Reinforcement Learning In Partially Verifiable Environments for Colon Cancer Treatment Planning
Authors: Li-Ching Chen, Andrés Franco Valiente, Yuta Ishiyama, Zachary R. Chalmers, William Chen, Kelsey Natsuhara, Taema Brinjikji, Madhumita Sushil, Travis Zack, Julian C. Hong
Organizations: University of California, San Francisco · Weill Cancer Hub West · Vokram Inc. · OpenEvidence
Clinical decision-making is a sequential process of information collection, clinical inference, and forecasting under partial observability, often without a uniquely correct treatment decision. Large language models (LLMs) have demonstrated strong medical question-answering capabilities but extending these advances to clinical reasoning remains challenging because many clinical tasks are only partially verifiable. Recent clinical reinforcement learning (RL) work has therefore largely focused on diagnostic endpoints, where correctness can be more directly verified. Oncology treatment decision making is a particularly challenging instance of this problem that extends beyond medical question-answering in which multiple decision trajectories can be clinically defensible for the same partially observed patient state. We formulate oncology treatment planning as an interactive RL problem under partial observability and construct patient-specific, process-aware rewards from decision processes observed in real world clinical records. The agent must learn to sequentially acquire information from a structured patient representation before committing to a first-line treatment recommendation, and is evaluated on information gathering, treatment selection, and reasoning alignment. Using GRPO and GDPO to optimize Llama-3.1-8B-Instruct within this environment, RL substantially improves the base policy beyond frontier model capabilities. The GDPO-trained policy increases Mean@3 scalar clinical reward by 79.60% over base Llama and exceeds GPT-5.2 by 18.82% under the same interactive environment, while reducing query count during training. Overall, our results show that patient-specific, partially verifiable rewards can provide an effective learning signal for interactive clinical RL when both the patient state and the underlying clinical decision process are only partially observed.
Figures & tables
Figure 1: The system consists of five functional components: a patient environment constructed from retrospective clinical data, a trainable clinical agent, a deterministic action parser, a frozen patient-record mediator, and a frozen judge.
Mean@3
Best@3
SD
95% CI
GRPO Llama-3.1-8B-Instruct
0.5712
0.6446
0.1465
[0.547, 0.595]
GDPO Llama-3.1-8B-Instruct
0.6085
0.6718
0.1264
[0.588, 0.629]
GRPO Qwen3.5-9B
0.1994
0.4878
0.2096
[0.165, 0.234]
GDPO Qwen3.5-9B
0.3429
0.5808
0.2174
[0.307, 0.379]
GRPO GLM-4-9B-0414
0.5313
0.6263
0.1321
[0.510, 0.553]
GDPO GLM-4-9B-0414
0.5105
0.6192
0.1474
[0.486, 0.535]
Table 1: Overall reward performance across different agent policies. Results are evaluated on n=142 cases with three generations per case. Mean@3 is the mean scalar reward across three generations; Best@3 is the mean of the highest scalar reward among the three generations for each case. Best results are shown in bold and second-best results are underlined .
Policy
Information (0 – 5)
Regimen (0 – 5)
Reasoning (0 – 5)
Complete (0 – 1)
Format (0 – 1)
GRPO Llama-3.1-8B-Instruct
2.754
3.366
2.688
0.960
1.000
GDPO Llama-3.1-8B-Instruct
2.953
3.453
2.791
0.988
1.000
GRPO Qwen3.5-9B
2.606
1.453
2.298
0.439
1.000
GDPO Qwen3.5-9B
2.725
2.033
2.399
0.664
1.000
GRPO GLM-4-9B-0414
2.728
2.967
2.444
0.972
1.000
GDPO GLM-4-9B-0414
2.629
2.854
2.455
0.953
1.000
Table 2: Mean@3 performance on each reward axis. Information, treatment, and reasoning are scored from 0–5; completeness and format are scored from 0–1. Best results are shown in bold and second-best results are underlined .
Figure 2: Learning dynamics of GRPO and GDPO with Llama-3.1-8B-Instruct. Dark curves show a 15-step moving average and faint curves show the unsmoothed training trajectory. Each curve corresponds to a single training run.
Policy
n
Scalar Reward
Information (0 – 5)
Regimen (0 – 5)
Reasoning (0 – 5)
Complete (0 – 1)
Queries per case
Oncologists
34
0.573
3.000
2.912
2.676
1.000
9.412
GRPO Llama
34
0.537
2.647
3.206
2.608
0.931
4.598
GDPO Llama
34
0.600
2.931
3.382
2.804
0.980
11.275
GPT-5.2
34
0.544
2.971
2.951
3.000
0.873
37.824
Table 3: Comparison between oncologists and language-model policies in the same interactive treatment-planning environment. Four oncologists each evaluated 6 to 10 unique cases from the held-out test set, for a total of 34 clinician trajectories. Agent results are evaluated on the same 34 cases under the same five-turn interaction protocol and averaged over three generations per case. Information, treatment, and reasoning rewards are scored from 0–5; completeness is scored from 0–1.
