arXiv subjects

Dennis Baidoo

Publications and source records attributed to Dennis Baidoo.

4 recordsLinked to original sources

arXiv2026

Adaptive Weighting for Time-to-Event Continual Reassessment Method: Improving Safety in Phase I Dose-Finding Through Data-Driven Delay Distribution Estimation

Background: Phase I dose-finding trials increasingly encounter delayed-onset toxicities, especially with immunotherapies and targeted agents. The time-to-event continual reassessment method (TITE-CRM) handles incomplete follow-up using fixed linear weights, but this ad hoc approach doesn't reflect actual delay patterns and may expose patients to excessive risk during dose escalation. Methods: We replace TITE-CRM's fixed weights with adaptive weights, posterior predictive probabilities derived from the evolving toxicity delay distribution. Under a Weibull timing model, we get closed-form weight updates through maximum likelihood estimation, making real-time implementation straightforward. We tested our method (AW-TITE) against TITE-CRM and standard designs (3+3, mTPI, BOIN) across three dose-toxicity scenarios through simulation (N = 30 patients, 2,000 replications). We also examined robustness across varying accrual rates, sample sizes, shape parameters, observation windows, and priors. Results: Our AW-TITE reduced patient overdosing by 40.6% compared to TITE-CRM (mean fraction above MTD: 0.202 vs 0.340; 95% CI: -0.210 to -0.067, p < 0.001) while maintaining comparable MTD selection accuracy (mean difference: +0.023, p = 0.21). Against algorithm-based methods, AW-TITE achieved higher MTD identification: +32.6% vs mTPI, +19.8% vs 3+3, and +5.6% vs BOIN. Performance remained robust across all sensitivity analyses. Conclusions: Adaptive weighting offers a practical way to improve Phase I trial safety while preserving MTD selection accuracy. The method requires minimal computation and is ready for real-time use.

stat.ME↗

arXiv2026

Time-Varying Hazard Patterns and Co-Mutation Profiles of KRAS G12C and G12D in Real-World NSCLC

Background: KRAS mutations are the largest oncogenic subset in NSCLC. While KRAS G12C is now targetable, no approved therapies exist for G12D. We examined time-to-next-treatment (TTNT) and overall survival (OS) differences between G12C and G12D, allowing for time-varying hazard effects. Methods: De-identified data from AACR Project GENIE BPC NSCLC v2.0-public were analyzed. TTNT served as a real-world surrogate for progression-free survival. Co-mutations (TP53, STK11, KEAP1, SMARCA4, MET), TMB, and PD-L1 were harmonized. Kaplan-Meier, multivariable Cox, and a pre-specified piecewise Cox model (split at median TTNT = 23 months) were applied. Schoenfeld residuals assessed proportional hazards; bootstrap resampling (B=1000) evaluated stability. Results: Among 162 TTNT-evaluable patients (G12C n=130; G12D n=32), median TTNT was 28.6 versus 32.0 months (log-rank p=0.79). Adjusted Cox regression showed no overall hazard difference (HR=0.85; 95% CI 0.53-1.37; p=0.50), but Schoenfeld testing indicated borderline non-proportionality (p=0.053). Piecewise Cox modeling revealed time-varying effects: early TTNT hazard favored G12D (HR=0.41; 95% CI 0.17-0.97; p=0.043) with significant KRAS x period interaction (HR=3.33; p=0.021) and late-period attenuation (HR=1.38; 95% CI 0.77-2.47; p=0.285). Bootstrap resampling confirmed this pattern (median HRearly=0.39; HRlate=1.41). Among 278 OS-evaluable patients (133 deaths), G12D showed improved OS (adjusted HR=0.63; 95% CI 0.39-0.99; p=0.048). G12C tumors exhibited higher TMB (9.79 vs 7.83 mut/Mb; p=0.002) and greater STK11/KEAP1 enrichment. Conclusions: KRAS G12D demonstrated early TTNT advantage and improved OS. Late-period TTNT differences were non-significant (post-hoc power: 12.3%). These exploratory findings require validation in larger cohorts but support allele-specific therapeutic development for G12D.

q-bio.QM↗

arXiv2025

Assessing the Influence of Locational Suitability on the Spatial Distribution of Household Wealth in Bernalillo County, NM

This study applies Multiscale Geographically Weighted Regression (MGWR) to examine the spatial determinants of household wealth in Bernalillo County, New Mexico. The model incorporates sociodemographic, environmental, and proximity-based variables to evaluate how locational suitability influences economic outcomes. Key factors considered include income, home value, elevation, PM2.5 concentration, and distances to essential services such as schools, markets, and hospitals. The MGWR model demonstrates strong performance, explaining approximately 63 percent of the variation in household wealth. Results show that proximity to markets, schools, and parks significantly increases wealth in over 40 percent of neighborhoods. In contrast, closeness to hospitals and bus stops is negatively associated with wealth, suggesting that nearby disamenities can reduce housing desirability. Strong spatial autocorrelation (Morans I = 0.53, p < 0.001) indicates that wealthier households are significantly clustered, highlighting the influence of localized factors. Overall, the study reveals that the relationship between locational suitability and household wealth is spatially variable across the county.

stat.AP↗

arXiv2025

Integrative Prognostic Modeling of Breast Cancer Survival with Gene Expression and Clinical Data

Background: Accurate survival prediction in breast cancer is essential for patient stratification and personalized therapy. Integrating gene expression data with clinical factors may enhance prognostic performance and support precision medicine. Objective: To develop an integrative survival prediction model combining clinical variables and gene expression signatures, and to assess their contributions using penalized Cox regression and machine learning. Methods: We analyzed 1,867 patients from the METABRIC cohort with clinical annotations and microarray-based gene expression profiles. The top 5,000 most variable genes were retained. Elastic Net-penalized Cox regression identified 75 predictors (70 genes and 5 clinical variables: tumor size, stage, surgery type, age at diagnosis, and Nottingham Prognostic Index). Model performance was evaluated with Harrell's concordance index (C-index) and 36-month time-dependent AUC. Random Survival Forests (RSF) trained on the top 20 genes assessed nonlinear effects and validated variable importance. PCA and heatmaps visualized gene expression patterns across risk groups. Results: The integrative Cox model achieved a C-index of 0.922 and a 36-month AUC of 0.94, outperforming clinical-only models (C=0.64). RSF confirmed the prognostic value of top genes (e.g., OR2T27, TBATA, LINC01165, SLC10A4), yielding a 36-month AUC of 0.88. Conclusions: Combining gene expression signatures with clinical variables substantially improves survival prediction in breast cancer and provides a framework for individualized prognostic assessment and clinical decision-making.

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