Extensive small cell lung cancer (SCLC) chemotherapy: A population kinetics assessment.
Bibliographic record
Abstract
e21101 Background: Most progression-free (PFS) and overall survival (OS) curves fit exponential decay models on nonlinear regression analysis (NLRA). Log-linear curve shape varies with tumor & therapy type: straight line vs inflection to right (2 phase decay due to 2 distinct subpopulations with differing sensitivities) vs convex (downward inflection, eg due to stopping therapy that is slowing tumor growth). 1 We compared SCLC to other cancers. Methods: As previously described, 1 we did NLRA of published PFS & OS curves for etoposide-platinum in SCLC. We also assessed various therapies in other cancers. We calculated PFS & OS half-lives and classified curves by log-linear shape. Results: Of 18 evaluable SCLC PFS curves, 14 (78%) were highly convex & 18 (100%) were moderately or highly convex, compared to 35/888 (4%) highly convex & 186 (21%) moderately or high convex curves for other cancers (p < 0.0001). Of 24 evaluable SCLC OS curves, 12 (50%) were highly convex & 24 (100%) were moderately or highly convex, compared to 15/363 (4%) being highly convex & 87 (24%) moderately or highly convex for other cancers (p < 0.0001). In SCLC, 6 vs 4 cycles induction therapy minimally changed PFS half-life (median across studies 5.5 vs 5.2 months, p = 0.27) or OS half-life (9.5 vs 10.4 months, p = 0.06). PFS half-life correlated with OS half-life for other cancers (n 320, Spearman r 0.81, p < 0.0001) but not for SCLC (n 18, r 0.04, p = 0.86). Post progression survival (PPS) correlated positively with PFS half-life for other cancers (n 376, r 0.68, p < 0.0001) but correlated negatively for SCLC (n 18, r -0.43, p = 0.07). SCLC PFS curves had an initial downward inflection at a median of 2.9 months (where 87% of patients are still progression-free), followed by a 2nd inflection point at 4.5 months (where 71% are still progression-free). Median PFS half-life was 14.6 months prior to the 1st inflection point vs 1.9 months after the 2nd inflection point. Our analysis methods 1 suggest that after the 2 nd PFS inflection point, 23% of patients would progress by the next scan if scans are done every 3 weeks, while 40% would progress by the next scan if they are done every 6 weeks. Conclusions: PFS & OS curves for SCLC are more often highly convex than for other cancers since SCLC is sensitive to chemotherapy but progresses rapidly after induction therapy is completed. Giving 6 rather than 4 induction cycles makes no OS difference. New maintenance strategies are needed. Very short PFS half-lives post induction suggest that frequent follow up scans should be done for patients who are candidates for 2 nd line therapy. 1. Stewart. Cancer Med 2019; 8:6871
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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".