BACKGROUND: Patient-derived tumor organoid culture has emerged as a preclinical model that has the potential to predict individual drug response. However, the predictive accuracy of patient-derived tumor organoid culture models for responses to chemotherapy regimens in stage IV colorectal cancer remains unknown. OBJECTIVE: The purpose of this study was to evaluate the predictive accuracy of the patient-derived tumor organoid culture model for responses to chemotherapy regimens in stage IV colorectal cancer. DESIGN: A pilot study was performed to define the half-maximal inhibitory concentration of the response to chemotherapy regimens in the patient-derived tumor organoid culture model. Then, a blinded study was performed to evaluate the predictive accuracy of the patient-derived tumor organoid culture model for responses to chemotherapy regimens. SETTINGS: Cancer samples were collected from patients with stage IV colorectal cancer at Nanfang Hospital of Southern Medical University in China. PATIENTS: In the pilot study, 30 patients were enrolled, and 43 samples were collected. In the blinded study, 71 patients were enrolled, and 96 samples were collected. INTERVENTION: Patient-derived tumor organoid culture and chemotherapy regimens were tested. MAIN OUTCOME MEASURES: The predictive accuracy of the patient-derived tumor organoid model for responses to chemotherapy regimens was measured. RESULTS: The median (range) time of organoid culture and drug testing was 9 days (range, 7–14 d). In the pilot study, 30 samples (69.77% [30/43]) were successfully cultured. The half-maximal inhibitory concentration of the chemotherapy response was 10 µmol/L according to clinical chemotherapy outcomes. In the blinded study, 77 samples (80.21% [77/96]) from 57 patients were successfully cultured. The sensitivity, specificity, and accuracy of the patient-derived tumor organoid model for predicting responses to chemotherapy regimens were 63.33%, 94.12%, and 79.69%. LIMITATIONS: This was a blinded study rather than a prospective randomized controlled study. CONCLUSIONS: The patient-derived tumor organoid culture model effectively predicts responses to existing chemotherapy regimens for individual patients. Video Abstract at http://links.lww.com/DCR/B511. PRECISIÓN EN EL USO DE MODELOS DE CULTIVO DE ORGANOIDES TUMORALES DERIVADOS DE PACIENTES PARA PREDECIR LA RESPUESTA DEL RÉGIMEN DE QUIMIOTERAPIA EN CÁNCER COLORRECTAL ESTADIO IV: ESTUDIO CIEGO ANTECEDENTES: El cultivo de organoides tumorales derivado del paciente ha surgido como un modelo preclínico que tiene el potencial de predecir la respuesta a un fármaco individual. Sin embargo, la exactitud predictiva en los modelos de cultivo de organoides tumorales derivados de pacientes para las respuestas a los regímenes de quimioterapia en el cáncer colorrectal en estadio IV sigue siendo desconocida. OBJETIVO: Evaluar la exactitud predictiva del modelo de cultivo organoide tumoral derivado de pacientes para las respuestas a los regímenes de quimioterapia en el cáncer colorrectal en estadio IV. DISEÑO: Se realizó un estudio piloto para definir la concentración inhibitoria media máxima de la respuesta a los regímenes de quimioterapia en el modelo de cultivo organoide tumoral derivado de pacientes. Luego, se realizó un estudio ciego para evaluar la exactitud predictiva del modelo de cultivo organoide tumoral derivado de pacientes para las respuestas a los regímenes de quimioterapia. AJUSTE: Se recolectaron muestras de cáncer de pacientes con cáncer colorrectal en estadio IV en el Hospital Nanfang de la Universidad Médica del Sur en China. PACIENTES: En el estudio piloto, se inscribieron 30 pacientes y se recolectaron 43 muestras. En el estudio ciego, se inscribieron 71 pacientes y se recolectaron 96 muestras. INTERVENCIÓN: Se probaron cultivos de organoides de tumores derivados del paciente y regímenes de quimioterapia. PRINCIPALES MEDIDAS DE RESULTADO: La precisión predictiva del modelo organoide tumoral derivado del paciente para las respuestas a los regímenes de quimioterapia. RESULTADOS: La mediana (rango) de tiempo de cultivo organoide y prueba de drogas fue de 9 (7-14) días. En el estudio piloto, se cultivaron con éxito 30 (69,77% [30/43]) muestras. La concentración inhibidora media máxima de la respuesta a la quimioterapia fue de 10 µmol / L según los resultados de la quimioterapia clínica. En el estudio ciego, se cultivaron con éxito 77 muestras (80,21% [77/96]) de 57 pacientes. La sensibilidad, especificidad y precisión del modelo organoide tumoral derivado del paciente para predecir las respuestas a los regímenes de quimioterapia fueron 63,33%, 94,12% y 79,69%, respectivamente. LIMITACIONES: Este fue un estudio ciego en lugar de un estudio prospectivo, aleatorizado y controlado. CONCLUSIONES: El modelo de cultivo organoide tumoral derivado de pacientes predice eficazmente las respuestas a los regímenes de quimioterapia existentes para pacientes individuales. Consulte Video Resumen en http://links.lww.com/DCR/B511.

BACKGROUND: Recent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid–based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown. OBJECTIVE: This study aimed to explore the prognostic value of patient-derived tumor organoid–based drug tests in patients with stage IV colorectal cancer after surgery. DESIGN: Retrospective cohort study. SETTINGS: Surgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital. PATIENTS: A total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019. INTERVENTIONS: Patient-derived tumor organoid culture and chemotherapeutic drug testing. MAIN OUTCOMES MEASURES: Progression-free survival. RESULTS: According to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84–6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71–7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34–4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61–4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid–based drug test model, which includes the patient-derived tumor organoid–based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001). LIMITATIONS: A single-center cohort study. CONCLUSIONS: Patient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.