1. The document discusses neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma (HCC), including transarterial chemoembolization (TACE), transarterial radioembolization (TARE), systemic therapy, and antiviral therapy in the neoadjuvant setting as well as antiviral therapy, systemic therapy, hepatic artery infusion, TACE, radiolabeled lipiodol, ablation, and radiation therapy in the adjuvant setting. 2. While neoadjuvant strategies are not routinely recommended, some studies have found that preoperative TACE can lead to complete tumor necrosis and improved disease-free survival for patients who achieve this. 3. Adjuvant

1. Neoadjuvant and adjuvant treatment
strategies for hepatocellular carcinoma
Clifford Akateh, Sylvester M Black, Lanla Conteh, Eric D Miller, Anne Noonan, Eric Elliott,
Timothy M Pawlik, Allan Tsung, Jordan M Cloy, World J Gastroenterol 2019 July 28, Ohio
State University
EKO RISTIYANTO
JURNAL READING Prospect of novel approaches

2. INTRODUCTION : HCC
1. High mortality, third in men, seventh in woman
2. Majority of HCC : chronic liver disease (CLD), chronic hepatitis B (HBV)
and hepatitis C (HCV) infections, non-alcoholic steatohepatitis (NASH)
and non-alcoholic fatty liver disease (NAFLD)
3. Simultaneous challenges HCC : malignancy itself and underlying liver
disease
4. Numerous systemic and locoregional treatments for HCC
5.Curative-intent mainly: surgical resection, liver
transplantation (LT), and ablative therapies

3. Core tip
1. Neoadjuvant and adjuvant treatment strategies aimed at
improving resectability and decreasing recurrence rates
2. While high-level evidence to guide treatment decision
making is lacking
3. Locoregional and systemic therapies (neoadjuvant or
adjuvant) as novel approaches that may improve the
outcomes HCC

4. The role of NEOADJUVANT STRATEGIES
FOR HCC
1. Less well defined.
2. Relatively little research exists to support the concept of neoadjuvant
therapy
3. Current guidelines do not recommend this strategy for patients with
otherwise potentially resectable cancers.
4. Unique characteristics of HCC, including its relatively aggressive
biology, frequent diagnosis at late stages, and the need to preserve
normal liver function at the time of surgery

5. 1. Transarterial chemoembolization
TACE was originally developed for management of advanced
unresectable disease, but its role in the neoadjuvant treatment of
potentially resectable
TACE is commonly used as a bridging therapy prior to LT,
neoadjuvant setting prior to resection remains unclear and is not
routinely recommended
Qi et al, 2015 Meta-analysis: preoperative TACE did not improve
DFS or OS. a subgroup analysis
◦ Complete tumor necrosis following TACE, preoperative TACE had significantly
better DFS and OS compared to resection alone
◦ Incomplete or no tumor necrosis, the OS did not differ between the two
groups.

6. 2. Transarterial radioembolization (TARE)
1. As an alternative to TACE  90Yttrium (Y-90), for potentially
resectable patients,
2. TARE leads to hypertrophy of the contralateral future liver
remnant (FLR) and combined with PVE to successfully
downstage HCC

7. 3. Systemic therapy
1. Few effective systemic therapy for HCC.
2. In 2007, the tyrosine kinase inhibitor (TKI) Sorafenib : Childs
A cirrhosis and unresectable or metastatic HCC  new
agents: Lenvatinib, cabozantinib, regorafenib, and
ramucirumab
3. Imunotherapy? Nivolumab, etc. Investigations in the neoadjuvant
setting are ongoing at this time

8. 4. Anti-viral therapy
Antiviral therapy prior to resection of HCC should be
considered as part of the multidisciplinary treatment of
these patients

9. ADJUVANT STRATEGIES FOR HCC
1. Decrease incidence of HCC recurrence
2. recurrences following resection two patterns: early and late.
◦ Early : margin positivity, vascular invasion, etc.)
◦ late recurrences are more likely related to underlying CLD and the
development of de novo tumors

