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Imaging in
Clinical Oncology
Second Edition

Athanasios D. Gouliamos
John A. Andreou
Paris A. Kosmidis
Editors

123
Imaging in Clinical Oncology
Athanasios D. Gouliamos
John A. Andreou • Paris A. Kosmidis
Editors

Imaging in Clinical
Oncology
Second Edition
Editors
Athanasios D. Gouliamos John A. Andreou
School of Medicine Imaging Department
National and Kapodistrian Hygeia and Mitera Hospitals
University of Athens Athens
Athens Greece
Greece

Paris A. Kosmidis
Medical Oncologist
Head, Medical Oncology Department
Hygeia Hospital
Athens
Greece

ISBN 978-3-319-68872-5    ISBN 978-3-319-68873-2 (eBook)

https://doi.org/10.1007/978-3-319-68873-2

Library of Congress Control Number: 2018947506

1st edition: © Springer-Verlag Italia 2014

2nd edition: © Springer International Publishing AG, part of Springer Nature 2018
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, express or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
This book is dedicated to all cancer patients and their families.
We are grateful to our teachers and thankful to our staff.
Foreword

Biomedical imaging techniques play an essential and ever more increasing

role in clinical oncology. Today, imaging is used in all phases of cancer man-
agement, including screening, image-guided biopsy, planning and guidance
of treatment, assessment of therapy response, detection of recurrence, and
even in palliative care patients, for whom minimally invasive interventional
radiological techniques provide a valuable alternative to surgery.
During the last decade, the impact of imaging in cancer care has greatly
expanded. Clinical oncologists rely increasingly on imaging information to
make decisions about a patient. Specialists in oncological imaging have
become trusted and highly valued members of the teams involved in tumor
board reviews. It is now generally accepted that confrontation of the clinical,
radiological, and pathological data is essential to establish a final diagnosis,
to develop the management plan of a cancer patient, and to obtain follow-up
of such a patient under treatment. The growing impact of imaging has been
driven by technological improvements, which have provided new insights
into the pathophysiology and behavior of tumors, by combining morphologi-
cal, functional, and molecular techniques. There is no doubt that imaging
constitutes a cornerstone in oncological research and patient management.
Traditionally, the role of imaging in cancer management has been mainly
focused on screening and disease management, i.e., diagnosis and staging,
treatment monitoring and follow-up. But, as the expression goes, there is
much more than meets the eye. The term “radiomics” has been coined to
describe the process of extracting quantitative features from medical imaging
data of tumor phenotypes, by applying advanced data-mining and character-
ization algorithms. Such methods can potentially disclose tumor characteris-
tics that are not seen, or at least not recognized, by the naked eye. The term
“radiogenomics” refers to the correlation between imaging features and the
underlying gene-expression patterns. Thanks to ongoing technological
advances, imaging has gained a foothold in presymptomatic risk assessment
(discovering a genetic predisposition to a certain disease through molecular
diagnostics). Targeted imaging of receptors on tumor cells and the study of
gene therapy expression are being introduced into clinical medicine. A com-
pletely different, but no less important, direction in imaging research is the
rapid evolution of image-guided and targeted minimally invasive procedures,
as an alternative to open surgery. Such imaging-guided therapy holds great
promise to reduce complications and collateral effects of cancer treatment
and eventually to improve patient outcome.

