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Medical Radiology · Diagnostic Imaging
Series Editors: H.-U. Kauczor · H. Hricak · M. Knauth

Hans-Ulrich Kauczor
Tobias Bäuerle Editors

Imaging of
Complications and
Toxicity following
Tumor Therapy
Medical Radiology

Diagnostic Imaging

Series Editors

Hans-Ulrich Kauczor
Hedvig Hricak
Michael Knauth

Editorial board

Andy Adam, London

Fred Avni, Brussels
Richard L. Baron, Chicago
Carlo Bartolozzi, Pisa
George S. Bisset, Durham
A. Mark Davies, Birmingham
William P. Dillon, San Francisco
D. David Dershaw, New York
Sam Sanjiv Gambhir, Stanford
Nicolas Grenier, Bordeaux
Gertraud Heinz-Peer, Vienna
Robert Hermans, Leuven
Hans-Ulrich Kauczor, Heidelberg
Theresa McLoud, Boston
Konstantin Nikolaou, Munich
Caroline Reinhold, Montreal
Donald Resnick, San Diego
Rüdiger Schulz-Wendtland, Erlangen
Stephen Solomon, New York
Richard D. White, Columbus

For further volumes:

http://www.springer.com/series/4354
Medical Radiology—Diagnostic Imaging is a unique series that aims to
document the most innovative technologies in all fields within diagnostic
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Hans-Ulrich Kauczor • Tobias Bäuerle
Editors

Imaging of
Complications and
Toxicity following Tumor
Therapy
Editors
Hans-Ulrich Kauczor Tobias Bäuerle
Dept. of Radiology Institute of Radiology
University Hospital Heidelberg University Hospital Erlangen
Heidelberg Erlangen
Germany Germany

ISBN 978-3-319-12840-5 ISBN 978-3-319-12841-2 (eBook)

DOI 10.1007/978-3-319-12841-2

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© Springer International Publishing Switzerland 2015
Medical Radiology
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Contents

Part I Basics of Toxicity of Tumor Therapies

1 Chemotherapy and Targeted Therapy. . . . . . . . . . . . . . . . . . . . 3

Florian Lordick and Ulrich Hacker
2 Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
T. Bostel and F. Sterzing

Part II Brain

3 Brain: Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Marco Essig
4 Central Nervous System Complications
in Patients Undergoing Chemotherapy . . . . . . . . . . . . . . . . . . . 61
Dimitri Psimaras, D. Leclercq, D. Ricard, and J.Y. Delattre

Part III Head and Neck

5 Therapy-Induced Changes in Head and Neck . . . . . . . . . . . . . 95

Michael M. Lell

Part IV Thorax, Lung and Breast

6 Complications and Toxicity of Radiotherapy

for the Breast, Lung and Heart. . . . . . . . . . . . . . . . . . . . . . . . . . 115
John T. Murchison and Edwin J.R. van Beek
7 Drug-Induced Interstitial Lung Disease
in Oncology Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Rianne Wittenberg, Santiago Rossi, and Cornelia Schaefer-Prokop

Part V Cardiovascular System

8 Cardiovascular Toxicity and Monitoring Methods

in Oncologic Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Maxim Avanesov, Andreas Block, and Gunnar K. Lund

v
vi Contents

Part VI Pediatrics

9 Pediatric Brain Tumors: Imaging of Late Effects

in Pediatric Brain Tumor Survivors. . . . . . . . . . . . . . . . . . . . . . 171
G. Tallen, M. Warmuth-Metz, P. Hernáiz Driever,
and Stefan M. Pfister

Part VII Pelvis and Genitourinary

10 Imaging of Complications and Toxicity Following

Tumour Therapy: Pelvis and Genitourinary (Male) . . . . . . . . 195
A. Shah, S.A. Sohaib, and D-M. Koh
11 Female Pelvis: Genital Organs . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Rosemarie Forstner and Teresa Margarida Cunha

Part VIII Bone Marrow and Spine

12 Radiotherapy Induced Changes in Spine

and Spinal Contents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
Joana Ramalho and Mauricio Castillo
13 Bone Marrow: Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Björn Jobke and Hans Bloem

Part IX Liver and Gastrointestinal

14 Imaging of Gastrointestinal Complications

and Toxicity Following Tumor Therapy . . . . . . . . . . . . . . . . . . 277
Chitra Viswanathan
15 Imaging Liver Complications of Cancer Therapy . . . . . . . . . . 287
Sharon Z. Adam, Michal Mauda-Havakuk, Ravit Geva,
and Arye Blachar

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Contributors

Sharon Z. Adam Department of Radiology, Tel Aviv Sourasky Medical

Center, Tel Aviv, Israel
Department of Diagnostic Radiology, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA
Maxim Avanesov Department of Diagnostic and Interventional Radiology,
Center for Radiology and Endoscopy, University Medical Center Hamburg-
Eppendorf, Hamburg, Germany
Edwin J.R. van Beek Queen’s Medical Research Institute, University of
Edinburgh, Edinburgh, UK
Arye Blachar Computed Tomography and Magnetic Resonance Imaging
Division, The Tel Aviv University Sackler School of Medicine, Tel Aviv,
Israel
Department of Radiology, Tel Aviv Sourasky Medical Center, Tel Aviv,
Israel
Andreas Block Department of Internal Medicine II and Clinic
(Oncology Center), Center for Oncology, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
Hans Bloem Department of Radiology, Leiden University Medical Center,
Leiden, The Netherlands
T. Bostel Department of Radiooncology and Radiation Therapy, Heidelberg
University Hospital, Heidelberg, Germany
Mauricio Castillo Division of Neuroradiology, University of North
Carolina, Chapel Hill, NC, USA
Teresa Margarida Cunha Department of Radiology, Instituto Português
de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
J.Y. Delattre AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de
Neurologie 2-Mazarin, 47 Bd de l’hôpital, Paris, France
Centre OncoNeuroTox, Paris, France
Sorbonne Universités, Sorbonne Universités, UPMC Univ. Paris 06, Inserm,
CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France

vii
viii Contributors

P. Hernáiz Driever Department of Pediatric Oncology/Hematology,

Charité-Universitätsmedizin Berlin, Berlin, Germany
Marco Essig Department of Radiology, University of Manitoba, Winnipeg,
MB, Canada
Rosemarie Forstner Department of Radiology, Landeskliniken Salzburg,
Paracelsus Medical University, Salzburg, Austria
Ravit Geva Department of Oncology, Tel Aviv Sourasky Medical Center,
Tel Aviv, Israel
Ulrich Hacker University Cancer Center Leipzig (UCCL), University
Hospital Leipzig, Leipzig, Germany
Björn Jobke Department of Radiology, Deutsches
Krebsforschungszentrum (DKFZ), German Cancer Research Center,
Heidelberg, Germany
D-M. Koh Department of Diagnostic Radiology, Royal Marsden Hospital,
Sutton, Surrey, UK
D. Leclercq Centre OncoNeuroTox, Paris, France
Sorbonne Universités, Sorbonne Universités, UPMC Univ. Paris 06, Inserm,
CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France
Service de Neuroradiologie, Hôpital Salpêtrière, Paris, France
Michael M. Lell Department of Radiology, University Erlangen, Erlangen,
Germany
Florian Lordick University Cancer Center Leipzig (UCCL), University
Hospital Leipzig, Leipzig, Germany
Gunnar K. Lund Department of Diagnostic and Interventional Radiology,
Center for Radiology and Endoscopy, University Medical Center Hamburg-
Eppendorf, Hamburg, Germany
Michal Mauda-Havakuk Department of Radiology, Tel Aviv Sourasky
Medical Center, Tel Aviv, Israel
John T. Murchison Department of Radiology, Royal Infirmary of
Edinburgh, Edinburgh, UK
Stefan M. Pfister Division of Pediatric Neurooncology (B062), Deutsches
Krebsforschungszentrum (DKFZ), Heidelberg, Germany
Department of Pediatric Hematology and Oncology, Heidelberg University
Hospital, Heidelberg, Germany
Dimitri Psimaras AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de
Neurologie 2-Mazarin, 47 Bd de l’hôpital, Paris, France
Centre OncoNeuroTox, Paris, France
Sorbonne Universités, Sorbonne Universités, UPMC Univ. Paris 06, Inserm,
CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France
Contributors ix

