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1.
Int J Cancer ; 155(4): 697-709, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577882

RESUMEN

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.


Asunto(s)
Neoplasias de la Mama , Organoides , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Organoides/patología , Organoides/efectos de los fármacos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Medicina de Precisión/métodos , Supervivencia sin Progresión , Metástasis de la Neoplasia , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piperazinas/uso terapéutico , Piperazinas/administración & dosificación , Resultado del Tratamiento
2.
Disaster Med Public Health Prep ; 15(4): 403-408, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-32301409

RESUMEN

OBJECTIVES: We aimed to explore and create an evaluation model to assess hospital response capability for a public health emergency (PHE). METHODS: Grounded theory was used to construct a comprehensive evaluation index system. Combining with the index system and previous studies and policy documents, we investigated surge capability of hospitals in a PHE. The factor analysis method was used to establish the model. RESULTS: The comprehensive evaluation system with 11 primary and 30 secondary indicators was constructed. A total of 89 secondary and tertiary hospitals were surveyed in China. The evaluation model (C = 0.587C1 + 0.151C2 + 0.140C3 + 0.122C4) was established. Four factors were identified, namely, preparation factor, treatment factor, emergency awareness factor, and prehospital first-aid factor. CONCLUSIONS: A public health emergency could bring huge losses and a capable hospital response was necessary. There was an urgent need to evaluate hospital capability for a PHE.


Asunto(s)
Urgencias Médicas , Hospitales , Salud Pública , China , Investigación sobre Servicios de Salud , Humanos , Modelos Teóricos
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