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A risk stratification schema for patients with non–small cell lung cancer with multiple organ metastases.

11138 Background: The majority of patients with non-small cell lung cancer (NSCLC) will have multiple organ sites of metastasis and poor overall survival (rwOS). Specific organ involvement influences patient outcomes, but the impact of overarching patterns of metastasis on rwOS and response to systemic therapy (ST) is poorly understood. Prior studies have been limited in their scale, availability of detailed data on sites of metastasis, and inclusion of patients receiving immunotherapy (IO) or targeted therapy (TT). We leveraged a large-scale, real-world database to characterize and assess the prognostic value of patterns of metastasis on rwOS and time to next therapy (rwTTNT) in patients with metastatic NSCLC receiving ST. Methods: This retrospective study utilized the Flatiron Health Research Database of patients with NSCLC treated with first-line (1L) ST (n = 327,044). Patient, tumor, and treatment variables were summarized descriptively and compared across patterns of metastasis. rwOS and rwTTNT from 1L start were estimated via Kaplan Meier method and compared with logrank test. Bernoulli mixture models were used to cluster patients by metastatic sites at 1L start. Results: Sites of disease were evaluated for 75,304 patients. Data from 5 metastatic sites revealed 6 clusters reflective of real-world patterns of metastasis: bone (n = 33,882), pleural (n = 12,123), liver (n = 6,133), brain (n = 11,441), adrenal avid (n = 6,975), and high metastatic burden (HMB, ≥3 sites with frequency ≥0.5, n = 4,750). While HMB (7.2 months median rwOS, 4.8 months median rwTTNT) and liver avid disease (9.4, 5.2 months) had poor outcomes as expected, we also found that bone (11.0, 5.9 months) and adrenal (11.8, 6.0 months) avid clusters had worse median rwOS and shorter rwTTNT compared to pleural (15.7, 7.6 months) and brain (15.3, 7.4 months, p < 0.001). Outcomes associated with a specific site of metastasis varied based on patient cluster assignment. Compared to the cluster equivalent (e.g., brain avid), individual metastatic site (e.g., brain) as a prognostic factor was associated with worse median rwOS by 1.0-2.9 months and shorter median rwTTNT by 0.1-0.9 months. Compared to individual sites and site-avid clusters, HMB more often had EGFR mutations (20.7% vs 13.6% overall). IO was associated with greater median rwOS over TT in the adrenal cluster (17.7 vs 15.6 months), and IO + CTX had better rwOS vs IO alone in pleural (15.7 vs 12.9 months) and liver clusters (10.7 vs 9.4 months, p < 0.001). Conclusions: The survival outcomes and treatment response associated with defined clusters of metastases are distinct from those associated with individual organ sites or widespread disease alone. A risk-stratification framework that uses “risk phenotypes” representative of real-world patterns of metastasis may have better prognostic and predictive significance in patients with multiple sites or higher burden of disease.

A clinical prediction score to identify symptomatic patients at high risk for colorectal cancer in South Africa.

1606 Background: Colorectal cancer (CRC) is the third most diagnosed cancer globally with a rising incidence across sub-Saharan Africa. In South Africa (SA), advanced stage at diagnosis drives poor outcomes and limited endoscopic capacity makes early CRC diagnosis guidelines difficult to implement. We developed a clinical prediction score to identify patients with lower gastrointestinal (GI) symptoms at high risk for CRC in SA. Methods: Adults (≥18 years old) with ≥1 “red flag” lower GI symptom (weight loss, change in bowel habits, rectal bleeding, anemia, abdominal mass) referred for colonoscopy at two public hospitals in Durban were eligible for this prospective study (Sept 23, 2022 – Dec 9, 2025). Demographic and clinical data, results from a pre- or intra-colonoscopy POC-FIT, and colonoscopy results were recorded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of POC-FIT for CRC were calculated. A clinical prediction score was derived using this cohort. The optimal number of prognostic factors for a predictive multivariate logistic regression model were determined using LASSO and model validation was done using bootstrapping technique. Overall performance was assessed using the scaled Brier score, Hosmer-Lemeshow test, and AUC. Analysis was performed using R (v 4.4.1). Results: Of 393 enrolled patients (median age 52 years, 54.5% female), 306 (77.9%) had a valid FIT result, with 194 (63.4%) positives. In this symptomatic cohort, the adenoma detection rate was 19.6%, with 15 low-risk (3.8%), 14 high-risk (3.6%) adenomas, and 31 (7.9%) CRCs. POC-FIT had 75% sensitivity, 38% specificity, 9% PPV and 95% NPV for CRC. If patients with a negative POC-FIT had not immediately proceeded to colonoscopy, 102 (33.3%) urgent colonoscopies could have been avoided, but diagnosis would have been delayed for 4 patients with high-risk adenomas and 6 with CRC. The LASSO model, utilizing λ=0.017, selected 3 variables associated with CRC: age greater/less than 50, weight loss (yes/no), symptom duration >3 months (yes/no) (risk score 0-3), with AUC 78.6% for predicting CRC (Table 1). Adding negative FIT result to the clinical prediction score (risk score 0-4) improved performance (AUC 79.2%). Setting a symptom score of ³2 as positive, the specificity for diagnosing CRC was 47.9%, and sensitivity 95.8%. Conclusions: Among South African patients referred for diagnostic colonoscopy, FIT has a strong NPV but weak PPV for CRC. A clinical prediction score for CRC among symptomatic South African patients was derived with good performance for ruling out CRC. Future studies will validate this model in the primary care setting. Clinical prediction score derived from cohort of symptomatic patients undergoing colonoscopy in Durban, South Africa. Clinical Score No CRC % CRC % Total 0 30 100 0 0 30 1 105 99 1 1 106 2 112 91 11 9 123 3 32 74 11 26 43 4 3 75 1 25 4 Total 282 92 24 8 306

