Management Of Unresectable Hepatocellular Carcinoma Research Articles

A retrospective study of PD-1/PD-L1 combination therapy versus TKI monotherapy in elderly patients with uHCC.

e16191 Background: The rising elderly population worldwide has led to an increase in cases of liver cancer among individuals aged ≥65 years. With the advancement of medical treatments, the management of unresectable hepatocellular carcinoma (uHCC) now predominantly involves immunotherapy combination therapy. However, existing data in elderly patients are limited. Therefore, we conducted a retrospective analysis on the efficacy and safety of immune combination therapy compared with TKI monotherapy in elderly uHCC patients. Methods: A retrospective analysis was conducted on uHCC patients aged ≥65 years at the First Hospital of Jilin University between March 2019 and July 2023. The targeted therapy used in this study included, but not limited to, sorafenib, lenvatinib. PD-1/PD-L1 inhibitors such as pembrolizumab and atezolizumab were also utilized. Follow-up was conducted until death, loss to follow-up, or December 2023. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs) and immune-related AEs (irAEs). Results: A total of 70 patients were included in this study, with 33 patients receiving monotherapy, and 37 patients receiving immune combination therapy. The median age was 68 years old, with 78.8% being male. The combination therapy group had a higher ORR (10.8% vs. 3.0%) DCR (48.5% vs. 45.9%) compared to the monotherapy group. However, there were no statistically significant differences in median PFS (7.0 vs. 12.0 months) and median OS (9.8 vs. 17.5 months) between the two groups. Among the subgroups, combination therapy showed better results except for patients with ascites. Immune combination therapy appeared to be superior to monotherapy in terms of both PFS (6.2 vs. 6.8 months, P = 0.888) and OS (6.8 vs. 10.2 months, P = 0.888). Multivariate analysis showed that elevated total bilirubin may be a risk factor for OS in patients ≥65 years old. Regarding safety, the adverse event (AE) rate was 39.3% in the monotherapy group. The most common AEs reported were abdominal distension (18.2%), fatigue (15.2%), and proteinuria (6.1%). In the combination therapy group, the AE rate was higher at 59.4%, with the most common AEs being thyroid function abnormalities (24.3%), fatigue(24.3%), decreased appetite(18.9%), and hypertension(18.9%). The rate of drug withdrawal due to adverse reactions was significantly higher in patients receiving combination therapy compared to those receiving monotherapy (40.5% vs. 12.1%, P = 0.008). Conclusions: In elderly uHCC patients (≥65 years old), immune combination therapy shows a higher ORR and potentially longer PFS and OS except patients with ascites. AEs and drug withdrawal rates are higher in the combination therapy group. Further discussions are needed to determine the optimal treatment strategy for elderly uHCC patients.

Safety, efficacy, and survival of different transarterial chemoembolization techniques in the management of unresectable hepatocellular carcinoma: a comparative single-center analysis

PurposeTransarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE).MethodsThis retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4–6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4–6 weeks post-TACE and PFS were analyzed.ResultsThere were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4–6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436].ConclusionOur study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup.

Evaluation of the Safety and Efficacy of Conventional Transarterial Chemoembolization (cTACE) and Drug-Eluting Bead (DEB)-TACE in the Management of Unresectable Hepatocellular Carcinoma: A Systematic Review.

Transarterial chemoembolization (TACE) is considered the preferred loco-regional treatment option for hepatocellular carcinoma (HCC) not amenable to resection due to its distinctive blend of precise drug administration, localized tumor management, and reduced systemic adverse effects, setting it apart from the plethora of alternative treatments available. There is an ongoing debate regarding the optimal choice for managing HCC using TACE, particularly between its two major types: conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE). The medical community remains divided on which approach offers superior safety and efficacy, with conflicting evidence and varied outcomes adding to the complexity of this nuanced decision. Given the lack of consensus surrounding the preferred TACE technique in treatment-naive patients for HCC, we conducted a rigorous systematic review to assess and contrast the relative safety and efficacy of cTACE versus DEB-TACE in patients diagnosed with HCC who did not receive any prior treatment for HCC. Our study aimed to provide much-needed clarity on this controversial topic, shedding light on thetwo approaches' comparative safety and efficacy to inform clinical decision-making. After a comprehensive search of databases and search enginesand through a methodical screening process, including standardized quality assessmentsand relevant filterapplication based on our eligibility criteria, we identified 10 articles pertinent to our research query comprising two randomized controlled trials, one meta-analysis, and seven observational studies. The collective sample size of the studies was 5,288 patients with HCC, of which 2,959 were in the cTACE armand 2,324 were in the DEB-TACE arm.