vii
viii Foreword

Screening examinations are performed in asymptomatic individuals for

early detection of cancer, at a stage where it is easier to treat and potentially
cure the disease. Early diagnosis of cancer through screening, based on imag-
ing, offers the best hope to reduce the human and financial burden of cancer
management and is a major contributor to a reduction in mortality for certain
cancers. Different imaging techniques can be applied to screen for different
types of cancer. Traditional examples of imaging-based screening include
detection of breast cancer with mammography or of lung cancer with CT
scans of the thorax. Computer-aided detection/diagnosis (CAD) has been
successfully applied to improve lesion detection, for example in discovering
breast cancer in digital mammography examinations. Artificial intelligence
(AI) methods can extract volumetric and contrast enhancement features from
imaging data sets in different types of cancer. There is hope that the develop-
ment of specific imaging biomarkers to identify the presence of cancer will
open the door to molecular diagnostics, thus heralding a new era in
screening.
Once a cancer has been detected, the information derived from clinical
imaging studies becomes essential to establish a certain diagnosis. Though
pathology remains the gold standard (“the issue is tissue”), imaging studies
are an essential part of the diagnostic work-up of the patient. Moreover,
image-guided biopsy offers a good way to obtain tissue samples in a safe and
minimally invasive way.
Staging is needed to gain information about how advanced the cancer is.
Accurate staging is the cornerstone to determine treatment options and pre-
dict the prognosis. Staging involves looking at the primary tumor, the lymph
nodes, and distant metastases in other organs. This is the so-called TNM clas-
sification system (tumor—nodes—metastasis). Imaging techniques allow us
to perform a focused, noninvasive exploration of those organs in the human
body where we know that cancer cells will thrive.
In recent years, treatment of cancer has made a giant leap forward. Thus,
since more patients survive, it becomes ever more important to assess the
response to treatment. Imaging can inform us whether there is a change in the
tumor burden. The most commonly used imaging response assessment tool
for solid tumors is the Response Evaluation Criteria in Solid Tumors
(RECIST). RECIST recognizes four categories of response: complete
response (i.e., complete disappearance of the target lesions); partial response
(i.e., a 30% decrease in the sum of the target lesions); progressive disease
(i.e., a 20% increase in the sum of the target lesions); and stable disease (i.e.,
smaller changes that don’t quite meet any of the above criteria). The RECIST
guidelines rely on comparison of the baseline scan with the images after
treatment (i.e., surgery, radiation, chemotherapy). Unfortunately, the concept
of using relatively crude measurements to monitor the tumor (e.g., longest
diameter of a mass, or approximate appraisal of the tumor volume) is inade-
quate; such visual comparisons can only indicate a delayed response to ther-
apy and hold no information about the metabolism, vascularization, cell
density, or other parameters of the tumor. This has led researchers to develop
quantitative imaging biomarkers to accurately monitor changes in tumor vol-
ume and structure, angiogenesis and vascularization (perfusion imaging),
Foreword ix

biochemical composition (MR spectroscopy), cell proliferation (diffusion

weighted imaging), microscopic environment (diffusion tensor imaging), and
metabolism (PET, SPECT). The inherent limitations of traditional imaging
methods have led to the development of hybrid imaging techniques, such as
PET-CT or PET-MR, which combine the metabolic sensitivity of nuclear
medicine with the spatial and temporal resolution of radiological methods,
such as CT or MRI.
Monitoring and follow-up refer to the process of following a patient after
successful eradication of a tumor. Imaging studies are performed at regular
intervals to monitor therapy response and screen the patient for detection of
tumor relapse. The great advantage of imaging is that it can provide essential
information without tissue destruction, in a noninvasive (or minimally inva-
sive) way, over wide ranges of time. The biggest challenge here is to stan-
dardize imaging methodology, so that the technical parameters between
baseline and follow-up studies are kept identical, to allow accurate
comparisons.
The growing importance of imaging in cancer management has created
new opportunities for the radiologist, but also new challenges. In order to
function in a multidisciplinary cancer environment, the radiologist must
understand and speak the language of the clinicians, and needs to acquire
more clinical background knowledge in the field of oncology. At the same
time, the imaging specialist should also have a profound understanding of
tumor pathophysiology and how different characteristics of a tumor are
reflected in morphological, structural, metabolic, and functional imaging
studies. Together with oncologists, pathologists, surgeons, radiation thera-
pists, and many other specialists, radiologists and nuclear medicine physi-
cians are an essential part of the tumor board, to assist in the multidisciplinary
decision-making on patients with cancer.
On a personal note, I am indebted to the editors of this book, my Greek
friends Athanasios D. Gouliamos, John Andreou, and Paris A. Kosmidis, for
giving me the opportunity to write this foreword. It is a great honor and a
privilege to be invited; I’m very happy to oblige and to write this modest
contribution. The editors have pooled their combined experience, wisdom,
and skill to create a kaleidoscopic overview of the role of imaging in clinical
oncology. They have managed to successfully aggregate an “all-star” team of
distinguished authors, to cover a wide range of biomedical imaging tech-
niques, in a variety of tumor types, including all phases of cancer manage-
ment. The individual chapters in this book are well written and superbly
illustrated; this greatly facilitates the task of the reader to comprehend this
complex subject matter. Careful attention is given to the concepts that are
crucial in understanding modern “multimodality,” “multiparametric,” and
“hybrid” imaging techniques. Integration of different kinds of imaging tech-
nology helps the reader to better understand the pathophysiology of tumors
and provides complementary information for improved staging and therapy
planning. The information in this book is presented in a logical and straight-
forward manner, thus offering an enjoyable learning experience. I am con-
vinced that Imaging in Clinical Oncology will become a standard textbook,
useful not only to imaging specialists (including radiologists, nuclear medicine
x Foreword