Joana Ramalho Division of Neuroradiology, University of North Carolina,

Chapel Hill, NC, USA
D. Ricard Centre OncoNeuroTox, Paris, France
Sorbonne Universités, Sorbonne Universités, UPMC Univ. Paris 06, Inserm,
CNRS, UM 75, U 1127, UMR 7225, ICM, F-75013, Paris, France
Service de Neurologie, Hôpital d’instruction des armées du Val-de-Grâce,
Service de Santé des Armées, Paris, France
Santiago Rossi Centro de Diagnostico Dr Enrique Rossi, Buenos Aires,
Argentina
Cornelia Schaefer-Prokop Department of Radiology, Meander Medical
Center, Amersfoort, The Netherlands
Department of Radiology, Radboud University, Medical Center, Nijmegen,
The Netherlands
A. Shah Department of Diagnostic Radiology, Royal Marsden Hospital,
Sutton, Surrey, UK
S.A. Sohaib Department of Diagnostic Radiology, Royal Marsden
Hospital, Sutton, Surrey, UK
Department of Diagnostic Radiology, Royal Marsden NHS Foundation
Trust, Sutton, Surrey, England, UK
F. Sterzing Department of Radiooncology and Radiation Therapy,
Heidelberg University Hospital, Heidelberg, Germany
G. Tallen Department of Pediatric Oncology/Hematology, Charité-
Universitätsmedizin Berlin, Berlin, Germany
Department of Pediatrics, Faculty of Medicine, University of Calgary,
Calgary, AL, Canada
Chitra Viswanathan Division of Diagnostic Imaging, Department of
Diagnostic Radiology, University of Texas MD Anderson Cancer Center,
Houston, TX, USA
M. Warmuth-Metz Department of Neuroradiology, Universität Würzburg,
Würzburg, Germany
Rianne Wittenberg Department of Radiology, Meander Medical Center,
Amersfoort, The Netherlands
 Part I
Basics of Toxicity of Tumor Therapies
 Chemotherapy and Targeted
Therapy
Florian Lordick and Ulrich Hacker
Contents
1 Basic Principles of Medical Anticancer
Therapy .........................................................
2 Definitions of Anticancer Drug
Therapy .........................................................
2.1 Mono- Versus Combination Therapy .............
2.2 Induction Chemotherapy ................................
2.3 Consolidation Therapy ...................................
2.4 Maintenance Therapy .....................................
2.5 Perioperative (Neoadjuvant and/
or Adjuvant) Chemotherapy .......................
2.6 Palliative Therapy ...........................................
3 Classification of Anticancer Drugs ..............
4 Classification of Treatment Toxicity ............
5 Specific Toxicities Associated
with Anticancer Treatment ..........................
Conclusions .............................................................
References ...............................................................
F. Lordick (*) • U. Hacker
University Cancer Center Leipzig (UCCL),
University Hospital Leipzig,
Liebigstr. 20, Leipzig D- 04103, Germany
e-mail: direktion.uccl@medizin.uni-leipzig.de
Med Radiol Radiat Oncol (2014)
DOI: 10.1007/174_2014_1040, © Springer International Publishing Switzerland
Abstract
A precise knowledge of antineoplastic drugs
4 is an indispensable basis for the care of
patients with cancer. The mechanisms of
6 action and resistance, cross-resistance pat-
6 terns, pharmacodynamics and pharmacokinet-
6 ics, pharmacological interaction, and last but
6
7 not least potential adverse effects should be
part of this knowledge. As contemporary can-
7 cer care requires interdisciplinary and multi-
7 professional structures, the radiologist is an
7 important and integral part of the oncological
8 treatment team. He has several key roles.
Besides the determination of an accurate clini-
10
cal staging which is the basis for all treatment
recommendations, he evaluates the response
15
to anticancer treatment and defines the remis-
15 sion status following treatment. Importantly,
he assesses acute and long-term treatment tox-
icities, both having a tremendous impact on
patients’ safety and quality of life. This article
summarizes the principles of medical antican-
cer treatment and outlines the major side
effects associated with drug classes and spe-
cific antineoplastic compounds.
Abbreviations
2-CDA 2-Chlordeoxyadenosine
5-FU 5-Fluorouracil
6-MP 6-Mercaptopurine
6-TG 6-Thioguanine
3
4 F. Lordick and U. Hacker

ACNU Nimustine 1 Basic Principles of Medical

ADL Activity of daily living Anticancer Therapy
AE Adverse event
ALK Anaplastic lymphoma kinase Besides the locally active treatment modalities
AMSA Amsacrine (surgery and radiation therapy), drug therapy is
AraC Cytosine arabinoside the third important column of anticancer treat-
ARDS Acute respiratory distress syndrome ment. Applied via the bloodstream, medical ther-
BCNU Carmustine apy can hit not only the primary tumor but also
bcr/ablBreakpoint cluster region protein/ lymphatic and hematogenous disseminated tumor
Abelson murine leukemia viral onco- cells and metastases.
gene homolog 1 “Cytotoxic drug” denominates a compound
CCDP Cisplatin that inhibits cell division and kills cells. By its
CCNU Lomustine effects on nucleic acid formation, DNA synthesis
CD Cluster of differentiation and repair, and protein synthesis and by the inhi-
c-KIT Hardy-Zuckerman 4 feline sarcoma bition of particular protein functions that are
viral oncogene homolog associated with survival, proliferation, and
CTC Common Toxicity Criteria migration, these drugs exert antiproliferative
CTCAE Common Terminology Criteria for cytostatic effects or cytotoxic effects as pro-
Adverse Events grammed cell death (apoptosis), cell destruction
CTLA-4 Cytotoxic T-lymphocyte-associated (necrosis), and induction of senescence. Of note,
protein 4 all these effects do not only occur in neoplastic
DNA Deoxyribonucleic acid tumor cells but can alter also cells of the healthy
DTIC Dacarbazine tissue, depending on the susceptibility of particu-
EGFR Epidermal growth factor receptor lar organs to the cytotoxic drug effects. Therefore,
EML4 Echinoderm microtubule-associated cancer chemotherapy has transitioned from the
protein-like 4 use of cytotoxic drugs to the era of agents with an
HDAC Histone deacetylase apparent selectivity for a cancer-specific target
HER2 Human epidermal growth factor (Phelps and Sparreboom 2014). However, targets
receptor 2 which are completely specific for cancer cells
ILD Interstitial lung disease seem to be rare. And even if such characteristics
mTOR Mammalian target of rapamycin exist, like the Philadelphia chromosome translo-
MTX Methotrexate cation in chronic myeloid leukemia coding for
NCI National Cancer Institute the cancer-specific bcr/abl tyrosine kinase
NSCLC Non-small cell lung cancer (Heisterkamp et al. 1985), drugs hitting that tar-
PD-1 Programmed cell death protein 1 get do not work absolutely target specific and do
PDL-1 Programmed cell death ligand 1 have an impact on functional structures of healthy
PET Positron emission tomography tissue cells as well.
PlGF Placental growth factor A classification of anticancer treatment into
PRES Progressive reversible encephalopa- classical cytostatic or cytotoxic chemotherapy,
thy syndrome antihormonal therapy, monoclonal antibody treat-
RAF Rapidly accelerated fibrosarcoma ment, or treatment with tyrosine kinase inhibitors
SOC System Organ Class has historic reasons and appears arbitrary as the
TKI Tyrosine kinase inhibitor cell biological effects of those therapies are pleio-
VEGF Vascular endothelial growth factor tropic and have a great overlap. A certain relevance
VEGFR2 Vascular endothelial growth factor lies in the discrimination of the mostly non-cancer
receptor 2 selective classical cytotoxic treatment (“chemo-
VP-16 Etoposide therapy”) and the so-called selective targeted treat-
WHO World Health Organization ment forms like antihormonal therapy, therapeutic
Chemotherapy and Targeted Therapy 5

