Circulating tumor cell counts is a better predictor of overall survival than dynamic tumor size changes – a quantitative modeling framework

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Fältnamn	Indikatorer	Metadata
000		03678naa a2200325 4500
001		oai:DiVA.org:uu-390191
003		SwePub
008		190808\| \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3901912 URI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a vet2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Netterberg, Ida,d 1988-u Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University,Pharmacometrics4 aut0 (Swepub:uu)idane961
245	1 0	a Circulating tumor cell counts is a better predictor of overall survival than dynamic tumor size changes – a quantitative modeling framework
338		a print2 rdacarrier
520		a Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We here present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS.Experimental design: A pharmacometric approach (i.e., population pharmacodynamic modeling) was used to characterize the changes in tumor size and CTC count and evaluate them as predictors of OS in 451 patients with mCRC treated with chemotherapy and targeted therapy in a prospectively randomized phase 3 study (CAIRO2).Results: A tumor size model of tumor quiescence and drug-resistance, was used to characterize the tumor size time-course, and was, in addition to the total normalized dose (i.e., of all administered drugs) in a given cycle, related to the CTC counts through a negative binomial model (CTC model). A CTC count≥3/7.5 mL (hazard ratio=3.51, 95% confidence interval: 2.85-4.32), as described by the CTC model, was a better predictor of OS than tumor size changes. The modeling framework was applied to explore if dose-modifications (increased and reduced) would result in a CTC count below 3/7.5 mL after 1-2 weeks of treatment.Conclusions: Time-varying CTC counts can be useful for early predicting OS in patients with mCRC, and may therefore have potential for model-based treatment individualization. Although tumor size had a strong connection to CTC, its link to OS was weaker.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
653		a Farmakokinetik och läkemedelsterapi
653		a Pharmacokinetics and Drug Therapy
700	1	a Karlsson, Mats Ou Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics4 aut
700	1	a Terstappen, Leon WMMu Department of Medical Cell BioPhysics, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands4 aut
700	1	a Koopman, Miriamu Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands4 aut
700	1	a Punt, Cornelis JAu Department of Medical Oncology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands4 aut
700	1	a Friberg, Lena Eu Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics4 aut
710	2	a Uppsala universitetb Institutionen för farmaceutisk biovetenskap4 org
773	0	t Clinical Cancer Researchx 1078-0432x 1557-3265
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-390191

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Av författaren/redakt...: Netterberg, Ida, ...; Karlsson, Mats O; Terstappen, Leon ...; Koopman, Miriam; Punt, Cornelis J ...; Friberg, Lena E

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