10. 1. Antiviral therapy
Therapy following resection of HBV or HCV related
HCC may improve outcomes
◦ pegylated interferon (PEG-IFN)
◦ direct-acting antiviral drugs (DAA)
◦ nucleoside analogs

11. 2. Systemic therapy
1. Systemic chemotherapy with is commonly used advanced and
metastatic HCC, its use following curative resection is controversial.
2. Some early studies suggested adjuvant systemic chemotherapy
3. Some studies have shown associated with worse outcomes

12. 3. Hepatic artery infusion pump
1. Raarely used in clinical practice for HCC
2. More commonly used in the management of colorectal liver
metastases, its role in HCC remains limited.
3. Decreased intrahepatic recurrence, decreased RFS and OS at 5 years
4. Regimen: 5-fluorouracil (1000 mg/m2), oxaliplatin (85 mg/m2), and
mitomycin-C (6 mg/m2) was used in this trial, and started within 3 wk
of surgery

13. 4.TACE
1. Patients in the TACE arm had significantly less recurrence and longer
RFS and OS
2. Benefit in high-risk patients (tumor > 5 cm or vascular invasion)

14. 5. Radiolabeled lipiodol
1. Ability of lipiodol to accumulate in HCC relative to normal liver
2. Injection into hepatic artery resulted in tumor necrosis
3. Ability of lipiodol to accumulate in HCC relative to normal liver
4. Not routinely used in clinical practice

15. 6. Ablation
Local-regional directed therapy in patients with nonmetastatic disease.
◦ radiofrequency ablation (RFA)
◦ percutaneous ethanol injection (PEI),
◦ microwave ablation
◦ Irreversible electroporation

16. 7. Radiation therapy
1. dose-volume effects has allowed for the use stereotactic body radiation
(SBRT)
2. benefit in patients where adequate margins are not attainable

17. CONCLUSION
1. Resection remains an important curative-intent treatment that should be
pursued for patients with resectable disease and appropriate liver
function
2. Multimodality therapy is increasingly being explored in order to increase
the number of patients who are surgical candidates
3. Neoadjuvant transarterial therapies can successfully downstage
advanced tumors to resection and more commonly used as a bridging
therapy prior to LT
4. HCC and Viral hepatitis, aggressive treatment with antivirals, before or
after resection, improves outcomes and should be pursued
5. Multidisciplinary management of HCC

18. Thank You

19. Introduction
Surgical resection and liver transplantation are recognized as the
most effective treatments to patients with HCC
For some resectable HCC, surgical resection is comparable with
liver transplantation on the long-term prognosis and more affordable
on physical, psychological or economic conditions
pre-TACE for curative resection of HCC is still controversial
Evaluated the prognostic indicators, postoperative morbidity
rate,
perioperative mortality, blood loss, operation time and
combined
resection rate of perihepatic organs into consideration

20. Tengfei Si, Yongjun Chen, Di Ma, Xiaoyong Gong, Kui Yang, Ruoyu Guan &
Chenghong Peng, 2016
Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong
University School of Medicine, Shanghai, China
Preoperative transarterial chemoembolization for
resectable hepatocellular carcinoma in Asia area: a
meta-analysis of random controlled trials

21. ConclusionThis meta-analysis
1. Statistical difference between pre-TACE group and Control group on
perioperative mortality, blood loss, OS or DFS.
2. Pre-TACE treatment cannot improve the long-term prognosis of
resectable hepatocellular carcinoma.
3. Subgroup analysis revealed that in subgroup with tumor diameter
above 5 cm, pre-TACE would result in longer operation time, higher
postoperative morbidity rate and combined resection rate of
perihepatic organs.
4. Pre-TACE is not suitable to be recommended as the routine therapy for
resectable HCC patients

22. Hepatic resection alone versus in combination with preand
post-operative transarterial chemoembolization for the
treatment of hepatocellular carcinoma: A systematic review and
meta-analysis
1. Preoperative TACE can lead to complete necrosis of HCC in selected cases, thereby improving
the DFS after hepatic resection.