antibodies, and kinase inhibitors. The therapeutic Therapeutic Toxic

index of classical cytotoxic drugs like alkylating
agents is often smaller than that of biologically tar-
geted forms of therapy (Fig. 1).
Classical cytotoxic drugs have different mech-
anisms of action which are outlined in Fig. 2.
Hanahan and Weinberg described the hall-
marks of cancer in a previous landmark article
that was updated in 2011. These hallmarks
include sustaining proliferative signaling, evad-
ing growth suppressors, resisting cell death,
enabling replicative immortality, inducing angio-
genesis, and activating invasion and metastasis.
Conceptual progress in the last decade has added
two emerging hallmarks of potential generality to
this list – reprogramming of energy metabolism
and evading immune destruction. The “tumor
microenvironment” that consists of apparently
normal cells adds to the complexity of current
tumor characteristics which forms the basis for
contemporary drug development and targeted
treatment of cancer (Fig. 3) (Hanahan and
Weinberg 2011).
effect effect
Therapeutic
index
50%
ED50 TD50
Fig. 1 The concept of therapeutic index refers to the rela-
tionship between toxic and therapeutic doses. This pharma-
codynamic parameter is relevant to clinical practice because
it determines how safe or toxic a drug is. Both ED50 and
TD50 are calculated from dose-response curves, which rep-
resent the frequency with which each dose of drug elicits the
desired response or toxic effect in the population. The dose
required to cause a therapeutic effect (positive response) in
50 % of a population is the ED50. The dose required to pro-
duce a toxic effect in 50 % of the studied population is the
TD50 (Redrawn from Craig and Stitzel (2003))

Nucleic Acids DNA Proteins Mitosis

Purine DNA polymerase Proteine degradation Vinca alcaloids

analogues inhibitor L-Asparaginase Vincristine
6-MP Cytarabine Vinblastine
6-TG Vindesine
MTX Vinorelbine
DNA alkalyting
agent
N-Lost-derivatives
Pyrimidine Nitrosoureas Taxanes
analogues Oxaphosphorines Paclitaxel
5-FU Platinum compounds Docetaxel
Raltitrexed Da-/Procarbazine Cabazitaxel
Pemetrexed Thiotepa
MTX Mitomycine C

Ribonucleotide Topoisomerase
reductaseinhibitors inhibitors
Hydroxyurea Etoposide
Anthracyclines
Irinotecan
Topotecan

Fig. 2 Target structures of classical cytotoxic drugs: DNA deoxyribonucleic acid, MTX methotrexate, 5-FU
5-fluorouracil, 6-MP 6-mercaptopurine, 6-TG 6-thioguanine
6 F. Lordick and U. Hacker

EGFR Cyclin-dependent
inhibitors kinase inhibitors

Sustaining Evading
Aerobic glycolysis proliferative growth Immune activating
inhibitors signaling suppressors anti-CTLA4 mAb
Deregulating Avoiding
cellular immune
energetics destruction

Resisting Enabling
Proapoptotic cell Telomerase
BH3 mimetics replicative
death Inhibitors
immortality

Genome Tumor-
instability & promoting
mutation inflammation

PARP Activating Selective anti-

inhibitors Inducing inflammatory drugs
angiogenesis invasion &
metastasis

Inhibitors of Inhibitors of
VEGF signaling HGF/c-Met

Fig. 3 The hallmarks of cancer (Redrawn from Hanahan and Weinberg (2011)) are the basis for contemporary drug
development and targeted anticancer treatment

2 Definitions of Anticancer 2.2 Induction Chemotherapy

Drug Therapy
2.1 Mono- Versus Combination
Therapy
In principle, combination chemotherapy has advan-
tages over monotherapy due to additive or multipli-
cative effects of tumor cell kill. Primary or secondary
resistant tumor cell clones can be eradicated or sup-
pressed by different mechanisms of action. Ideally,
combinations have the following features:
• The combined agents are equally effective.
• Lack of cross-resistance.
• Different mechanisms of action.
• Additive or synergistic mechanisms of action.
• No overlapping toxicities.
For most combinations, this ideal situation
does not exist. Especially with regard to side
effects, some addition of toxicity must always be
accepted when combinations are used.
Induction chemotherapy is used when at the time
of diagnosis no acceptable therapeutic alterna-
tive exists. Induction chemotherapy shall bring
the cancer into a state of better therapeutic
options. The goal is “the induction” of an opti-
mal remission, which is at best a “complete
remission.” High treatment intensities are usu-
ally necessary for an optimal induction.
Therefore, the probability of inducing adverse
effects is usually high.
2.3 Consolidation Therapy
The consolidation therapy shall provide the erad-
ication of clinically occult residual tumor. It shall
improve the rate of true complete remissions.
Thereby, consolidation shall increase the chances
of cure or increase the duration of response.
Chemotherapy and Targeted Therapy
2.4 Maintenance Therapy
Maintenance therapy, in its classical sense used
in the treatment of hematological malignancies
like acute leukemia, follows consolidation and
shall eradicate or control further residual tumor
cells, e.g., those that – due to kinetic resistance –
were not yet eradicated by the previous treat-
ment. Maintenance therapy can increase the
chance of cure or prolong the time interval until
further tumor progression. The latter goal is now-
adays often chosen in the palliative treatment of
solid tumors when a remission has been achieved
by a more intensive treatment period preceding
maintenance.
2.5 Perioperative (Neoadjuvant
and/or Adjuvant)
Chemotherapy
Neoadjuvant (also primary or preoperative) ther-
apy is a treatment in patients with localized or
locoregional tumor extension in which the appli-
cation of local treatment alone (operation or radi-
ation therapy) may lead to an unsatisfactory
outcome. Neoadjuvant chemotherapy is applied
to reduce the extent of surgery (e.g., in breast
cancer, where size reduction of large tumors
allows for more breast-conserving surgery fol-
lowing neoadjuvant chemotherapy) and to
increase the chances of cure (like in gastric or
muscle invasive bladder cancer). In some cancers
(e.g., osteosarcoma and Ewing sarcoma), postop-
erative treatment is tailored on the basis of the
achieved response during neoadjuvant therapy.
The goal of adjuvant chemotherapy is the
eradication of subclinical metastases (“microme-
tastases”) following primary local treatment
(operation or radiation therapy). The clinical goal
of treatment is to increase the cure rate.
Accepted indications for perioperative che-
motherapy are shown in Table 1. As increased
cure rates are the goal of neo-/adjuvant chemo-
therapy, optimal dose intensity is necessary and
some toxicity must be accepted. On the other
hand, treatment safety is of utmost importance as
patients may survive with the operation alone. In
addition, long-term side effects should be avoided
7
Table 1 Examples for tumors with an established indica-
tion for perioperative (neoadjuvant or adjuvant) therapy
Breast cancer
Ovarian cancer
Esophageal cancer
Gastric cancer
Pancreatic cancer
Colon cancer
Rectal cancer
Lung cancer
Testicular cancer
Urothelial cancer
Ewing sarcoma
Osteosarcoma
Rhabdomyosarcoma
as they may lead to a significant impairment of
quality of life of cancer survivors; alter physical,
cognitive, and social functioning; and may even
induce secondary diseases (cancers, leukemia,
organ dysfunctions, cardiovascular diseases, etc.)
leading to a negative impact on life expectancy.
2.6 Palliative Therapy
Palliative chemotherapy is a treatment intended
to prolong life, to control symptoms, and to aug-
ment quality of life. In case of symptomatic dis-
ease, more intensive induction treatment
regimens are often applied. For a further stabili-
zation of the tumor, most often less intensive
monotherapies are regarded as standard of care.
Treatment-emergent side effects must be care-
fully weighed against potential treatment
benefits.
3 Classification
of Anticancer Drugs
The classification of anticancer drugs can follow
different criteria. Traditionally, the World Health
Organization (WHO) chose the mechanisms of
action (e.g., alkylating agent) and the origin of
compounds (e.g., antitumor antibiotics) as their
leading criteria for classification. Table 2 groups
the compounds predominantly according to their
mechanisms of action.
8 F. Lordick and U. Hacker

