Radiological response and inflammation scores predict tumour recurrence in patients treated with transarterial chemoembolization before liver transplantation

To investigate the prognostic value of the radiological response after transarterial chemoembolization (TACE) and inflammatory markers in patients affected by hepatocellular carcinoma (HCC) awaiting liver transplantation (LT).METHODSWe retrospectively evaluated the preoperative predictors of HCC recurrence in 70 patients treated with conventional (n = 16) or doxorubicin-eluting bead TACE (n = 54) before LT. The patient and tumour characteristics, including the static and dynamic alpha-fetoprotein, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) measurements, were recorded. Treatment response was classified according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and the European Association for the Study of the Liver (EASL) criteria as complete response (CR), partial response (PR), stable disease or progressive disease. After examination of the explanted livers, histological necrosis was classified as complete (100% of the cumulative tumour area), partial (50%-99%) or minimal (< 50%) and was correlated with the preoperative radiological findings.RESULTSAccording to the pre-TACE radiological evaluation, 22/70 (31.4%) and 12/70 (17.1%) patients were beyond Milan and University of San Francisco (UCSF) criteria, respectively. After TACE procedures, the objective response (CR + PR) rates were 71.4% and 70.0% according to mRECIST and EASL criteria, respectively. The agreement between the two guidelines in defining the radiological response was rated as very good both for the overall and target lesion response (weighted k-value: 0.98 and 0.93, respectively). Complete and partial histological necrosis were achieved in 14/70 (20.0%) and 28/70 (40.0%) patients, respectively. Using histopathology as the reference standard, mRECIST criteria correctly classified necrosis in 72.9% (51/70) of patients and EASL criteria in 68.6% (48/70) of cases. The mRECIST non-response to TACE [Exp(b) = 9.2, p = 0.012], exceeding UCSF criteria before TACE [Exp(b) = 4.7, p = 0.033] and a preoperative PLR > 150 [Exp(b) = 5.9, p = 0.046] were independent predictors of tumour recurrence.CONCLUSIONThe radiological response and inflammatory markers are predictive of tumour recurrence and allow the proper selection of TACE-treated candidates for LT.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Evaluation of ^(177)Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors

BACKGROUND^177Lu peptide receptor radionuclide therapy(PRRT)is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors.AIM To determine the impact of PRRT on quality of life,radiologic and metabolic response,overall survival,prognostic factors and toxicity.METHODS Thirty-six patients treated with^177Lu-PRRT from 2016 to 2019 were included.The most frequent location of the primary tumor was the gastrointestinal tract(52.8%),pancreas(27.8%),and nongastropancreatic neuroendocrine tumor(11.1%).The liver was the most common site of metastasis(91.7%),followed by distant nodes(50.0%),bone(27.8%),peritoneum(25.0%)and lung(11.1%).Toxicity was evaluated after the administration of each dose.Treatment efficacywas evaluated by two parameters:stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested.RESULTS From 36 patients,55.6%were men,with a median age of 61.1±11.8 years.Regarding previous treatments,55.6%of patients underwent surgery of the primary tumor,100%of patients were treated with long-acting somatostatin analogues,66.7%of patients were treated with everolimus,27.8%of patients were treated with tyrosine kinase inhibitor,and 27.8%of patients were treated with interferon.One patient received radioembolization,three patients received chemoembolization,six patients received chemotherapy.Hematological toxicity was registered in 14 patients(G1-G2:55.5%and G3:3.1%).Other events presented were intestinal suboclusion in 4 cases,cholestasis in 2 cases and carcinoid crisis in 1 case.The median follow-up time was 3 years.Currently,24 patients completed treatment.Nineteen are alive with stable disease,two have disease progression,eight have died,and nine are still receiving treatment.The median overall survival was 12.5 mo(95%confidence interval range:9.8–15.2),being inversely proportional to toxicity in previous treatments(P<0.02),tumor grade(P<0.01)and the presence of bone lesions(P=0.009)and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT(P<0.01),,primary tumor surgery(P=0.03)and metastasis surgery(P=0.045).In a multivariate Cox regression analysis,a high Ki67 index(P=0.003),a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT(P<0.01)and a preceding toxicity in previous treatments(P<0.05)were risk factors to overall survival.CONCLUSION Overall survival was inversely proportional to previous toxicity,tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.

Radiologic-histological correlation of hepatocellular carcinoma treated via pre-liver transplant locoregional therapies

BACKGROUND:Locoregional therapies(LRTs) are treatments to achieve local control of hepatocellular carcinoma(HCC).Correlation between radiologic response to LRT and degree of induced tumor necrosis is not well understood.The aim of this study was to evaluate different levels of radiologic response after pre-liver transplant(LT) LRT and its correlation with percentage of tumor necrosis on explanted histopathology.METHODS:Institutional Review Board approved LT database was queried for treated HCC in patients undergoing LT.Radiologic response was evaluated to predict tumor necrosis in the explanted liver.Tumor response was evaluated 1 to 3 months after LRT with computed tomography or MRI via Response Evaluation Criteria in Solid Tumors(RECIST),and European Association for the Study of the Liver(EASL) guidelines.LRT was repeated as needed until time of LT.Histological tumor necrosis was graded as complete(100%),partial(50%-99%),or poor(【50%).RESULTS:Between 2002 and 2011,128 patients(97 men and 31 women) received pre-LT LRT including transarterial therapy(93),radiofrequency ablation(20),or combination of both(15).The mean age of the patients was 58±9 years.Their mean follow-up was 35±27 months.The median waitlist time was 55 days.One hundred(78%) patients had HCC within the Milan criteria at the initial radiologic diagnosis.Nineteen(15%) of the patients had complete tumor necrosis on histopathology analysis.Fifty(39%) of the patients exhibited partial necrosis,52(41%) showed poor or no necrosis and 7(5%) showed progressive disease.The overall pre-LT radiologic staging was correlated with explant pathology in 73(57%) of the patients.Underestimated tumor stage was noted in 49(38%) patients,and overestimated tumor stage in 6(5%) patients.The post-LT 3-year overall survival and disease free survival were 82% and 80%,and the rates for complete and partial tumor necrosis were 100% vs 78%(P=0.02) and 100% vs 75%(P=0.03),respectively.CONCLUSIONS:In the current era,interpretation of radiologic response after LRT for HCC does not correlate accurately with histologic tumor necrosis.Total tumor necrosis is the goal of LRT;therefore,evolution in its performance is needed.Similarly,ways to predict therapy induced tumor necrosis via radiological investigation need to be improved.