Table Of ContentRadiotherapy
of Liver Cancer
Jinsil Seong
Editor
123
Radiotherapy of Liver Cancer
Jinsil Seong
Editor
Radiotherapy of Liver
Cancer
Editor
Jinsil Seong
Department of Radiation Oncology
Yonsei Cancer Center
Yonsei University College of Medicine
Seoul
Korea
ISBN 978-981-16-1814-7 ISBN 978-981-16-1815-4 (eBook)
https://doi.org/10.1007/978-981-16-1815-4
© Springer Nature Singapore Pte Ltd. 2021
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Preface
Liver cancer is the world’s leading cancer not only in incidence but also in
lethality. Considering its age prevalence in 4th to 6th decades, which are the
main axis of socioeconomic activity, liver cancer needs special attention to
overcome. During the past decades, efforts have been focused on how to
improve therapeutic outcome in parallel with how to detect early cancer.
Actually there has been remarkable development particularly in the therapeu-
tic aspect.
Radiotherapy is one of the major cancer therapy modalities. However, it
has long been underestimated in the management of liver cancer. It could be
attributable to the old concept that required the whole liver as a volume to be
irradiated while radiation dose tolerance of the whole liver is far less than that
for tumor control. Now, we have gone through two big changes: first, a con-
ceptual change of a focal but not whole liver as a radiation volume and, sec-
ond, more importantly, emergence of modern radiotherapy technology to
deliver therapeutic dose precisely to the tumor while avoiding radiosensitive
adjacent organ. Consequently, we have witnessed a rapid increase in clinical
application of radiotherapy for liver cancer, followed by numerous reports of
excellent outcomes.
Despite clinical demand, the guidance available to clinicians has remained
limited on radiotherapy of liver cancer. This book was intended to address
this deficit on the basis of the best available evidence by providing up-to-date
information on all aspects of radiotherapy for liver cancer, from the basic sci-
ence to clinical practice. The first two sections explain the relevant basic sci-
ence and present detailed information on the available technologies and
techniques, including the most recent advances. The radiotherapy strategies
appropriate in different patient groups are then fully described, covering the
use of ablative, adjuvant, neoadjuvant, definitive radiotherapy, radiotherapy
as a bridge to liver transplantation, and palliative radiotherapy. The final sec-
tion addresses a range of specific issues of concern to the clinician.
As an editor, I am very honored to invite world-class experts in liver can-
cer as contributors to this book. Thank you so much for your time and dedica-
tion! I am quite sure that Radiotherapy of Liver Cancer will be an ideal
reference for clinical radiation oncologists, radiation oncology residents,
oncologists, and hepatologists.
Seoul, Korea Jinsil Seong
v
Contents
Part I Basic Science in Radiotherapy of Liver Cancer
1 Principle of Cancer Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . 3
Victor Ho-Fun Lee and Anne Wing-Mui Lee
2 Radiobiology of the Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Rafi Kabarriti and Chandan Guha
3 Imaging Anatomy for the Radiation Oncologist . . . . . . . . . . . . . 31
Yeun-Yoon Kim and Jin-Young Choi
4 Functional Assessment of Liver for Radiation Oncologist . . . . . 51
Jun Yong Park
5 Antiviral Therapy in Liver Cancer . . . . . . . . . . . . . . . . . . . . . . . . 59
Bo Hyun Kim and Joong-Won Park
Part II Technologies and Techniques in Radiotherapy
of Liver Cancer
6 Technological Advances in Radiotherapy . . . . . . . . . . . . . . . . . . . 73
Belal Abousaida, Cheng-en Hsieh, Bhanu P. Venkatesulu, and
Sunil Krishnan
7 Basics of Ablative Radiotherapy: The Background
Knowledge Necessary to Practicing Stereotactic Body
Radiotherapy for Hepatocellular Carcinoma . . . . . . . . . . . . . . . . 93
Alejandra Méndez Romero, Steven Habraken, and
Dave Sprengers
8 Image-Guided Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Pablo Munoz-Schuffenegger, Teo Stanescu, and
Laura A. Dawson
9 Particle Beam Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Masashi Mizumoto, Yoshito Oshiro, and Hideyuki Sakurai
10 Internal Radiotherapy Using Radionuclides . . . . . . . . . . . . . . . . 139
Aaron Kian-Ti Tong, David Chee-Eng Ng, and
Pierce Kah-Hoe Chow
vii
viii Contents
Part III R adiotherapeutic Strategies in Liver Cancer
11 Therapeutic Guidelines for Patients with Liver Cancer from
the Perspective of Radiation Oncologists . . . . . . . . . . . . . . . . . . . 155
Chai Hong Rim and Jinsil Seong
