Metformin with neoadjuvant chemoradiation to improve pathologic response in rectal cancer: A pilot phase I/II trial
Bibliographic record
Abstract
Abstract Background: Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for stage II or III rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. We asked if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. A single-institutional pilot study was performed to build a confidence interval for the pCR rate and to determine the sample size for a phase 2 trial.Methods: Non-diabetic patients with biopsy confirmed adenocarcinoma of the rectum, and deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions. Capecitabine (825 mg/m2 twice daily, Monday-Friday) was self-administered during the 28 days of radiation only. The primary outcome was pCR. The study was designed to accrue 15 participants to construct a confidence interval (CI) for the pCR rate. Results: A total of 16 patients were accrued from January 2017 to May 2018. One patient withdrew from the study prior to CRT. Only grade 1 or 2 adverse events were observed from the intervention. Three patients had a clinical complete response (cCR) and did not have surgical resection. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19-47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. Conclusions: Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates. Trial registration: NCT03053544. Registered December 20, 2016, https://clinicaltrials.gov/ct2/show/record/NCT03053544
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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) | 0.003 | 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 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".