Jhanelle Elaine Gray

Radiomic features derived from longitudinal imaging offer a non-invasive approach to quantify tumor heterogeneity, but their integration with clinical variables in small cohorts remains methodologically challenging. We analyzed 23 patients with advanced non-small cell lung cancer (NSCLC) enrolled in a Phase I study of pembrolizumab and vorinostat. Radiomic features were extracted from baseline and two-month follow-up computed tomography scans, aggregated to the patient level, and transformed into delta features representing early changes over time. A unified modeling framework was implemented using strict leave-one-out cross-validation (LOOCV), incorporating both radiomic and clinical variables. Within each training fold, outcome-guided feature screening was performed using elastic net penalized Cox regression, followed by category-aware principal component analysis and ridge-penalized Cox modeling. Model performance was evaluated using out-of-fold concordance indices for overall survival (OS) and progression-free survival (PFS). Radiomics-only models demonstrated moderate discrimination for OS (C-index 0.609) and favorable discrimination for PFS (C-index 0.770), whereas clinical-only models showed weaker performance (OS 0.605; PFS 0.571). The combined radiomics and clinical model demonstrated numerically higher discrimination without statistically distinguishable differences for OS (C-index 0.648) while maintaining favorable discrimination for PFS (C-index 0.718). Stable features were predominantly texture-based and included Laws filter and co-occurrence-derived metrics associated with spatial heterogeneity. In this exploratory analysis, early changes in radiomic features reflecting tumor heterogeneity suggest potential associations with survival outcomes in advanced NSCLC. Integration of radiomic and clinical variables showed trends toward improved performance for overall survival while maintaining favorable discrimination for progression-free survival. These findings support further investigation of longitudinal radiomic features as candidate imaging biomarkers in larger, independently validated cohorts.

1. 1.1. Lung cancer is the second most diagnosed cancer worldwide, with approximately 2.2 million cases diagnoses in 2020, representing about 11.4% of the total cancer cases [1]. Non-small cell lun...

Background: Former and current smokers in lung cancer screening remain at elevated risk for lung cancer despite smoking cessation. We and others have shown that curcumin (CUR) exhibits anti-inflammatory and antiproliferative effects but is limited by poor bioavailability. However, since CUR is lipophilic, co-administration with ω-3 FAs represents a mechanistically rational strategy to enhance delivery and target complementary pathways, including signal transducer and activator of transcription 3 (STAT3) and the transcription factor NF-κB (NF-κB) signaling for lung cancer chemoprevention. Methods: We conducted a randomized, single-blind, placebo-controlled Phase II pilot study evaluating CUR combined with ω-3 FAs in high-risk former and current smokers with CT-detected pulmonary nodules. Participants received intervention agents with active-dose groups (low dose = 3; high dose = 9) or a placebo (n = 7) for 6 months. Primary endpoints included radiologic changes in nodule size, number, and density. Secondary endpoints included safety, adherence to the study agent and exploratory biomarker analyses. Correlation analyses of imaging-derived metrics were performed to assess relationships among LDCT parameters. Results: Nineteen participants were enrolled (intervention, n = 12; placebo, n = 7). Eighteen (11 intervention, 7 placebo) subjects completed post-intervention imaging. One subject was unable to complete follow-up and study-related procedures. Data from the treatment arms were pooled for analysis and comparison with the placebo arm. No statistically significant between-group differences were observed in primary imaging endpoints. The intervention was well tolerated, with predominantly grade 1 adverse events. Exploratory analyses demonstrated consistent positive correlations among established imaging biomarkers, with clustering of size-based metrics (mean diameter, volume, sum of longest diameters) and density-based parameters. Multidimensional scaling supported this structure, indicating internal coherence among imaging-derived endpoints. Conclusions: Although no statistically significant treatment effect on the image biomarkers was observed, this pilot study demonstrates feasibility challenges and identifies coherent imaging biomarkers that may serve as intermediate endpoints in early-phase chemoprevention trials. These results support further investigation of strategies utilizing agent combinations with enhanced bioavailability and safety and refinement of trial design in high-risk lung cancer patient populations.

