Meeting Milan Criteria Research Articles

Liver transplantation for pediatric liver malignancies.

In the last few decades, collaboration between the international pediatric oncology groups has resulted in significant improvement in survival after liver transplantation (LT) for pediatric liver tumors, and LT has become the accepted standard of care for unresectable pediatric liver tumors - either living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT). Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the common pediatric liver malignancies treated by LT, and LT is now the accepted treatment modality for unresectable non-metastatic cases. The long-term survival rate is more than 80% in HB transplants. Furthermore, with the advent of LDLT, the waitlist mortality, availability of a better graft quality with shorter ischemic times, and performance of LT with the appropriate timing between chemotherapy have all improved. Up to 80% of pediatric HCCs are unresectable, and studies have shown that LT for pediatric HCC has better outcomes than liver resection. Furthermore, LT has also shown better results than liver resection for cases of HCC not meeting Milan criteria. Given the rarity of pediatric liver malignancies and challenges in optimal management, a multidisciplinary treatment approach, research models building on what is already known, and consideration of newer treatment modalities are required for further improving the treatment of pediatric liver malignancies.

Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma meeting Milan criteria: a focus on tumor progression and recurrence patterns.

The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria. This retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded. A total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment. RFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.

Prognostic Factors for Mortality in Hepatocellular Carcinoma at Diagnosis: Development of a Predictive Model Using Artificial Intelligence.

Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed. In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered. Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF). The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC.

Liver Stereotactic Body Radiation Therapy (SBRT) to Downstage Patients with Hepatocellular Carcinoma prior to Liver Transplant

Orthotopic liver transplantation (OLT) marks the most successful treatment for hepatocellular carcinoma (HCC) patients meeting Milan criteria. The process of reducing the disease burden of HCC patients not currently meeting criteria for OLT with local therapy is referred to as "downstaging" and has proven to be a feasible approach. RTOG 1112 recently demonstrated the efficacy and acceptable toxicity of liver SBRT for treating HCC. However, limited data currently exists describing the efficacy of SBRT for downstaging HCC patients and facilitating OLT. A single institution IRB approved prospective liver SBRT registry was surveyed for all patients outside of Milan criteria (1 lesion >5 cm; 2-3 lesions >3 cm) without vascular invasion or extrahepatic disease. Patients felt least likely to become OLT candidates with downstaging (age >80, >4 lesions, lesion >12 cm) were excluded. The primary endpoints were downstaging and OLT. Secondary endpoints were time to transplant, local control (LC), recurrence free survival (RFS) and overall survival (OS). A total of 38 HCC patients with a median age of 65 years (range 28 - 80) met inclusion criteria. Median follow up was 14 months (IQR 3 - 35). At baseline, median KPS was 80 (range 60 - 100) with 16 Child-Pugh (CP) A (42%), 13 CP B (34%), and 9 CP C patients (24%). All patients were outside of Milan criteria and 25 patients (66%) were outside of UCSF criteria at time of SBRT. No patients had extrahepatic disease or vascular invasion. Median number of lesions, largest tumor size, and total sum of lesions were 2 (range 1 - 4), 5.0 cm (IQR, 4.0 - 6.5), and 6.6 cm (IQR 5.9 - 9.2), respectively. Prior to SBRT, 22 patients (58%) had received non-SBRT local therapy. At time of SBRT a variety of dose fractionation schedules were selected with a median BED10 of 78 (IQR 62 - 100). Concurrent sorafenib was used in 2 patients (8%). Following completion of SBRT, 21 patients (55%) were successfully downstaged at a median 3.0 months (IQR 1.9 - 6.1) after treatment, most frequently secondary to decrease in size of the largest lesion (86%). Twelve patients (32%) proceeded to undergo OLT at a median 7 months (IQR 3 - 14) after SBRT and 105 days (IQR 18 - 344) following successful downstaging. Of the 25 patients initially exceeding UCSF criteria, 7 (28%) underwent OLT. Among those receiving OLT, 5 patients (42%) remain alive without evidence of disease, 3 patients (25%) have recurred, 3 patients (33%) died within 2 years from transplant complications, and 1 patient (8%) died from an unrelated cause. LC at 2 years was 83%. Median RFS and OS for the overall cohort were 7 months (95% CI 0 - 21) and 24 months (95% CI 11 - 36), respectively. Among the transplant recipients, the median OS was 37 months (95% CI 30 - 44) compared to 15 months (95% CI 6 - 23) among those not receiving transplant. With careful patient selection, liver SBRT serves as a feasible downstaging method to facilitate OLT in HCC patients.

