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Sökning: WFRF:(Gatto Francesco 1987) > (2023) > Plasma and Urine Fr...

Plasma and Urine Free Glycosaminoglycans as Monitoring and Predictive Biomarkers in Metastatic Renal Cell Carcinoma: A Prospective Cohort Study

Gatto, Francesco, 1987 (författare)
Karolinska Institutet
Bratulic, Sinisa, 1981 (författare)
Chalmers tekniska högskola,Chalmers University of Technology
Jonasch, Eric (författare)
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Limeta, Angelo, 1996 (författare)
Chalmers tekniska högskola,Chalmers University of Technology
Maccari, F. (författare)
Universita Degli Studi Di Modena E Reggio Emilia,University of Modena and Reggio Emilia
Galeotti, Fabio (författare)
Universita Degli Studi Di Modena E Reggio Emilia,University of Modena and Reggio Emilia
Volpi, Nicola (författare)
Universita Degli Studi Di Modena E Reggio Emilia,University of Modena and Reggio Emilia
Lundstam, Sven, 1944 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för urologi,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Urology,Institute of Clinical Sciences, Department of Oncology
Nielsen, Jens B, 1962 (författare)
Chalmers tekniska högskola,Chalmers University of Technology
Stierner, Ulrika, 1952 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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 (creator_code:org_t)
2023
2023
Engelska.
Ingår i: JCO PRECISION ONCOLOGY. - 2473-4284. ; 7
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • PURPOSENo liquid biomarkers are approved in metastatic renal cell carcinoma (mRCC) despite the need to predict and monitor response noninvasively to tailor treatment choices. Urine and plasma free glycosaminoglycan profiles (GAGomes) are promising metabolic biomarkers in mRCC. The objective of this study was to explore if GAGomes could predict and monitor response in mRCC.PATIENTS AND METHODSWe enrolled a single-center prospective cohort of patients with mRCC elected for first-line therapy (ClinicalTrials.gov identifier: NCT02732665) plus three retrospective cohorts (ClinicalTrials.gov identifiers: NCT00715442 and NCT00126594) for external validation. Response was dichotomized as progressive disease (PD) versus non-PD every 8-12 weeks. GAGomes were measured at treatment start, after 6-8 weeks, and every third month in a blinded laboratory. We correlated GAGomes with response and developed scores to classify PD versus non-PD, which were used to predict response at treatment start or after 6-8 weeks.RESULTSFifty patients with mRCC were prospectively included, and all received tyrosine kinase inhibitors (TKIs). PD correlated with alterations in 40% of GAGome features. We developed plasma, urine, and combined glycosaminoglycan progression scores that monitored PD at each response evaluation visit with the area under the receiving operating characteristic curve (AUC) of 0.93, 0.97, and 0.98, respectively. For internal validation, the scores predicted PD at treatment start with the AUC of 0.66, 0.68, and 0.74 and after 6-8 weeks with the AUC of 0.76, 0.66, and 0.75. For external validation, 70 patients with mRCC were retrospectively included and all received TKI-containing regimens. The plasma score predicted PD at treatment start with the AUC of 0.90 and at 6-8 weeks with the AUC of 0.89. The pooled sensitivity and specificity were 58% and 79% at treatment start. Limitations include the exploratory study design.CONCLUSIONGAGomes changed in association with mRCC response to TKIs and may provide biologic insights into mRCC mechanisms of response.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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