A phase 1 study of CT-01, a dual molecular glue degrader of GSPT1 and NEK7, as monotherapy and in combination with everolimus in patients with hepatocellular carcinoma.

e15108 Background: Targeted protein degradation (TPD) using molecular glues enables pharmacological modulation of previously “undruggable” targets. CT-01 is a first-in-class molecular glue designed to induce the selective degradation of GSPT1 and NEK7. GSPT1 degradation triggers the Integrated Stress Response (ISR) and apoptosis in cancer cells, while NEK7 degradation reduces IL-1β production, a key pro-tumorigenic mediator. Reduction of IL-1𝛽 levels within the tumor microenvironment promote immune activation and enhance compound antitumor activity. Preclinical data has demonstrated that the combination of CT-01 with the mTOR inhibitor everolimus, an approved anticancer drug, results is clear synergy both in vitro and in vivo . Methods: Preclinical biological activity was assessed using CellTiter-Glo viability assay, Western blotting for protein degradation/MoA, and hepatocellular carcinoma (HCC) xenograft in vivo models to assess the therapeutic potential of CT-01. The ongoing clinical study is a Phase 1, open-label, multicenter, dose escalation, and dose expansion study to evaluate the safety, tolerability, PK and PD of CT-01 as monotherapy and combination therapy with everolimus in subjects with intermediate or advanced HCC. Up to 77 subjects may be enrolled in Part 1, including up to 37 dose-limiting toxicity (DLT)-evaluable subjects in Part 1a (monotherapy, dose escalation). Part 1b (monotherapy, randomized dose expansion) is optional where 2 CT-01 dose levels from phase 1a will be evaluated to determine the monotherapy RP2D. Part 1b can run in parallel to Part 2a (combination, dose escalation). Part 2b (combination, randomized dose expansion) will evaluate 2 doses of CT-01 in combination with a fixed dose of everolimus to determine the combination RP2D. Up to 64 subjects will be enrolled in Part 2, including up to 24 DLT-evaluable subjects in Part 2a (monotherapy, dose escalation). The study was opened in May 2025. Results: Preclinical studies demonstrated that CT-01 induces rapid degradation of GSPT1 and NEK7, leading to potent cytotoxicity and tumor growth inhibition in HCC xenografts. In NHP models, CT-01 showed a favorable PK profile and robust target engagement. The clinical study was initiated in May 2025. Conclusions: Targeted degradation of GSPT1 and NEK7 represents a promising new therapeutic strategy for cancer treatment. CT-01, a molecular glue, has successfully completed preclinical development. Its safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy is being evaluated in a Phase 1 clinical trial. This open-label study includes dose-escalation and dose-expansion cohorts assessing CT-01 administered as monotherapy and in combination with everolimus in patients with intermediate or advanced hepatocellular carcinoma.

Post-neoadjuvant Prognostic Nutritional Index as a predictor of pathological response and survival in locally advanced rectal cancer.

