Sjoerd G. Elias

Baseline characteristics of the study population, with key demographic, clinical, and molecular details from regular diagnostic sequencing.

Genomic landscape of 36 tumors and/or PDOs derived from patients with mCRC. Top, microsatellite stability, tumor mutational load, tumor mutational burden, and whether the sequencing was performed on the PDOs or the tumor of origin; bottom, somatic driver mutations. MS, microsatellite status; MSI, microsatellite instability; MSS, microsatellite stability; Seq, sequencing; TML, tumor mutational load.

Tables S1-S6 and Figures S1–S8

Clinical variables related to PDO establishment success: CEA, LDH, mutational status, sex, primary tumor sidedness, prior chemotherapeutic treatment, metastatic site of the biopsy, WGS success, and aggregated biopsy color (brown, pink, red, and white). CEA, carcinoembryonic antigen; mut, mutant.

A, Heatmap of the drug sensitivity per PDO for different types of systemic treatment. The columns show the normalized GRAUC (left) and AUC (right), respectively. Potential other treatment options for intermediate or high 5-FU and oxaliplatin–resistant PDOs, as well as intermediate or high 5-FU and oxaliplatin–sensitive but 5-FU and irinotecan–resistant PDOs, are shown in black bars. PDOs that were not screened are shown in gray. B, Sensitivity (GRAUC) to doublet and triplet chemotherapy showing increased sensitivity with the addition of irinotecan. C, Sensitivity (normalized GRAUC) to panitumumab for PDOs categorized according to the tumor’s mutational status and primary tumor sidedness (RAS-mutant, BRAF-mutant, and/or right-sided; RAS/BRAF-WT and left-sided. Boxplots show the minimum, median, maximum, upper and lower quartiles, and individual data points. iri, irinotecan; oxa, oxaliplatin; TT, trifluridine/tipiracil.

Correlations between patient response (best RECIST response, size change of all target lesions, and the biopsied lesion) and PDO response (normalized GRAUC per treatment in A–C and AUC in D–F). ROC curves showing the performance of the PDO classification based on GRAUC. The curve plots the true-positive rate (sensitivity) against the false-positive rate (1 − specificity). The AUC indicates the model’s ability to distinguish between responders and nonresponders to 5-FU and oxaliplatin, defined by size change of all target lesions (G) and the biopsied lesion (H). Kaplan–Meier PFS (I) and OS (J) curves of patients stratified by PDO sensitivity to 5-FU and oxaliplatin, based on normalized GRAUC (cutoff = 0.63). Censored events are indicated by vertical bars on the corresponding curve. The table underneath each plot denotes the numbers at risk. Log-rank test–based P value is shown. SN-38, active metabolite of irinotecan.

Schematic overview of the study. Patients underwent a biopsy of a metastasis for PDO culture and WGS, before starting a new line of systemic treatment. Predictors of successful PDO establishment were identified: male sex, increased LDH, biopsy in academic hospitals, optimized culture conditions, and experience. A total of 42 PDOs were screened for standard-of-care treatments, and the patient received standard systemic treatment. PDO response was correlated with patient response, and the association between PDO response and survival was assessed. (Created in BioRender. Roodhart, J. [2025] https://BioRender.com/by1f1uq.)

Flow-chart patients according to RECIST-defined PD. *All patients had clinical disease progression; no CT-imaging was performed before initiation of systemic treatment ** In total 7 patients choose best supportive care. Three other patients underwent radiotherapy or surgery of all target lesions.