a retrospective cohort study of lung cancer patients with and without preexisting COPD who received ICIs from 2011-2021 at The Ohio State University (OSU). For all patients, number of steroid courses and respiratory related hospitalizations were recorded. For those with COPD, COPD medications were collected at and after ICI initiation. Pulmonary function tests, COPD exacerbations, and COPD-related hospitalizations were compared before and after ICI treatment. Linear and generalized mixed models were used to account for potential confounders of worsening COPD. Among 1083 lung cancer patients who received ICIs, 585 (54.0%) had pre-ICI COPD. Patients with COPD were prescribed more COPD medications (3 [1, 4] vs 1 [0, 3], p < 0.001), had more COPD exacerbations (38.3% vs 25.8%, p < 0.001), and more COPD-related hospitalizations (27.9% vs 16.9%, p < 0.001) after ICI initiation compared to before. These findings persisted after multivariable analysis controlling for patients who received chemotherapy or chemoradiation within 12 months of ICI initiation, cancer type, age, BMI, sex, smoking status, type of ICI, and number of ICI doses (p < 0.001). This is a comprehensive study that describes lung cancer patients with COPD treated with ICIs have increased COPD disease burden after ICI initiation.

OBJECTIVE:Depression and systemic inflammation at diagnosis are associated with poor oncologic outcomes for lung cancer (LC) patients. Research has not explored the interaction of these biomarkers and potential for subsequent psychological morbidity. The aim determines if the co-occurrence of depression and systemic inflammation predicts a worsened trajectory of depressive symptoms from diagnosis through 8 months. METHODS:An observational longitudinal cohort design was used (ClinicalTrials.gov Identifier: NCT03199651). Individuals ( N =182) with advanced non-small cell lung cancer were enrolled at diagnosis/pretreatment, had blood drawn, and completed a depression assessment and followed with 8 monthly reassessments. Measures were the Advanced Lung Cancer Inflammation Index (ALI) and self-reported depressive symptoms (Patient Health Questionnaire-9). Using validated cutoffs for biomarkers of inflammation (ALI <24 vs. ALI ≥24) and depression (PHQ <8 vs. PHQ ≥8), the sample was subdivided into 4 cohorts: (1) no/low depression and low inflammation (neither); (2) no/low depression but high inflammation (inflammation); (3) high depression but low inflammation (depression); and (4) high depression and high inflammation (depression+inflammation). RESULTS:Linear mixed models were tested for Group, Time, and Group × Time effects predicting the depression trajectory, adjusting for baseline depression/inflammation, age, partner status, education, smoking history, and cancer treatment. Overall, depressive symptoms did not change across time ( p =0.26), but as predicted, only for Cohort 4 (depression+inflammation) was the interaction significant [ F(24,945) =-0.04, p =0.001], with patients having an elevated depression trajectory. CONCLUSIONS:Novel data contribute to the depression pathophysiology literature, showing that co-occurring depression and inflammation can predict depression. Clinically, data suggest a new biobehavioral metric for the identification of depression maintenance in LC patients. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT03199651.

ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) have revolutionized metastatic NSCLC treatment. Acute kidney injury (AKI) is a common complication of ICI‐based therapies, alone or with chemotherapy. This study investigates the association between early AKI and 12‐month survival among patients with metastatic NSCLC receiving front‐line ICI‐based treatment. Methods This retrospective study included metastatic NSCLC patients who received ICI‐based therapy (2017–2022). Early AKI was defined as a creatinine increase ≥ 1.5 times baseline within 21 days of the fourth cycle or last cycle if fewer than four were given. Clinical characteristics were compared using t‐tests and chi‐squared tests. Survival differences were assessed by Kaplan–Meier and log‐rank tests, with Cox models evaluating the association between AKI and 12‐month survival. Results Of the 310 patients, AKI occurred in 38 patients (12.6%), with 8 patients (2.3%) missing follow‐up creatinine data. The hazard ratio (HR) for death within 12 months for patients who developed early AKI was 1.733 (95% CI 1.060–2.835, p = 0.026). The highest rate of early AKI was seen in patients receiving pemetrexed, pembrolizumab, and carboplatin (16.7%), compared to 11.1% for pembrolizumab monotherapy and 4.5% for pembrolizumab with paclitaxel and carboplatin. Although patients who recovered renal function were more likely to continue immunotherapy, 12‐month survival rates did not significantly differ (52.2% vs. 46.7%). Conclusions Early AKI during pembrolizumab‐based treatment in metastatic NSCLC patients was associated with reduced 12‐month survival. These findings highlight the need for close monitoring and preventive strategies to manage AKI in this population.

With increasing incidence, identifying modifiable risk factors contributing to early-onset colorectal cancer (EOCRC) is critically important. We examined if history of binge drinking was more associated with EOCRC than with late-onset colorectal cancer (LOCRC). Data from the Ohio Colorectal Cancer Prevention Initiavtive (OCCPI), a multi-center study conducted between 2013-2016, were used in this case-case comparison of EOCRC to LOCRC. Ohio residents with newly diagnosed primary colorectal cancers (CRC) were included in the OCCPI. Binge drinking was self-reported for the year before CRC diagnosis and during the decade in the particpants' life with the heaviest alcohol consumption. Binge drinking was defined as consuming >3 drinks within a two-hour period for both men and women. EOCRC cases were defined as those aged <50 at CRC diagnosis and LOCRC cases as those > age 49. The association between binge drinking and EOCRC was assessed with logistic regression, adjusting for sex, race, education, smoking status, and family history of CRC. Included in the OCCPI were 323 EOCRC and 1,256 LOCRC cases. Engaging in binge drinking the year before one's CRC diagnosis was more associated with EOCRC than LOCRC (OR:3.15, 95%CI:2.31-4.30). Those with EOCRC were also more likely to report binge drinking during the time in their life with the heaviest alcohol consumption than LOCRC cases (OR:3.22, 95%CI:2.37-4.40). When we compared the youngest EOCRC (age 59), the unadjusted associations observed were stronger with wider confidence intervals (OR: 6.65, 95%CI: 3.86-11.48; OR:4.44, 95%CI: 2.63-7.53 for the year before CRC diagnosis and the decade of most consumption, respectively). Compared to LOCRC, those with EOCRC were more likely to engage in binge drinking. Interventions to reduce binge drinking, particularly among younger adults, may have potential for EOCRC prevention. Electra D. Paskett, Samantha Rees, Rachel Pearlman, Peter Shields, Heather Hampel, Jo Freudenheim. Association of Binge Drinking with Early-Onset Colorectal Cancer: A Comparison to Late-Onset Cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr C027.