PURPOSE Survival discrepancy between male and female patients in lung cancer is a well-known, but still poorly understood phenomenon. Previous studies have used different patient cohorts and clinical covariates and have not included obesity, which is associated with longer lung cancer survival. We evaluated the relationship between survival, obesity, sex and other covariates using comprehensive, harmonized patient cohorts and a federated analysis approach. MATERIALS AND METHODS Initial analyses were done in a retrospective, real-world cohort of 7,327 patients with lung cancer diagnosed at the Helsinki University Hospital from 2015 to 2024. Patients were stratified by BMI, and univariate and multivariate analyses of survival were performed. External validation of univariate analyses was performed on data from four European university hospitals (n = 12,700). RESULTS Higher BMI was associated with a smaller sex-related survival difference. In the normal BMI cohort (18.5-25 kg/m(2)), the 2-year overall survival was 46% in females and 29% in males (P < .01). In the high BMI cohort, the difference was 51% versus 41% (P < .01). Similar trends were observed in the validation sites, with some variation. The largest effect of high BMI was observed in squamous cell carcinoma. When full multivariate analysis was performed separately for high and normal BMI patients, the effect of male sex on survival was 32% smaller among high BMI patients. CONCLUSION Higher BMI was associated with reduced survival gap between sexes, emphasizing the value of comprehensive covariate reporting in future clinical trials and observational studies.

1553 Background: Despite rapid global adoption of immune checkpoint inhibitors (ICI) for metastatic non–small cell lung cancer (mNSCLC), real-world treatment access, selection, time on treatment and transitions between regimens remain poorly characterized across health systems and patient populations. Whether observed outcomes are consistent across regions, data sources, and age groups is largely unknown. Addressing these gaps at scale requires a federated analytic approach with standardized analyses across sites, enabling reliable and comparable results while preserving patient privacy. Methods: We launched FALCON (Federated Alliance for Large-scale Cancer Observational Network), the largest federated, most diverse oncology network supporting observational cancer research, and its subnetwork FALCON-Lung. FALCON-Lung includes 23 sites (hospitals, registries, public-private) providing longitudinal cancer data from 2015 onwards standardized to OMOP common data model, from 11 countries in Europe, US and Australia. All sites completed data quality assessments and targeted improvements to improve completeness and overall cancer data quality. Analyses were executed locally using shared analytic code without sharing patient-level data. Results: Among 111,574 NSCLC pts included, 62% developed metastatic disease, of whom 59% initiated antineoplastic drugs within three months; 88% received a guideline-recommended 1 st line regimen. ICI uptake rose sharply between 2017 - 2019; by 2022 59% received ICI (± platinum) in 1 st line. ICI monotherapy showed a tendency toward longer overall survival (OS) compared with platinum (±ICI), although no single regimen demonstrated a consistent advantage across all databases. OS decreased with age across sites. Patients aged ≥81 years were less likely to receive systemic therapy and, when treated, more often received ICI monotherapy. No clear or consistent differences in OS were observed between different treatment regimens in this age group. Conclusions: In this global federated study, ICI uptake showed consistent patterns across sites and regions. OS varied across sites and no consistent survival advantage was observed for ICI regimens, either as monotherapy or in combination, although higher OS with ICI monotherapy was observed in some settings. Older patients (aged ≥81 years) were more frequently treated with ICI monotherapy without a corresponding survival advantage, possibly reflecting real-world treatment selection driven by tolerability rather than biomarkers. Total 18-64y 65-81y ≥81y NSCLC 111,574 36,239 62,328 13,007 Metastatic NSCLC 68,678 24,059 36,397 8,222 1st line systemic therapy 40,619 15,226 21,397 3,980 1st line guideline-approved systemic therapy 35,560 13,458 18,725 3,361 1st line in 2022 (%) ICI monotherapy 17 12 18 32 ICI + platinum doublet 42 43 45 26 Other guideline-approved regimen 41 45 37 43