CON: Is liver organ allocation with MMaT-3 appropriate prioritization for patients with liver cancer?

CON: Is liver organ allocation with MMaT-3 appropriate prioritization for patients with liver cancer?

Long-term outcomes of resection versus transplantation for neuroendocrine liver metastases meeting the Milan criteria

Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver-only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow-up of 158 months for the transplantation group and 126 for the resection group, the 10-year survival rate was 93% for transplantation and 75% for resection (p= .007). The 10-year disease-free survival rate was 52% for transplantation and 18% for resection (p< .001). Transplantation was associated with improved survival at univariate analysis. The median disease-free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p< .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p= .001), while most recurrences in the resection group were intra-hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.

Management of hepatocellular carcinoma in patients who are 70 years or older

BackgroundAlthough liver transplantation has been done successfully in elderly patients with hepatocellular carcinoma, these are likely well-selected patients. This study uses a large database of patients with hepatocellular carcinoma to explore treatment and potential candidacy for liver transplantation in the elderly. MethodsRetrospective review of 1,533 hepatocellular carcinoma cases identified 2 groups: 475 patients 70 years or older (70+) and 1,058 patients <70 years. Demographics, risk factors, tumor characteristics, treatments, and survival were compared. Three- and 5-year survival rates were determined, and logistic regression was used to identify factors predictive of 3-year survival. ResultsPatients 70+ were more likely to have metabolic factors and less likely to have viral hepatitis, cirrhosis, hepatocellular carcinoma found with surveillance (21.7% vs 28.4%, P = .005), and hepatocellular carcinoma within Milan criteria (37.3% vs 43.8%, P = .019). Model for End-stage Liver Disease score was similar, but patients 70+ had higher mean creatinine and lower mean bilirubin. Patients 70+ were equally likely to undergo liver resection but less likely to undergo liver transplantation (0.4% vs 10.2%, P < .001). Three- and 5-year survival rates were significantly worse in 70+, and predictors of 3-year survival included hepatocellular carcinoma found with surveillance, meeting Milan criteria, and normal alpha fetoprotein. DiscussionElderly patients with hepatocellular carcinoma were less likely to undergo liver transplantation potentially due to metabolic factors and advanced disease. Although there is no age cutoff for liver transplantation, elderly patients should be given realistic expectations of liver transplantation candidacy. Continued surveillance for hepatocellular carcinoma in elderly patients may allow for earlier diagnosis and improved liver transplantation candidacy. Key MessageHepatocellular carcinoma in patients who are 70 years or older can be managed with liver transplantation in select cases, but more patients will be managed with liver resection and nonoperative therapies.

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis.

Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vsLT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P<.001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vsLT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vsLT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Poorly Differentiated Hepatocellular Carcinoma: Resection is Equivalent to Transplantation in Patients with Low Liver Fibrosis

Introduction: Organ allocation criteria for liver transplantation (e.g. Milan) focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). Methods: The National Cancer Database was queried between 2004-2016 for solitary HCC meeting Milan criteria undergoing SX vs. LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. Results: 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P<.001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stay, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs. LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. Discussion: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs. LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis

Presenter: Omid Salehi MD | Saint Elizabeth's Medical Center Background: Organ allocation criteria for liver transplantation (e.g. Milan) focus on tumor size and multifocality to determine candidacy, while tumor differentiation and degree of liver damage are omitted. This study investigates a synergistic effect of hepatocellular carcinoma (HCC) differentiation grade with degree of liver fibrosis on survival when comparatively analyzing resection (SX) vs transplantation (LT) and whether these parameters should be included in organ allocation algorithms. Methods: The National Cancer Database was queried between 2004-2016 for patients with solitary HCC meeting Milan criteria undergoing SX vs. LT. Two groups were created based on liver damage (low fibrosis (LF) vs high fibrosis (HF)) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. Results: 1515 patients met inclusion criteria; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months and 5-year survival (5YS) was 58.2%; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001), LT 5YS was 68.7% vs SX 5YS of 44.2% (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital length of stay, and age to be factors associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, type of surgery did not impact survival for poorly differentiated HCC in LF patients. This pattern was independent of tumor size. Conclusion: HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs. LT. Therefore, to optimally allocate organs for HCC transplantation, current criteria should give more weight to tumor grade or liver fibrosis compared to tumor size.

