An updated meta-analysis of randomized controlled trials (RCTs) examining continuous (CS) versus intermittent strategies (IS) of delivering systemic treatment (Tx) for untreated metastatic colorectal cancer (mCRC).
Bibliographic record
Abstract
e14641 Background: The median life expectancy for unresectable mCRC is now 30 months. Traditionally, CS are used to treat mCRC; however, to reduce treatment-related toxicity, IS have been developed. Our previously published meta-analysis has now been updated with the results from the AIO KRK 07 study. Methods: A systematic review was conducted to identify RCTs comparing CS to IS. The results of identified trials were clinically homogenous, so the data were pooled using RevMan 5.3 software. Overall survival (OS) hazard ratios (HR) were extracted from the most recently presented trial results. Random effects models were used for all pooling. Results: Twelve RCTs are now identified (N=5,381), 9 with available HRs (N evaluable=5,025). In the experimental arm of these trials, the treatment given after induction included none (“chemotherapy free interval” (CFI), 5 trials, N=3,081), or a maintenance treatment: fluoropyrimidine (1 trial, N=620), or biologic (2 trials, N=852). The AIO KRK 07 trial (N=472) had two IS arms: 1 with a CFI and 1 with biologic maintenance. Results are summarized in the table. Sensitivity analyses demonstrated results were robust across induction and maintenance regimens. The sensitivity analysis of the trials with combination Tx induction and a CFI until progression (CAIRO3, OPTIMOX2, COIN, KRK 0207 n=2,706) is no longer statistically significant when the KRK 0207 data is included (HR=1.08, 95% CI 0.99-1.18, p=0.07). QOL (data from 4 trials) was either the same with both strategies (3 trials, n=1384) or improved in the IS arm (1 trial with CFI, n=1,630). Conclusions: IS of delivering systemic Tx for mCRC do not result in a significant reduction in OS compared to a CS of delivery whether or not maintenance therapy is included. QOL is the same or better with an IS. OS HR (95% CI) Test for Overall Effect, p Heterogeneity, Chi2 (df), p Tau2 (%) I2 (%) All Trials (N=9, 4869 pts) 1.03 (0.96-1.10) p=0.43 6.32 (8), p=0.61 0 0 All Trials with CFI (N=6, 3397 pts) 1.03 (0.95-1.12) p=0.46 5.41 (5), p=0.37 0 8 All Trials with Maintenance Tx (N=4, 1786 pts) 0.99 (0.88-1.11) p=0.84 0.94 (3), p=0.82 0 0
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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 | 0.040 | 0.108 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.017 | 0.053 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 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".