e15632 Background: The response to neoadjuvant therapy in locally advanced rectal cancer (LARC) may be influenced by tumor and host-related characteristics, including nutritional and immune status. The prognostic nutritional index (PNI) has emerged as a potential biomarker; however, data on the prognostic value of post-neoadjuvant PNI in LARC remain limited. Methods: We performed a retrospective analysis of 240 patients with LARC who received neoadjuvant therapy from January 2018 to December 2023. The PNI was calculated post-neoadjuvant therapy [10 x serum albumin (g/dL) + 0.005 x total lymphocyte count (mm3)]. Pathologic complete response (pCR) was defined as a Ryan score of 0. To evaluate the association between PNI and pCR, a logistic regression model was employed. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier analysis. Results: A cohort of 240 patients was included in the study, median age 58 years, gender distribution was comparable, lower rectum in 70% of cases and 72.5% presented positive lymph nodes. 59% received total neoadjuvant therapy (TNT) and 40% chemoradiotherapy (CRT). Following neoadjuvant therapy, 86% went to surgery, with a Ryan score of 0 in 27% of cases. The median post-neoadjuvant PNI was 45. The optimal PNI cutoff for discriminating OS was determined using the receiver operating characteristic (ROC) curve, yielding an area under the curve (AUC) of 0.681 (95% CI 0.584 to 0.778, p-value = 0.001). In multivariate analysis, a higher PNI remained independently associated with pCR (OR 1.10; 95% CI 1.02-1.19, p = 0.009). Patients with a PNI > 45 exhibited mproved RFS (mean RFS of 67.3 m vs 55 m; log-rank test, p = 0.031; median not reached) and OS (mean OS of 82.6 m vs 64.6 m; log-rank test, p = 0.002; median not reached, p = 0.002). Conclusions: Post-neoadjuvant PNI serves as an independent prognostic indicator for pathological response and is correlated with improved long-term outcomes in LARC. These findings underscore the importance of evaluating the nutritional and immunological status of patients with LARC, who may benefit from nutritional interventions. Univariate and multivariate analyses of factors for complete pathological response. Univariate analyses Multivariate analyses Factors OR 95% IC P value OR 95% IC P value Age 1.03 0.97 – 1.03 0.79 1.00 0.97 - 1.03 0.70 SexMaleFemale 10.78 0.41 – 1.50 0.46 10.83 0.42 – 1.66 0.60 Tumor grade123 0.511.221 0.12 – 2.190.51 – 2.93 0.360.64 0.591.281 0.12 – 2.760.49 – 3.32 0.500.60 Tumor siteLowerMiddleUpper 11.460.48 0.70 – 3.010.10 – 2.23 0.300.34 10.890.44 0.39 – 2.030.08 – 2.28 0.790.33 Lymph nodePositiveNegative 12.61 1.33 – 5.11 0.01 12.52 1.24 – 5.11 0.01 Neoadjuvant therapyTNTCRT 10.52 0.27 – 1.01 0.05 10.46 0.22 – 0.95 0.03 PNI 1.09 1.02 – 1.17 0.01 1.10 1.02 – 1.19 0.009 TNT: Total neoadjuvant therapy. CRT: Chemoradiotherapy. PNI: Prognostic Nutritional Index.

EA1181: Accuracy of pre-surgery MRI to predict pathologic complete response after taxane, trastuzumab, and pertuzumab (THP) in HER2-positive breast cancer.

603 Background: Accurate prediction of pathologic complete response (pCR) after preoperative therapy for HER2-positive (HER2+) breast cancer can help triage patients to immediate surgery vs additional preoperative therapy. Pre-surgery (i.e., after neoadjuvant therapy) imaging studies may help estimate the likelihood of pCR. In EA1181, patients (pts) with stage II-IIIA HER2+ breast cancer received four cycles of preoperative taxane, trastuzumab, and pertuzumab (THP×4). Pre-surgery imaging was required, though the specific imaging modality was not mandated. Here, we report the accuracy of pre-surgery breast MRI to predict pCR (ypT0/Tis, ypN0). Methods: Among 2,141 pts treated with THPx4, 1,378 had pre-surgery breast MRI and were representative of the overall cohort, although T3 tumors were more common (16% vs 9%). MRI reports were available for 1,351 pts; all reports were centrally reviewed and classified as radiologic complete response (rCR; no residual tumor enhancement and normalization of lymph nodes, if applicable) or radiologic residual disease (rRD). Reports with indeterminate radiologic response were independently reviewed by two study radiologists blinded to pathology outcomes. Among pts with rCR who had pathologic residual disease (pRD), we also assessed the extent of residual disease by residual cancer burden (RCB) score. Among pts with rRD who had a pCR, we determined the proportion who only had residual ductal carcinoma in situ (DCIS). Results: See Table. Conclusions: After neoadjuvant therapy, preoperative MRI accurately predicted pCR in 86% of patients with HER2+/ER− disease and may help identify patients who can proceed directly to surgery. MRI is insufficient to predict pCR for pts with HER2+/ER+ disease, as only 55% with complete response on MRI had a pCR at surgery. A pre-surgery MRI that indicated residual disease was accurate in 80% of pts with HER2+/ER+ disease, but in only 45% of pts with HER2+/ER- cancer. Accurately predicting residual disease after THPx4 allows for consideration of additional therapy that may increase the chance of pCR. Combining imaging like MRI with other biomarkers, such as tissue-based markers or circulating tumor DNA, may improve prediction of pCR and facilitate personalization of treatment decisions in HER2+ breast cancer. All pts with pre-surgery MRI (n=1351)pCR rate overall in this cohort = 47% MRI result Pathology pCR pRD  rCR 70.6% (341/483) 29.4%(142/483) 78% had RCB1  rRD 34%(295/868) 21% of 295 had DCIS only 66.01% (573/868)  ER- (n=589)*Overall pCR rate in ER- subset = 68% MRI result Pathology pCR pRD  rCR 86.1% (205/238) 13.9% (33/238) 85% had RCB1  rRD 55.3% (194/351) 19% of 194 had only DCIS 44.7% (157/351)  ER+ (n= 762)*Overall pCR rate in ER+ subset = 31% MRI result Pathology pCR pRD  rCR 55.5% (136/245) 44.5% (109/245) 76% had RCB1  rRD 19.5% (101/517) 26% of 101 had only DCIS 80.5% (416/517)

Use of immune checkpoint inhibitors in soft tissue sarcoma: A meta-analysis.

