There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The Western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.
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Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines Sun Hyun Bae, Seok-Joo Chun, Joo-Hyun Chung, Eunji Kim, Jin-Kyu Kang, Won Il Jang, Ji Eun Moon, Isaure Roquette, Xavier Mirabel, Tomoki Kimura, Masayuki Ueno, Ting-Shi Su, Alison C. Tree, Matthias Guckenberger, Simon S. Lo, Marta Scorsetti, Ben J. Slotman International Journal of Radiation Oncology*Biology*Physics.2024; 118(2): 337. CrossRef
Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis? Jung Wan Choe, Hye Yoon Lee, Chai Hong Rim World Journal of Gastroenterology.2022; 28(7): 704. CrossRef
A prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal
that the median survival is 2 to 4 months without treatment. Sorafenib, the standard regimen of
advanced HCC, can prolong median survival only 1.5 months. A 50-year-old man with a history
of chronic hepatitis B was diagnosed advanced HCC with PVTT. By a multidisciplinary medical
team approach, the combination of 3-demensional conformal radiation therapy with sequential
sorafenib was challenged. 4 months after initiation of treatment, he achieved partial response
as modified response evaluation criteria in solid tumors criteria. Sorafenib was continued so
far, and stable disease has been maintained up to now, without significant adverse effect.
Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients
with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative
treatment because of relatively high local recurrence rate. Moreover, many clinicians
frequently experience treatment failure (incomplete necrosis or stage progression etc.) after
repeated TACE, but no clear guidelines have been recommended about salvage treatment
modalities for this situation. Recently, studies for combination of radiation therapy and TACE
for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy.
Based on above suggestions, we herein offer our experience of a patient with macrovascular
invasion developed after repeated TACE that achieve complete remission by stereotactic
body radiation therapy. Further study, maybe regarding a combination of locoregional and
systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.
Background/Aims To investigate the feasibility of Bakri balloon and Coda balloon placement
as a spacer between the liver and bowels using a swine model. Methods Six adult female swine weighing from 24.0 to 41.5 kg (mean, 31.5 kg) were included
for the study. After peritoneal puncture using a 21-G micro-puncture needle under ultrasound
and fluoroscopic guidance, a 0.035-inch guidewire (Terumo, Tokyo, Japan) was advanced
through the micro-introducer sheath. With sequential dilation of the tract with dilators up
to 18-Fr or 10 mm balloon, the Coda and Bakri balloon was advanced between the liver and
bowels. 50 mL and 200 mL of contrast were inflated for Coda and Bakri balloon, respectively.
Gross examinations focused on whether placement of the Coda or Bakri balloon was at the
correct location. Results Technical success was achieved for Coda balloon placement in six of the six (100%)
swine, and for Bakri balloon placement in five of the six (83.3 %) swine. The median placement
time for the Coda balloon was 10 minutes (range, 7-15 minutes), while the median placement
time for the Bakri balloon was 25 minutes (range, 17-35 minutes), which was significantly
longer (p<0.05). Gross observations at necropsy revealed that the Coda and Bakri balloon was
well placed between the liver and bowel. Conclusions Placement of Coda and Bakri balloons between the liver and bowels was
feasible. These balloons have a potential role as spacers between the liver and bowel during
radiation therapy for hepatocellular carcinoma patients. (J Liver Cancer 2015;15:106-111)
Infiltrative hepatocellular carcinoma (HCC) patients have a poor prognosis because most
patients present with advanced disease. Although tumor size is small, ablation therapy
is difficult because it is difficult to delineate tumor boundary and tumor often combined
vascular invasion. Therefore many clinicians still try locoregional therapy (LRT) such as
transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT
and sorafenib in this situation. Stereotactic body radiation therapy (SBRT) is new technology
providing very highly conformal ablative radiation dose and is expected to salvage modality
for HCC showed incomplete response of TACE due to combined arteriovenous (AV) shunts.
Based on above suggestions, we herein offer our experience of a complete remission of tumor
by combination of SBRT and TACE in a patient with infiltrative HCC. Further study, maybe
regarding a combination of locoregional and systemic therapy is necessary on how to manage
infiltrative HCC with AV shunts.
