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The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms' performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models' performance. We found that the annotators' object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure., (© 2024. The Author(s).)

Introduction: Multidisciplinary tumor boards are meetings where a team of medical specialists, including medical oncologists, radiation oncologists, radiologists, surgeons, and pathologists, collaborate to determine the best treatment plan for cancer patients. While decision-making in this context is logistically and cost-intensive, it has a significant positive effect on overall cancer survival. METHODS : We evaluated the quality and accuracy of predictions by several large language models for recommending procedures by a Head and Neck Oncology tumor board, which we adapted for the task using parameter-efficient fine-tuning or in-context learning. Records were divided into two sets: n=229 used for training and n=100 records for validation of our approaches. Randomized, blinded, manual human expert classification was used to evaluate the different models. RESULTS : Treatment line congruence varied depending on the model, reaching up to 86%, with medically justifiable recommendations up to 98%. Parameter-efficient fine-tuning yielded better outcomes than in-context learning, and larger/commercial models tend to perform better., Conclusion: Providing precise, medically justifiable procedural recommendations for complex oncology patients is feasible. Extending the data corpus to a larger patient cohort and incorporating the latest guidelines, assuming the model can handle sufficient context length, could result in more factual and guideline-aligned responses and is anticipated to enhance model performance. We, therefore, encourage further research in this direction to improve the efficacy and reliability of large language models as support in medical decision-making processes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)