Quantitative digital histopathology and machine learning to predict pathological complete response to chemotherapy in breast cancer patients using pre-treatment tumor biopsies
Bibliographic record
Abstract
Complete pathological response (pCR) to neoadjuvant chemotherapy (NAC) is a prognostic factor for breast cancer (BC) patients and is correlated with improved survival. However, pCR rates are variable to standard NAC, depending on BC subtype. This study investigates quantitative digital histopathology coupled with machine learning (ML) to predict NAC response a priori. Clinicopathologic data and digitized slides of BC core needle biopsies were collected from 149 patients treated with NAC. The nuclei within the tumor regions were segmented on the histology images of biopsy samples using a weighted U-Net model. Five pathomic feature subsets were extracted from segmented digitized samples, including the morphological, intensity-based, texture, graph-based and wavelet features. Seven ML experiments were conducted with different feature sets to develop a prediction model of therapy response using a gradient boosting machine with decision trees. The models were trained and optimized using a five-fold cross validation on the training data and evaluated using an unseen independent test set. The prediction model developed with the best clinical features (tumor size, tumor grade, age, and ER, PR, HER2 status) demonstrated an area under the ROC curve (AUC) of 0.73. Various pathomic feature subsets resulted in models with AUCs in the range of 0.67 and 0.87, with the best results associated with the graph-based and wavelet features. The selected features among all subsets of the pathomic and clinicopathologic features included four wavelet and three graph-based features and no clinical features. The predictive model developed with these features outperformed the other models, with an AUC of 0.90, a sensitivity of 85% and a specificity of 82% on the independent test set. The results demonstrated the potential of quantitative digital histopathology features integrated with ML methods in predicting BC response to NAC. This study is a step forward towards precision oncology for BC patients to potentially guide future therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".