physicians, and radiation therapists) but also to all clinicians with an interest
in oncology. Close multidisciplinary collaboration, within a well-trained and
experienced team, is the cornerstone in the management and care of onco-
logical patients; and, as this book eloquently illustrates, imaging holds the
key to success in the screening, detection, staging, treatment monitoring, and
follow-up of patients with cancer.

Paul M. Parizel
David Hartley Chair of Radiology, Royal Perth Hospital & University of
Western Australia (UWA) Medical School
Past President, European Society of Radiology (ESR)
Institutional Representative, European Board of Radiology (EBR)
Honorary President, African Society of Radiology (ASR)
Preface

This new edition features many exciting changes since the first edition, pub-
lished in 2013. Four new chapters are included while some of the original
chapters have additional contributors. One of the new chapters covers the role
of radiogenomics in oncologic imaging. Three new chapters elucidate multi-
ple myeloma. Chapters on lymphomas have been extensively revised by the
same authors who participated in the book PET/CT in Lymphomas: A Case-­
Based Atlas, published in 2015.
The new edition of Imaging in Clinical Oncology is divided in 20 parts.
The first part covers a general approach to molecular imaging in oncology,
imaging criteria for treatment response evaluation, imaging in radiation ther-
apy, interventional radiology in oncology, imaging principles in pediatric
oncology, and the role of radiogenomics in oncologic imaging. In the follow-
ing 19 parts, the main types of cancers are addressed in different chapters and
organized by organ systems (bone and soft tissue tumors, CNS tumors, head
and neck tumors, lung cancer, breast cancer, gynecologic cancer, gastrointes-
tinal cancer, neuroendocrine tumors, urogenital cancer, lymphomas, multiple
myeloma, and melanoma).
The aim of this book is to promote the understanding between radiologists
and clinical oncologists, presenting all the currently available imaging modal-
ities and covering a broad spectrum of oncologic diseases from most organ
systems. In each chapter the clinical oncologist begins with a brief introduc-
tion of each type of tumor. All relevant conventional and advanced imaging
techniques and technologies of ultrasound, MRI, CT, and PET are then
addressed by radiologists and nuclear medicine experts in their respective
fields. Finally, the clinical oncologist provides a critical analysis of the treat-
ment implications, usefulness, sequence, and combination of the imaging
studies presented. Quantitative imaging data combined with laboratory bio-
markers can help the clinical oncologist to recognize at the earliest possible
time whether the applied treatment is ineffective so that therapy can be
modified.
Incorporation of new data has not changed our initial aim to keep the con-
tent of this book as compact as possible. It is hoped that practitioners and

xi
xii Preface

r­esidents in radiology, nuclear medicine, clinical oncology, hematology,

radiotherapy, and other specialties involved in cancer management will find
this a true companion in their daily practice.

