The Large Cancer Assistant (LCA): A Model-Agnostic Orchestration Framework for Scalable Clinical Decision Support in Oncology

We present Multi-Agent Reasoning and Coordination (MARC), an open-source framework that replaces monolithic LLM prompting with deterministic multi-agent orchestration for clinical reasoning. MARC coordinates role-specialized agents for extraction, reasoning, answer generation, and evaluation, with explicit context passing and traceable intermediate outputs, enabling stage-wise failure attribution. We additionally introduce a Decomposer module that generates task-specific agent prompts from a plain-language description, eliminating manual prompt engineering. The framework supports both API-based and local CPU-compatible deployments and is entirely configurable via YAML, without code modifications. MARC is designed to be model-agnostic, interpretable, and accessible to clinical domain experts without programming expertise. The full framework is available at https://github.com/Penn-RAIL/MARC-v1.

Large language models (LLMs) are increasingly being explored for clinical decision support, but their reliability in complex oncology treatment planning remains unclear. We evaluated agentic LLM systems for breast cancer treatment recommendation generation using 72 real clinical cases across stages I to IV and 1,147 case-specific rubrics generated through Asymmetric Information Rubric Generation (AIRG), in which the rubric generator had access to real clinical decisions unavailable to the evaluated models. Seven pipelines were compared, including single-LLM baselines, tool-augmented systems, and multi-agent architectures with fact checking and autonomous subagent spawning. The best-performing configuration, Claude Opus 4.8 with the D&C+SA pipeline, achieved a global score of 0.594 $\pm$ 0.025. Tool use and increased agent autonomy had mixed effects, improving performance in some settings but degrading it in others. Performance varied by clinical domain and disease stage, and oncologist-led error analysis revealed persistent clinically relevant failures, including incorrect or missing recommendations, flawed justifications, citation errors, outdated claims, and overconfidence. These findings suggest that agentic LLM systems can generate clinically relevant breast cancer recommendations, but remain insufficient for unsupervised clinical use.

Does every cancer patient truly need a complete diagnostic workup for accurate survival prediction? In multimodal clinical oncology, diagnostic modalities follow a clinically mandated order of escalating burden -- from demographics collected at intake to genomic profiling requiring specialized tissue analysis. Current multimodal survival methods either assume all modalities are available or passively handle missing data, but none actively reason about whether acquiring the next modality is justified for a given patient along this ordered workflow. We formulate this as a sequential decision problem and propose SAGEAgent (Sequential Acquisition Guided by Experience), a self-evolving LLM-based clinical agent that decides which diagnostic modalities to acquire for each patient, balancing predictive accuracy against clinical invasiveness. SAGEAgent reasons about each patient's evolving diagnostic state through clinical tools that translate numerical predictions into text, an episodic memory that retrieves similar past cases, and a semantic memory that accumulates reusable decision patterns from experience. Experiments on a glioma cohort combining TCGA-LGG, TCGA-GBM, and BraTS with four diagnostic modalities demonstrate that SAGEAgent achieves competitive survival prediction accuracy while reducing average acquisition burden by 55%.