4 Classification of Treatment National Cancer Institute (NCI, Bethesda, USA)

Toxicity
Side effects of medical treatment have been clas-
sified according to uniform criteria as long as the
drug is applied within a clinical study.
Internationally, the so-called Common Toxicity
Criteria (CTC) or the newer Common
Terminology Criteria for Adverse Events
(CTCAE) as developed and published by the
are most commonly used. Meanwhile, these cri-
teria have been well implemented into clinical
practice and proved useful. Therefore, thorough
oncologists and multidisciplinary teams use it
outside of clinical studies in routine cancer care.
The current version of CTCAE V4.03 can be
downloaded from the Internet (http://evs.nci.nih.
gov/ftp1/CTCAE/CTCAE_4.03_2010-06- 14_
QuickReference_8.5x11.pdf).

Table 2 Classification of anticancer drugs according to their mechanisms of action and biochemical properties
Drug class Group Compound
Alkylating agent N-lost-derivatives Bendamustine
Busulfan
Chlorambucil
Nitrosourea derivatives Nimustine (ACNU)
Carmustine (BCNU)
Lomustine (CCNU)
Oxaphosphorines Cyclophosphamide
Ifosfamide
Trofosfamide
Platinum derivatives Cisplatin (CDDP, DDP)
Carboplatin
Oxaliplatin
Tetrazines Dacarbazine (DTIC)
Temozolomide
Aziridines Thiotepa
Others Amsacrine (AMSA)
Estramustinphosphate
Procarbazine
Treosulfan
Antibiotics Anthracyclines Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Anthracenedione Mitoxantrone
Others Actinomycin-D
Bleomycin
Mitomycin C
Alkaloids Podophyllotoxin derivative Etoposide (VP-16)
Vinca alkaloids Vinblastine
Vincristine
Vindesine
Vinorelbine
Taxanes Cabazitaxel
Docetaxel
Paclitaxel
Camptothecin derivatives Irinotecan
Topotecan
Chemotherapy and Targeted Therapy 9

Table 2 (continued)
Drug class Group Compound
Antimetabolite Antifolates Methotrexate (MTX)
Pemetrexed
Purine analogues 6-Mercaptopurine (6-MP)
6-Thioguanine (6-TG)
Fludarabine
2-Chlordeoxyadenosine (2-CDA)
Pyrimidine analogues 5-Fluorouracil (5-FU)
Capecitabine
Clofarabine
Cytosine arabinoside (AraC)
Gemcitabine
RNR inhibitor Hydroxyurea
DNA demethylation Demethylating agents Azacytidine
Decitabine
Protein degradation Enzyme L-asparaginase
Aromatase inhibition Nonsteroidal inhibitors Anastrozole
Letrozole
Steroidal inhibitor Exemestane
Other hormonal therapies Antiandrogens Abiraterone
Bicalutamide
Flutamide
Nilutamide
Antiestrogen Fulvestrant
Gestagens Medroxyprogesterone acetate
Megestrol acetate
Selective estrogen receptor Raloxifene
modulators Tamoxifen
Immune modulators Cytokines Interferon alpha
Interleukin 2
IMIDs Lenalidomide
Thalidomide
Pomalidomide
Immune checkpoint inhibitors Ipilimumab
Lambrolizumab
Monoclonal antibodies CD20 antibodies Rituximab
Ofatumumab
CD30 antibody-toxin conjugate Brentuximab vedotin
CD33 antibody Gemtuzumab ozogamicin
CD52 antibody Alemtuzumab
EGFR antibodies Cetuximab
Panitumumab
HER2 antibodies Trastuzumab
Pertuzumab
HER2 antibody-toxin conjugate Trastuzumab emtansine
VEGF antibody Bevacizumab
VEGF recombinant fusion protein Aflibercept
VEGFR2 antibody Ramucirumab
(continued)
10 F. Lordick and U. Hacker

Table 2 (continued)
Drug class Group Compound
Tyrosine kinase inhibitors Bcr/abl Imatinib
Dasatinib
Nilotinib
cKIT Imatinib
EGFR Afatinib
Erlotinib
Gefitinib
HER2 Lapatinib
Histone deacetylase (HDAC) Romidepsin
Vorinostat
mTOR Temsirolimus
Everolimus
Multiple kinases Axitinib
Nintedanib
Pazopanib
Regorafenib
Sorafenib
Sunitinib
Proteasome Bortezomib
Carfilzomib
RAF Vemurafenib
Smoothened receptor (hedgehog Vismodegib
signaling)
Somatostatin receptors Octreotide
Lanreotide
Compounds are listed with their generic names. Where appropriate, commonly used abbreviations are listed in
parentheses

