WHO, RECIST, EASL And MRECIST Criteria For Evaluating Preoperative Chemotherapy Response And Long-term Survival In Children With Hepatoblastoma

Objective 1.To explore the intercriterion agreement of WHO,EASL,RECIST and m RECIST imaging criteria in childhood hepatoblastoma(HB)after chemotherapy.2.To evaluate the predictive value of WHO,EASL,RECIST and m RECIST imaging criteria in assessing long-term survival of children with HB.3.To analyze prognostic factors that influence long-term survival of HB.Materials and Methods This study retrospectively analyzed the basic clinicopathological and imaging(spiral CT)data of 92 children with HB in the clinical database system of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2012 to November 2017.The diagnosis of HB in all children was confirmed by liver biopsy.After admission,the clinical stage of PRETEXT and the presence of extrahepatic metastases in HB children were first determined.Systemic intravenous chemotherapy was then given,and the initial treatment regimen was cisplatin,5-fluorouracil and vincristine(C5V).For patients with no tumor response,poor tumor response,or tumor progression during chemotherapy,the chemotherapy protocol was switched to cisplatin and doxorubicin(PLADO).Salvage transcatheter arterial chemoembolization(TACE)was performed in some HB with poor response to the 6-cycle C5V+PLADO regimen.For systemic intravenous chemotherapy,spiral CT scan of liver tumors was performed every 2 cycles to evaluate the tumor imaging manifestation and determine whether the tumor was resectable.For patients who underwent TACE for HB,a spiral CT scan was performed within 4 weeks after TACE.The WHO,RECIST,EASL and m RECIST imaging criteria were used to evaluate the manifestation of HB in patients with spiral CT before and after systemic intravenous chemotherapy/TACE.Each imaging criteria included of complete response(CR),partial response(PR),stable disease(SD)and progression tumor(PD).The kappa test was used to compare the intercriterion agreement of the WHO,RECIST,EASL and m RECIST criteria for assessing of imaging manifestation following systemic chemotherapy/TACE in children with HB.The area under the curve(AUC)of the receiver operating curve(ROC curve)was used to compare the predictive value of event-free survival(EFS)and overall survival(OS)of the four imaging criteria.Kaplan-meier method was used to calculate the survival rates for each imaging criteria,and log-rank test was used to compare the survival differences among imaging criteria.COX proportional hazard mode was used to determine prognostic factors affecting long-term survival of children with HB.Results 1.Basic clinical data: of the 92 enrolled patients,55(59.8%)were boys and 37(40.2%)were girls,with a median age of 17(0.1-124)months.Seventy-four(80.4%)children with HB who were identified as PRETEXT stage III and IV.For the children receiving surgical resection,the median interval from HB diagnosis to surgical resection was 3.1(1.2-8.9)months,the median number of preoperative chemotherapy was 4(1-8),and postoperative chemotherapy was 4(1-8).For HB patients without surgical resection,chemotherapy cycles were 7(4-15).Twenty-one patients with salvage TACE who unresponsed to systemic intravenous chemotherapy had a median number of TACE treatments of 2(1-3),of which 17 cases underwent surgical resection.Sixty-eight patients(73.9%)underwent surgical resection after systemic chemotherapy/TACE.2.The evaluation of the intercriterion agreement of WHO,RECIST,EASL and m RECIST imaging criteria for HB preoperative treatment response: the number of cases idendtified as CR,PR,SD,and PD by WHO and RECIST imaging criteria based on tumor diameter measurement criteria were 1(1),57(59),27(25),and 7(7),respectively;whereas,the number of EASL and m RECIST imaging criteria based on tumor enhancement criteria were 12(12),53(50),20(23),and 7(7),respectively.The kappa coefficients for WHO vs.RECIST criteria was 0.832,and for EASL vs.m RECIST criteria was 0.875;the kappa coefficients for WHO vs.EASL and WHO vs.m RECIST was 0.354 and 0.310,respectively,and RECIST vs.EASL and RECIST vs.m RECIST was 0.441 and 0.396,respectively.3.The assessment of the predictive value of WHO,RECIST,EASL and m RECIST imaging criteria for long-term survival in children with HB: according to ROC test,the AUC under the WHO and RECIST curves of EFS/OS were 0.658(95% CI: 0.546-0.771)and 0.636(95% CI: 0.521-0.750)/0.735(95% CI: 0.612-0.859)and 0.771(95% CI: 0.654-0.888),respectively;the AUC under the EASL and m RECIST curve of EFS/OS were 0.775(95% CI: 0.679-0.870)and 0.785(95% CI: 0.691-0.878)/0.909(95% CI: 0.835-0.982)and 0.914(95% CI: 0.845-0.983),respectively.4.Surgical resection and preoperative imaging criteria were independent prognostic factors affecting long-term survival of children with HB after the adjustment of COX proportional hazard model.Conclusions 1.WHO and RECIST imaging criteria based on tumor diameter measurements and the EASL and m RECIST criteria based on enhancements had good intercriterion agreement in assessing HB treatment response;while WHO and RECIST criteria had poor intercriterion agreement with EASL and m RECIST.2.WHO and RECIST imaging criteria have lower predictive value for long-term survival of HB;while EASL and m RECIST have higher survival predictions for HB.Compared with WHO and RECIST imaging criteria,EASL and m RECIST imaging criteria had better predictive accuracy in terms of long-term survival of HB.3.Salvage TACE can further improve the surgical resection rate of unresectable HB.Surgical resection is still an important means to improve long-term survival for HB with good response to chemotherapy/TACE.