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A Prediction Model of Tumor Progression and Survival in HER2-Positive Metastatic Gastric Cancer Patients Treated with Trastuzumab and Chemotherapy

 Dongwoo Chae  ;  Chung Mo Nam  ;  Joo Hoon Kim  ;  Choong-Kun Lee  ;  Seung-Seob Kim  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Jae Ho Cheong  ;  Hyun Cheol Chung  ;  Sun Young Rha  ;  Kyungsoo Park 
 AAPS Journal, Vol.20 : 72, 2018 
Journal Title
 AAPS Journal 
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HER2-positive gastric cancer ; dose-response model ; prediction model ; trastuzumab ; tumor progression model
The effects of different patient factors and dose levels of chemotherapeutic agents on clinical outcomes in advanced gastric cancer are not as yet fully characterized. We aimed at developing an integrative model that incorporates dose and covariate information to predict tumor growth and patient survival in advanced gastric cancer patients treated with trastuzumab (T), 5-FU(F)/capecitabine (X) (F or X), and cisplatin (P). Sixty-nine patients (training dataset) were used for model building and a separate 86 patients (test dataset) for model validation. A fraction of tumor cells sensitive to each drug was incorporated as a model parameter, and T was assumed as cytostatic and X/F and P as cytotoxic. Cox proportional hazards analyses were performed on model parameters and patient covariates. The model well described the time course of observed tumor size changes, and revealed that the pretreatment tumor growth rate constant k g , which was formulated as a function of pretreatment disease duration and baseline tumor size, was positively correlated with baseline tumor size (p = 0.0084) and histologic grade (p = 0.034), and the efficacy of 5-FU with body weight (p < 2e-16) and that of cisplatin with histologic grade (p = 0.00013). Prior gastrectomy and Eastern Cooperative Oncology Group scores were significant prognostic factors for progression-free survival (PFS). For hazards analysis, a unit increase of k g was associated with a relative risk of 3.19 for PFS (p = 0.00055) and 4.45 for OS (p = 2e-04) in the test dataset, with a similar trend observed in the training dataset. Dose-response simulations showed that, for small baseline tumor size or low histologic grade, a maximum cytotoxic effect was attainable with a dose smaller than the current recommended dose.
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1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
김승섭(Kim, Seung-seob) ORCID logo https://orcid.org/0000-0001-6071-306X
김효송(Kim, Hyo Song) ORCID logo https://orcid.org/0000-0002-0625-9828
남정모(Nam, Jung Mo) ORCID logo https://orcid.org/0000-0003-0985-0928
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
박경수(Park, Kyungsoo) ORCID logo https://orcid.org/0000-0002-6972-1143
정민규(Jung, Min Kyu) ORCID logo https://orcid.org/0000-0001-8281-3387
정재호(Cheong, Jae Ho) ORCID logo https://orcid.org/0000-0002-1703-1781
정현철(Chung, Hyun Cheol) ORCID logo https://orcid.org/0000-0002-0920-9471
채동우(Chae, Dong Woo) ORCID logo https://orcid.org/0000-0002-7675-3821
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