Appendix figures & tables9 assets
Supplementary material from the paper’s appendix.
Appendix
Figure 3: Illustrative example of trajectories from the clinical agent given a patient case. The clinical agent interacts the patient environment in order to retrieve relevant information necessary for selecting the treatment. In the process, they will describe the reasoning behind the retrieval certain information, and the inference on the retrieved information.
Figure 4: Learning dynamics of GRPO and GDPO with Llama-3.1-8B-Instruct. We report the total scalar reward and the average number of queries issued by the policy. Dark curves show a 15-step moving average and faint curves show the corresponding unsmoothed training trajectory. Each curve corresponds to a single training run.
Information (0 – 5)
Regimen (0 – 5)
Reasoning (0 – 5)
Complete (0 – 1)
Format (0 – 1)
GRPO Llama-3.1-8B-Instruct
Mean@3
2.754
3.366
2.688
0.960
1.000
Best@3
3.000
3.789
2.944
1.000
1.000
GDPO Llama-3.1-8B-Instruct
Mean@3
2.953
3.453
2.791
0.988
1.000
Best@3
3.176
3.845
3.077
1.000
1.000
GRPO Qwen3.5-9B
Mean@3
2.606
1.453
2.298
0.439
1.000
Best@3
3.007
2.796
2.768
0.824
1.000
Appendix
Table 4: Performance on each reward axis. Information, treatment, and reasoning are scored from 0–5; completeness and format are scored from 0–1. Best results are shown in bold and second-best results are underlined .
Figure 5: GRPO and GDPO training dynamics on Qwen3.5-9B policy backbone. Dark curves show a 15-step moving average and faint curves show the corresponding unsmoothed training trajectory. Each curve corresponds to a single training run.
Figure 6: GRPO and GDPO training dynamics on GLM-4-9B-0414 policy backbone. Dark curves show a 15-step moving average and faint curves show the corresponding unsmoothed training trajectory. Each curve corresponds to a single training run.
Policy
Queries/case
Unique fields
Information Reward
Llama-3.1-8B (Base)
8.98[8.42,9.57]
6.21
2.12
GRPO-Llama
4.33[4.17,4.51]
4.12
2.75
GDPO-Llama
11.20[10.84,11.57]
8.86
2.95
Qwen (Base)
7.26[6.87,7.65]
5.20
2.41
GRPO-Qwen
6.96[6.66,7.25]
5.18
2.61
GDPO-Qwen
7.96[7.57,8.35]
5.73
2.73
Appendix
Table 5: Patient-level changes in information-gathering behavior on the held-out test set. Values report the mean paired difference between each RL-trained policy based on Llama-3.1-8B-Instruct and the reference policy, with 95% bootstrap confidence intervals.
Figure 7: Policy performance across primary-oncologist subgroups. (a) Per-patient reward distributions for each policy. (b) Per-patient reward difference between the specialized GDPO policy and GPT-5.2. Positive values indicate higher reward for GDPO.
Provider
Policy
n
Mean Δ
95% CI
Median Δ
Holm p
A
GRPO Llama
47
0.071
[0.009, 0.137]
0.044
0.109
GDPO Llama
47
0.100
[0.036, 0.169]
0.067
0.018
Llama base
47
-0.165
[-0.239, -0.087]
-0.200
7.6×10−4
Qwen base
47
-0.544
[-0.619, -0.463]
-0.556
1.6×10−8
B
GRPO Llama
33
0.032
[-0.055, 0.124]
0.000
0.674
GDPO Llama
33
0.063
[-0.015, 0.149]
0.044
0.396
Appendix
Table 6: Paired comparisons of policy reward against GPT-5.2 within physician-associated patient subgroups. Differences are computed per patient using Mean@3 scalar reward. Confidence intervals are 95% bootstrap confidence intervals for the mean paired difference. p -values are from paired Wilcoxon signed-rank tests with Holm correction within each provider subgroup.
Policy
Provider A
Provider B
Provider C
H
p
GRPO Llama
0.599
0.519
0.604
5.400
0.067
GDPO Llama
0.627
0.550
0.644
8.585
0.014
GPT-5.2
0.528
0.487
0.549
1.784
0.410
Llama base
0.363
0.329
0.311
1.426
0.490
Qwen base
-0.017
-0.032
0.002
0.248
0.883
Appendix
Table 7: Per-patient Mean@3 scalar reward across physician-associated patient subgroups. Kruskal–Wallis comparisons are descriptive because provider subgroups may differ in patient case mix.