e23560 Background: Soft tissue sarcomas (STS) have historically been treated with surgery, radiation, or chemotherapy. Recent studies and clinical trials have investigated the use of immune checkpoint inhibitors (ICI) either alone or in combination with chemotherapy. Here we present a meta-analysis examining ICI use in STS. Methods: A systemic search with terms encompassing STS and ICI was conducted in PubMed and Embase on January 11, 2026. A total of 1494 records were identified, which were imported into Rayyan, and titles were screened independently by 2 reviewers. 134 records were relevant, and full texts were reviewed. Only studies in which ICI was utilized for STS treatments were included. RevMan was used for analysis, and the Binary Random-Effects (RE) model was used for Pooled Proportions (PP) analyses. Results: ICI cohort had a total of 4455 patients. Using the RE model, the pooled proportions of patients achieving Complete Response (CR) was 1.7% (1.3% - 2.1%, p < 0.001, I^2 0), Partial Response (PR) was 17.7% (15.5-20.0, p < 0.001, I^2 79.057), and Stable Disease (SD) was 43% (39% - 47.1%, p < 0.001, I^2 84.044) while no response was seen in 33.5% patients (28.4% - 38.6%, p < 0.001, I^2 91.06). Overall Response Rate, (not including SD) was estimated to be 23.1% (20.4%-25.8%, p < 0.001). There was substantial heterogeneity across studies (I^2 86.629) for ORR. Current literature shows that using chemotherapy, mainly anthracycline based, has CR < 10%, PR 15-30%, and ORR 20-40%. Conclusions: Pooled data using ICI in sarcoma shows good overall response rates, especially the partial response rates. Current literature shows that using chemotherapy, mainly anthracycline based, has CR < 10%, PR 15-30%, and ORR 20-40%. Our data is very comparable to chemotherapy regimens. While meta-analysis results can be confounded by heterogeneity between studies, results of ongoing clinical studies that may result in near future may help better answer this question.

Local tourism experiences at World Heritage rice terrace sites in China: A comparative study of Hani Terraces and Longji Terraces

Rice terraces, as quintessential cultural landscapes shaped by long-term human-land interactions, embody productive, ecological, and cultural value while evolving into significant rural tourism destinations. This study examines two World Heritage–listed sites in China—Hani Terraces in Yunnan Province and Longji Terraces in Guangxi Province—using 4,018 visitor reviews collected from the Ctrip platform. Word frequency analysis was conducted to identify recurrent terms in visitor comments and to determine key dimensions of tourism experience. Semantic co-occurrence network analysis was then applied to explore structural relationships among core terms and to reveal differences in visitor perceptions. In addition, chi-square tests were used to identify statistically significant differences in evaluation characteristics and to examine patterns of negative feedback. The results show that Longji Terraces benefit from higher tourism visibility and a larger volume of online reviews, whereas visitors to Hani Terraces place greater emphasis on cultural and heritage values. In contrast, visitors to Longji Terraces tend to focus more on leisure-oriented tourism services. Negative feedback for both sites primarily centers on transportation and management issues. Weather conditions significantly impacted sightseeing at Hani Terraces, while Longji Terraces faced complaints mainly related to service quality. Overall, this study highlights the heterogeneity of tourism experiences across terraced heritage landscapes and identifies key factors shaping visitor perceptions. By extending the application of user-generated content (UGC) in agricultural heritage tourism research, the findings provide empirical evidence to support tourism management, landscape conservation, and the sustainable development of agricultural heritage sites.

Recent advances in the green synthesis of metal and metal oxide nanoparticles from plant extracts for biomedical and water remediation applications

Turing equations capture living skin patterns

Quasi-ohmic electron extraction in perovskite solar cells through controlled burstein–moss shifts in rare-earth doped SnO2 ETLs

Targeting frizzleds with small-molecule compounds—back to square one or light at the end of the tunnel?

Non-invasive strategy for gastric cancer detection: Integration of cell-free DNA fragmentomics and protein biomarkers.

4071 Background: Gastric cancer (GC) ranks the fifth most common cancer worldwide. Although gastroscopy is widely acknowledged as the gold standard for GC detection, its invasiveness limits its utility in large-scale screening. Accurate, non-invasive diagnostic modalities are urgently needed. Cell-free DNA (cfDNA) fragmentomics has emerged as a promising tool for cancer detection. This study aimed to develop and validate a novel non-invasive model for GC detection based on cfDNA fragmentomics and protein biomarkers. Methods: A total of 257 participants, comprising 120 GC patients and 137 non-cancer individuals, were enrolled and divided into a training cohort (n = 129) and a test cohort (n = 128). Low-coverage whole-genome sequencing was performed on plasma cfDNA. We evaluated eight multi-dimensional cfDNA fragmentomics features individually, and selected four, including fragment size ratio, copy number variation, 9-bp end motif, and fragment size at transcription starting sites, to build an ensemble model (GaFraD) to detect GC. Furthermore, conventional protein biomarkers of GC were assessed and integrated with GaFraD model to generate a CONFIRM model aimed at improving diagnostic performance. Results: The GaFraD model achieved an area under the receiver-operating characteristic curve (AUC) of 0.953 (95% CI: 0.918 – 0.979) in the training cohort and 0.970 (95% CI: 0.944 – 0.990) in the test cohort, with a sensitivity of 95.0% and a specificity of 80.9%. By incorporating protein biomarkers CA19-9 and PG-I/PG-II, the CONFIRM model further reached an AUC of 0.967 (95% CI: 0.929 – 0.992) in the training cohort and 0.986 (95% CI: 0.966 – 1.000) in the test cohort, attaining a sensitivity of 95.0% and specificity of 95.6%. Moreover, the CONFIRM model also exhibited remarkable performance in discriminating early-stage GC patients from controls (AUC = 0.983, sensitivity: 95.6%, specificity: 94.2%). Conclusions: Our model exhibits high discriminatory power in distinguishing GC patients from controls, highlighting the strong clinical potential of combining cfDNA fragmentomics with protein biomarkers for non-invasive, early GC detection. This approach offers a promising pathway towards earlier, accurate, and non-invasive clinical diagnosis of GC.

