Tumor Bud Classification in Colorectal Cancer Using Attention-Based Deep Multiple Instance Learning and...

Identifying tumor budding (TB) in colorectal cancer (CRC) is vital for better prognostic assessment as it may signify the initial stage of metastasis. Despite its importance, TB detection remains challenging due to subjectivity in manual evaluations. Identifying TBs remains difficult, especially at high magnification levels, leading to inconsistencies in prognosis. To address these issues, we propose an automated system for TB classification using deep learning.

We trained a deep learning model to identify TBs through weakly supervised learning by aggregating positive and negative bags from the tumor invasive front. We assessed various foundation models for feature extraction and compared their performance. Attention heatmaps generated by attention-based multi-instance learning (ABMIL) were analyzed to verify alignment with TBs, providing insights into the interpretability of the features. The dataset includes 29 WSIs for training and 70 whole slide images (WSIs) for the hold-out test set.

In six-fold cross-validation, Phikon-v2 achieved the highest average AUC (0.984 ± 0.003), precision (0.876 ± 0.004), and recall (0.947 ± 0.009). Phikon-v2 again achieved the highest AUC (0.979) and precision (0.980) on the external hold-out test set. Moreover, its recall rate (0.910) was still higher than that of UNI's (0.879). UNI exhibited a balanced performance on the hold-out test set, with an AUC of 0.960 and a precision of 0.968. CtransPath showed strong precision on the external hold-out test set (0.947) but had a slightly lower recall (0.911).

The proposed technique enhances the accuracy of TB assessment, offering potential applications for CRC and other cancer types.