A Prediction Model of Tumor Progression and Survival in HER2-Positive Metastatic Gastric Cancer Patients Treated with Trastuzumab and Chemotherapy.
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.
['Chae|Dongwoo|D|', 'Nam|Chung Mo|CM|', 'Kim|Joo Hoon|JH|', 'Lee|Choong-Kun|CK|', 'Kim|Seung-Seob|SS|', 'Kim|Hyo Song|HS|', 'Jung|Minkyu|M|', 'Cheong|Jae Ho|JH|', 'Chung|Hyun Cheol|HC|', 'Rha|Sun Young|SY|', 'Park|Kyungsoo|K|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D066264:Datasets as Topic D018450:Disease Progression D004305:Dose-Response Relationship, Drug D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D008954:Models, Biological D060787:Neoplasm Grading D011379:Prognosis D000077982:Progression-Free Survival D018719:Receptor, ErbB-2 D066066:Response Evaluation Criteria in Solid Tumors D013274:Stomach Neoplasms D016019:Survival Analysis D000068878:Trastuzumab D047368:Tumor Burden
prediction model trastuzumab HER2-positive gastric cancer dose-response model tumor progression model