Athens, Greece Athanasios D. Gouliamos

Athens, Greece John A. Andreou
Athens, Greece Paris A. Kosmidis
Acknowledgments

We would like to express our gratitude to the staff of Springer Milan and
especially to Antonella Cerri for their enormous support to get this book
published. Our sincere thanks also go to Sara Kaka Soor for her help in the
preprint process. Project coordinator Mahalakshmi Sethish Babu, Project
Manager Kalpana Venkataramani and her team provided outstanding book
production services.
We would also like to thank Ioanna Konti for her secretarial assistance.

xiii
Contents

Part I Introductory

1 Molecular Imaging in Oncology:

Hybrid Imaging and Personalized Therapy of Cancer��������������    3
George N. Sfakianakis
2 Imaging Criteria for Tumor Treatment Response
Evaluation��������������������������������������������������������������������������������������   11
Arkadios Chr. Rousakis and John A. Andreou
3 Imaging in Radiation Therapy������������������������������������������������������   25
Despina M. Katsochi, Panayiotis Ch. Sandilos,
and Chryssa I. Paraskevopoulou
4 Interventional Radiology in Oncology ����������������������������������������   41
Michael K. Glynos and Katerina S. Malagari
5 Imaging Principles in Pediatric Oncology ����������������������������������   63
Georgia Ch. Papaioannou and Kieran McHugh
6 Introduction to Radiogenomics����������������������������������������������������   71
Vassilios Raptopoulos and Leo Tsai

Part II Bone and Soft Tissue Tumors

7 Introduction to Soft Tissue Sarcomas������������������������������������������   81

Ioannis P. Boukovinas
8 Introduction to Bone Sarcomas����������������������������������������������������   83
Ioannis D. Papanastassiou and Nikolaos S. Demertzis
9 Introduction to Retroperitoneal Tumors ������������������������������������   87
Dionysis C. Voros and Theodosios C. Theodosopoulos
10 Conventional Radiology of Bone and Soft Tissue Tumors ��������   89
Spyros D. Yarmenitis
11 US-CT-MRI Findings: Staging-­Response-­Restaging of Bone
and Soft Tissue Tumors ����������������������������������������������������������������   95
Andreas P. Koureas

xv
xvi Contents

12 Positron Emission Tomography in Bone and Soft

Tissue Tumors�������������������������������������������������������������������������������� 103
Sofia N. Chatziioannou and Nikoletta K. Pianou
13 Clinical Implications of Soft Tissue Sarcomas���������������������������� 111
Ioannis P. Boukovinas
14 Clinical Implications of Bone Sarcomas�������������������������������������� 121
Ioannis D. Papanastassiou and Nikolaos S. Demertzis
15 Clinical Implications of Retroperitoneal Sarcomas�������������������� 123
Dionysis C. Voros and Theodosios C. Theodosopoulos

Part III CNS Tumors

16 Introduction to Brain Tumors������������������������������������������������������ 131

Panagiotis V. Nomikos and Ioannis S. Antoniadis
17 Conventional Imaging in the Diagnosis of Brain Tumors���������� 135
Athanasios D. Gouliamos and Nicholas J. Patronas
18 Diagnostic Issues in Treating Brain Tumors ������������������������������ 151
Nicholas J. Patronas and Athanasios D. Gouliamos
19 Tumors of the Spinal Cord and Spinal Canal ���������������������������� 161
Athanasios D. Gouliamos and Nicholas J. Patronas
20 Advanced MRI Techniques in Brain Tumors������������������������������ 169
Stefanos B. Lachanis and Ioannis E. Papachristos
21 PET/CT: Is There a Role? ������������������������������������������������������������ 177
Julia V. Malamitsi
22 Clinical Implications of Brain Tumors���������������������������������������� 185
Panagiotis V. Nomikos and Ioannis S. Antoniadis

Part IV Head and Neck Cancer

23 Introduction to Head and Neck Cancer�������������������������������������� 191

Panagiota Economopoulou and Amanda K. Psyrri
24 US Findings in Head and Neck Cancer��������������������������������������� 195
Angelos A. Kalovidouris
25 CT and MR Findings in Head and Neck Cancer������������������������ 207
Elias C. Primetis and Apostolos V. Dalakidis
26 PET-CT Findings in Head and Neck Cancer������������������������������ 215
Fani J. Vlachou
27 Clinical Implications of Head and Neck Cancer������������������������ 227
Panagiota Economopoulou and Amanda K. Psyrri
Contents xvii

