Dissociation Between Tumor Response and PTTM Progression During Entrectinib Therapy in NTRK Fusion-Positive Colon Cancer
Bibliographic record
Abstract
We report a rare case of pulmonary tumor thrombotic microangiopathy (PTTM) in a patient with metastatic neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive transverse colon cancer who exhibited a marked radiologic and biochemical response to entrectinib. Despite significant tumor shrinkage, progressive dyspnea and hypoxemia developed approximately four weeks after therapy initiation. Chest CT revealed diffuse interstitial infiltrates, initially interpreted as drug-induced pneumonitis or infection. Entrectinib was discontinued, but respiratory failure progressed, and the patient died shortly thereafter. Autopsy revealed widespread pulmonary microangiopathy with fibrocellular intimal proliferation and tumor emboli in small pulmonary arteries, consistent with PTTM. Notably, no hematogenous metastases were identified; instead, tumor spread appeared to occur via an atypical lymphatic route through the thoracic duct. The tumor exhibited microsatellite stability and a modest mutation burden, suggesting that lymphatic dissemination and microvascular pathology may progress independently of these genomic features. This case underscores a critical dissociation between oncologic response and vascular complications, indicating that tropomyosin receptor kinase (TRK) inhibitor monotherapy may be insufficient to prevent PTTM. Comprehensive management may require concurrent strategies targeting the pulmonary microvasculature, including antiangiogenic therapy and modulation of cytokine and growth factor signaling.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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".