The NCI Common Terminology Criteria for
Adverse Events is a descriptive terminology
which can be utilized for adverse event (AE)
reporting. A grading (severity) scale is provided
for each AE term. System Organ Class (SOC),
the highest level of the reporting hierarchy, is
identified by anatomical or physiological system,
etiology, or purpose (e.g., SOC Investigations for
laboratory test results). Within each SOC, adverse
events are listed and accompanied by descrip-
tions of severity (grade).
An AE is any unfavorable and unintended sign
(including an abnormal laboratory or imaging find-
ing), symptom, or disease temporally associated
with the use of a medical treatment or procedure that
may or may not be considered related to the medical
treatment or procedure. An AE is a term that is a
unique representation of a specific event used for
medical documentation and scientific analyses.
Grade refers to the severity of the AE. The
CTCAE displays grades 1 through 5 with unique
clinical descriptions of severity for each AE
based on this general guideline (Table 3). Not all
grades are appropriate for all AEs. Therefore,
some AEs are listed with fewer than five options
for grade selection.
5 Specific Toxicities Associated
with Anticancer Treatment
All organ systems can be subject to treatment-
emergent toxicities.
With classical cytotoxic treatment, myelosup-
pression (neutropenia, thrombocytopenia, and
anemia) is a common side effect. Between 80 and
100 % of all patients undergoing chemotherapy
have some grade of myelosuppression leading to
Chemotherapy and Targeted Therapy
Table 3 Toxicity grades according to the “Common
Terminology Criteria for Adverse Events” (CTCAE)
reporting system provided by the National Cancer
Institute, Bethesda, USA
Grade Severity
Grade Mild; asymptomatic or mild symptoms;
1 clinical or diagnostic observations only;
intervention not indicated
Grade Moderate; minimal, local, or noninvasive
2 intervention indicated; limiting age-
appropriate instrumental activity of daily
living (ADL)a
Grade Severe or medically significant but not
3 immediately life-threatening; hospitalization
or prolongation of hospitalization indicated;
disabling; limiting self-care ADLb
Grade Life-threatening consequences; urgent
4 intervention indicated
Grade Death related to an adverse event
5 to toxicity, and grade 3 or grade 4 adverse events
A semicolon indicates “or” within the description of the
grade
a
Instrumental ADL refer to preparing meals, shopping for
groceries or clothes, using the telephone, managing
money, etc.
b
Self-care ADL refer to bathing, dressing and undressing,
feeding self, using the toilet, taking medications, and not
bedridden
alterations of the differential blood counts.
Severity and duration depend of course on the
applied cytotoxic drug and schedule as well as
additional risk factors, like age and general health
status. In case of neutropenia, patients are at par-
ticular risk of acquiring infections. Febrile neutro-
penia is an emergency situation during
antineoplastic treatment. It requires immediate
clarification and start of empiric antibiotic treat-
ment. In most cases (except low-risk neutropenia
in otherwise unimpaired and compliant patients),
this should be done following hospitalization, and
intravenous broad-spectrum antibiotics should be
given (Klastersky and Paesmans 2013). In more
than two thirds of patients, the focus of febrile
neutropenia remains unknown, but pulmonary
infections, bloodstream infections, urinary infec-
tions, infections of the skin and soft tissues, as
well as infections of the upper aerodigestive tract
should be excluded by appropriate clinical, para-
clinical, and radiological diagnostics.
Apart from myelosuppression, non-
hematological adverse events are common and
11
need to be well known by the treatment team.
Table 4 outlines a selection of substance- and
group-specific non-hematological toxicities of
anticancer drugs.
Our expectation was that with the introduction
of new, more specific and biologically targeted
drugs, the efficacy of anticancer treatment would
increase, while the side effects would decrease.
This hope was desperately disappointed (Niraula
et al. 2012). International investigators analyzed
all randomized controlled trials evaluating agents
approved for the treatment of solid tumors by the
US Food and Drug Administration between 2000
and 2010. Odds ratios were computed for three
end points of safety and tolerability: treatment-
related death, treatment discontinuation related
(AEs). These were then pooled in a meta-analysis.
Correlations between these end points and the
hazard ratios for overall survival and progression-
free survival were also assessed. The investiga-
tors came to the conclusion that new anticancer
agents that lead to improvements in time-to-event
end points also increase morbidity and treatment-
related mortality. The balance between efficacy
and toxicity may be less favorable in clinical
practice because of selection of fewer patients
with good performance status and limited comor-
bidities. Patients’ baseline health characteristics
should be considered when choosing therapy.
With the use of targeted therapies, novel side
effects have emerged that are closely related to
the specific mechanisms of action of the respec-
tive drug. Targeted therapies in general block cer-
tain signaling pathways that play important roles
in promoting tumor cell survival and proliferation
or interfere with stromal cells like vascular endo-
thelial cells to inhibit tumor angiogenesis or with
immune cells to modify antitumor immune
responses. Monoclonal antibodies and tyrosine
kinase inhibitors (TKI) represent the drug classes
that are most commonly used for targeted cancer
therapy. Furthermore, specific intracellular sig-
naling checkpoints can be blocked by chemical
compounds (i.e., mTOR inhibitors). Another
group of drugs targets immune function to
improve host anticancer immunity. CTLA-4 anti-
bodies are used to enhance T-cell co-stimulation,
12 F. Lordick and U. Hacker

Table 4 Selection of substance and group-specific non-hematological toxicities of anticancer drugs

Substance/group Typical adverse effect
Alemtuzumab Opportunistic infection
Anthracyclines/mitoxantrone Cardiomyopathy, cardiac arrhythmia
Aromatase inhibitors Bone and joint pain, osteoporosis
Bevacizumab Arterial hypertension, proteinuria, impaired wound healing, gut
perforations, bleeding
Bleomycin Pulmonary toxicity, lung fibrosis
Bortezomib Neuropathy
Busulfan Pulmonary toxicity, veno-occlusive disease
Cetuximab/panitumumab Acneiform exanthema, allergic reactions
Chlorambucil Pulmonary toxicity, lung fibrosis
Cytarabine Central nervous toxicity (especially high-dose AraC leads to
cerebellar alterations)
Docetaxel Finger- and toenail alterations, edema, neuropathy, taste alterations
Erlotinib/gefitinib Pneumonitis, acute respiratory distress syndrome (ARDS)
Fluoropyrimidines Diarrhea, stomatitis, hand-foot syndrome, cardiotoxicity
(arrhythmias, heart burn, myocardial infarction)
Imatinib Edema, skin rash
Irinotecan Diarrhea, cholinergic syndrome
Methotrexate Central nervous toxicity, hepatic and pulmonary toxicity,
nephrotoxicity in case of inadequate renal elimination
Mitomycin C Hemolytic-uremic syndrome, pulmonary toxicity
Sunitinib/pazopanib/sorafenib/regorafenib Arterial hypertension, hand-foot syndrome, thyroid disorders
mTOR inhibitors (everolimus, temsirolimus) Arterial hypertension, pneumonitis, mucositis, erythema, hand-foot
syndrome, hyperlipidemia
Nitrosoureas Pulmonary toxicity, lung fibrosis, renal toxicity
Oxazaphosphorines (cyclophosphamide, Urothelial toxicity, renal toxicity, central nervous toxicity
ifosfamide) (reversible psychosyndrome with high-dose ifosfamide)
Paclitaxel/docetaxel Neuropathy, allergic reactions, onycholysis
Platinum compounds Renal impairment (cisplatin), ototoxicity (cisplatin), neuropathy
(oxaliplatin > cisplatin > > carboplatin)
Tamoxifen Thromboembolic events
Trastuzumab/pertuzumab/lapatinib Cardiac toxicity
Vinca alkaloids Neuropathy