Former smokers in lung cancer screening remain at elevated risk for lung cancer despite smoking cessation. We and others have shown that curcumin exhibits anti-inflammatory and antiproliferative effects but is limited by poor bioavailability. However, since curcumin is lipophilic, co-administration with omega-3 fatty acids (ω-3 ω-3 ω-3 FA) represents a mechanistically rational strategy to enhance delivery and target complementary pathways, including STAT3 and NF-κB signaling for lung cancer chemoprevention. Methods: We conducted a randomized, single-blind, placebo-controlled pilot study evaluating curcumin combined with ω-3 FA in high-risk former and current smokers with CT-detected pulmonary nodules. Participants received intervention agents or placebo for 6 months. Primary endpoints included radiologic changes in nodule size, number, and density. Secondary endpoints included safety, adherence, bioavailability, and exploratory biomarker analyses. Correlation analyses of imaging-derived metrics were performed to assess relationships among LDCT parameters. Results: Nineteen participants were enrolled (intervention, n=12; placebo, n=7). No statistically significant between-group differences were observed in primary imaging endpoints. The intervention was well tolerated, with predominantly grade 1 adverse events. Exploratory analyses demonstrated consistent positive correlations among LDCT-derived measures, with clustering of size-based metrics (mean diameter, volume, sum of longest diameters) and density-based parameters. Multidimensional scaling supported this structure, indicating internal coherence among imaging-derived endpoints. Conclusions: Although no statistically significant treatment effect on the image biomarkers was observed, this pilot study demonstrates feasibility challenges and identifies coherent imaging biomarkers that may serve as intermediate endpoints in early-phase chemoprevention trials. These results support further investigation of strategies utilizing agent combinations with enhanced bioavailability and safety and refinement of trial design in high-risk lung cancer patient populations.

Purpose:EVOKE-02 (NCT05186974) is a multicohort, phase II trial evaluating first-line sacituzumab govitecan (SG) plus pembrolizumab with or without platinum-based chemotherapy in patients with metastatic non–small cell lung cancer (mNSCLC).Patients and Methods:Adults with mNSCLC, no prior systemic treatment, and no actionable genomic alterations received SG 10 mg/kg intravenously (reduced to 7.5 mg/kg following a preplanned safety evaluation) on days 1 and 8, plus pembrolizumab 200 mg intravenously on day 1 and carboplatin area under the curve 5 on day 1 in 21-day cycles. The primary endpoint was objective response rate (ORR) per independent review committee; secondary endpoints included progression-free survival (PFS) and safety.Results:As of June 3, 2024, 54 and 41 patients had nonsquamous and squamous histology, respectively. ORR (95% confidence interval [CI]) was 45.1% (3.1–59.7) for nonsquamous and 39.0% (24.2–55.5) for squamous histology. Median (95% CI) PFS was 8.1 (5.2–15.0) months for nonsquamous and 8.3 (4.3–11.2) months for squamous histology. ORR (95% CI) was 66.7% (34.9–90.1) for programmed cell death-ligand 1 tumor proportion score greater than or equal to 50%. SG dose was adjusted to 7.5 mg/kg due to myelosuppression. Grade greater than or equal to 3 treatment-emergent adverse events (TEAEs) occurred in 57 patients (86.4%). TEAEs leading to discontinuation of any study drug occurred in 12 patients (18.2%).Conclusions:SG plus pembrolizumab and carboplatin had activity in mNSCLC. When combined with pembrolizumab and carboplatin, SG was tolerated at a dose of 7.5 mg/kg.

Supplementary Table 2 shows different metastatic sites used for biopsy collection in this study.

Supplementary Table 3 describes the classification statistics using LOOCV for SVM and NN SDM based on the number of patients correctly classified.

Figure S5 shows the RoGM analysis for the non-spatial setting.