Part V Lung Cancer

28 Lung Cancer ���������������������������������������������������������������������������������� 231

Paris A. Kosmidis
29 Lung Cancer Screening in High-­Risk Patients
with Low-Dose Helical CT������������������������������������������������������������ 233
Despina I. Savvidou
30 CT-MRI in Diagnosis and Staging in Lung Cancer�������������������� 237
John A. Papailiou
31 PET-CT in Lung Cancer �������������������������������������������������������������� 245
Roxani D. Efthymiadou
32 EBUS Staging and Lung Cancer�������������������������������������������������� 251
Nikolaos I. Papanikolaou, Charalampos A. Papagoras,
Georgios N. Chrisocherakis, and Emmanuil K. Zachariadis
33 Clinical Implications of Lung Cancer������������������������������������������ 257
Paris A. Kosmidis

Part VI Breast Cancer

34 Introduction to Breast Cancer������������������������������������������������������ 263

Dimitris-Andrew D. Tsiftsis
35 Mammographic Diagnosis of Breast Cancer������������������������������ 265
Evangelia C. Panourgias
36 US Findings in Breast Cancer������������������������������������������������������ 273
Elias C. Primetis and Irene S. Vraka
37 MR Mammography ���������������������������������������������������������������������� 279
Arkadios Chr. Rousakis and Dimitrios G. Spigos
38 Breast Cancer: PET/CT Imaging ������������������������������������������������ 293
Vasiliki P. Filippi
39 Clinical Implications of Breast Cancer���������������������������������������� 299
Dimitris-Andrew D. Tsiftsis

Part VII Gynecologic Cancer

40 Introduction to Gynecologic Cancer�������������������������������������������� 307

Georgios E. Hilaris
41 US Findings in Gynecologic Cancer�������������������������������������������� 311
Charis I. Bourgioti and Aristeidis Antoniou
42 CT-MR Findings in Cervical and Endometrial Cancer ������������ 321
Charis I. Bourgioti
xviii Contents

43 PET/CT with [18F]FDG in Cervical Cancer�������������������������������� 331

Evangelia V. Skoura and Ioannis E. Datseris
44 PET/CT with [18F]FDG in Endometrial Cancer ������������������������ 337
Evangelia V. Skoura and Ioannis E. Datseris
45 CT-MR Findings in Ovarian Cancer������������������������������������������� 341
Dimitra G. Loggitsi
46 PET/CT with [18F]FDG in Ovarian Cancer�������������������������������� 347
Evangelia V. Skoura and Ioannis E. Datseris
47 Clinical Implications of Gynecologic Cancer������������������������������ 353
Georgios E. Hilaris

Part VIII Gastrointestinal Cancer: Esophagus, Stomach

48 Esophageal and Gastric Tumors: Where the Clinician

Requires Imaging �������������������������������������������������������������������������� 359
Ioannis K. Danielides and Antonis N. Nikolopoulos
49 Imaging Findings in Gastrointestinal Cancer:
The Esophagus and Stomach�������������������������������������������������������� 361
Spyros D. Yarmenitis
50 Clinical Implications���������������������������������������������������������������������� 369
Ioannis K. Danielides and Antonis N. Nikolopoulos

Part IX Gastrointestinal Cancer: Solid Organs (Liver Pancreas)

51 Introduction to Liver Cancer�������������������������������������������������������� 375

Georgios P. Fragulidis
52 Imaging Findings in Liver Malignancies ������������������������������������ 379
Christos N. Mourmouris
53 Clinical Implications of Liver Malignancies�������������������������������� 391
Elissaios A. Kontis and Georgios P. Fragulidis
54 Introduction to Pancreatic Cancer ���������������������������������������������� 399
Georgios P. Fragulidis
55 Imaging in Pancreatic Cancer������������������������������������������������������ 401
Christos N. Mourmouris
56 Clinical Implications of Pancreatic Cancer �������������������������������� 405
Eirini V. Pantiora and Georgios P. Fragulidis

Part X Gastrointestinal Cancer: Peritoneal Cavity

57 Introduction to Peritoneal Cavity Carcinoma���������������������������� 411

Paris A. Kosmidis
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