Reply to M.J. Rother
Bibliographic record
Abstract
It Just a Now-or-Never Result?TO THE EDITOR: I read with interest the updated analysis of the overall survival results according to tumor KRAS and BRAF mutational status from the CRYSTAL (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer) trial. 1 The study demonstrated a statistically significant and clinically meaningful increase of 3.5 months of life in patients with KRAS wild-type tumors treated with initial fluorouracil, leucovorin, and irinotecan (FOL-FIRI)/cetuximab.However, was this a function of the use of cetuximab in first-line therapy or simply a result of the use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies somewhere in the course of the disease?Earlier trials in metastatic colorectal cancer clearly demonstrated that the initial use of multiple drugs in combination was no better from a survival perspective than the sequential use of the same drugs.2,3 Also, the National Cancer Institute of Canada CO17 trial 4 revealed that single-agent cetuximab added 4.7 months of survival benefit in individuals with KRAS wild-type tumors when given after all standard chemotherapy failed.Because only approximately 30% of patients in the FOLFIRI control arm in the current trial ever received an anti-EGFR drug in the course of their illness, it is difficult to attribute the survival gain to the addition of cetuximab to first-line FOLFIRI chemotherapy.It is equally plausible that the survival benefit was simply a function of the fact that all patients in the experimental group had access to cetuximab, whereas this was not the case in the initial FOLFIRI group.It would be interesting to know whether a post hoc survival analysis of the 30% of the control arm who received cetuximab in later lines had been performed and how this group fared compared with the experimental arm.These types of analyses are flawed with multiple biases, but until the results from well-designed treatment-strategy trials that use all active agents are carried out in metastatic colorectal cancer, we will never truly understand how best to treat our patients.
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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 | 0.007 | 0.044 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.005 | 0.008 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.029 | 0.055 |
| Insufficient payload (model declined to judge) | 0.010 | 0.011 |
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".