Reserved liver function is one of the most important determinants of survivial in advanced
hepatocellular carcinoma (HCC). Especially in cirrhotic patient with decompensated liver
function, sorafenib for HCC with main portal vein invasion have limited efficacy and survival
benefit. Therefore many clinicians or centers still try locoregional therapy (LRT) such as
transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT
and sorafenib in this situation. However this multidisciplinary approach may increase
treatment related toxicity such as liver failure, etc. Recently, studies for combination of RT
and sorafenib for HCC with portal vein invasion have been tried and reported not only better
therapeutic efficacy, but also more hepatic toxicity.Based on above suggestions, we herein
offer our experience of a patient that although achieved survival gain via partial remission
of intrahepatic tumor and main portal vein thrombosis and metastatic lymph node by
combination therapy of RT and sorafenib, finally expired due to hepatictoxicity. Further study,
maybe regarding a combination of locoregional and systemic therapy, is necessary on how to
manage decompenstated cirrhotic patients with HCC with main portal vein invasion. (J Liver
Cancer 2014;14:120-126)
Hepatocellular carcinoma (HCC) patients with bile duct invasion have a poor prognosis because many do not receive effective treatment. Surgical resection is thought to be only option of curative treatment, increasing chance of survival, but it is possible to minor group of patients because of poor reserved liver function associated with underlying liver disease and obstructive jaundice. Therefore many clinicians or centers still select locoregional therapy such as transarterial chemoembolization (TACE), radiation therapy (RT) etc. Stereotactic body radiation therapy (SBRT) is new technology providing very highly conformal ablative radiation dose for a small numbers (1-5 fractions) of large fraction size and is expected to salvage modality for HCC showed incomplete response of TACE due to vascularity or accessibility of feeding artery. Based on above suggestions, we herein offer our experience of a patient with partial remission of tumor by combination therapy of TACE, SBRT and sorafenib. Further study, maybe regarding a combination of locoregional and systemic therapy (so called multidisciplinary approach), is necessary on how to manage HCC patients with bile duct invasion or sparse vascularity.
Before the introduction of radiation therapy (RT) in the clinical management guidelines for hepatocellular carcinoma (HCC), radiation was used not very frequently in the course of HCC management. According to the “Practice guidelines for management of HCC 2009” published by the Korean Liver Cancer Study Group and the National Cancer Center, Korea, RT can be used for HCC with portal vein tumor thrombosis and can be effective to relieve the symptoms caused by HCC and its metastases once the RT is believed safe in terms of radiobiological considerations. The introduction of RT in the Korean HCC management guideline did the pivotal role in accentuating research efforts to enlighten the role of RT in HCC management. Recently, the application of stereotactic ablative body radiotherapy (SABR), an extra-cranial version of radiosurgery such as Gamma-knife, is tested as an ablative modality for HCC. There are already some published prospective series to test SABR for HCC. In Korea, there is a prospective trial published by Korea Cancer Center Hospital. A multicenter prospective trial (KROG 12-02) is on-going as a Korean Radiation Oncology Group (KROG) study and already 26 patients were accrued to the target number of 54 patients. In this review, the background, rationale and the discussion points in the application of SABR as an ablative modality for HCC will be covered. And the experience of hypofractionated ablative RT for small size HCC less than 3 cm by the author will be introduced.
Extrahepatic metastasis (EHM) associated with hepatocellular carcinoma (HCC) has been increasing due to prolonged
survival with recent advances in therapeutic approaches including locoregional therapy such as transarterial chemoemoblization
(TACE), radiofrequency ablation and radiation therapy (RT). Though many guidelines recommended systemic therapy such as
sorafenib in this situation, some clinicians or centers still select locoregional therapy because the survival improvement of 2 or 3
months by sorafenib is far from optimal. Moreover, some studies showed that complete and partial response of intrahepatic
tumors can result in significant improvement of patient survival even in situation of EHM. Based on above suggestions, we herein
offer our experience of a patient with complete remission of intrahepatic tumor and adrenal gland metastasis treated with
combination therapy of TACE and RT and sorafenib. Further study, maybe regarding a combination of locoregional and systemic
therapy (so called multidisciplinary approach), is necessary on how to manage HCC patients with EHM.
According to the 2003 clinical practice guideline reported by Korean Liver Cancer Study Group (KLCSG) and National
Cancer Center (NCC), Radiation therapy (RT) has been considered as alternative or complementary modality in cases where
surgical resection is not possible, local treatment or trans-hepatic arterial chemo-embolization (TACE) does not provide a cure.
At that time, the guideline suggested that further studies are needed to confirm the beneficial role of RT in the management
of HCC because RT lacked the high quality scientific evidences at that time. However, the 2003 guideline did the pivotal
role in accentuating research efforts to enlighten the role of RT in HCC management. Recently, many scientific evidences
are piled up strengthening the level of evidence. Also there was the quantitative expansion of reported studies dealing with
RT role in HCC management. In the 2009 Practice guidelines for the management of HCC, radiation oncologists participated
as member of revision committee put every efforts to make good of RT related guideline. And to place RT related guidelines
as a special feature of Korean version of HCC management guidelines. Discussions were made among radiation oncologists
in the revision committee. The participating radiation oncologists realized that still there are no randomized controlled trials
exploring the role of RT in HCC management. The role of RT in the management of HCC is underestimated still. To prepare
the next version of practice guideline, the every effort must go on to invigorate the role of RT in the management of HCC.
Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is not suitable candidates for surgical treatment at
the most of diagnosis because of poor liver function, extensive tumor involvement of the liver, vascular involvement, and/or
intra/extrahepatic metastasis. We attempted localized concurrent chemo-radiation therapy (CCRT) in patients having locally
advanced HCC with left and main portal vein thrombosis. We report a case of locally advanced HCC patient who became
surgically resectable by downstaging after localized CCRT. Localized CCRT was performed with a total radiation dose of
5,040 cGy (180 cGy×28 times) and hepatic arterial infusion of 5-fluorouracil (5-FU, 250 mg/day) and cisplatin (10 mg/day)
for 5 days via implantable port system during the second and the fifth weeks of the radiotherapy. Marked contraction of HCC
was noted on follow up computerized tomography (CT) after localized CCRT, and subsequently surgical resection with
curative aim was performed. He was gave a additional transcatheter arterial chemoembolization (TACE) because follow up
CT revealed intrahepatic metastasis at subcapsular portion of right hepatic lobe after 3 months of operation. The patient is
in complete remission status without recurrence to date.
Jang Eun Lee, Na Ri Yoon, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Dong Goo Kim, Ho Jong Chun, Byung Gil Choi, Hae Giu Lee, Hong Seok Jang, Chan Kwon Jung, Eun Sun Jang
Journal of the Korean Liver Cancer Study Group. 2009;9(1):82-85. Published online June 30, 2009
The prognosis of young patients with hepatocellular carcinoma is remains controversial. Here we report a case of advanced
hepatocellular carcinoma in twenty, successfully treated with transarterial chemolipidolization (TACL), systemic chemotherapy,
radiation therapy and surgical resection. Previously healthy 28 years old woman was admitted for treatment of hepatocellular
carcinoma. Abdominal CT showed a diffuse infiltrative HCC involving both lobes with intrahepatic bile duct invasion and
pericardial lymphadenopathy. She was treated TAC with systemic chemotherapy and external beam radiotherapy. 6 months
after these treatments, main tumor and the pericardial lymph node were decreased in size. And then extended left lobectomy
and systemic chemotherapy were done. The pericardial lymph node was markedly decreased. The patient has been followed
for 10 months without evidence of regional tumor recurrence.
The optimal treatment of hepatocellular carcinoma has become increasingly complex with myriad of available
treatment options. Although recently the liver transplantation has been accepted the best treatment for survival,
the shortage of donor limits the extension of this procedures. As the neoadjuvant chemotherapy is being
increasingly employed to downsize colorectal metastasis, the clinical trials have been extended to the
hepatocellular carcinoma. Therefore we reviewed the use of liver resection following tumor downstaging with
chemotherapeutic agents and Radiation therapy to treat unresectable HCC.
Key Words: Hepatic resection․Downstaging․Transarterial chemoembolization․Radiation
Most patients with advanced hepatocellular carcinoma (HCC) are not suitable candidates for surgical treatment
at the time of diagnosis because of poor liver function, extensive tumor involvement of the liver, vascular
involvement, and/or intra/extrahepatic metastasis. We attempted localized concurrent chemo-radiation therapy
(CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in patients having locally advanced HCC with
vascular involvement and preserved hepatic function. We report a case of locally advanced HCC patient who
became surgically resectable by downstaging after localized CCRT followed by HAIC. Localized CCRT was
performed with a total radiation dose of 4,500 cGy (180 cGy × 25 times) and hepatic arterial infusion of
5-fluorouracil (5-FU, 500 mg/day) via implantable port system during the first and the last weeks of the
radiotherapy. Following localized CCRT, the patient was scheduled to receive HAIC with 5-FU (500 mg/m2 for
5 hours, days 1~3) and cisplatin (60 mg/m2 for 2 hours, day 2) every 4 weeks. Marked contraction of HCC was
noted on follow up computerized tomography (CT) and positron emission tomography (PET) after localized CCRT
and HAIC, and subsequently surgical resection with curative aim was performed. The patient is in complete
remission status without recurrence to date.
Hepatocellular carcinoma (HCC) usually takes an intrahepatic spread via portal vein branches, and the incidence
of portal vein invasion is reported to be 34~40% in surgical resected series. On the other hand, the rate of
intrabiliary growth of HCC is rare, ranging from 2.3~13% in surgical and autopsy cases. Here, we report a case
of the patient treated with localized concurrent chemo-radiation therapy (CCRT) for hilar HCC with invasion of
bilateral bile duct. The tomotherapy was performed with a total radiation dose of 4,240 cGy (20 times, 212
cGy/time) on tumor bed and hepatic arterial infusion of 5-fluorouracil (1,000 mg/day, day 1~5 and day 16~20)
and cisplatin (60 mg/m2, day 3 and day 18) was done via implantable port system during the radiotherapy. After
that, tumor size and tumor marker was decreased and treatment response was achieved as partial response. CCRT
is expected as one of the appropriated treatment options for inoperable HCC with bile duct invasion.