Tumor mutational burden by smoking status in small cell lung cancer: Insights from a limited cohort.

e20122 Background: Tumor mutational burden (TMB) is a potential biomarker in small cell lung cancer (SCLC) and is often influenced by tobacco exposure. We evaluated the relationship between TMB and smoking history in publicly available SCLC datasets, acknowledging the limited sample size. Methods: We analyzed 120 patients with SCLC (median age 65 years; 76 male, 44 female). Smoking status was categorized as current (n=56), former (n=47), or never (n=3); 14 patients with missing smoking data were excluded from analyses. TMB was obtained from whole-genome sequencing, with a median of 7.5 mutations per megabase (range 0–24.43). TMB was compared between ever-smokers (current or former) and never-smokers using the Mann–Whitney U test. Correlation between TMB and reported pack-years was assessed using Spearman’s rank correlation. Results: Median TMB in ever-smokers was 7.5 (mean 8.19, range 0–24.43) versus 7.63 (mean 8.36, range 0–17.43) in never-smokers (Mann–Whitney U p=0.980). There was a weak, non-significant correlation between TMB and pack-years (Spearman rho=0.12, p=0.294). Exploratory survival analyses were not performed due to the limited sample size and incomplete treatment annotation. Conclusions: In this limited public SCLC cohort, no clear association between smoking history and TMB was observed. These findings should be interpreted cautiously given the small number of never-smokers and highlight the need for larger studies to evaluate the impact of tobacco exposure on TMB and its potential clinical relevance.

Coordinated care interventions and time to treatment initiation in a public health system in Brazil.

e13513 Background: Delays in cancer treatment initiation are associated with increased morbidity and mortality. In Brazil, federal policy mandates treatment initiation within 60 days after diagnosis; however, many patients experience delays, particularly those with clinical or social barriers. Care coordination and navigation strategies may improve timely access to treatment in complex public health systems. Methods: Retrospective cohort study including all consecutive patients undergoing first oncologic evaluation at a public cancer center in São Paulo (2022–2025). Patients with clinical and/or social barriers to treatment initiation were identified through institutional dashboards. Interventions included multidisciplinary case management, structured assessment, therapeutic optimization, active monitoring, patient education, and psychosocial support. In 2023, institutional care pathways and communication flows were standardized. Descriptive and comparative analyses were performed to evaluate changes in time to treatment initiation (TTI). Results: A total of 9,455 patients were analyzed. In 2022, 2,956 patients were included, of whom 439 had relevant comorbidities and 180 had low adherence. In 2023, 2,325 patients were included (315 with comorbidities; 135 with low adherence); in 2024, 2,165 (188; 80); and in 2025, 2,029 (203; 87). The proportion of patients with significant clinical or social barriers decreased from 20.9% in 2022 to 14.3% in 2025. Major clinical barriers included decompensated heart failure, advanced chronic kidney disease, severe infections, malnutrition, severe anemia, and the need for cardiology interventions. Social barriers involved low adherence, socioeconomic vulnerability, and limited access to care. Following the implementation of standardized care pathways in 2023, median TTI decreased from 72 to 44 days, representing a 38.9% reduction. Improvements were consistent across both clinical and social risk subgroups. Conclusions: Coordinated care and navigation-based interventions were associated with substantial reductions in treatment delays and improved care delivery for oncology patients facing complex barriers. Findings support the adoption of integrated care models to optimize treatment initiation in resource-constrained public health systems.

Projected burden of lung cancer and tobacco usage among older adults ≥ 65 in the United States: A CDC WONDER forecasting analysis, 1999–2035.