and drugs targeting the PD-1/PD-L1 pathway
have been developed to block inhibitory immune
checkpoints.
An overview of key side effects can be found
in Table 2. Specific side effects resulting in path-
ological radiological findings are shortly summa-
rized in the following section.
Agents Targeting the Epidermal Growth
Factor Receptor (EGFR): The monoclonal anti-
bodies (cetuximab, panitumumab) are used for
the treatment of RAS wild-type metastatic
colorectal cancer, while TKI (gefitinib, erlotinib,
afatinib) represent a standard of care in the treat-
ment of EGFR-mutated non-small cell lung can-
cer (NSCLC) patients. Skin toxicities occur with
high frequency in both groups of drugs. In con-
trast, interstitial lung disease (ILD) represents a
rare complication, and the mechanism is not fully
understood. Disruption of the alveolar epithelial
function however may play a role. Based on this,
the frequency of ILD is higher in smokers and in
patients with preexisting lung disease (Ando
et al. 2006).
Agents Targeting Her-2: Chemotherapy com-
bined with monoclonal antibodies (trastuzumab,
pertuzumab) represents a treatment standard in
Chemotherapy and Targeted Therapy
Her2-positive breast cancer and in Her2 gastric
cancer (trastuzumab). The TKI lapatinib targeting
EGFR and Her2neu is approved for the treatment
of breast cancer. An important side effect of this
class of drugs is cardiotoxicity that is related to
the expression of Her2 on cardiomyocytes.
Mechanistically, Her2 signaling results in sarco-
mere stability and initiates repair processes that
are important to counteract toxic stress (Tocchetti
et al. 2012).
Agents Targeting Tumor Angiogenesis: The
monoclonal antibody bevacizumab binds vascu-
lar endothelial growth factor (VEGF), and the
fusion construct aflibercept binds VEGF and pla-
cental growth factor (PlGF). Both drugs are used
in combination with chemotherapy for the treat-
ment of metastatic colorectal cancer. Additionally,
a large number of TKI targeting VEGF receptors
and other receptors are in clinical use for the
treatment of a wide variety of cancer types
(Table 2). Hypertension and proteinuria represent
common side effects of VEGF-targeting therapy.
Furthermore, the rate of thromboembolic compli-
cations is increased. Other side effects are related
to impaired tissue repair capacity and comprise
gastrointestinal pneumatosis perforations and the
formation of fistulas (Shinagare et al. 2012).
Overall, bleeding is a rare side effect. However,
frequent bleeding complications have resulted in
the exclusion of the use of bevacizumab in squa-
mous cell carcinoma of the lung. Progressive
reversible encephalopathy syndrome (PRES) is a
very rare (≤0.1 %) but severe neurological com-
plication that has been reported in patient treat-
ment with bevacizumab or aflibercept (Seet and
Rabinstein 2012). The disruption of cerebrovas-
cular endothelial cell signaling is related to the
disruption of cerebrovascular autoregulation
preferentially in the posterior circulation of the
brain. Finally, pancreatitis (sunitinib, sorafenib,
pazopanib) and acalculous cholecystitis (suni-
tinib) have been reported in the literature on a
casuistic basis.
Anaplastic Lymphoma Kinase (ALK)
Inhibitors: ALK inhibitors are used for the treat-
ment of NSCLC harboring specific genomic rear-
rangements (EML4-ALK). Pneumonitis has been
13
reported with the use of the ALK inhibitor crizo-
tinib and symptoms started within two months of
treatment. The underlying mechanisms are not
yet clarified.
RAF-Targeting Agents: RAF-targeting agents
include the multi-TKI sorafenib for the treatment
of renal cell and hepatocellular cancer as well as
vemurafenib and dabrafenib, which are used for
the treatment of melanoma harboring the B-Raf
mutation V600E and other B-Raf mutations. An
increase in the occurrence of cutaneous squamous
cell carcinomas has been reported, and nodular
panniculitis (Monfort et al. 2012) may result in
increased radiotracer uptake during 18F-FDG
positron emission tomography (PET).
Agents Targeting Mammalian Target of
Rapamycin (mTOR) and Targeted Immune
Modulators: These agents (everolimus, temsiroli-
mus) are used for the treatment of breast and
renal cancers and pancreatic neuroendocrine
tumors. Mucositis and aphthous mucosal lesions
are common side effects. Additionally, interstitial
pneumonitis is an important side effect of this
class of drugs with up to 36 % of patients show-
ing any pulmonary abnormalities during treat-
ment (Duran et al. 2014).
Ipilimumab is a novel targeted immune modu-
lator that interacts with CLTA-4, thus fostering
co-stimulatory function to improve host antitu-
mor immune response. Due to immune function
deregulation, autoimmune-related side effects
like enterocolitis and hypophysitis may occur.
Additionally, unspecific lymph node enlargement
and soft tissue changes like myositis or fasciitis
as well as retroperitoneal fat opacities due to
lymphocyte infiltration may interfere with treat-
ment response assessment (Bronstein et al. 2011).
As examples of “new toxicities” emerging from
biologically selective targeted drugs, Fig. 4 dis-
plays a perforation at the rectosigmoid level that
occurred during treatment of metastatic colorectal
cancer with the anti-VEGF antibody bevacizumab.
Another patient who was also treated for meta-
static colorectal cancer received the monoclonal
anti-EGFR antibody cetuximab plus chemother-
apy and developed a grade 3 skin rash during
weeks 4–6 of this combined treatment (Fig. 5).
14 F. Lordick and U. Hacker

a b

Fig. 4 Gut perforation leading to an ileus and peritonitis,
emerging from a pararectal abscess in a patient with
colorectal cancer with simultaneous liver and lung metas-
tases. (a) Is illustrating the coronary section through the
abdomen; (b) is illustrating a transversal section through
the pelvis. The two white arrows in b are highlighting the
formation of a pararectal abscedation. This patient was
treated with the anti-VEGF monoclonal antibody bevaci-
zumab in combination with chemotherapy

a b

Fig. 5 (a, b) Patient who developed severe (grade 3 according to CTCAE V4.03) skin rash during weeks 4–6 of che-
motherapy combined with the anti-EGFR-directed monoclonal antibody cetuximab
Chemotherapy and Targeted Therapy
Conclusions
For clinical practice, we have to state that
medical anticancer treatment is more demand-
ing than ever, as toxicities are very common,
polymorphic and allotropic. They may lead to
severe impairment of the patients’ safety and
quality of life. All members of the treatment
team, including the radiologist, need to do
their best to support patients during anticancer
treatment. Treatment-emergent as well as
tumor-related complications may not be
missed, and the severity of events must be
appropriately classified. In addition, for drug
development it has been advocated to move
“Toward Patient-Centered Drug Development
in Oncology” (Basch 2013).
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 Radiotherapy

T. Bostel and F. Sterzing

Contents 6.2 General Pathogenesis of Chronic

Radiation Effects ............................................ 32
1 Introduction .................................................. 18 6.3 Dose Dependency of the Latency Period ....... 32
2 Radiation Delivery Techniques .................... 20 6.4 Chronic Radiation Effects
2.1 Traditional External-Beam Radiation in the Vascular System.................................... 33
Therapy (EBRT) ............................................. 20 6.5 Chronic Radiation Effects
2.2 Conformal Radiation Therapy ........................ 20 in the Mesenchymal Tissues ........................... 34
2.3 Intensity-Modulated Radiation 6.6 General Chronic Radiation Effects
Therapy (IMRT) ............................................. 21 in the Epithelia and Organ Parenchyma ......... 35
2.4 Stereotactic Body Radiation 6.7 Modulation of the Immune System ................ 37
Therapy (SBRT) ............................................. 22 7 Radiation-Induced Cancers ......................... 38
2.5 Particle Therapy .............................................. 23 7.1 Secondary Cancer Rate................................... 38
2.6 Brachytherapy................................................. 24 7.2 Secondary Cancers in Adults.......................... 38
3 Radiation Biology: A Refresher................... 25 7.3 Secondary Cancers in Children ...................... 39
7.4 Development and Manifestation
4 Basics of Radiation Effects of Normal of Secondary Tumors...................................... 40
Tissues ............................................................ 26
4.1 Classification of Radiation Effects ................. 26 Conclusion .............................................................. 40
4.2 Radiobiological Characteristics of Early References ............................................................... 40
and Late Radiation Effects ............................. 26
4.3 Consequential Late Effects (CLE) .................. 27
4.4 Cellular Basis of Radiation Effects ................ 27
4.5 Tolerance Dose Concept ................................. 27 Abstract
4.6 Classification Systems .................................... 28 The focus of this chapter lies on the description
5 Early Radiation Effects ................................ 29 of the general basics of early and late radiation
5.1 Pattern of Cell Divisions in Early-Reacting effects and the translation of these pathogenetic
Tissues ............................................................ 29 processes into imaging; furthermore, a few short
5.2 Pathogenesis of Early Radiation Reactions .... 30 clinical examples including imaging patterns of
6 Chronic Radiation Effects............................ 31 those underlying pathogenetic normal tissue
6.1 Concepts of Radiation Pathophysiology......... 31 reactions are given to provide a better under-
standing. In addition, the margin concepts used
in radiotherapy as well as the important radiation
T. Bostel • F. Sterzing (*) techniques are summarized, as it is very impor-
Department of Radiooncology and Radiation Therapy, tant for diagnostic radiologists to correlate post-
Heidelberg University Hospital, therapeutic tissue and organ changes in follow-up
Im Neuenheimer Feld 400,
examinations with dose characteristics of a cer-
Heidelberg 69120, Germany
e-mail: bostel.tilmann@med.uni-heidelberg.de; tain treatment to achieve a higher degree of reli-
sterzing.florian@med.uni-heidelberg.de ability in image interpretation. Furthermore, for