Real-world registry of patients with unresectable hepatocellular carcinoma: The OREIOS study.

TPS618 Background: A majority of patients with hepatocellular carcinoma (HCC) are diagnosed with unresectable disease due to extensive extrahepatic spread, presence of multifocal tumors, poor hepatic function or tumor location near major intrahepatic vessels. The treatment landscape for unresectable HCC is rapidly evolving with availability of novel agents, mandating evidence-based therapeutic algorithm for optimum clinical outcomes. Integrating newly approved and emerging therapies in this extremely heterogeneous HCC population with coexisting risk factors (performance status, Child-Pugh class, macrovascular invasion or extrahepatic metastases, and alpha-fetoprotein levels) may pose challenge without understanding survival outcomes with the current treatment practices. Also, application of immunotherapy and targeted agents in clinical practice displays significant regional variations. Real-world evidence on the management of unresectable HCC is sparse across different geographies. The OREIOS study aims to describe the management patterns, clinical characteristics, possible predictors, and survival outcomes in patients with unresectable HCC in 12 countries across Asia, Latin America and the Middle East. The data may serve in devising policies on optimal patient selection and sequencing of novel systemic therapies for unresectable HCC. Methods: OREIOS is an ongoing multicenter, retrospective, non-interventional registry in adults diagnosed between 01 January 2017 and 31 December 2019 with unresectable BCLC stage B HCC, ineligible for initial loco-regional therapy or stage C advanced or metastatic disease, with at least 12 months (or until death if it occurs within 12 months of diagnosis) of available records. Patients with BCLC stage D and other concomitant metastatic cancers are excluded. Data collection includes socio-demographics, clinico-pathological characteristics, treatment modalities, survival outcomes, comorbidities and liver function status. Primary outcome measures include median overall survival using the Kaplan–Meier method and survival rates at 6, 12, 18 and 24 months. Secondary outcomes include clinico-demographic characteristics, treatment regimens (alone or combination) in each line of therapy and real-world progression-free survival. Additionally, prognostic and predictive factors for survival outcomes will be evaluated. Of the planned sample size of 1440 patients, a total of 473 patients with unresectable HCC have been enrolled until August 2022 across 7 countries (Egypt: 105, Hong Kong: 107, India: 79, Russia: 100, Saudi Arabia: 27, Singapore: 50, South Korea: 05). Data collection is currently ongoing and results are expected by 2024. Clinical trial information: NCT05239507 .

Hepatocellular Carcinoma Supplied by the Inferior Phrenic Artery or Cystic Artery: Anatomic and Technical Considerations.

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. ©RSNA, 2022.

Hepatic arterial infusion chemotherapy versus trans-arterial chemoembolization in unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

e16141 Background: Trans-arterial chemoembolization (TACE) has been one of the standard options for patients with unresectable hepatocellular carcinoma (HCC). Recent studies have shown that liver arterial infusion chemotherapy (HAIC) has favorable outcomes in these patients, but its use has been limited due to the need for technical expertise. In this systematic review and meta-analysis, we compared the efficacy and safety of HAIC vs. TACE for unresectable HCC. Methods: We performed a comprehensive literature search of PubMed, Embase, and Cochrane databases through January 12, 2022, for all peer-reviewed studies that compared the outcomes of HAIC vs. TACE in patients with large, unresectable HCC. Our primary outcomes were the objective response rate (ORR), disease control rate (DCR), and progressive disease (PD). The secondary outcomes were overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events (AEs). Pooled risk ratio (RR) and hazard ratio (HR) with the corresponding 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model. Heterogeneity was assessed using the Higgins I2 index. Results: Six studies (one randomized controlled trial [RCT], two non-randomized trials, and three retrospective cohort studies) were eligible for final analysis. A total of 899 patients were included for the final evaluation. HAIC was associated with significantly higher ORR (RR 2.70, 95% CI 2.06-3.55, P &lt; 0.001, I2= 10.1%) and DCR (RR 1.42, 95% CI 1.19-1.70, P &lt; 0.001, I2= 54.5%) and substantially reduced PD (RR 0.55, 95% CI 0.40-0.75, P &lt; 0.001, I2= 56.6%) compared to TACE. The median OS was significantly longer in the HAIC group, ranging from 11.4 to 23.1 months vs. TACE, ranging from 4 to 16.1 months (HR 0.49, 95% CI 0.28-0.85, P = 0.01 I2= 84.7%). The median PFS was significantly longer in the HAIC group, ranging from 5.5 to 9.6 months, vs. TACE, ranging from 1.5 to 5.4 months (HR 0.45, 95% CI 0.26-0.79, P = 0.001, I2= 84.6%). Notably, the incidence of grade≥3 AEs was lower in the HAIC group than in TACE (RR 0.61, 95% CI 0.47-0.80, P &lt; 0.001, I2= 16.4%). Conclusions: Compared to TACE, HAIC significantly improved ORR, DCR, and OS in unresectable HCC with a significantly better safety profile. However, our meta-analysis is hampered by the limited number of studies. Future large-scale multicenter RCTs are warranted to further evaluate the outcomes of HAIC vs. TACE in the management of unresectable HCC.

