Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma

Mazzaferro, Vincenzo; Sposito, Carlo; Zhou, Jian; Pinna, Antonio D.; Carlis, Luciano De; Fan, Jia; Cescon, Matteo; Sandro, Stefano Di; He, Yuchao; Lauterio, Andrea; Bongini, Marco; Cucchetti, Alessandro

doi:10.1053/j.gastro.2017.09.025

Cited by 475 publications

(505 citation statements)

References 27 publications

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“…This observation is in line with many studies showing the detrimental role of poor radiological response on delisting, intention‐to‐treat death, transplant benefit, posttransplant tumor recurrence, and posttransplant death . The diameter of the largest lesion, AFP levels at first referral, and MELD scores were also risk factors for HCC‐dependent failure by previous reports …”

Section: Discussionsupporting

confidence: 89%

The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation

Lai¹,

Vitale²,

Iesari³

et al. 2019

Liver Transpl

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In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC‐dependent LT failure, defined as pretransplant tumor‐related delisting or posttransplant recurrence. The study was registered at http://www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC‐in patients (no LRT = 182; LRT = 901) were balanced using 8 variables: age, sex, Model for End‐Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha‐fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo‐population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n = 1077) and LRT‐treated (n = 942) patients. Tumor progression after LRT was the most important independent risk factor for HCC‐dependent failure (subhazard ratio [SHR], 5.62; P < 0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait‐list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P < 0.001). The positive effect was still observed when 2‐3 treatments were performed (SHR, 0.66; P = 0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P = 0.27). In conclusion, for MC‐in patients, up to 3 LRTs are beneficial for success in intention‐to‐treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC‐dependent transplant failure.

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Section: Discussionsupporting

confidence: 89%

The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation

Lai¹,

Vitale²,

Iesari³

et al. 2019

Liver Transpl

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“…Among MC‐in patients, VI and PDC on explant pathology were present in 19.2% and 11.1% of patients; MC‐out status increased the incidences to 38.3% and 18.4%, respectively ( P < 0.0001). The Metroticket 2.0 paradigm has introduced three groups of candidates among which LT should have comparable outcomes . There was an increase in both VI and PDC from Group 1 (AFP < 200 and Up‐to‐7; VI, 19.0% [95% confidence interval {CI},17.3‐20.6] and PDT [poorly differentiated tumor], 11.0% [95% CI, 9.7‐12.3]) to Groups 2 (AFP, 200‐400 and Up‐to‐5; VI, 40.7% [95% CI, 27.5‐54.0] and PDT, 22.2% [11.0‐33.4]) and 3 (AFP, 400‐1,000 and Up‐to‐4; VI, 32.1% [95% CI, 14.5‐49.8] and PDT, 14.3% [95% CI, 10.8‐27.5]).…”

Section: Resultsmentioning

confidence: 99%

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

et al. 2019

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Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre‐LT levels of alpha‐fetoprotein, Model for End‐Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest‐risk patients (HALTHCC 0‐5) had lower rates of VI and PDC than the highest‐risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2‐14.2] vs. 70.6% [48.3‐92.9] and PDC:4.6% [0.1%‐9.8%] vs. 47.1% [22.6‐71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C‐index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C‐index = 0.71) and OS (C‐index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre‐LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

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“…This prognostic tool has been demonstrated to stratify accurately HCC patients with regard to long‐term survival, as prognosis worsened with increasing tumor size and number, just as longer trips on the “metro” result in a higher “ticket” price. The system was recently updated to incorporate tumor size, number and AFP as continuous rather than dichotomous variables, thus, providing a better prognostic stratification of patients with HCC . Sasaki et al recently applied the metro‐ticket concept using the maximum tumor size and number of lesions to define prognosis of patients undergoing resection for CRLM.…”

Section: Discussionmentioning

confidence: 99%

“…The initial metro‐ticket scheme predicted survival after liver transplantation among patients with HCC that exceeded the Milan criteria . More recently, an updated HCC metro‐ticket system incorporated individual tumor characteristics (ie, tumor size and number) and alpha‐fetoprotein (AFP) levels . While the metro‐ticket approach has been applied to other malignancies such as colorectal liver metastases (CRLM) and gastric cancer, its applicability to ICC has never been investigated.…”

Section: Introductionmentioning

confidence: 99%

A novel online prognostic tool to predict long‐term survival after liver resection for intrahepatic cholangiocarcinoma: The “metro‐ticket” paradigm

Sahara

Tsilimigras

Mehta

et al. 2019

Journal of Surgical Oncology

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Background The aim of the current study was to develop an online calculator to predict survival after liver resection for intrahepatic cholangiocarcinoma (ICC) based on the “metro‐ticket” paradigm. Methods Between 1990 and 2016, patients who underwent liver resection for ICC were identified in an international multi‐institutional database. The final multivariable model of survival was used to develop an online prognostic calculator of survival. Results Among 643 patients, actual 5‐year overall survival (OS) after resection for ICC was 42.7%. On multivariable analysis, CA19‐9 > 200 (hazard ratio (HR), 2.62; 95% CI, 2.01‐3.42), sum of the number and largest tumor size >7 (HR, 1.88; 95% CI, 1.46‐2.42), N1 disease (HR, 2.87; 95% CI, 1.98‐4.16), R1 resection (HR, 1.72; 95% CI, 1.21‐2.46), poor/undifferentiated tumor grade (HR, 1.74; 95% CI, 1.25‐2.44), major vascular invasion (HR, 1.47; 95% CI, 1.03‐2.10), and adjuvant chemotherapy (HR, 0.64; 95% CI, 0.45‐0.89) were significantly associated with survival and were included in the online calculator. The predictive accuracy of the model was good to very good as the C‐statistics to predict 5‐year OS was 0.696 in the training dataset and 0.672 with bootstrapping resamples (n = 5000) in the test dataset. Conclusion A novel, online calculator was developed to estimate the 5‐year survival probability for patients undergoing resection for ICC. This tool could help provide useful information to guide treatment decision‐making and inform conversations about prognosis.

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Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma

Cited by 475 publications

References 27 publications

The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation

The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients

A novel online prognostic tool to predict long‐term survival after liver resection for intrahepatic cholangiocarcinoma: The “metro‐ticket” paradigm

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