e20083 Background: Lung cancer and tobacco use are closely linked, with smoking responsible for most cases. Evaluating long-term mortality trends related to lung cancer among tobacco users is essential to assess the impact and limitations of public health efforts. This study examines lung cancer mortality trends among U.S. adults aged ≥65 years, stratified by demographic and geographic factors. Methods: We performed a retrospective analysis of CDC WONDER mortality data (1999–2024) for individuals aged ≥65 years. Lung cancer and tobacco use were identified using ICD-10 codes C34 and F17. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes with 95% confidence intervals, and future mortality was projected using an optimized ARIMA model. Results: From 1999–2024, 1,013,170 lung cancer deaths occurred among tobacco users. AAMRs were highest in Kentucky (171.2) and lowest in California (5.3). Overall AAMRs increased from 11.4 in 1999 to 80.5 in 2024, with projected declines from 77.42 in 2025 to 46.62 in 2035 (AAPC 4.81; 95% CI 3.62–6.02; p<0.001). Mortality was consistently higher in males than females. In 2024, AAMRs were highest among non-Hispanic Whites and in the Midwest, followed by the South. Nonmetropolitan areas had higher AAMRs than metropolitan regions. Conclusions: Lung cancer mortality among tobacco users increased disproportionately among males, non-Hispanic White populations, and rural residents, with the highest burden in the Midwest and South. These findings underscore the need for targeted tobacco-related cancer prevention and improved access to care. Characteristic Number of Deaths (N) Age-Adjusted Mortality Rate (per 100,000):1999 Age-Adjusted Mortality Rate (per 100,000):2024 Average Annual Percent Change (AAPC) (1999–2024) with 95% CI Overall 1,013,170 11.4 80.5 8.72 (6.67 to 10.81) Sex Female 440,665 8.5 65.9 9.00 (7.24 to 10.79) Male 572,505 15.7 99.2 8.01 (6.03 to 10.02) Race and Ethnicity White 913,042 11.6 92.6 9.22 (6.97 to 11.51) Black or African American 77,340 11.3 74 8.43 (6.05 to 10.87) Hispanic or Latino 24,179 5.7 24.8 6.72 (4.02 to 9.48) Census Region West 146,261 17.2 49.7 3.81 (1.38 to 6.31) South 366,699 11.9 81.5 7.95 (5.81 to 10.14) Northeast 197,266 6 73 11.74 (7.74 to 15.88) Midwest 302,944 10.6 118.2 10.72 (7.89 to 13.61) Urbanization (1999–2020) Age-Adjusted Mortality Rate (per 100,000): 1999 Age-Adjusted Mortality Rate (per 100,000):2020 Metropolitan 632,106 10.8 84.8 11.11 (8.66 to 13.60) Non-metropolitan 190,179 13.8 132.2 11.85 (9.13 to 14.65) Age Group Crude Mortality Rates per 100,000:1999 Crude Mortality Rates per 100,000:2024 65–74 years 478,274 11.5 63 7.37 (5.55 to 9.23) 75–84 years 408,955 12.4 101.8 9.20 (7.13 to 11.31) 85+ years 125,941 8 93.8 11.38 (9.04 to 13.76)

Efficacy and safety of immune checkpoint inhibitors after platinum-based therapy for refractory or recurrent malignant pleural mesothelioma: A systematic review and meta-analysis.

e20064 Background: Malignant pleural mesothelioma (MPM) remains highly aggressive. While immune checkpoint inhibitors (ICIs) are established in first-line therapy, their efficacy in the refractory setting, followed by platinum-based doublet chemotherapy (CT) failure, remains uncertain. Hence, this systematic review and meta-analysis aim to evaluate the clinical benefit of ICIs for recurrent malignment mesothelioma after platinum based therapy. Methods: We systematically searched PubMed, Embase, and Cochrane for studies of ICIs in adults with MPM progressing after platinum-based CT. Studies including treatment-naïve patients, potentially resectable disease, or non-isolable combination therapies were excluded. We compared monotherapy and doublet ICIs regimens and performed subgroup analysis based on the therapeutic class combinations (anti-PDL1, anti-CTLA4, anti-PD1). The outcomes of interest were progression free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs). All the statistical analyses were performed in R version 5.3 using a random-effects model and meta-analysis of proportions, with heterogeneity assessed via I² statistics and Cochran’s Q test. Results: Among 1.220 screened studies, 13 met the inclusion criteria, representing 1.014 patients with recurrent MPM treated with ICIs. The 1-year OS was 60.4% (95% CI, 50.3–69.7; I² = 0%) for studies with doublet ICIs and 45.9% (95% CI, 41.9–49.9; I² = 0%) for studies utilizing monotherapy (p value for subgroup difference = 0.009). The pooled 1-year PFS was 17.1% (95% CI, 11.6–24.4; I² = 0%). ORR were 25.3% (95% CI, 17.1–35.7; I² = 49.8%) in doublet ICIs studies and 11% (95% CI, 6.7–17.5; I² = 79.9%) in monotherapy (p= 0.0072). Stratified by class, anti-PD1 plus anti-CTLA4 shows an ORR of 25.4%, anti-PD1 of 16.6%, and anti-CTLA4 of 4.7% (p=0.0001). Disease control rates were 58.6%, 51.7%, and 28.0%, respectively (p = 0.0001). Any-grade TRAEs occurred in 93.7% (95% CI, 86.7–97.1; I² = 0%) of patients receiving doublet therapy and 70.5% (95% CI, 61.2–78.3; I² = 81%) of those receiving monotherapy (p = 0.0001), with grade ≥3 TRAEs reported in 23.4% of patients and treatment discontinuation in 10.8%. Conclusions: ICIs demonstrate clinical activity in patients with MPM previously exposed to chemotherapy, particularly in combination regimens, albeit with a toxicity burden. However, randomized clinical trials are needed to confirm these findings, define the optimal therapeutic strategy, and refine patient selection in this setting.

Early symptom signals preceding end-of-life decline in outpatient palliative oncology.