The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC)

Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BEDα/β = 10) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.

Comparison of two transarterial chemoembolization strategies for hepatocellular carcinoma

This retrospective study aimed to compare the efficacy of and tolerance to two center-related conventional transarterial chemoembolization (TACE) strategies in the management of unresectable hepatocellular carcinoma (HCC). All HCC patients in whom TACE was initiated in the two centers from July 2008 to June 2016 were included. The TACE strategy performed in center 1 was "on demand" with selective injections of idarubicin, whereas the TACE strategy in center 2 was based "on scheduled" non-selective injections of epirubicin. Toxicity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events. One hundred and fifty HCC patients were included. Median time to treatment failure was significantly higher in center 1, 13.1 months vs. 7.9 months in center 2 (hazard ratio, 2.32; p < 10-3 in multivariate analysis). Median overall survival was 21.1 months in center 1 vs. 18.4 months in center 2 (p = NS). The proportion of grade ≥ 3 adverse events and mean hospitalisation duration for the overall TACE treatment were significantly greater in center 2 than in center 1: 56% vs. 32% (p < 0.01) and 14.2 ± 7.2 days vs. 10.3 ± 7.0 days (p < 0.01), respectively. Our results failed to show any significant survival differences between two center-related TACE strategies but showed a significantly smaller proportion of grade ≥ 3 adverse events and shorter hospitalisation for the overall treatment when the "on-demand" strategy was used.

Safety of nivolumab in combination with prior or concurrent radiation therapy in hepatocellular carcinoma

Nivolumab has been demonstrated to be effective for the treatment of unresectable hepatocellular carcinoma (HCC). While many patients may additionally benefit from radiation therapy (RT), the toxicity of combination nivolumab and RT is unknown. Patients who underwent liver-directed RT prior to or concurrent with nivolumab for HCC at our institution were reviewed. Toxicity was assessed by Common Terminology Criteria for Adverse Effects v5.0 criteria until disease progression, change in systemic therapy, additional liver-targeted locoregional therapy (LRT), or death. Prevalence ratios (PR) were compared for patients undergoing prior and concurrent RT. Childs-Turcotte-Pugh (CTP) and Albumin-Bilirubin (ALBI) scores at 1-, 3-, and 6-months were compared with baseline. We identified 55 patients with median follow-up 6.0 months; 34 (62%) received prior and 21 (38%) received concurrent RT. Grade 3+ toxicity occurred in 8 patients (17%). Grade 3+ toxicities did not differ between prior and concurrent RT cohorts on the univariable analysis (PR 1.91; 95% CI 0.42, 8.59) but were higher in the prior RT cohort on the multivariable analysis (PR 5.42; 95% CI 1.42, 20.67; p = 0.013). Mean CTP scores increased from baseline (6.33) at 1 month (7.04; 95% CI 6.80, 7.27) and 3 months (6.81; 95% CI 6.43, 7.19) and thereafter normalized; mean ALBI scores increased from baseline (− 1.93) at 1 month (− 1.75; 95% CI − 1.84, − 1.66) with no difference thereafter. Combination RT and nivolumab is generally safe in the management of unresectable HCC with a low rate of serious adverse events. Prospective trials investigating the efficacy of combination nivolumab and RT are warranted.

