Selective utilization of circulating tumor DNA testing enables disease monitoring in endometrial and ovarian carcinomas
Bibliographic record
Abstract
OBJECTIVE: Biomarkers reflecting real-time response to therapy and recurrence are lacking. We assessed the clinical value of detecting cell-free circulating tumor DNA (ctDNA) mutations in endometrial cancer (EC) and ovarian cancer (OC) patients. METHODS: EC/OC patients undergoing primary surgery were consented for tissue banking and 2-year serial blood draws. Tumor tissue DNA and plasma ctDNA underwent next generation sequencing using a targeted gene panel for somatic mutations. RESULTS: Of 44 patients (24 EC, 17 OC, 2 synchronous endometrial and ovarian carcinomas [SEOC] and 1 endocervical adenocarcinoma [EA]) at least one somatic mutation was identified in tumor tissue in 40 (91%, 20/24 EC, all OC/SEOC/EA), and in preoperative plasma ctDNA in 12 (27%) patients (6/24 [25%] EC and 6/17 [35%] OC). Detection of preoperative ctDNA mutations was associated with advanced stage, higher preoperative CA125, and subsequent disease recurrence. In 5/12 (42%) patients with preoperative ctDNA mutations, examination/imaging suggested clinical stage I however final pathology revealed stage II/III. In 11 patients where serial timepoints were assessed during treatment for ctDNA and CA125, ctDNA clearance preceded normalization of CA125. Thirteen patients developed recurrent disease (4 EC, 8 OC, 1 EA); 8 in whom ctDNA mutations were detected postoperatively, and 4 followed through time of recurrence with ctDNA mutations identified 2-5 months prior to clinical/radiologic/biomarker progression in 3. CONCLUSION: ctDNA can reflect larger tumor volume/metastases, treatment response and subsequent disease recurrence in EC and OC. Careful patient selection is critical to direct resources to patients most likely to benefit, considering disease burden and risk group.
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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 | 0.005 |
| 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".