Complete Pathologic Response to Pretransplant Locoregional Therapy for Hepatocellular Carcinoma Defines Cancer Cure After Liver Transplantation

Agopian, Vatche G.; Morshedi, Maud M.; McWilliams, J.; Harlander-Locke, Michael P.; Markovic, Daniela; Zarrinpar, Ali; Kaldas, Fady M.; Farmer, Douglas G.; Yersiz, Hasan; Hiatt, Jonathan R.; Busuttil, Ronald W.

doi:10.1097/sla.0000000000001384

Cited by 125 publications

(103 citation statements)

References 40 publications

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“…This finding is entirely consistent with 2 recent studies demonstrating a very low probability of HCC recurrence (0%to 2.4%)in patients who achieve complete response to LRT based on explant pathologic findings. 27,28 In the present study, the sum of the largest diameter of viable tumor (cm) plus the number of viable tumors in the explant predicted HCC recurrence better than other categories in assessing tumor burden, namely tumors outside (vs within) Milan criteria and the total tumor diameter. Similarly, Mazzaferro et al 10 proposed using a combination of the size of the largest tumor and the total number of tumors on explant to better estimate post-LT survival in the Metroticket forecast.…”

Section: Discussionmentioning

confidence: 46%

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant

et al. 2017

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IMPORTANCE Several factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence. OBJECTIVE We aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging. DESIGN, SETTING, AND PARTICIPANTS Predictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California–San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index. MAIN OUTCOMES AND MEASURES Characteristics associated with post-LT HCC recurrence. RESULTS A total of 1061 patients participated in the study; 77.8%(825) were men, and the median (IQR) age was 58.2 (53.3–63.9) years in the development cohort and 56.4 (51.7–61.0) years in the validation cohort (P < .001). In the development cohort of 721 patients (542 men), median α-fetoprotein (AFP) level at the time of LT was 8.3 ng/mL; 9.4% had microvascular invasion (n = 68), and 22.1% were beyond Milan criteria on explant (n = 159) owing to understaging by pretransplantation imaging. Cumulative probabilities of HCC recurrence at 1 and 5 years were 5.7% and 12.8%, respectively. On multivariable Cox proportional hazards regression, 3 variables were independently associated with HCC recurrence: microvascular invasion, AFP at time of LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RETREAT score was created using these 3 variables, with scores ranging from 0 to 5 or higher that were highly predictive of HCC recurrence (C statistic, 0.77). RETREAT was able to stratify 5-year post-LT recurrence risk ranging from less than 3%with a score of 0 to greater than 75% with a score of 5 or higher. The validation cohort (n = 340; 283 men) had significantly higher microvascular invasion (23.8% [n = 81], P < .001), explant beyond Milan criteria (37.3% [n = 159], P < .001), and HCC recurrence at 5 years (17.9% [n = 159], P = .03). RETREAT showed good model discrimination (C statistic, 0.82; 95%CI, 0.77–0.86) and superior recurrence risk classification compared with explant Milan criteria (net reclassification index, 0.40; P = .001) in the validation cohort. CONCLUSIONS AND RELEVANCE We have developed and validated a simple and novel prognostic score that may improve post-LT HCC surveillance strategies and help identify patients who may benefit from future adjuvant therapies.

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Section: Discussionmentioning

confidence: 46%

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant

et al. 2017

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“…In two large series of patients, complete or nearly complete histological response to LRT was shown to improve long-term survival after LT[47,48]. At the per-patient level, the accuracy of the mRECIST overall response was 72.9%, whereas EASL criteria correctly defined histological necrosis in 68.6% of our patients.…”

Section: Discussionmentioning

confidence: 72%

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

Nicolini

Agostini

Montalti

et al. 2017

WJG

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AIMTo 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.

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“…19-22 Recent data demonstrate significant improvement in long-term survival in patients with complete pathologic response to pretransplant neoadjuvant therapy. 23 In contrast, preoperative TACE before liver resection did not improve either disease-free or overall survival in two recent randomized trials, one of which largely enrolled BCLC B patients beyond Milan criteria. 24, 25 Importantly, there is significant heterogeneity in patient enrollment strategies, reported tumor biology, as well as TACE technique and drug/dosage selection within studies evaluating role of TACE in patients with HCC selected for liver resection.…”

Section: Discussionmentioning

confidence: 97%

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

et al. 2016

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Objectives To assess survival after liver resection and transplantation in patients with HCC beyond Milan criteria. Summary Background Data The role of liver resection and transplantation remains controversial for patients with hepatocellular carcinoma (HCC) beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center Methods Patients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival. Results Of 608 patients beyond Milan without vascular invasion, 480 (79%) underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (p<0.001). Resection patients had larger tumors (median 9 cm, IQR: 6.5-12.9 cm versus median 4.1, IQR: 3.4-5.3 cm, p<0.001); transplant patients were more likely to have multiple tumors (78% versus 28%, p<0.001). Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all p<0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared to propensity-matched liver resection patients (p≥0.176); DFS in this propensity matched cohort was greater after liver transplantation (p≤0.017). Conclusions Liver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

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Complete Pathologic Response to Pretransplant Locoregional Therapy for Hepatocellular Carcinoma Defines Cancer Cure After Liver Transplantation

Cited by 125 publications

References 40 publications

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant

Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant

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

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

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