12 Ablative Radiation Therapy for Early
Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Naoko Sanuki, Atsuya Takeda, and Yuichiro Tsurugai
13 Transarterial Chemoembolization Plus External
Beam Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Woong Sub Koom and Hwa Kyung Byun
14 Definitive Radiotherapy for Locally Advanced
Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Sang Min Yoon
15 Neoadjuvant Radiotherapy Converting to Curative Resection . 209
Gi Hong Choi
16 Bridging Therapy for Liver Transplantation . . . . . . . . . . . . . . . . 215
Pablo Munoz-Schuffenegger, Tommy Ivanics,
Marco P. A. W. Claasen, Laura A. Dawson, and
Gonzalo Sapisochin
17 Palliative Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Zhao-Chong Zeng and Qian-Qian Zhao
Part IV S pecific Issues
18 Multidisciplinary Team Approaches for the Management of
Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Kwang-Hyub Han
19 Response Evaluation After Radiotherapy . . . . . . . . . . . . . . . . . . 285
Cheng-Hsiang Lo, Jen-Fu Yang, Po-Chien Shen, and
Wen-Yen Huang
20 Liver Hypertrophy Following Radiotherapy . . . . . . . . . . . . . . . . 295
Chai Hong Rim and Jinsil Seong
21 Hepatic Dysfunction Following Radiotherapy
and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Do Young Kim
22 Lymphopenia Following Radiotherapy for
Hepatocellular Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
Hwa Kyung Byun and Jinsil Seong
23 Perspectives of Radiotherapy in Immuno- oncology Era . . . . . . . 325
Yvonne Chiung-Fang Hsu and Jason Chia-Hsien Cheng
Part I
Basic Science in Radiotherapy
of Liver Cancer
1
Principle of Cancer Radiotherapy
Victor Ho-Fun Lee and Anne Wing-Mui Lee
Abstract tumors. Further radiation dose escalation in
the form of hypofractionated stereotactic body
Radiotherapy is one of the most common
radiation therapy (SBRT) is also now feasible,
types of nonsurgical anticancer treatment
which delivers a high dose of radiation to the
modality, employed in more than 50% of
tumors while sparing the adjacent normal
cases. Almost half of cancer patients are cured
organs from unnecessary irradiation, leading
of their cancer by radiotherapy as part of their
to a much better tumor response and favorable
anticancer treatment. Radiotherapy kills can-
safety profile. Furthermore, endovascular
cer by the use of ionizing radiation which
radioembolization with radioisotope also pro-
causes permanent and irreversible double-
duced encouraging results in the treatment of
strand DNA breaks in cancer cells leading to
unresectable HCC. In this chapter, we will
cell death. Unfortunately, it can also kill nor-
describe how radiotherapy works in cancer
mal cells leading to acute and chronic
cells and elucidate different types of radiation
treatment- related complications. Traditionally,
therapy for HCC.
radiotherapy was seldom employed in the
treatment of hepatocellular carcinoma (HCC)
Keywords
because of the risk of severe and sometimes
irreversible radiation-induced liver injury Radiotherapy · External beam radiotherapy ·
(RILD), since a large volume of normal liver Charged particle therapy · Radioembolization ·
which took into account the physiological Radiation-induced liver injury
movement of the liver and the tumors inside
during breathing might be irradiated. However,
with the advent of new radiation technologies
1.1 Introduction
and motion management devices, radiation
therapy can now be safely delivered to liver
Radiotherapy is an effective and commonly used
treatment modality in the treatment of many can-
cer types. The treatment objective can be either
V. H.-F. Lee · A. W.-M. Lee (*) radical (aiming at cure) or palliative (aiming at
Department of Clinical Oncology, LKS Faculty of symptom relief). Forty percent of patients cured
Medicine, The University of Hong Kong,
of their cancer have received radiotherapy as a
Hong Kong, Hong Kong
part of their therapy, either on its own or in com-
Clinical Oncology Center, The University of Hong
bination with surgery or chemotherapy or more
Kong-Shenzhen Hospital, Shenzhen, China
recently targeted therapy and immunotherapy
e-mail: [email protected]
© Springer Nature Singapore Pte Ltd. 2021 3
J. Seong (ed.), Radiotherapy of Liver Cancer, https://doi.org/10.1007/978-981-16-1815-4_1
4 V. H.-F. Lee and A. W.-M. Lee
[1]. Radical treatment can be as the definitive more recently selective internal radiation ther-
therapy (e.g., for head and neck, skin or prostate apy, also known as radioembolization, are the
cancers), neoadjuvant prior to surgery (e.g., most commonly used radiation modalities for
chemoradiotherapy for esophageal or rectal HCC.