Descriptive Analysis of Everolimus Conversion in Liver Transplant Recipients With Malignant Neoplastic Disease

BackgroundCalcineurin inhibitors are associated with the development of de novo tumors and increased recurrence of hepatocellular carcinoma after liver transplant. It has been suggested that mammalian target of rapamycin inhibitors (everolimus [EVR]) may improve prognosis. We analyzed our experience on the use of EVR in malignant neoplasms in liver transplantation. Methods. We performed a retrospective descriptive analysis of 477 transplants performed between 2002 and 2019 at Virgen de las Nieves Hospital. A total of 100 patients received EVR; 23 transplants were because of tumor disease (23%), with de novo tumor in 12 patients and hepatocarcinoma in 11. The statistical study was carried out using the statistical program SPSS 17.0 software. ResultsThe study included 18 male patients (78.3%) and 5 female patients (21.7%) with an average age of 59.67 years. The most common indications of liver transplant have been alcoholic cirrhosis in 39% and hepatitis C virus cirrhosis in 21.7%. De novo tumors were lung neoplasm in 4 patients (33.3%), lymphoma in 2 patients(16.7%), oropharynx in 2 patients (16.7%), skin tumors in 2 patients (16.7%), and a kidney tumor (8.3%) in 1 patient. As for hepatocellular carcinoma, 8 patients met Milan criteria on the explant (61.5%). Tacrolimus was discontinued in all cases. The average onset time of post-transplant EVR was 2231.42 days in the de novo neoplasms and 307.45 days in those receiving transplants because of hepatocellular carcinoma (P = .05). We observed 5 deaths (21.7%). ConclusionAlthough the beneficial long-term role of EVR in liver transplant recipients with tumor disease is not demonstrated, it is used by most transplant units, both in de novo neoplasms and those receiving transplants because of hepatocellular carcinoma.

Microwave ablation after downstaging of hepatocellular carcinoma: outcome was similar to tumor within Milan criteria.

The aim of this study was to evaluate the clinical outcome of patients receiving microwave ablation (MWA), either after downstaging of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE), or without downstaging when meeting initially the Milan criteria. From January 2012 to January 2018, 66 patients with HCC beyond the Milan criteria who were downstaged by TACE previous to MWA comprised the study group. The control group comprised 190 patients who underwent MWA as first-line treatment as they met initially the Milan criteria. Cumulative overall survival (OS) and recurrence-free survival (RFS) rates were compared. The propensity score analysis was performed to reduce potential bias. Baseline characteristics were balanced between the two groups after 1:1 propensity score matching. The OS rates were 100%, 79%, and 73% at 1, 3, and 5years in the downstaging group and 95%, 83%, and 72%, respectively, in the Milan group. The corresponding RFS rate were 77%, 40%, and 31% in the downstaging group and 76%, 45%, and 34% in the Milan group. There were no significant differences in the OS and RFS rates between the two groups (p = 0.981 and p = 0.586). The long-term therapeutic outcomes of MWA for downstaged HCC with TACE were similar to HCC that initially met the Milan criteria. • Patients treated with MWA of HCC after downstaging with transarterial chemoembolization (TACE) were similar to those with HCC that initially met Milan criteria. • Microwave ablation (MWA) can be an effective treatment for hepatocellular carcinoma (HCC) that is downstaged to the Milan criteria.

