基本资料

Male, 55 yo, Hepatitis B virus (+), Cirrhosis

2008, sHCC(1cm), 4 times TACE, normal AFP

TACE: 2009.1, 2009.4, 2010.1, 2011.8

2014.12 HCC recurrence, AFP 41ng/ml

2015.2.15 Orthotopic Liver Transplant (piggy back)

Liver function: Child C

                            辅助检查

Pathology:

Cirrhosis, far advanced HCC (10cm, LL)

Portal vein tumor thrombosis (Vp3)

Moderate-poor differentiation

“no touch” technique

Total Hepatectomy

-Clamping infrahepatic vena cava

-Clamping suprahepatic vena cava

-Mobilize the liver

-Remove the diseased liver

Benefits & advantages

-Reduce intraoperative hemorrhage

-Reduce risk of pulmonary embolism

-Reduce the risk of tumor metastasis

Customized Immunosuppression

POD immunosuppressant:

-Steroid-free (1000mg intraoperative) regimen 

-Induction with IL2RA (basiliximab 20mg on POD 0&4),     delaying Tac initiation by 3-5 days

-Low dose Tac (Through 6-10ng/ml within 3 months, 6-12 months 3-5ng/ml, beyond 12 months less than 3ng/ml)

-Mycophenolate mofetil (MMF) 1000mg BID 

Post-transplant management

-2015.8.31 Lung metastasis (1.5cm, right)

-Video-assisted thoracoscopic wedge resection 

-Pathology: poorly differentiated metastatic tumor

-2016.8.3 Lung metastasis (multiple, bilateral)

-3 times of mFOLFOX6 chemotherapy

mFOLFOX6:奥沙利铂130mg d1+CF 700mg d1+5-FU 3500mg civ 46h Q2W 

Date: 2016-09-12、2016-9-26、2016-10-10 

-1 time of GS chemotherapy

 GS :吉西他滨1.8g d1+替吉奥60mg bid d1-7

 Intolerance: III°骨髓抑制，不能耐受停用

-TKI: Sorafenib 400mg BID

 PD

-2016.12.19 Immunotherapy (NK cell)

2 times of NK cell therapy

Injection of 6.4 × 109 NK cells for 3 days

Date: 2016.12.19-2016.12.21; 2017.1.1-2017.1.3

-1 time of bronchial artery chemoembolization

-2017.9.29: T3, T4 bone metastasis

唑来膦酸Zoledronic acid

SD→PD

-2017.10.6-2019.4.9 Immunotherapy (PD-1 inhibitor)

Opdivo 200mg Q2W x 31 times

Date: 2017-10-6，2017-10-20，2017-11-03，2017-11-21，2017-12-06，2017-12-20，2018.01.04，2018.1.18，

2018-2-3，2018.2.20，2018.03.06，2018-03-20，2018-04-04，2018.4.17，2018.5.2，2018-5-17，2018.6.5，

Initial: Sorafenib 400mg BID

PD

2018-6-21，2018-7-12，2018-8-3，2018.9.13，2018.9.28，2018.10.11, 2018.10.31，2018.11.20，2018-12-13，

Intolerance

2019-1-4，2018-01-24，2019-2-22，2019-03-15，2019-04-09 

Pleural effusion

-TKIs

2018.3.19 Regorafenib 80mg qd

2018.3.26 Anlotinib 12mg qd D1-14 q3w

2019.2.22 Apatinib 250mg qd

2019.3.6   Levatinib 8mg qd

SD, no rejection

One month before treatment

September 2017

One year after treatment

September 2018

Biological response: AFP

Biological response: PIVKA-II

Summary of treatment with ICIs for recurrent HCC

DISCUSSION

Liver 15–40%   Extrahepatic 50–60% 

Liver + Extrahepatic 30–40% 

Lung metastasis 40~60%

Bone metastasis 25~30%

Management of Recurrent HCC: 

Hangzhou experience

Data from our center (293 HCC, 64 pts recurrence) (2016.1.1-2017.12.31)

Treatment modality for recurrence % 

Surgery: 15/64 (23.4%)

TACE: 14/64 (21.9%)

RFA: 6/64 (9.4%)

Systematic chemotherapy: 32/64 (50%)

Molecular targeted therapy (sorafenib,    

     regorafenib, lenvatinib, apatinib): 33/64 (51.6%)

External beam radiation: 5/64 (7.8%)

Immunotherapy (PD-1 inhibitor): 3/64 (4.7%)

Best supportive care: 9/64 (14.1%)

Recurrent HCC treatment: 

surgical treatment is the priority 

TKIs for advanced HCC

Sorafenib as the First-line 

systemic treatment

PFS:  ≈   1 y

Combinated with immunotherapies  such as:  NK cell, PD-1 inhibitor

索拉非尼耐药后瑞戈非尼序贯治疗

Retrospective, multicentre, international study

索拉非尼耐药后瑞戈非尼序贯治疗: 肝癌肝移植术后肿瘤复发患者总体生存时间平均延长38.4个月

肝癌的免疫治疗疗效

局部治疗+免疫治疗/靶向治疗的联合

TKIs+ICIs: long-lasting response

SUMMARY