Inpatient clinical reasoning is a sequential decision under partial observability: the clinician sees the admission so far and must choose the next action whose downstream consequences are not yet visible. Existing clinical-LLM evaluations and RL rewards signals collapse this into closed-form retrieval, clinical journey leakage, or unanchored LLM-as-judge scoring. We introduce CLR-voyance, a framework that reformulates inpatient reasoning as a Partially Observable Markov Decision Process (POMDP) and supervises it with rewards that are simultaneously outcome-grounded and clinician-validated. We instantiate the formulation as CLR-POMDP, which partitions successful patient journeys into a policy-visible past and an oracle-only future. Using the past information, an oracle LLM generates a case-specific query-answer pair, and the first adaptive rubric for clinical reasoning which is verifiable in the future of the patient journey. These rubrics are used for both post-training and evaluation of models for inpatient clinical reasoning. We post-train Qwen3-8B and MedGemma-4B with GRPO followed by model merging, yielding state-of-the-art inpatient clinical reasoning while retaining generalist capabilities. CLR-voyance-8B achieves 84.91% on CLR-POMDP, ahead of frontier medical reasoning models like GPT-5 (77.83%) and MedGemma-27B (66.66%) and has comparable or better performance on existing medical benchmarks. To ensure a clinically meaningful setting, we conduct a large-scale clinician alignment study, where physicians curate per-case rubrics, grade candidate responses, and provide blinded pairwise preferences of model reasoning. This study provides insights on clinical LLM-as-a-judge and clinical preference-model selection, which can inform the community at large. CLR-voyance has been deployed for 6+ months at a partner public hospital, drafting thousands of reasoning-heavy inpatient notes.
Aishik Nagar, Arun-Kumar Kaliya-Perumal, Yu-Hsuan Han +5
ASUS Intelligent Cloud Services (AICS) · Rehabilitation Research Institute of Singapore, Nanyang Technological University · Department of Family Medicine,2026 Taipei Veterans General Hospital +2
Clinical development is sequential decision-making under uncertainty, where a sponsor must plan a portfolio of experiments from heterogeneous evidence. We study this setting by framing oncology clinical development as an offline decision-making problem in which an agent predicts the next six-month trial portfolio of an oncology drug program from information available at the decision date. To support this, we construct a temporal dataset that combines 31.7k heterogeneous public data records, including trial registries, regulatory reviews, sponsor filings, utilization data, and epidemiology, into 881 offline decision episodes across 45 historical programs. We compare four offline objectives: behavioral cloning, reward-weighted behavioral cloning, learned-reward training, and value-based implicit Q-learning against four frontier LLM agents that share a common date-gated retrieval scaffold across held-out drug, sponsor, drug-class, and temporal splits. Models trained offline outperform the non-fine-tuned baselines, particularly in the post-August 2025 contamination-clean holdout. Reward-weighted behavioral cloning performs the best, obtaining 46.2% indication F1 and 14.2% strict F1 against 25.0% and 2.1%, respectively, for the best-performing tool agent on each metric. These results suggest that structured offline learning can teach agents to plan clinical experiments.
William Bolton, Philip Torr
Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Recent reasoning-centric Large Language Models (LLMs) have made significant strides, yet they predominantly operate on a passive-inference pattern that assumes complete information. In contrast, real-world clinical intelligence is inherently an iterative investigative process requiring strategic evidence acquisition. To bridge this gap, we formalize medical diagnosis as an Iterative Evidence-Seeking Task. We leverage Reinforcement Learning with Verifiable Rewards (RLVR) to elicit intrinsic reasoning within a closed-loop environment, guided by a novel suite of rewards that enforce diagnostic precision and examination consistency. To facilitate this, we introduce the Retrieval-Augmented Generation-based Examination Simulator (RAGES), a high-fidelity clinical oracle that provides realistic, knowledge-grounded follow-up evidence. Empirical results across diverse datasets demonstrate that our framework enables LLMs to transition from passive responders to autonomous assistants. Notably, our model demonstrates comparable performance to larger and reasoning-enhanced baselines, while RAGES proves superior to vanilla LLMs in generating biologically plausible clinical feedback.
Shengyi Hua, Kangzhe Hu, Conghui He +2
Qing Yuan Research Institute, Shanghai Jiao Tong University · Shanghai AI Laboratoty · Shanghai Innovation Institute