23/07/2023
问题 1：
陈医生你好，
我的母亲今年 60 岁，患有肝癌第三期，肝肿瘤有 5 公分大，而且侵犯到门静脉。专科医生的
建议是放疗、化疗和手术，我看到有关你说的介入治疗，所以想知道是否还有转机？
我妈妈没有糖尿病、高血压，只有高胆固醇，有吃胆固醇药。 医生认为我的妈妈的情况
还算健壮。
My mother is 60 years old and has stage 3 liver cancer. The liver tumor is 5 cm large and invades the portal vein. The specialist's suggestion is radiotherapy, chemotherapy and surgery.
I saw about the interventional treatment you mentioned, so I wonder if there is still a chance?
My mother does not have diabetes, high blood pressure, only high cholesterol, and takes cholesterol medicine. The doctor thinks my mom's condition is srill fairly strong.
Q1： 请问我妈妈的情况是否适合做介入治疗？ 程序是如何？May I ask whether my mother's condition is suitable for interventional therapy? What is the procedure?
Based on the clinical information provided, the patient is a 60 year old female with good clinical status. The liver cancer is a 5 cm tumor with portal vein invasion, stage 3, which means BCLS stage C.
She has hypercholesterolaemia. No DM or HPT. The hepatitis status is not mentioned.
Answer:
HCC is usually associated with liver cirrhosis/hepatitis. We have two diseases to manage simultaneously, and the treatment involves an intricate balance between one and another.
In the management of liver cancer, an MDT team encompassing a hepatologist/
gastroenterologist, interventional radiologist, oncologist and a hepatobiliary surgeon, is necessary.
On the clinical front, we need to ascertain if the liver cancer is arising de -novo, or it is
related to background liver cirrhosis (of hepatitis B, C in origin, or alcohol/other
diseases related). The survival outcome varies.
Optimal management of back ground cirrhosis and control of hepatitis are utmost critical in the suppression of background hepatitis, improving liver function, survival prolongation, optimising tumor control and suppression of tumor recurrence.
In this patient, the presence of portal vein invasion (BCLC-C) is a poor prognostic factor and it
impedes severely on the survival outcome. The survival in stage C is less than 2 years in general.
The treatment intent in a HCC BCLC stage C disease would be primarily palliative, i.e., reducing tumor burden (or eradication of tumor if feasible), prolonging objective survival (OS), and improving quality of life.
The current clinical management options of a BCLC stage 3 liver cancers are:
a. Interventional oncology management:
1. Transarterial chemoembolization (conventional TACE, cTACE or drug eluting bead (DEB) TACE).
DEB TACE is similar to cTACE in survival outcome, but has fewer side effects and toxicity to the liver.
Both procedures involve the insertion of a tiny catheter via an artery in the groin or the left wrist, guided under fluoroscopic control. The catheter is navigated into the artery supplying the tumor in the liver.
Chemotherapeutic drugs are injected directly in to the tumor. The blood vessel is closed (embolised) with gelatin
sponges or microsphere after the chemotherapy drug administration.
For TACE as a monotherapy in BCLC stage C HCC, the local disease control rate of a 5 cm tumor with PV invasion is suboptimal. It must be
in combination with another treatment modality as a complete respond (CR) of a 5 cm tumor in the absence of PV invasion is < 20%. In those
without portal vein invasion, an adjunctive microwave ablation post TACE offers a good respond with 95% tumor control rate.
In the presence of portal vein invasion, the portal venous thrombus is often not
adequately eradicated by TACE.
2. SIRT, selective intraarterial radiation therapy with Yttrium 90
A SIRT is an amenable option in the consideration of transarterial
therapy. It is also a transarterial therapy technique, but a radioactive substance is injected into the tumor, instead of the chemotherapy agents.