Treatment outcomes of unresectable hepatocellular carcinoma by transarterial chemoembolisation combined with radiofrequency ablation

Background: Hepatocellular carcinoma (HCC) is one of the most common cancer and ranks third in terms of cancer related deaths. The majority of patients are not eligible for curative treatment because of local or distal progression of tumor. RFA treatment following TACE has some advantages over TACE alone. The purpose of this study was to evaluate the effectiveness and survival benefits of the TACE+RFA approach to the management of unresectable HCCs in Hue Central Hospital, Vietnam. Methods: A prospective, cohort study on 60 patients, diagnosed with unresectable HCCs and treated with TACE combined with RFA at Hue Central Hospital from 1/2016 – 1/2019. All clinical and paraclinical data and adverse effects of each treatment, tumor response rate assessed by m-RECIST criteria, survival rate and other adverse events from the first treatment were documented. Results: There were no major complications after combined therapy except for two cases (1.4%) of liver failure treated successfully with conservative therapy. Tumor control rate (CR+PR) at three months after the last treatment was 81.6%. All patients were followed-up closely after treatment and additional treatments were decided based on imaging and laboratory results. The mean follow-up time was 19.3 (4 – 30) months. The 1-year and 2-year survival rates were 71.7% and 58.3%, respectively. Conclusion: Combination therapy with TACE and RFA is an effective, safe and feasible option for patients with unresectable HCCs. Key words: Hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE), radiofrequency ablation (RFA) 1

Gas Embolization in a Rodent Model of Hepatocellular Carcinoma Using Acoustic Droplet Vaporization.

Trans-arterial embolization is a commonly used therapy in unresectable hepatocellular carcinoma. Current methods involve the careful placement of an intraarterial catheter and the deposition of embolizing particles. Gas embolotherapy has been proposed as an embolization method with the potential for high spatial resolution without the need for a catheter. This method involves vaporizing intravenouslyadministered droplets into gas bubbles using focused ultrasound - a process termed acoustic droplet vaporization. The bubbles can become lodged in the vasculature, thereby creating an embolus. Here, we initially demonstrate the feasibility of achieving significant targeted embolization with this method in the rat cremaster using intravital microscopy. The therapy was then tested in an ectopic xenograft mouse model of hepatocellular carcinoma. Gas embolotherapy was shown to maintain the tumor volume at baseline over a twoweek treatment course while control groups showed significant tumor growth. These preliminary results demonstrate thatgas embolotherapy could serve as an effective noninvasive method for the management of unresectable hepatocellular carcinoma.

Current guidelines for chemoembolization for hepatocellular carcinoma: Room for improvement?

Transarterial chemoembolization (TACE) is the most common oncologic therapy used according to the American Association for the Study of Liver Diseases (AASLD) guidelines established in 2005, revised in 2011. The purpose of this study was to determine how AASLD criteria for the management of hepatocellular carcinoma (HCC) have impacted TACE practice in the community. Clinical, demographic, and cause of death information were collected for patients diagnosed with HCC in the 2012 linkage of the Surveillance, Epidemiology, and End Results Medicare database. Propensity score survival analysis was used to compare survival outcomes in patients whose HCC tumor characteristics were less than, met, or were beyond AASLD criteria. The proportion of patients with HCC receiving TACE who met the AASLD‐recommended criteria increased after the 2005 guidelines were published. Up to 17% of patients treated with TACE had tumor characteristics less than the AASLD criteria and were not offered potentially curative therapies. Propensity score matching demonstrated the largest survival advantage in patients with HCC whose tumor characteristics met the AASLD criteria (hazard ratio, 0.42; 95% confidence interval, 0.38‐0.47). A significant survival advantage was also observed in patients with HCC whose tumor characteristics exceeded the AASLD criteria. Conclusion: The AASLD criteria successfully identify a population of patients with HCC that maximally benefit from TACE therapy. However, patients with HCC with tumor characteristics beyond the AASLD criteria also appear to receive a significant survival advantage with TACE. Further studies are necessary to improve referral patterns and appropriate use of chemoembolization in the management of unresectable HCC. (Hepatology Communications 2017;1:338–346)

Sorafenib-based regimens in the management of unresectable hepatocellular carcinoma: an updated meta-analysis of randomized controlled trials

Sorafenib-based regimens in the management of unresectable hepatocellular carcinoma: an updated meta-analysis of randomized controlled trials

