Evidence map›Paper›PMID 40982295›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025

Patient-Derived Organoids Predict Treatment Response in Metastatic Colorectal Cancer.

Lidwien P Smabers, G Emerens Wensink, Carla S Verissimo, Mayke Doorn, Tao Yang, Timo Voskuilen, Maarten A Huismans, Liselot B J Valkenburg-van Iersel, Geert A Cirkel, Elske C Gootjes and 13 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Lidwien P SmabersDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0009-0007-9631-1012
G Emerens WensinkDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-4103-5811
Carla S VerissimoHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0009-0009-2254-0968
Mayke DoornHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0009-0002-2265-0672
Tao YangHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0009-0005-1162-0517
Timo VoskuilenHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0009-0000-4759-5177
Maarten A HuismansDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-1556-0820
Liselot B J Valkenburg-van IerselDepartment of Internal Medicine, Division of Medical Oncology, GROW, Maastricht University Medical Center, Maastricht, the Netherlands.ORCID 0000-0003-2925-9908
Geert A CirkelDepartment of Medical Oncology, Meander Medical Center, Amersfoort, the Netherlands.ORCID 0009-0007-8712-9825
Elske C GootjesDepartment of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0009-0000-9898-2767
Henk M W VerheulDepartment of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID 0000-0001-5981-922X
Frank J JeurissenDepartment of Internal Medicine, Haaglanden Medical Center, The Hague, the Netherlands.ORCID 0009-0005-3881-1065
Guus M BolDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-4021-3823
Hilde H NienhuisDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0009-0003-6016-7814
Manon N G J A BraatDepartment of Radiology, UMCU, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0001-6580-4331
Edwin CuppenDepartment of Molecular Cancer Research, Center for Molecular Medicine, UMCU, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-0400-9542
Robert G J VriesHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0009-0009-1408-1175
Frederieke H van der BaanDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-7421-6547
Sjoerd G EliasDepartment of Epidemiology, Julius Center for Health Sciences and Primary Care, UMCU, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-3903-4024
Onno KranenburgDivision of Imaging and Cancer, Laboratory of Translational Oncology, UMCU, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0002-2112-4390
Miriam KoopmanDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-1550-1978
Sylvia F BojHUB Organoids B.V., Utrecht, the Netherlands, Part of the Life Science Business of Merck KGaA, Darmstadt, Germany.ORCID 0000-0002-6910-1083
Jeanine M L RoodhartDepartment of Medical Oncology, University Medical Center Utrecht (UMCU), Utrecht University, Utrecht, the Netherlands.ORCID 0000-0003-1398-8970

Funding

Cancer Genomic CenterHartwig Medical FoundationHUB Organoids B.V.
6 · The paper itself

Abstract

purposeAccurately predicting treatment response in metastatic colorectal cancer (mCRC) is critical to avoid unnecessary toxicity and improve patient outcomes. Patient-derived organoids (PDO) are promising models, but larger prospective studies are needed to confirm their predictive value. EXPERIMENTAL

designPatients with mCRC underwent a metastatic biopsy for PDO establishment, before starting new systemic treatment. Predictors of PDO establishment were identified. PDOs were incubated with a seven-drug panel, including the patient's treatment, to determine drug sensitivity as measured by CyQUANT cell viability [area under the nonfitted "curve" of the raw viability or growth rate inhibition values (AUC and GRAUC) and concentration that gives half-maximal viability or GR inhibition (IC50 and GR50)]. Patient response was measured by size change of biopsied and all target lesions. The diagnostic performance was evaluated by positive predictive value, negative predictive value, and area under the ROC curve. Additionally, the association between PDO response and survival was assessed.

resultsA total of 232 patients were included, and 205 biopsies were obtained. PDO establishment success increased from 22% to 75%, yielding 52% overall. Male sex, increased lactate dehydrogenase, biopsy in academic hospitals, optimized culture conditions, and experience were related to PDO establishment success. In this interim analysis, focused on oxaliplatin-based doublet chemotherapy, 42 PDOs were screened. PDO drug sensitivity significantly correlated with the response of the biopsied lesion (R = 0.41-0.49, P < 0.011) and all target lesions (R = 0.54-0.60, P < 0.001) for all treatments combined. The 5-fluorouracil and oxaliplatin PDO screens demonstrated high predictive accuracy (positive predictive value: 0.78; negative predictive value: 0.80; area under the ROC curve: 0.78-0.88) and were associated with progression-free survival and overall survival (P = 0.016 and 0.049).

conclusionsWe identified predictors for successful mCRC PDO establishment and validated that PDOs can accurately predict patient outcomes during systemic treatment, specifically with 5-fluorouracil and oxaliplatin.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsOrganoidsAdultAgedAged, 80 and overBiopsyFemaleHumansMaleMiddle AgedNeoplasm MetastasisPrognosisTreatment Outcome

Identifiers

PMID40982295
PMCPMC12666313

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.