The impact of body mass index (BMI) on treatment outcome of targeted therapy in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Cancer Database Consortium.
Bibliographic record
Abstract
4576 Background: Obesity increases risk for RCC, yet recent report suggest that tumors developing in an obesogenic environment may be more indolent. We investigated the effect of BMI on treatment outcome in patients (pts) treated with targeted therapy (TT) for mRCC. Methods: Baseline characteristics and outcomes on 1975 pts from 19 centers of the IMDC were analyzed to study the impact of BMI on survival and treatment outcome of first and second line TT. Toxicity profile in relation to BMI was also assessed. Results: Median follow-up was 21.1 months. Median time to treatment failure on first-line TT was 7.2 months and median overall survival (mOS) was 21.5 months [95%CI: 20.1-23.3]. At therapy initiation, 785(40%) pts were considered underweight or normal weight (BMI<25 kg/m2), 663(33.5%) overweight (BMI 25-<30 kg/m2) and 527 (26.5%) obese (BMI≥30 kg/m2). Overweight/obese pts had a longer mOS (25.6 vs. 17.1 months) than underweight/normal weight pts (p<0.0001). After adjusting for the IMDC prognostic risk factors, the mOS difference persisted in favor of the overweight/obese pts group (HR=0.84, (95%CI: 0.73-0.95), p=0.008). In addition, pts with higher BMI indices (overweight/obese) had improved time on therapy in both first-line (8.1 vs. 5.7 months, p<0.0001) and second-line (4.2 vs. 3.0 months, p=0.0006), and the difference remained after adjustment for the IMDC prognostic risk factors (p<0.01). Estimates of the cumulative incidence of treatment failure because of toxicity did not differ between the underweight/normal and overweight/obese groups (p=0.936), but the cumulative incidence of treatment failure because of progression/death favored the overweight/obese group after adjustment for the IMDC risk groups (p<0.002). Conclusions: We found that being overweight or obese is independently associated with an improved outcome in mRCC pts treated with TT. Increased toxicity was ruled out as a potential bias for treatment discontinuation or dose reduction in normal/underweight pts. Biological investigation in tissues collected from the IMDC cohort is in process to better characterize the obesity paradox in mRCC.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".