PURPOSE:Among responders to PD-1/PD-L1 blockade, it remains unclear whether tumour type and traditional baseline patient and tumour characteristics provide additional prognostic information for progression risk beyond response depth. METHODS:In this nationwide, population-based cohort study, we identified adults with metastatic melanoma (MM), renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 monotherapy or dual checkpoint blockade. Analyses were restricted to responders by investigator-assessed RECIST (complete or partial response) with outcomes administratively censored at 5 years. Prespecified baseline and on-treatment variables were evaluated for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox models and assessed for consistency across tumour types. RESULTS:Among 2127 responders, PFS trajectories within response depth categories (complete response and partial response) were highly similar across MM, RCC, and NSCLC. Prespecified variables with prognostic value in the overall population, including performance status and treatment line, provided limited additional prognostic information once response depth was known. Depth of response (complete vs partial) was the strongest independent factor associated with progression risk within each tumour cohort. CONCLUSIONS:Among patients with MM, RCC, or NSCLC who achieved an objective response to PD-1/PD-L1 blockade, tumour type and traditional baseline prognostic factors provided limited additional stratification of progression risk once response depth was known. These findings suggest that, within the tumour types studied, response durability is primarily associated with response depth rather than other known clinical features, supporting prospective evaluation of response-guided follow-up strategies and interventions designed to deepen responses.

BACKGROUND:Breast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important. METHODS:This real-world cohort study is based on electronic health records from Capital Region of Denmark. All women with metastatic breast cancer initiating first-line treatment with CDK4/6 inhibitor between May 2017 and October 2022 were included. RESULTS:A total of 546 patients were eligible for inclusion in the 12-week landmark analysis and 192 (35%) experienced dose reduction. These patients were older, had worse ECOG PS, more received prior adjuvant endocrine treatment, and more received fulvestrant as the endocrine backbone. Dose reduction was associated with reduced overall survival (39.9 vs. 54.3 months) and shorter treatment duration (18.0 vs. 26.9 months). Adjusted hazard ratio for death was 1.38 (95% CI: 1.01-1.89). CONCLUSIONS:Dose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

We discuss the One Stop Shop for Clinical Research (OSCAR) project that links clinical data, patient-reported outcomes, genomic data, and health registry data, employing a rigorous data privacy protection technology, to provide insights into treatment efficacy and safety and serve as a comparator for single-arm trials. This could inspire further initiatives to advance precision medicine.

Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all FOBT‐positive persons have screen‐detected adenomas. Despite removal of these, patients with large/multiple adenomas have increased risk of later developing new advanced adenomas and CRC. International guidelines exist for colonoscopic surveillance following adenoma removal. These divide patients into low‐, intermediate‐ and high‐risk groups. We followed 711 FOBT‐positive patients with screening adenoma identified during population‐based CRC screening in two Danish counties in 2005–2006. As reference population, we included 1,240,348 persons in the same age group from the rest of Denmark not included in the screening. We estimated the long‐term CRC risk stratified by adenoma findings during screening and compared to the reference group. After 12 years follow‐up, the CRC incidence among all adenoma patients was 322 cases per 100,000 person‐years (95% confidence interval [CI]: 212–489) ranging from 251 (95% CI: 94–671) to 542 (95% CI: 300–978) cases per 100,000 person‐years in the low‐ and high‐risk groups, respectively. In the reference population, the CRC incidence was 244 (95% CI: 242–247) per 100,000. Patients with screen‐detected high‐risk adenomas after a positive FOBT had an almost doubled risk of CRC compared to the reference population (adjusted hazard ratio [aHR] 1.95, 95% CI: 1.08–3.51), and the incidence in those with no follow‐up visits was over 3.6 (aHR 3.64, 95% CI: 1.82–7.29) times the incidence in the reference population. The increased CRC risk could be controlled if high‐risk patients underwent follow‐up colonoscopy (aHR 0.87, 95% CI: 0.28–2.69).

Faecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all screen positive persons have negative colonoscopy, but consensus is lacking on how these persons should be followed up. Health authorities in Denmark and The Netherlands recommend suspending screening for 8-10 years, while patients in UK are invited to screening after 2 years. In this cohort-study, we followed 166,277 individuals invited to FOBT-screening in 2005-2006 and a reference group comprising the remaining 1,240,348 Danes of the same age. We linked Danish population and health service registers to obtain information about colonoscopy outcome and incident CRC. We estimated CRC risk by colonoscopy outcome (adenoma, other colorectal pathology or negative colonoscopy) for the reference group, the screening group, and subgroups. Persons with positive screening FOBT followed by negative colonoscopy had the same long-term CRC risk as persons with adenoma detected due to a positive screening FOBT (aHR 1.33, 95% CI: 0.65-2.71). We found no difference in the long-term CRC risk between persons with negative colonoscopy after a positive FOBT screening test and the unscreened reference population (aHR 1.05, 95% CI: 0.62-1.78). Since FOBT screen positive persons in our study remained at average risk of CRC despite of a negative index colonoscopy, we question the safety of suspending FOBT screening for this group. It needs to be monitored whether recent efforts to improve colonoscopy quality have been successful in ensuring low CRC risk after negative colonoscopy also in FOBT positive persons.

Background In Denmark, colorectal cancer (CRC) is the third most frequent cancer. Randomised trials have shown that guaiac faecal occult blood test (gFOBT) screening can reduce CRC mortality, but a recent large randomised study from Finland did not find any effect. A feasibility study was carried out in Denmark in 2005–2006 where residents aged 50–74 years in 2 Danish counties were invited once to participate in gFOBT screening. We used the unique Danish registers to assess the impact of gFOBT screening in this group on CRC incidence and mortality. Methods In this cohort study, we followed a group comprising 166 277 individuals invited to screening and a reference group comprising the remaining 1 240 348 Danes of the same age. We linked the Danish population and health service registers to obtain information about colonoscopies, polypectomies, incident CRC and cause of death. Results After a median follow-up time of 8.9 years, the CRC mortality was significantly lower in the screening group than in the reference group with an adjusted HR (aHR) of 0.92 (95% CI 0.86 to 0.99), while the aHR for all-cause mortality was 0.95 (95% CI 0.94 to 0.96). For screening participants, the aHR for CRC mortality and all-cause mortality was 0.72 (0.64 to 0.80) and 0.59 (0.57 to 0.60), respectively. Conclusions About 10 years after a single round of gFOBT screening, we found a significant 8% deficit in CRC mortality in the screening group compared with other Danes. We found almost the same deficit in all-cause mortality, and on this basis, it is not possible to conclude that one screening round had an effect on CRC mortality. Our study indicated that close monitoring of the outcome of CRC screening is warranted.

Background Limited data exist on adenoma surveillance as recommended in the European guidelines for quality assurance in colorectal cancer (CRC) screening and diagnosis after faecal occult blood test (FOBT) screening. Objective To assess the European guidelines for adenoma surveillance after CRC screening with FOBT. Materials and methods This was a population-based cohort-study of 176 782 Danish individuals aged 50–74 years invited for CRC screening in 2005–2006. Adenoma patients were stratified into risk groups (low A, medium B, high C) in accordance with the European guidelines and followed up for recurrence of new neoplasms until the end of 2011. Risk ratios (RR) between the risk groups were calculated to assess differences in the recurrence rates of neoplasms. Results Among 84 803 screening participants, 2059 had positive FOBT, of whom 1861 underwent colonoscopy, and 709 patients had screen-detected adenomas. During a median follow-up period of 72.7 months, detection of new advanced adenomas (B+C) was significantly higher in risk group C than group A (RR 2.25, 95% confidence interval: 1.13–4.48). Nine patients were diagnosed with CRC: one in risk group A, two in B and six in C. The detection rate of CRC was higher in risk group C than A (RR 5.20, 95% confidence interval: 0.63–42.58), but not statistically significant. In risk group C, half of new advanced adenomas were detected within the first year and four of nine CRC were detected within 3 years. Conclusion Risk stratification of adenoma patients, as recommended by the European guidelines, is appropriate for postpolypectomy surveillance after FOBT screening.