12053 Background: Timely recognition of clinical decline is challenging in palliative oncology. Symptom trajectories that precede global deterioration are unclear. We aimed to characterize longitudinal changes in total and domain-specific Integrated Palliative Outcome Scale (IPOS) scores and identify early indicators of decline in outpatient palliative oncology care (OPOC). Methods: We conducted a longitudinal study within an OPOC embedded in Brazil. Adults with advanced cancer enrolled for ≥6 months were included. IPOS was assessed at baseline, 3 months, 6 months, and the month of death. Paired comparisons evaluated changes in total IPOS scores and individual domains between baseline-3 months and 6 months-month of death. Clinically relevant decline was defined as worsening between 6 months and death. Logistic regression examined associations between IPOS decline, chemotherapy use near death, and place of death. Results: Among 126 patients (mean age 64.1 [SD 14.4]; 62.7% women), gastrointestinal (33.3%), breast (19.8%), and lung cancers (11.1%) were most common. At program entry, mean PPS was 65 (SD 13.5). Total IPOS scores improved from baseline to 3 months (mean difference 2.69, p=0.007). However, a marked deterioration occurred between 6 months and the month of death (mean difference -3.98, p<0.001). Domain-level analyses demonstrated early improvement in appetite loss (mean 1.56 to 1.28, p=0.020) and weakness (1.91 to 1.64, p=0.034) from baseline to 3 months, followed by significant worsening as death approached (appetite: 1.42 to 1.75, p=0.006; weakness: 1.94 to 2.25, p=0.003). Anxiety increased significantly between 6 months and the month of death (1.99 to 2.23, p=0.008), whereas pain and depressive symptoms remained relatively stable over time. Neither chemotherapy use in the last 30 days of life (OR 0.78, p=0.58) nor place of death (OR 0.56, p=0.21) was associated with clinically relevant IPOS decline. Conclusions: OPOC is associated with early symptom stabilization, followed by a predictable phase of accelerated deterioration near death. Appetite loss and weakness emerge as early and clinically meaningful indicators of decline within the terminal trajectory, independent of treatment or place of death. Routine longitudinal IPOS monitoring may facilitate earlier recognition of impending decline and support more proactive, patient-centered palliative care.

Closing the distance and the Specialist Nursing Optimal Placement Tool (SN-OPT): Strategic placement of specialist cancer nurses to achieve resource and geographic equity in Australia.

11082 Background: Cancer workforce planning that enables effective specialist nurse placement is critical for delivering high-quality, patient-centered care. Inequitable access to specialist nursing represents a significant gap in cancer care delivery. No standardized tools assess specialist cancer nursing resource needs across national healthcare systems. We developed SN-OPT, an innovative resource allocation tool, using 30 new centrally funded specialist melanoma nurse positions for Australia as a case study. Methods: A multidisciplinary panel developed SN-OPT via expert consensus, incorporating three data domains: Clinical Infrastructure Assessment: Analysis of facility capabilities including multidisciplinary team (MDT) structures, clinical trial programs, and existing nursing and support services Demand Assessment: Quantitative analysis of case load, treatment complexity, and nursing workload benchmarks Health Equity: Population-level analysis incorporating geographic accessibility and socioeconomic disadvantage SN-OPT combines cancer incidence data with facility metrics to allocate nursing resources operating within a MDT framework. Equity assessment utilized Australian Statistical Geography Standard, Index of Relative Socio-Economic Disadvantage and Travel Time to Hospitals in Australia dataset. Results: SN-OPT evaluated 46 Australian facilities for melanoma nursing allocation. The weighted scoring algorithm ranked 33 sites for nurse allocation, with a mean allocation of 0.87 full time equivalent (FTE) positions per metro facility and 0.64 FTE per regional facility. The tool achieved equitable geographic distribution of specialist nursing expertise: regional facilities, treating 25% of patients, received 36% of nursing FTE (167 patients/FTE/year). Metro facilities, managing 75% of patients, received 64% of FTE (212 patients/FTE/year). Allocations largely aligned with facility-determined resource need, with 58% receiving their requested FTE. Among the remaining facilities, median allocation variance was -0.4 FTE (range -0.1 -1.0). On a population level, 89% of Australians would have geographic access to specialist melanoma nursing care within 2-hours of travel, including 81% of the most socioeconomically disadvantaged regions. Conclusions: SN-OPT offers a reproducible framework for data-driven allocation of specialist cancer nurses. While implemented using melanoma nurses as a case study, SN-OPT's framework has the potential to be adapted across cancer streams and countries, providing a scalable approach to equitable cancer workforce planning. Early implementation balances clinical service delivery and demand requirements within a MDT framework, while allowing adequate geographical access including socioeconomically disadvantaged regions.

Stage-dependent divergence of immune prognostic signatures in non–small cell lung cancer.