Role of yttrium-90 in the management of unresectable hepatocellular carcinoma and hepatic metastases.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The management of unresectable HCC and hepatic metastases from various solid tumors is a clinical dilemma. There is paucity of data on the treatment of unresectable HCC and hepatic metastases with yttrium-90 (90Y) radioembolization. Thirty patients (mean age; 55.2years; range 43-82years) comprising 21 patients with HCC (12 patients have cirrhosis of which 3 patients belong to Child-Pugh class A and 9 patients belong to Child-Pugh class B), 7 patients with metastasis from colorectal cancer, 1 patient with metastasis from melanoma, and 1 patient with metastasis from ovarian carcinoma underwent resin-based 90Y radioembolization between 2013 and 2015 in our study. In all the patients, after embolization of non-target vasculature, SPECT and planar scintigraphy were done with the injection of 5-6mCi (185-222MBq) of 99mTc-labeled macroaggregated albumin (MAA) into the hepatic artery. Then, lung shunt fraction was assessed and dose was calculated based on body surface area (BSA) method for SIR-Spheres. Post therapeutic 90Y bremsstrahlung SPECT and 90Y PET was performed within 30 hours following therapy to see the hepatic and extrahepatic distribution of spheres. Side effects following therapy were noted in all the patients. All patients were followed up with triphasic CT liver 3months following therapy. Therapeutic response was evaluated with necrosis criteria used for therapy response assessment in solid tumors. On follow up, 14 patients (46%) developed minor side effects following treatment and resolved without active intervention. The most common side effects include mild abdominal pain in 11 patients (36%), nausea in 8 patients (26%), and fatigue in 6 patients (20%). On follow up imaging at 3months following treatment, a complete response was observed in two patients (7%), partial response in seven patients (23%), stable disease in 15 patients (50%), and progressive disease in six patients (20%). This study provides supportive evidence of the safety and efficacy on 90Y radioembolization for the treatment of unresectable HCC and hepatic metastases from various solid tumors. 90Y PET is a better radionuclide technique for assessing the hepatic and extrahepatic distribution of spheres following therapy compared to 90Y Bremsstrahlung SPECT. Thus, 90Y radioembolization is proving to be promising treatment with average disease control rates around 80% and should be widely utilized.

A Rare Primary Liver Tumor That Responded to Sorafenib

A Rare Primary Liver Tumor That Responded to Sorafenib

Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and published work review.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. In the last few decades, there has been a marked increase in therapeutic options for HCC and epidemiological characteristics at HCC diagnosis have also significantly changed. With these changes and advances in medical technology and surveillance program for detecting earlier stage HCC, survival in patients with HCC has significantly improved. Especially, patients with liver cirrhosis are at high risk of HCC development, and regular surveillance could enable early detection of HCC and curative therapy, with potentially improved clinical outcome. However, unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation, surgical resection or ablative therapies). Locoregional therapies such as radiofrequency ablation, percutaneous ethanol injection, microwave coagulation therapy and transcatheter arterial chemoembolization play a key role in the management of unresectable HCC. Currently, molecular-targeted agents such as sorafenib have emerged as a promising therapy for advanced HCC. The choice of the treatment modality depends on the size of the tumor, tumor location, anatomical considerations, number of tumors present and liver function. Furthermore, new promising therapies such as gene therapy and immunotherapy for HCC have emerged. Approaches to the HCC diagnosis and adequate management for patients with HCC are improving survival. Herein, we review changes of epidemiological characteristics, prognosis and therapies for HCC and refer to current knowledge for this malignancy based on our experience of approximately 4000 HCC cases over the last three decades.

Stereotactic body radiation therapy following transarterial chemoembolization for Child-Pugh A and B hepatocellular carcinoma.

321 Background: Hepatocellular carcinoma (HCC) incidence continues to increase, but recent improvements in treatment of localized tumors have contributed to modest gains in survival rates. Though transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) are increasingly used in the management of unresectable HCC, outcomes data regarding the combination of these treatments is limited. Here we report institutional outcomes for patients with Child-Pugh A (CPA) and B HCC treated with TACE followed by SBRT. Methods: We completed an institutional retrospective review of all patients treated with combination TACE and SBRT between 2009 and 2013. After compiling dosimetry, toxicity, and outcomes data for each patient we calculated descriptive statistics for the cohort and determined local control (LC), distant liver control (DLC), progression free survival (PFS), and overall survival (OS) utilizing the Kaplan-Meier method. We also compared these disease-related outcomes between CPA and CPB groups with the Mantel-Cox test for equality. Results: Thirty-one patients with HCC, median age 65, were treated with TACE and SBRT and followed for a median 16.6 months (range: 6.2-50.8). Twenty-two patients had CPA disease and 9 CPB at the time of initial treatment. Following TACE and a median interval of 10.5 days (range: 4.4-25.6) patients underwent SBRT, the majority (23) with 45 Gy in 3 fractions. All but 3 patients were treated with respiratory gating, and all had cone-beam CT for image guidance. One and 2 year disease-related outcomes were as follows: LC 92.0 and 82.8%, DLC 81.5 and 61.0%, PFS 73.6 and 61.8%, OS 96.8 and 64.2%. There were no statistically significant differences between CPA or CPB patients with respect to any of these disease-related outcome measures. Median survival times for class A and B patients were 34.2 months (95% CI 12.3-56.1) and 27.2 months (14.9-39.5) respectively. Conclusions: The combination of TACE and SBRT is generally well tolerated, and results in very good local control in both CPA and CPB patients. Distant liver failure remains a major problem in these patients and requires further study.

