Plasma protein biomarkers associated with venous thromboembolism (VTE) and mortality in patients with cancer: A substudy of the avert trial
Notice bibliographique
Résumé
Abstract Background Cancer is associated with a substantially elevated risk of venous thromboembolism (VTE), but this risk varies considerably between individuals depending on several clinical and laboratory variables. Biomarkers predictive of VTE are needed to better stratify risk. We had previously identified candidate biomarkers predictive of cancer-associated VTE in a substudy of CASSINI, a randomized trial of thromboprophylaxis in people with cancer with Khorana score (KS) of > 2. In this study, we evaluated these biomarkers for prediction of VTE or death in plasma specimens derived from patients enrolled in AVERT, a similarly designed trial of thromboprophylaxis. Methods We used available baseline plasma samples from 498 of 574 individuals enrolled in AVERT, a prospective randomized trial of apixaban prophylaxis in cancer with KS > 2. Levels of 9 proteins - C-reactive protein (CRP), chemokine ligand 13 (CCL13/MCP-4), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), human growth hormone (hGH), high sensitivity troponin T (hsTnT), C X C motif chemokine 12 (CXCL12/SDF-1), interleukin 1 receptor (IL1R1), thyroid stimulating hormone (TSH), and growth differentiation factor 15 (GDF-15) – were assessed for association with VTE, death, and VTE or death outcomes. Protein concentrations were log₂ transformed and analyzed using cause specific multivariate Cox proportional hazards models adjusted for age, sex, study arm, and Khorana VTE risk score with baseline hazards dependent on cancer type. Results The study population comprised 498 patients, evenly split between apixaban and placebo arms. Median age at enrollment was 68 years; 58% were female and 93% were White. The most common cancers were gynecologic (26.7%), lymphoma (25.7%), pancreas (12.4%), lung (9.8%), and gastric (7.8%). Baseline KS was 2 for the majority of patients (N = 325, 65.3%). Of the full cohort, 41 (8.2%) experienced VTE and 60 (12%) died. In multivariable analysis for VTE, only hsTnT was significantly associated with VTE (p = 0.011); TSH was non-significantly associated (p = 0.09). Patients who developed VTE had higher median hsTnT (11.2 pg/mL) and TSH (1.67 mIU/L) compared to those without VTE (6.9 pg/mL and 1.25 mIU/L, respectively). In multivariate analysis for mortality, elevated CRP (p = 1.1×10⁻⁵), GDF-15 (p = 0.00071), CCL13 (p = 0.0079), and NT-proBNP (p = 0.0099) were strongly associated with increased mortality. Median levels among those who died versus those who survived were: CRP (16.7 vs. 6.2 mg/L), GDF-15 (2645 vs. 1576 pg/mL), CCL13 (28.4 vs. 21.5 pg/mL), and NT-proBNP (251 vs. 102 pg/mL). For the composite outcome of VTE or death, CRP (p = 0.000011), GDF-15 (p = 0.0014), and hGH (p = 0.038) were the most significantly associated. Patients who experienced VTE or death had higher median levels compared to those without events: CRP (16.1 vs. 5.8 mg/L), GDF-15 (2413 vs. 1435 pg/mL), NT-proBNP (228 vs. 93 pg/mL), CCL13 (27.4 vs. 20.5 pg/mL), and hGH (0.51 vs. 0.38 ng/mL).Conclusions: Of previously identified candidate biomarkers, only hsTnT was significantly associated with VTE in this analysis of already-high-risk individuals (minimum KS of 2), with higher median levels observed in those who developed VTE. Elevated levels of CRP, GDF-15, NT-proBNP, and CCL13/MCP-4 were significantly associated with increased risk of mortality and the composite outcome of VTE or death, with affected patients showing notably higher median concentrations. These biomarkers need further study for their potential role in identifying individuals at risk for worse outcomes, and to inform personalized strategies for thromboprophylaxis and prognosis in oncology.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».