8066 Background: Tumor mutational burden (TMB) and immune activation are widely studied biomarkers in non–small cell lung cancer (NSCLC), yet their prognostic relevance outside the context of immunotherapy remains unclear. We investigated how age, histology, and disease stage modify the relationships between tumor genomics, immune contexture, and overall survival in NSCLC. Methods: We analyzed The Cancer Genome Atlas NSCLC cohort from the “Pan-cancer atlas” (2018) with a total of 1053 patients evaluating TMB, CD8A expression, cytolytic activity score (CYT), age at diagnosis, histology, and overall survival. Associations among continuous variables were assessed using Spearman correlation. Multivariable Cox proportional hazards models adjusted for age, sex, and tumor mutational burden were performed and stratified by stage (I–II vs III–IV). Results: Age demonstrated an inverse correlation with tumor mutational burden (ρ = −0.12, P < 0.001) but was not associated with CD8A expression and showed a weak positive association with CYT, driven by non-squamous tumors. Tumor mutational burden was not associated with overall survival in either early- or late-stage disease. In contrast, immune biomarkers demonstrated marked association with stage of disease. Higher CD8A expression was associated with improved survival in early stage (HR 0.77 per SD, P = 0.021) but not in advanced disease. CYT exhibited a significant interaction with stage with higher CYT showing association with improved survival in early-stage NSCLC (HR 0.79 per SD, P = 0.026) but with worse survival in late-stage disease (derived HR ≈ 1.14). Tumor stage remained the dominant prognostic factor across all models. Conclusions: In untreated NSCLC, immune prognostic signatures are strongly stage dependent. Immune infiltration and cytolytic activity confer survival benefits in early-stage disease but not in advanced disease, where cytolytic activity may reflect aggressive tumor-associated inflammation. Tumor mutational burden does not provide prognostic value across disease stages. These findings highlight the importance of disease context when interpreting immune biomarkers and provide critical baseline insight for immunotherapy-era studies. Patient characteristics. Characteristic Overall (N=1053) Early Stage (I–II) (N=517) Late Stage (III–IV) (N=479) Age, median (IQR) 67 68 67 Sex, % male 40.24 (402) 44.68 (231) 35.69 (171) Histology, %  Squamous 46.24 (487) 46 (238) 51.35 (246)  Non-squamous 53.7 (566) 56 (279) 50 (233) Stage  I–II 47%  III–IV 53% TMB, median (IQR) 7.3 (3.9-12.1) 7.35 (3.7-12.1) 7.36 (4.2-12.1) CD8A expression, median (IQR) 232 (112-469) 240 (122-471) 208 (103-460) CYT score, median (IQR) 183 (103.9-368.3) 191.3 (109.6-368.3) 175.9 (98-370)

mRNA-based profile to predict platin sensitivity in NSCLC assessed by Nanostring: A translational analysis of the ETOP/EORTC SPLENDOUR trial.

e20555 Background: Platinum-based chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC), yet clinical benefit is highly variable and no validated biomarkers are available to guide treatment selection. The Platin Drug Response Predictor (Platin-DRP) is a 205-gene mRNA signature previously validated in breast cancer and NSCLC using microarray-based platforms, including an analysis performed in the SPLENDOUR trial cohort using Affymetrix gene expression profiling and reported separately (abstract submitted to ELCC 2026). Here, we evaluated the clinical association of Platin-DRP with outcomes in patients from the randomized phase 3 SPLENDOUR trial, using tumor biopsies analyzed on the Nanostring platform (UIN: researchregistry11317). Methods: SPLENDOUR was a randomized trial enrolling 514 patients with advanced NSCLC treated with platinum chemotherapy with or without denosumab. This secondary, exploratory analysis included 93 patients with available tumor biopsies and tumor cell content ≥5% (cisplatin n = 33, carboplatin n = 60). The tumor biopsies were analyzed on the Nanostring platform, and the gene expression values were used to calculate platin DRP scores. Associations between the continuous DRP score and progression-free survival (PFS) and overall survival (OS) were assessed using Cox proportional hazards models at a one-sided (1s) type I error of 5%. Additional analyses evaluated pre-specified DRP thresholds (35, 50, 70) and response rate (RR). Results: In the analyzed cohort of 93 patients, the median PFS and OS were 3.9 and 5.6 months, respectively. Higher DRP scores were significantly associated with longer OS in the carboplatin cohort (n = 60; HR (per 50-point DRP increase) = 0.65; 95% upper confidence limit (uCL) 0.930; 1s p = 0.024) and in the pooled cohort stratified by chemotherapy regimen (n = 93; HR (per 50-point DRP increase) = 0.72; 95% uCL 0.957; 1s p = 0.029). In the cisplatin cohort, the association between DRP score and OS was not statistically significant (n = 33; HR (per 50-point DRP increase) = 0.87; 95% uCL 1.399; 1s p = 0.32). Threshold-based analyses showed improved OS in carboplatin-treated patients with high DRP scores, with a median OS of 16.9 months for scores > 70 (n = 16) versus 4.6 months for scores ≤70 (n = 44; 1s p = 0.045). Moreover, DRP scores derived from Affymetrix and Nanostring platforms were strongly correlated (Spearman ρ = 0.91, p < 0.001). Conclusions: Using a Nanostring-based assay, higher Platin-DRP scores were associated with improved OS, but not PFS, in platinum-treated advanced NSCLC patients. These findings suggest cross-platform robustness of the DRP signal and potential clinical relevance for guidance in NSCLC.