Humza Nusrat

Humza Nusrat, Luke Francisco, Bing Luo et al.

Stereotactic radiosurgery (SRS) demands precise dose shaping around critical structures, yet black-box AI systems have limited clinical adoption due to opacity concerns. We tested whether chain-of-thought reasoning improves agentic planning in a retrospective cohort of 41 patients with brain metastases treated with 18 Gy single-fraction SRS. We developed SAGE (Secure Agent for Generative Dose Expertise), an LLM-based planning agent for automated SRS treatment planning. Two variants generated plans for each case: one using a non-reasoning model, one using a reasoning model. The reasoning variant showed comparable plan dosimetry relative to human planners on primary endpoints (PTV coverage, maximum dose, conformity index, gradient index; all p > 0.21) while reducing cochlear dose below human baselines (p = 0.022). When prompted to improve conformity, the reasoning model demonstrated systematic planning behaviors including prospective constraint verification (457 instances) and trade-off deliberation (609 instances), while the standard model exhibited none of these deliberative processes (0 and 7 instances, respectively). Content analysis revealed that constraint verification and causal explanation concentrated in the reasoning agent. The optimization traces serve as auditable logs, offering a path toward transparent automated planning.

Humza Nusrat, Bing Luo, Ryan Hall et al.

Radiotherapy treatment planning is a complex and time-intensive process, often impacted by inter-planner variability and subjective decision-making. To address these challenges, we introduce Dose Optimization Language Agent (DOLA), an autonomous large language model (LLM)-based agent designed for optimizing radiotherapy treatment plans while rigorously protecting patient privacy. DOLA integrates the LLaMa3.1 LLM directly with a commercial treatment planning system, utilizing chain-of-thought prompting, retrieval-augmented generation (RAG), and reinforcement learning (RL). Operating entirely within secure local infrastructure, this agent eliminates external data sharing. We evaluated DOLA using a retrospective cohort of 18 prostate cancer patients prescribed 60 Gy in 20 fractions, comparing model sizes (8 billion vs. 70 billion parameters) and optimization strategies (No-RAG, RAG, and RAG+RL) over 10 planning iterations. The 70B model demonstrated significantly improved performance, achieving approximately 16.4% higher final scores than the 8B model. The RAG approach outperformed the No-RAG baseline by 19.8%, and incorporating RL accelerated convergence, highlighting the synergy of retrieval-based memory and reinforcement learning. Optimal temperature hyperparameter analysis identified 0.4 as providing the best balance between exploration and exploitation. This proof of concept study represents the first successful deployment of locally hosted LLM agents for autonomous optimization of treatment plans within a commercial radiotherapy planning system. By extending human-machine interaction through interpretable natural language reasoning, DOLA offers a scalable and privacy-conscious framework, with significant potential for clinical implementation and workflow improvement.

Humza Nusrat, Omar Nusrat

Agentic AI "scientists" now use language models to search the literature, run analyses, and generate hypotheses. We evaluate KOSMOS, an autonomous AI scientist, on three problems in radiation biology using simple random-gene null benchmarks. Hypothesis 1: baseline DNA damage response (DDR) capacity across cell lines predicts the p53 transcriptional response after irradiation (GSE30240). Hypothesis 2: baseline expression of OGT and CDO1 predicts the strength of repressed and induced radiation-response modules in breast cancer cells (GSE59732). Hypothesis 3: a 12-gene expression signature predicts biochemical recurrence-free survival after prostate radiotherapy plus androgen deprivation therapy (GSE116918). The DDR-p53 hypothesis was not supported: DDR score and p53 response were weakly negatively correlated (Spearman rho = -0.40, p = 0.76), indistinguishable from random five-gene scores. OGT showed only a weak association (r = 0.23, p = 0.34), whereas CDO1 was a clear outlier (r = 0.70, empirical p = 0.0039). The 12-gene signature achieved a concordance index of 0.61 (p = 0.017) but a non-unique effect size. Overall, KOSMOS produced one well-supported discovery, one plausible but uncertain result, and one false hypothesis, illustrating that AI scientists can generate useful ideas but require rigorous auditing against appropriate null models.