SIRT is primarily indicated in intermediate stage and stage C HCC. It involves two sessions of angiogram, the first session is in assessment of the blood supply to the tumor, and its potential arteriovenous shunting
to the lung. If the lung shunting measures >10%, or if the blood supply to the tumor has connection to bowel or extrahepatic c irculations, it is
contraindicated. If suitable, a full dose of the radioactive beads
(Yttrium90) will be administrated on the second angiogram.
In SIRT for HCC, Rognoni in his meta-analysis of 21 published reports (Rognoni et. al., Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: Systematic review and meta-analyses. Oncotarget. 2016;7(44):72343–55)
showed that the pooled OS was 63% and 27% at 1- and 3-years respectively in intermediate- stage HCC, whereas OS was 37% and 13% at 1- and 3-years respectively in advanced HCC because of the presence of portal vein thrombosis.
SHARP trial (A Phase III Study of Sorafenib with SIRT in Patients With Advanced
Hepatocellular Carcinoma) reported a median overall survival 14.5 months in BCLC B
stage patients, and 9.7 months in BCLC stage C patients in the presence of major vascular invasion. The disease control rates were 50% versus 42%, respectively. This denotes a dismay survival statics for a BCLC stage C HCC.
However, with the new treatment protocol using high dose radiation segmentectomy in isolated tumor, a better respond rate has been reported.
This is a feasible option to consider should she passes the lung shunting test.
b. Systemic therapy: Monotherapy with either immunotherapy, e.g. atezolizumab + bevacizumab (IMBrave150), or tyrosine kinase inhibitor, e.g. Lenvatinib.
Immunotherapy has become a mainstay therapy by the BCLC
recommendation.
On the IMBrave150 clinical trial, (Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma, J Hepatol 2022), 501 pts were enrolled. Median objective survival (OS) was 19.2 month with immunotherapy, comparing with 13.4 months
with control drug (sorafenib). The survival at 18 month was 52%. The objective response rate was 29.8%. Median progression free survival, PFS was 6.9 months.
Treatment-related grade 3/4 adverse events occurred in 43%, grade 5 in 2% of the patients.
Similarly, Lenvatinib also provide almost similar tumor control rate in 30% of the treated groups. This means in every 100 patients treated with immunotherapy or Lenvatinib, 70% of the patients will fail and the cancer will
progress.
c. Combination therapy with transarterial ethanol embolisatio n/DEB TACE, and systemic tyroxine kinase inhibitor.
In our experience, this treatment protocol has been giving good clinical respond. We achieved a good number of local tumor control with ethanol embolisation/DEB TACE; and maintenance systemic treatment
for tumor suppression with Lenvatinib. Our objective respond rates exceeds 90%.
Immunotherapy may be commenced if Lenvatinib shows
interval loss of efficacy.
Combination therapy is a mainstay of treatment
recommendation in advanced HCC for a better survival outcome.
d. Open surgery with hemihepatectomy: This is an BCLC off-guideline treatment
option and it is only feasible if the portal vein invasion is minimal. Major portal vein invasion is contraindicated as major recurrence in short term due to underlying occult transvenous metastases is a major concern. Open surgery
carries significant complications and major surgical risks. The liver reserve has to be good, and the clinical status has to be strong.
Surgery however is a possible adjunctive option should the tumor achieves a good downstaging and local control after the initial treatments for a better long-term outcome.
e. SBRT:
Stereotacticr adiotherapy. This is not a routine recommendation but is useful as an adjunctive or a combination treatment modality after TACE or systemic treatment.
Q2： 传统治疗后复发的机会是不是比介入治疗较高？
In the treatment of liver cancer, the primary aim is to have the tumor
eradicated and to put the disease into remission. The treatment outcome varies
between each patient, the tumor burden, disease stage and the liver reserve as well as
the compounding chronic medical illness. Whilst this patient is said to be “well”, we
have no detailed information on her liver function, degree of liver cirrhosis, presence
or absence of portal hypertension, etc. Overall, a stage C HCC has limited survival of