Combined interventional therapies of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis. Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades, the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone, and play more important roles in treating unresectable HCC.

Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon's perspective.

This article reviews the current results of various locoregional therapies for hepatocellular carcinoma (HCC), with special reference to the implications for surgeons. Resection or transplantation is the treatment of choice for HCC, but most patients are not suitable candidates. The past decade has witnessed the development of a variety of locoregional therapies for HCC. Surgeons are faced with the challenge of adopting these therapies in the management of patients with resectable or unresectable HCC. A review of relevant English-language articles was undertaken based on a Medline search from January 1990 to August 2001. Retrospective studies suggested that transarterial chemoembolization is an effective treatment for inoperable HCC, but its perceived benefit for survival has not been substantiated in randomized trials, presumably because its antitumor effect is offset by its adverse effect on liver function. Nonetheless, it remains a widely used palliative treatment for HCC not amenable to resection or ablative therapies, and it also plays an important role as a treatment of postresection recurrence and as a pretransplant therapy for transplantable HCC. Better patient selection, selective segmental chemoembolization, and treatment repetition tailored to tumor response and patient tolerance may improve its benefit-risk ratio. Transarterial radiotherapy is a less available alternative that produces results similar to those of chemoembolization. Percutaneous ethanol injection has gained wide acceptance as a safe and effective treatment for HCCs 3 cm or smaller. Uncertainty in tumor necrosis limits its potential as a curative treatment, but its repeatability allows treatment of recurrence after ablation or resection of HCC that is crucial to prolongation of survival. Cryotherapy affords a better chance of cure because of predictable necrosis even for HCCs larger than 3 cm, but its use is limited by a high complication rate. There has been recent enthusiasm for heat ablation by microwave, radiofrequency, or laser, which provides predictable necrosis with a low complication rate. Preliminary data indicated that radiofrequency ablation is superior to ethanol injection in the radicality of tumor ablation. The advent of more versatile radiofrequency probes has allowed ablation of HCCs larger than 5 cm. Recent studies have suggested that combined transarterial embolization and heat ablation is a promising strategy for large HCCs. Thus far, no randomized trials comparing various thermoablative therapies have been reported. It is also uncertain whether a percutaneous route, laparoscopy, or open surgery affords the best approach for these therapies. Thermoablative therapies have been combined with resection or used to treat postresection recurrence, and they have also been used as a pretransplant therapy. However, the value of such strategies requires further evaluation. Advances in locoregional therapies have led to a major breakthrough in the management of unresectable HCC, but the exact role of the various modalities needs to be defined by randomized studies. Novel thermoablative techniques provide the surgeon with an exciting opportunity to participate actively in the management of unresectable HCC. Locoregional therapies are also useful adjuncts in the management of patients with resectable or transplantable disease. Hence, surgeons must be equipped with the latest knowledge and techniques of ablative therapy to provide the most appropriate treatment for the wide spectrum of patients with HCC.

A LONG SURVIVED CASE OF UNRESECTABLE HEPATOCELLULAR CARCINOMA AFTER ONE-SHOT CHEMOTHERAPY AND TRANSCATHETER ARTERIAL EMBOLIZATION

We report a case of advanced liver cirrhosis with unresectable hepatoma for which one-shot chemotherapy and transcatheter arterial embolization resulted in a successful long survival. A 70-year-old woman was diagnosed to have unresectable hepatocellular carcinoma by clinical examinations such as angiography and serum α-fetoprotein (AFP) assay in October 1984. She was treated with intra-arterial one-shot injection of 5-FUR and Mitomycin CR for the first time in December 1984 and hereafter within 2 years, repeated TAE using mainly gelfoam powderR and so-called SMANCS/Lipiodol therapy were performed periodically. Treatment was well tolerated. She has been well during these treatments. A combination of intraarterial injection of anticancer drugs and transcatheter arterial embolization is an effective treatment in the management of unresectable hepatocellular carcinoma.