Whole brain radiation therapy (WBRT) with or without oral topotecan (TPT) in patients (pts) with non-small cell lung cancer (NSCLC) with brain metastases: Final analysis of an open-label phase III study.
Bibliographic record
Abstract
2031 Background: Brain metastases from NSCLC occur in ~ 20% of pts and if untreated are associated with a 1 to 2 month overall survival (OS). Pre-clinical studies show that TPT added to radiation results in a radiotherapy enhancement ratio of 1.4 to 1.6. This trial was designed to test the effect of TPT co-administered with WBRT on OS. Methods: Pts with NSCLC and at least one measurable brain lesion were eligible. 472 pts were randomized to WBRT (3 Gy/day x 10 days) or WBRT and TPT 1.1 mg/m2/day for 10 days. Stratification factors: number of brain metastases and recursive partitioning analysis (RPA) class. Two weeks following WBRT, systemic anti-cancer therapy could be restarted at the treating physician’s discretion. Results: 468 pts were in the modified ITT population; 235 pts (WBRT + TPT) and 233 pts (WBRT+ best supportive care [BSC]). Of the 235 pts administered WBRT + TPT, 91 also received TPT after WBRT. The treatment arms were balanced for gender, age and smoking history. Median daily TPT dose was 2.25 mg. The median OS in the TPT arm was not better than in the BSC alone arm; 4.0 months (95%CI 3.4,4.8) vs.3.6 months (95%CI 3.0, 4.0), respectively; HR 0.88 (0.73, 1.07), P=0.1862. In the ITT population analysis by stratification variables, RPA class (I vs. II/III) was significantly different (HR 0.59) whereas baseline brain lesions (1 vs >1) were not (HR 0.97). Complete response and overall response rates in the WBRT+ TPT were 10% and 27%, and with BSC 5% and 26%, respectively. There were no differences in time to response or neurologic signs and symptoms. All adverse events (AEs) were more frequent in the TPT arm (87% vs. 64%) as were AEs related to study treatment (57% vs. 21%), serious AEs (41% vs. 18%) and fatal AEs (5% vs. 0%). The AEs more frequently seen in the TPT arm were typical for TPT (hematologic toxicity, febrile neutropenia and diarrhea). Conclusions: The study did not achieve its primary objective. There was no difference in OS achieved by the addition of TPT to WBRT. AEs were more common in the TPT arm. Clinical trial information: NCT00390806.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| 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 | 0.001 |
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".