Living donor liver transplantation for combined hepatocellular-cholangiocarcinoma: A case series of four patients

IntroductionCombined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma whose components include both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Indications for liver transplantation for cHCC-CCA remain controversial. Case presentationsFour patients underwent living donor liver transplantation (LDLT) for cHCC-CCA. All patients had multiple tumor nodules preoperatively diagnosed as HCC. Postoperative pathological examinations revealed that one of the tumors was cHCC-CCA. Cases 1 and 2 underwent LDLT for cirrhosis with HCC tumors that met Milan criteria. Case 3 underwent LDLT for recurrent HCC tumors with nonalcoholic steatohepatitis. Although the preoperative examinations showed that the patient met the Kyoto, but not Milan criteria, postoperative pathological examinations revealed that the patient did meet Milan criteria. The three patients who met Milan criteria on postoperative pathological examination had no recurrences after LDLT. Case 4 had multiple tumors with alcoholic liver cirrhosis. Although the preoperative examinations showed that the patient did not meet Milan criteria—but did meet Kyoto criteria—, on postoperative pathological examinations, the patient met neither Millan nor Kyoto criteria. He died of tumor recurrence 15 months after LDLT. Discussion and conclusionsOur experiences suggested that patients who meet Millan or Kyoto criteria experienced acceptable outcomes of LDLT for cHCC-CCA. By itself, cHCC-CCA is not contraindication for liver transplantation.

Ultrasound-guided percutaneous microwave ablation of hepatocellular carcinoma in challenging locations: oncologic outcomes and advanced assistive technology

Purpose To assess the oncologic outcomes of the hepatocellular carcinoma (HCC) patients in challenging locations (CLs) underwent ultrasound-guided percutaneous microwave ablation (US-PMWA) and the efficacy and safety of the advanced assistive technology (AAT). Materials and methods Data for 489 treatment-naïve patients with HCC who met Milan criteria and subsequently underwent US-PMWA were reviewed from March 2012 to November 2016. According to the distance (<5 mm) between the tumor and surrounding structures, the patients were divided into two groups: a CL group and a non-CL group. Regarding MWA assisted by AAT, the CL group was further subdivided into two groups: an AAT group and a non-AAT group. Technique effectiveness, complications and survival outcomes (i.e., overall survival [OS] and recurrence-free survival [RFS]) were compared between CL and non-CL groups. Local tumor progression (LTP) was compared between AAT and non-AAT groups. Results Technique effectiveness and complications in the CL group were similar to those in the non-CL group (p = .873 and p = .828, respectively). The OS and RFS in six types of CL groups were comparable with those in non-CL group (p = .131–.117) including adjacent vital structures, gallbladder, hepatic hilar regions, major vessels, diaphragm and capsule, respectively. The LTP rates in the AAT group were significantly higher than those in the non-AAT group (p = .001). Conclusions US-PMWA assisted by AAT to treat HCC lesions in CLs was safe and effective; also, this technique had comparable success and survival outcomes with those of patients in non-CL.

Prolonged post-ablation fever may predict one-year tumor recurrence in hepatocellular carcinoma after radiofrequency ablation

Background The impact of prolonged post-ablation fever (PAF) defined as persistent fever > 24 h after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) had not been described before. This study aims to investigate the impact of prolonged PAF on early tumor recurrence in HCC patients after RFA. Methods From 2013 to 2015, a total of 135 patients with HCC meeting Milan criteria and all the tumors having confirmed complete ablation after RFA were enrolled. Study endpoint was any HCC recurrence within 1 year after ablation. Cox regression analysis was applied for multivariate analysis to determine the independent predictors of 1-year tumor recurrence. Results Post-ablation fever occurred in 42 (31.1%) patients after RFA, while prolonged PAF was found in 22 (16.3%) patients. Fifty-eight (42.8%) patients occurred any tumor recurrence within 1 year after complete ablation. Patients with prolonged PAF had a significantly higher rate of HCC recurrence within 1 year (72.7% vs. 37.1%, p = 0.002) and had a significantly shorter time-to-recurrence interval (19.6 vs. 40.5 months, Log rank test, p = 0.002) than those who had no prolonged PAF. Multivariate analysis by Cox regression showed the previous HCC recurrence history (aHR: 1.792, p = 0.0284), baseline AFP > 20 ng/ml (aHR: 1.868, p = 0.0211) and prolonged PAF (aHR: 2.092, p = 0.0138) were associated with early recurrence. Conclusions Prolonged PAF may associate with early HCC recurrence after complete ablation by RFA. Patients with prolonged PAF need to be more clinical attentions.

