Predicting survival post-liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma is the sixth most common malignancy worldwide and the third most common cause of death from cancer. In Australia, 1,778 patients were diagnosed with a primary liver cancer in 2013 with an age-standardised rate of 6.9/100,000 people. For a selected group of patients, liver transplantation represents the best chance of cure. Transplantation not only removes the disease, it also removes the abnormal liver parenchyma that provides a fertile ground for development and growth of new disease. Appropriate patient selection forms the cornerstone for any transplantation service, and organ shortages necessitate an efficient allocation of resources and careful prioritisation of the transplantation waiting list in order maximise benefit over a large patient cohort. Current allocation schemes are primarily based on tumour morphology. The goal of this thesis is to analyse pre-transplant radiological and biochemical markers in order to identify markers of poor prognosis that may be used to modify selection criteria

2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.ope

Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial

Background: IMbrave150 is a phase III trial that assessed atezolizumab + bevacizumab (ATEZO/BEV) versus sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (HCC) and demonstrated a significant improvement in clinical outcomes. Exploratory analyses characterized objective response rate (ORR), depth (DpR), and duration of response (DoR), and patients with a complete response (CR). Methods: Patients were randomized 2:1 to intravenous ATEZO (1200 mg) + BEV (15 mg/kg) every 3 weeks or oral SOR (400 mg) twice daily. Tumors were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and HCC-modified RECIST (mRECIST). ORR by prior treatment and largest baseline liver lesion size, DoR, time to response (TTR), and complete response (TTCR) were analyzed. Results: For both criteria, responses favored ATEZO/BEV versus SOR regardless of prior treatment and in patients with lesions ≥3 cm. Median TTR was 2.8 months per RECIST 1.1 (range: 1.2-12.3 months) and 2.8 months per mRECIST (range: 1.1-12.3 months) with ATEZO/BEV. Patients receiving ATEZO/BEV had a greater DpR, per both criteria, across baseline liver lesion sizes. Characteristics of complete responders were similar to those of the intent-to-treat population. In complete responders receiving ATEZO/BEV per mRECIST versus RECIST 1.1, respectively, median TTCR was shorter (5.5 vs. 7.0 months), mean baseline sum of lesion diameter was longer (5.0 [SD, 5.1] vs. 2.6 [SD, 1.4] cm), and mean largest liver lesion size was larger (4.8 [SD, 4.2] vs. 2.3 [SD, 1.0] cm). Conclusions: These data highlight the improved ORR, DpR, and CR rates with ATEZO/BEV in unresectable HCC. Keywords: Response Evaluation Criteria in Solid Tumors; hepatocellular carcinoma; immunotherapy

Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation

Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy

OBJECTIVES Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. MATERIALS AND METHODS Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1$^{st}$ follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1$^{st}$ post-treatment MRI was calculated. RESULTS Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). CONCLUSION mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. CLINICAL RELEVANCE STATEMENT Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). KEY POINTS • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy

Nuclear Imaging and Therapy:Towards a Personalized Approach in HCC and NET

This thesis explores new applications of nuclear imaging and therapy in patients with hepatocellular carcinoma (HCC) and neuroendocrine tumors (NET). These diseases are often detected late, making curative therapy not always possible. Developments in positron emission tomography (PET) and radionuclide therapy have led to new nuclear agents. The aim of this thesis is to provide insight into several new applications of current and new tracers in the diagnosis and treatment of HCC and NET.One of the investigated tracers is 18F-DOPA, which is currently used for NET tumors that are negative on 68Ga-labeled somatostatin analog (SSA) PET scans. Our study confirms the equivalent detection of 18F-DOPA in tumor detection compared to 68Ga-SSAs. Selective internal radiation therapy (SIRT) uses yttrium-90 radioactive resin spheres that are intravascularly injected into the liver. Higher than usual dosages (>120 Gy) appear to lead to better results in tumor reduction and the effects not only seem to be greater but also longer lasting.Furthermore, we demonstrated that 11C-Choline and 18F-FDG together find more tumors that are relevant for clinical decision-making in patients suspected of HCC recurrence. The thesis also offers two prospective study protocols, namely a comparison of 68Ga-DOTA-TOC with the new somatostatin tracer 18F-SiTATE in NET and a comparison of ablation with SIRT as a bridge strategy in liver transplantation. These results suggest that broader use of 18F-DOPA in PET diagnosis of NET is possible and that higher tumor-targeted dosages in SIRT can lead to better treatment

Management of Hepatocellular Carcinoma in Japan : JSH Consensus Statements and Recommendations 2021 Update

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC