PurposeTo evaluate the relationship between portal vein tumor thrombosis (PVTT) response and clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization followed by radiotherapy (TACE-RT). Materials and methodsThe study enrolled 329 patients in the training set and 179 patients in the validation set. All patients who were treated with TACE-RT from 2002 to 2008 and satisfied the inclusion criteria were enrolled in the study. The median follow-up period was 11.7months (range, 1.6-108.6) in the training set and 11.9months (range, 1.7–105.1) in the validation set. ResultsAfter TACE-RT, PVTT response was complete or partial in 32 (9.7%) and 134 (40.7%) patients of the training set and in 18 (10.1%) and 96 (53.6%) patients in the validation set, respectively. Failure to obtain PVTT response was significantly related with elevated post-treatment Child-Pugh score (P<0.001). Furthermore, progression-free survival was significantly related with PVTT response (P<0.001, hazard ratio 0.33, 95% confidence interval 0.25–0.42) in multivariate analysis. In receiver-operating characteristics analysis of 1-year progression prediction, the PVTT response showed an area under the curve of 0.74. Most of the findings were successfully reproduced in the independent external validation set. ConclusionsPositive PVTT response was closely associated with favorable clinical outcomes. The PVTT response to TACE-RT reduces metastasis and makes it possible to maintain normal liver function and achieve longer survival.