Complications of liver transplant.

Liver transplantation has become a definitive treatment for patients with end-stage liver disease and those meeting Milan criteria for hepatocellular carcinoma. The morbidity and mortality associated with liver transplantation continues to decrease thanks to refinements in surgical technique, immunosuppression, and imaging. In particular, imaging plays a vital role by facilitating early detection of post-operative complications and enabling prompt treatment. Post-operative complications that lead to graft failure and patient morbidity/mortality can be generally categorized as vascular, biliary, parenchymal, and malignant. Vascular complications include stenosis and thrombosis of the hepatic artery, portal vein, and inferior vena cava; hepatic artery pseudoaneurysm; arteriovenous fistula; and celiac stenosis. Biliary abnormalities include strictures, bile leak, obstruction, recurrent disease, and infection. While imaging is not primarily utilized to diagnose allograft rejection, it plays an important role in excluding mechanical causes of graft dysfunction that can mimic rejection. Ultrasound is routinely performed as the first-line imaging evaluation for the detection and follow-up of early and delayed complications. Cholangiography and magnetic resonance cholangiopancreatography are useful in detecting and characterizing biliary complications. Computed tomography is often used to further evaluate abnormal findings on ultrasound or for the characterization of post-operative fluid collections. The aim of this review is to discuss and illustrate the imaging findings of complications associated with liver transplantation and their role in facilitating treatment.

Downstaging of Hepatocellular Carcinoma Outside Milan Criteria Using SBRT

Orthotopic liver transplantation (OLT) offers the potential for cure in patients (pts) with hepatocellular carcinoma (HCC) who meet Milan criteria. Many pts are outside of Milan at diagnosis or after subsequent progression. Prior studies have shown that downstaging with local therapies can facilitate successful OLT leading to prolonged disease free survival. Stereotactic body radiotherapy (SBRT) is an established local therapy for HCC, though data for this specific indication is limited. From a survey of a large single institution database, the present study therefore reports on outcomes of patients treated with SBRT with the intention of downstaging to facilitate OLT. We surveyed our IRB-approved prospective liver SBRT data registry for pts not meeting Milan criteria and treated with the intention of downstaging. The primary outcome was undergoing OLT. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan Meier methods. Time to transplant, as well as local, liver, and extrahepatic failure, were estimated with cumulative incidence functions. 14 pts treated between 2010 and 2018 met criteria for analysis. Median follow up was 27 months and 7 pts were alive at time of analysis. Most were male (n=11), and median age was 60. Median KPS was 80 (range 60-90). 5 pts were Child-Pugh (CP) A, 3 CP B, and 6 CP C. Median size of the largest single lesion was 4.2 cm (1.8 - 6.8 cm). The most common reason for not meeting Milan criteria was multiple lesions larger than 3 cm (n=8). Median AFP at time of SBRT was 40 (3 - 3255). 11 pts (79%) had undergone prior liver directed therapy. Pts were treated a median of 6.5 months after diagnosis. Median dose was 40 Gy, and median number of fractions was 5. There were no local failures. 11 pts (79%) were successfully downstaged to within Milan Criteria after SBRT. 5 pts (36%) had subsequent disease progression within the liver, 2 of whom were successfully salvaged and proceeded to transplant. 2 pts became ineligible for OLT due to extrahepatic failure. In total, 7 pts (50%) underwent OLT at a median 3.6 months after SBRT. Percent necrosis was reported for 5 pts, 4 (80%) of whom had greater than 67%. 2 pts (29%) had recurrence after OLT, one with metastases to lung and the other with solitary recurrence in the transplanted liver. Median OS was 33.0 months for all pts, 14.5 months in pts not undergoing OLT, and not reached for those who did undergo OLT. No pts developed radiation induced liver disease. SBRT provides excellent local control and high rates of radiographic downstaging, however progression within the liver is common. Despite this significant risk, a sizeable number of patients are able to proceed to transplant and achieve prolonged survival. SBRT should be considered for patients requiring downstaging to meet transplant criteria.

