Phase I trial of sorafenib in high-risk hepatocellular carcinoma (HCC) patients after liver transplantation.
Bibliographic record
Abstract
280 Background: LT offers long-term survival for HCC patients within the Milan criteria. For those outside, rates of recurrence are higher. There are no known treatments which decrease risk of recurrence post-transplant. We began a multicenter Phase I study of sorafenib in high-risk HCC patients after LT. Methods: Eligible subjects had pathologically proven HCC that was either (1) outside Milan (pre- or post-transplant), (2) poorly differentiated (Edmondson and Steiner grade 4), or (3) had vascular invasion at explant. We used a standard phase I dose-escalation design, beginning drug between 4 and 16 weeks after LT, with a planned duration of treatment of 6 months. Cohort dosages are as follows: (1) 200 mg q day (6 enrolled), (2) 200 mg BID (3 enrolled), (3) 200 mg/400 mg (3 enrolled), and (4) 400 mg BID. Correlative studies include circulating endothelial cells (CECs) and plasma biomarkers which are being collected prior to treatment, at 1 month, and at recurrence. Results: We have enrolled 12 patients, 11 are reported here. Mean age is 62; 64% had underlying HCV, 27% HBV, and 9% ETOH. 45% were outside Milan based on preoperative imaging. On explant, 36% had high grade pathology, and 18% had vascular invasion. Grade 3-4 toxicities seen in >10% include: cytopenias (27% neutropenia), LFT abnormalities (T. bili 18%), HTN (18%), and diarrhea (18%). We are currently enrolling at the 3rd dose level. We had 1 episode acute rejection at the 3rd dose level. CEC data are available for 8 patients, with a baseline range from 15-91, and 1 month range from 2-254. Mean follow up time is 18.0 months. 3 patients have recurred, one who was on drug for < 1 month. Conclusions: To our knowledge, this is the only ongoing multicenter Phase I trial of sorafenib in the post-transplant setting in the US. Post-transplant sorafenib for high-risk patients is feasible, and toxicity has been manageable for the most part. DLT has not yet been defined. Clinical trial information: NCT00997022.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".