Med Radiol Diagn Imaging (2014) 17

DOI 10.1007/174_2014_1041, © Springer International Publishing Switzerland
18 T. Bostel and F. Sterzing

a better understanding of the cellular basis of the therapy like surgery, but beyond that it offers the
various radiogenic tissue effects, a short refresher chance for regional high-volume treatments of
about the underlying radiobiological principles microscopic tumor deposits or lymphatic path-
is given. The detailed description of specific ways as transition to systemic treatments. This
radiation effects and imaging patterns of clini- pivotal role of radiotherapy is also supported by
cally relevant organs and tissues, however, fol- epidemiological data: More than half of all can-
lows in the specific organ chapters in order to cer patients can be cured nowadays, owing to
avoid redundancy. improved efficacy of advanced and mostly multi-
modal cancer therapies, and around half of these
patients receive either radiotherapy alone or
Abbreviations radiotherapy in combination with other cancer
treatments. Moreover, about two thirds of cancer
CLE Consequential late effects patients gain valuable palliation by radiation to
COX-2 Cyclooxygenase-2 alleviate the symptoms and to improve the qual-
CT Computed tomography ity of life in the course of their advanced
CTV Clinical target volume disease.
3D Three dimensional In recent years, substantial advances in radio-
4D Four dimensional logical imaging as well as computer hardware
DNA Deoxyribonucleic acid and software along with improved design of
EBRT External-beam radiation therapy medical linear accelerators have contributed sig-
e.g. Exempli gratia nificantly to the development in radiation ther-
GTV Gross tumor volume apy. Nowadays, existing modern radiation
Gy Gray techniques enable the delivery of conformal dose
i.e. Id est distributions with steep dose gradients between
IL-1a Interleukin-1 alpha the tumor and adjacent normal tissue structures.
iNOS Inducible nitric oxide synthase Thus, intensification of the radiation dose to the
IGRT Image-guided radiotherapy tumor and reduction of high-dose irradiation of
IMRT Intensity-modulated radiation therapy sensitive organs and normal tissues are possible
MRI Magnetic resonance imaging resulting in higher curing rates and lower rates of
mRNA Messenger ribonucleic acid side effects (i.e., increased therapeutic ratio).
NTCP Normal tissue complication probability However, despite these advances, modern radio-
OAR Organs at risk therapy still leaves significant proportions of
PET Positron emission tomography healthy tissue structures exposed to relatively
PTV Planning target volume high doses. This is in part caused by the margin
RBE Relative biological effectiveness concepts used in radiotherapy. In general, the
RR Relative risk determination of the planning target volume
SBRT Stereotactic body radiation therapy (PTV) necessarily requires the inclusion of the
TD Tolerance dose visible or palpable extent of tumor (i.e., gross
TGF-ß Transforming growth factor-ß tumor volume, GTV) as well as an additional sur-
TNF-a Tumor necrosis factor alpha rounding area without visible branches of the
VOD Veno-occlusive disease tumor in order to take microscopic disease into
account (i.e., clinical target volume, CTV).
Furthermore, a patient-specific safety margin is
1 Introduction added, if necessary, to account for the range of
target motion related to breathing, pulsations, or
Radiotherapy plays a vital role in the oncological intestinal peristalsis (e.g., lung or liver lesions)
treatment concept besides surgical and systemic that is often based on four-dimensional (4D)
therapies. Moreover, it is an effective local cancer imaging information derived from the planning
Radiotherapy
CT. And finally, a margin to encompass variabil-
ity in patient positioning (setup) and mechanical
uncertainty is added to create the final PTV. This
PTV concept accounts for all available radiation
techniques, even though modern approaches such
as stereotactic radiation therapy or intensity-
modulated radiation therapy enable to adapt the
dose distribution more precisely to the tumor
boundaries than traditional radiation techniques,
which in turn helps to spare the adjacent healthy
organs and tissues. On the other hand, PTV can
encompass extended areas of normal tissues,
dependent on the tumor and disease stage, for
example, irradiations of the whole body, whole
brain, spinal column, or breast with or without
the supraclavicular lymph nodes after breast-
conserving surgical treatment.
In the follow-up care of cancer patients, how-
ever, it is very important that side effects after
therapeutic irradiations are not in general regarded
as an indicator for medical malpractice. Moreover,
it is an indicator for the best-possible treatment
and maximum cure probability when these radio-
genic effects manifest with only a defined low
incidence of sequelae of defined severity in cured
patients (Dorr 2009) (Fig. 1). Regarding the eval-
uation of side effects, it has also to be mentioned
that radiotherapy is increasingly combined with
other local and systemic therapeutic approaches
such as operation, chemotherapy, or molecular
targeting which may lead not only to additive but
also to synergistic effects for the tumor response
and for organ-specific injuries (Dische et al. 1989;
Pedersen et al. 1994). Furthermore, it has to be
considered that a certain number of pathological
conditions may be triggered by other reasons than
specific tumor therapies, such as comorbidities,
the tumor itself, or other non-oncological treat-
ments, for example, obstipation due to analgesia
with opioids.
As a consequence of increased numbers of
cancer survivors and prolongation of survival
times, late radiation sequelae as well as secondary
cancers are more frequently seen than in the past.
This subject has therefore gained more relevance
in oncological studies as well as clinical follow-
up examinations in recent years. Therefore, it is of
utmost importance that radiologists are familiar
19
% Local tumor control Complication
100
90
80
Toleranz
70 überscnritten
Probability
60
50
40 Therapeutic
30 window
20
10
0 7,500 75,000
Dose
Fig. 1 Dose dependency of tumor control (green sigmoid
curve) and side effect (red sigmoid curve) probability
(according to Holthusen): Due to the fact that both
curves overlap, there is no chance for complete tumor
destruction through radiotherapy without any risk of
normal tissue complications – the third blue curve depicts
the therapeutic window (Figure provided by courtesy of
Dr. Dr. Thieke)
with the imaging patterns of these therapy-related
tissue reactions as they may both mimic and
obscure tumor relapses. Beyond interpretation of
posttreatment imaging, diagnostic specialists can
make further valuable contributions to increase
the therapeutic ratio preceding the radiation treat-
ment process (Terezakis et al. 2011). First of all,
every cancer treatment, particularly radiotherapy,
heavily relies on accurate staging of the cancerous
disease in order to select an appropriate treatment
regimen for each patient. It is obvious that misdi-
agnosis in staging may have fatal consequences
for the patient with regard to therapy-associated
complications and treatment outcome. For exam-
ple, unrecognized local tumor extension in an
early stage of the disease may result in an insuffi-
cient local therapy with persistence of residual
tumor cells that trigger the further course of the
disease, either with new local symptoms or with
propagation of systemic spread of these cells.
Similar devastating consequences may result
from overtreatment, for example, through radio-
therapy, with avoidable early and late therapy
effects and worsening of the patient’s general con-
dition. This is especially important, since late
sequelae of any oncological treatment are thera-
peutically difficult to influence and characterized
by a progressive pattern in many cases (see
below). Taken together, accurate staging is an