Comparison of the outcome of radiofrequency ablation or hepatic resection between solitary hepatocellular carcinoma and oligonodular hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis

There are more literatures on the comparison of the outcome of small HCC between HR and RFA, but rare is about the comparison of the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria by HR or by RFA. Thus, the aim of the present study is to evaluate the outcome between small solitary HCC and small oligonodular HCC meeting Milan criteria treated by HR or by RFA. Total eighteen studies including 4,823 patients was included in this study. Among them LR group included 2,564 cases, and RFA group included 2,259 cases. We divided them into small solitary HCC sub-group and small oligonodular HCC sub-group and compared the survival difference between them. In the HR group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 93.9%, 81.3%, and 72.0%, and the small oligonodular HCC sub-group were 83.3%, 70.4%, and 45.4%, respectively. For the DFS in the HR group, 1, 3, and 5 years of the small solitary HCC sub-group were 76.4%, 56.0%, and 44.0%, and 65.9%, 40.7%, and 11.1% of the small oligonodular HCC sub-group, respectively. In the RFA group, 1, 3, and 5 years OS of the small solitary HCC sub-group were 91.2%, 74.1%, and 54.5%, and the small oligonodular HCC sub-group were 82.0%, 55.4%, and 38.2%, respectively. For the DFS in the RFA group, 1, 3, and 5years of the small solitary HCC sub-group were 74.1%, 49.8%, and 22.1%, and 62.6% and 37.3%, 8.2% of the small oligonodular HCC sub-group, respectively.

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan

Living donor liver transplantation (LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. Acceptable outcomes have been demonstrated in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria, with emphasis on poor prognostic factors. We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology. A total of 117 patients were included. Patients who died early after transplant (in <30 days) were excluded. For outcomes, patients were divided into prognostic groups. These groups were based on (1) alpha fetoprotein >600, (2) poor differentiation, and (3) the presence of lymphovascular invasion. Recurrence-free survival (RFS) was determined using Kaplan-Meier curves. Median age was 53 (30-73) years. Median follow-up was 20.3 (1-63.2) months. Median model for end stage liver disease (MELD) score was 19 (9-34). Of a total of 117 patients, 74 (63.2%) patients met Milan criteria. Recurrence rate was 12/117 (10.3%). Actuarial 5-year RFS was 88% and 82% (P=0.3) in patients within and outside Milan criteria. There was no difference in 3-year RFS in patients with 0, 1, or 2 poor prognostic factors within Milan criteria (92%, 87%, and 75%, respectively; P=0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93%, and 53%; P=0.03). Patients within Milan criteria have acceptable RFS even in the presence of poor prognostic factors. However, the presence of two or more poor prognostic variables significantly impacts RFS of patients outside Milan criteria.

A modified staging of early and intermediate hepatocellular carcinoma based on single tumour >7cm and multiple tumours beyond up-to-seven criteria.

The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used staging system for hepatocellular carcinoma (HCC). However, the classifications of early (BCLC-A) and intermediate (BCLC-B) stage HCC remain controversial. To refine the staging of BCLC-A and -B. A total of 986 patients with HCC undergoing liver resection from two institutions formed the training cohort, and 694 from another institution were the validation cohort. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of tumour size in predicting overall survival (OS), and determined the optimised cut-off. Discriminatory performance was evaluated using Harrell's concordance index (C-index). Patients with multiple tumours exceeding Milan criteria but within up-to-seven criteria had similar OS and disease-free survival (DFS) to those with multiple tumours meeting Milan criteria, and were assigned to the modified BCLC-A stage. The area under the ROC curve of tumour size for predicting OS was 0.778, and the diameter of 7cm was the optimal cut-off to identify patients with single tumours who had higher OS than BCLC-B stage patients. Due to the similar OS, patients with single HCCs >7cm were assigned to the modified BCLC-B stage. The C-indexes of the modified BCLC classification for OS and DFS were higher compared to the original version. The findings were supported by the validation cohort. The modified staging of BCLC-A and -B, based on single tumour >7cm and multiple tumours beyond up-to-seven criteria, could be more accurate to predict the prognosis of HCC patients. Liver resection could benefit patients with resectable multifocal HCCs beyond the Milan criteria.