We further investigated whether the MESIAH score can further clas

We further investigated whether the MESIAH score can further classify survival of patients within each stratum of the BCLC staging system (Fig. 4). Whereas patients in BCLC stage 0 or A did well overall, there was a large degree of variability in survival of patients with BCLC stage B to D. In BCLC stage B, patients in the lowest quartile of the MESIAH score had 77% 3-year survival compared with those in highest quartile with 17% survival. The gap was even wider in BCLC stage C patients, in whom the 3-year survival in the lowest

and highest quartiles was 49% and 0%, respectively. Sensitivity analyses were performed to test the robustness of the MESIAH score. First we examined the effect of censoring patients at the time of liver transplantation (n = 133), as the Epigenetics inhibitor procedure may fundamentally affect the natural history of HCC. The result, however, was that censoring liver transplantation did not affect the overall performance of the model. MLN0128 The c-statistic in the derivation cohort was 0.79 and validation 0.81, which were again better than other staging systems (Supporting Table). Second, we repeated

the validation analysis excluding nonviral hepatitis patients in the validation cohort. Again, the result did not change materially (data not shown). In general, patient characteristics that determine the prognosis in HCC tend to be more complex than those for other solid tumors, as the vast majority of patients with HCC have underlying liver cirrhosis and the degree of hepatic dysfunction, in addition to the extent of the tumor, affects prognosis. This analysis demonstrates that the extent of the tumor as represented by variables such as the number and size of the lesions, vascular invasion, and extrahepatic metastasis and the underlying liver function, measured by MELD, are important independent predictors of survival in HCC patients.

Although this is not 上海皓元医药股份有限公司 the first observation that MELD may be useful in prognosticating patients with HCC,19 one of the advantages of the MESIAH score is that it only includes objective, reproducible variables. The value of an objectively quantifiable measure of disease has been appreciated with MELD, which has been rapidly become a common language among physicians globally. Similarly, we believe that the MESIAH score could be applied in retrospective studies or in epidemiologic research where nuanced details of clinical information are unavailable. We are reassured of the validity of the MESIAH score model, as it performed well in our cross-validation as well as in the independent dataset of our validation cohort. The c-statistic in the validation cohort was higher than that in the derivation cohort, indicating that it was easier for the score to separate HCC patients according to their prognosis in the former. This is likely attributed to the wider range of the score (and thus survival) with fewer patients receiving treatment that potentially alters the natural history in that cohort.

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