cancer), or adjuvant following definitive treat-
ment (e.g., for head and neck and breast
cancers). 1.2 External Beam Radiotherapy
Different histological cancer types possess dif-
ferent inherent radiation sensitivities, which deter- This is the most common type of radiotherapy
mine whether radiotherapy should be considered employed to treat HCC. The high-energy (6–20
as part of anticancer treatment and also the dose megavoltage) photons generated are able to pen-
essential to achieve the treatment objective as etrate deep enough to reach and kill the tumor
mentioned above. HCC is considered moderately cells. In general, high-energy fast moving elec-
sensitive to radiation, when compared to the more trons are first produced by the powerful electron
sensitive types including small-c ell carcinoma, gun which accelerate through the electromagnet
seminoma, and lymphoma, and the less sensitive in the linear accelerator and ultimately collide
types like sarcoma and melanoma. with the target to generate X-rays. The linear
Radiation therapy can be broadly classified accelerator is housed in a specially-made bunker
and delivered in four main ways: (1) external surrounded by thick concrete and lead walls
beam radiotherapy in which the radiation (pho- which offer radiation protection and safety
tons, electrons, and charged particle) is emitted (Fig. 1.1). The international unit to describe radi-
by an external machine passing through the skin ation prescription and absorption is Gray (Gy),
before reaching the tumors, (2) implanted radio- which is defined as 1 Gy = 1 J/Kg. Conventional
isotopes in the form of brachytherapy, (3) inter- radical radiotherapy is usually given in multiple
nal radiation therapy in which the radioisotopes sessions (fractions) every day, 5 days per week,
through injection or ingestion are preferentially lasting for 5–7 weeks, depending on the dose to
taken up by specific body tissues, and (4) selec- be prescribed. The concept of fractionation is to
tive internal radiation therapy or endovascular enhance the therapeutic ratio or therapeutic win-
radiation therapy in which radioisotopes are dow so that a high radiation dose can be delivered
injected into the tributaries of the feeding ves- to the tumor cells while adequate time is allowed
sels which offer blood supply to the tumors for repair and repopulation of the adjacent nor-
(Table 1.1). External beam radiotherapy and mal cells (Fig. 1.2).
Table 1.1 Types and clinical indications of radiotherapy used
Types Clinical indications
Photons Capable of penetrating into the deeper structures of the body while relatively sparing the skin.
Suitable for deep-seated tumors, for example, bladder and rectal cancers.
Electrons Capable of delivering high radiation dose up to a few centimeters depth from the skin surface
with little dose beyond. Most suitable as superficial treatment for skin cancers.
Charged particle Capable of depositing most of its energy at a specific and characteristic depth after tissue
therapy penetration with high precision. Most suitable for pediatric tumors, brain tumors, and spinal
tumors.
Radioisotopes
Interstitial, Radioisotopes placed inside the tumors, or the lumens or cavities of the patient’s body.
implanted, or Examples include iodine-125 interstitial brachytherapy for prostate cancer and iridium-192
intracavitary intracavitary brachytherapy for cervical cancer.
Ingested or Radioisotopes ingested or injected which are preferentially taken up by specific body tissues/
injected cells with preferential avidity with these radioisotopes. Examples include iodine-131 for
thyroid cancer and Radium-223 for bone metastasis of prostate cancer.
Endovascular Radioisotopes injected intravascularly into the feeding vessels supplying the tumors. An
example is transarterial radioembolization with yttrium-90 microspheres for liver cancer.
