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Impact of statins and survival outcomes in patients with metastatic renal cell carcinoma.

2015· article· en· W2258915230 on OpenAlexaff
Rana R. McKay, Xun Lin, Laurence Albigès, André P. Fay, Marina D. Kaymakcalan, Suzanne S Mickey, P. Peter Ghoroghchian, Rupal S. Bhatt, Ronit Simantov, Toni K. Choueiri, Daniel Yick Chin Heng

Bibliographic record

VenueJournal of Clinical Oncology · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMedicineTemsirolimusInternal medicineRenal cell carcinomaHazard ratioSunitinibOncologyBevacizumabProportional hazards modelSorafenibStatinProgression-free survivalHepatocellular carcinomaOverall survivalChemotherapyConfidence intervalDiscovery and development of mTOR inhibitorsPI3K/AKT/mTOR pathwayApoptosis

Abstract

fetched live from OpenAlex

435 Background: A growing body of evidence has demonstrated the antineoplastic activity of statins. The objective of this study was to investigate the impact of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era. Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials. Statistical analyses were performed using Cox regression adjusted for age, sex, race, histology, prior therapy, body-mass index, and other known prognostic factors and the Kaplan-Meier method. Results: We identified 4,736 patients treated with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (n=457), temsirolimus + interferon-alpha (n=208), bevacizumab + temsirolimus (n=393), bevacizumab + interferon-alpha (n=391), or interferon-alpha (n=560), of whom 511 were statin users. Overall, statin users demonstrated a statistically significant improvement in overall survival (OS) but not progression-free survival (PFS) compared to non-users (OS: 25.6 versus 18.9 months; p=0.015; adjusted hazard ratio [aHR] 0.787; 95% CI, 0.648-0.955; PFS: 7.9 versus 6.9 months; p=0.823, aHR 1.018; 95% CI, 0.867-1.196). When stratified by therapy type, a benefit in OS was demonstrated in statin users compared to non-users in individuals receiving therapy targeting vascular endothelial growth factor (28.4 versus 22.2 months, p=0.023; aHR 0.749; 95% CI, 0.584-0.961) or mammalian target of rapamycin (18.6 versus 14.0; p=0.035; aHR 0.657; 95% CI, 0.445-0.972), but not in those receiving interferon-alpha (15.6 versus 14.8 months; p=0.410; aHR 1.292; 95% CI 0.703-2.275). Adverse events were similar between statin users and non-users. Conclusions: In the largest RCC analysis to date, we demonstrate that statin use improved survival outcomes in patients with mRCC treated in the targeted therapy era. Statins could represents a potential adjunct therapeutic option for patients with metastatic RCC; however, this hypothesis needs to be corroborated with preclinical work exploring the mechanisms underlying their anti-cancer effects and well-designed clinical trials investigating the clinical benefits of adding statins to modern therapies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.063
GPT teacher head0.412
Teacher spread0.350 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2015
Admission routes1
Has abstractyes

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