essential precondition for a successful treatment
20
of cancer patients. Further input of diagnostic spe-
cialists may be provided during the routine radia-
tion oncology workflow: Delineation of the
macroscopic tumor (GTV) often requires addi-
tional advanced imaging modalities such as MRI
or PET/CT and reaches beyond the normal ana-
tomic information. As tumor imaging has been
increasing in both the amount and the complexity
of information, an in-depth knowledge of onco-
logic radiology has become more and more cru-
cial in recent times. Furthermore, tumor tissue is
often difficult to distinguish from normal tissue
changes, for example, due to prior treatments or
stromal reactions seen in infiltrating cancers,
radiologic input may add to the precision in delin-
eating the GTV. In summary, radiation therapy
has become increasingly based on multimodal
imaging, and oncologically trained diagnostic
radiologists are increasingly important for the
successful application of modern radiotherapy
treatments (Terezakis et al. 2011).
2 Radiation Delivery
Techniques
For radiologists it is important to consider not
only the delivered overall dose for image interpre-
tation of normal tissue changes but also the used
treatment technique. This means that depending
on the irradiation technique, a given specific over-
all dose may be distributed in normal tissues in
completely different ways, and thus the organ
exposure can vary significantly with consecutive
different image presentations in the follow-up.
Furthermore, it would be extremely helpful for
radiologists if dose overlays from treatment plan-
ning software could be integrated into PACS
workstations in the near future to achieve a higher
degree of safety in image interpretation.
2.1 Traditional External-Beam
Radiation Therapy (EBRT)
First, therapeutic applications of ionizing radia-
tion started early after their discovery by Conrad
Roentgen in 1895. For many decades, irradiation
of cancerous tissues was performed with X-ray
T. Bostel and F. Sterzing
devices, which allowed only relatively low
energy doses with peak doses near the entrance
site of the beam. Thus, major drawbacks were
dose-limiting radiation effects in skin and epider-
mis and the rapid decline of the depth-dose curve
being unfavorable especially for the treatment of
deep-seated local tumors.
It was only in the 1950s until high-energy lin-
ear accelerators were developed – a milestone for
the specialty of radiation oncology. From the
1950s to the 1980s, radiation treatment was
administered by the use of planar radiographs in
two dimensions, which visualized osseous land-
marks. These bony landmarks were used for
delineation of radiation portals and localization
of therapeutic targets. Depending on the tumor
site, the number of beams used for radiotherapy
ranged from two to six. However, treatment plan-
ning was limited by poor tumor visualization of
mainly X-ray-based imaging methods and tech-
niques available for radiation delivery (Purdy
2008; Bortfeld and Jeraj 2011).
2.2 Conformal Radiation Therapy
In the 1980s, cross-sectional imaging procedures
(i.e., CT and MRI) entered clinical routine, which
were essential for a more accurate delineation of
cancerous tissues and risk structures. These
advances in radiological imaging were fundamental
for further progress in radiation oncology with
development of computerized treatment planning
and delivery systems that enabled an exquisite tai-
loring of 3D radiation dose distributions to the can-
cerous tissues (Bortfeld and Jeraj 2011). These 3D
conformal dose applications were reached by the
use of a larger number of lower-dose radiation
beams aimed at the target volume from different
directions (up to 10 beams) (Fig. 2). As a conse-
quence, the low-dose exposition of healthy tissues
was increased, but the amount of tissues receiving
high doses was significantly decreased (Bortfeld
and Jeraj 2011); thus, the dose in the tumor could be
escalated, while the surrounding healthy tissues and
organs at risk could be protected better than with
traditional EBRT helping to increase the therapeutic
ratio. Furthermore, dynamic multileaf collimators
were developed and clinically established for more
Radiotherapy
precise shaping of radiation beams compared to the
previously used lead blocks (Purdy 2008).
Modern conformal radiation therapy plans
may also include intensity-modulated radiation
therapy (i.e., IMRT) and stereotactic body radia-
tion therapy (i.e., SBRT), which are described in
the next two sections.
2.3 Intensity-Modulated
Radiation Therapy (IMRT)
The mathematical basis of IMRT was developed
in the early 1980s to address the problem of
irradiation of complex-shaped tumors in close
Fig. 2 Dose distribution for primary irradiation of an
NSCLC in the right upper lobe. The purple- and red-
colored inner region represents the high-dose region. The
yellow, green, and blue areas represent decreasing isodose
lines towards the periphery
a b
Fig. 3 Presentation of a mass along the dorso-cranial
thoracic wall left sided with infiltration of the paraverte-
bral space, upper part of the thoracic spine and spinal
canal in the planning CT (status post-laminectomy) (a). In
21
proximity to or within risk structures, for exam-
ple, paraspinal tumors (Fig. 3). But it still took a
while until theoretical knowledge was put into
practice, with first IMRT treatments applied to
patients in 1997. The concept of IMRT is based
on two decisive pillars, which are inverse treat-
ment planning and nonuniform photon intensities
across each of several radiation beams – usually
5–9 in modern treatment plans (Brahme et al.
1982). In the pre-IMRT era, physical dose distri-
bution was calculated by trial and error; this
means by trying out different intensities and
directions of radiation beams. IMRT, on the other
hand, takes the abovementioned path of inverse
treatment planning, that is, dose distribution is
tailored exactly to the target volume at the begin-
ning of the planning process. Subsequent model-
ing of the direction, contour, and intensity of each
treatment beam follows this by computerized
treatment planning systems. For this purpose,
radiation beams are subdivided into many seg-
ments and subsegments (i.e., often more than
100), in which intensities can be specified inde-
pendently of each other by the use of multiple
overlapping field segments or moving collimator
leaves. This enables reduction of the dose for a
certain beam direction, if risk structures are
included in the beam. However, this approach
would result in underdosing of the target volume,
if conventional radiation techniques were used
(Fig. 4). In IMRT plans, the lack of dose in the
target volume is compensated by additional dose
through another beam (Sterzing et al. 2009;
Paumier et al. 2011).
IMRT plan (b) with depiction of steep dose gradients to
the surrounding normal tissues and the myelon (red area
represent high-dose area; yellow, green, and blue areas
represent decreasing isodoses)
Another random document with
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Fig. 25. Charcoal sketch of native spearing kangaroo, Pigeon Hole, Victoria River
(× 2/5). Tracing.

Another method is to apply the paint in the form of a water mixture,

similar to that described when discussing the ochre drawings. For
this purpose, especially when an important event is pending, a
number of men are chosen to attend to the “make up” of the
performers. The assistants kneel beside those who are to act, and
apply the paste with their fingers. The most delicate parts to handle
are the eyelids. The actor is required to close his eyes whilst the
artist carefully applies the paste to the lids; but it occasionally
happens that some of the material slips on to the eyeball and is
rubbed against it before the sufferer can give the alarm. Vide Plate
XLV, 2.
We have already referred to the coloured down decorations which
are attached with human blood to the bodies of the performers taking
part in sacred and other ceremonies, and we have also mentioned a
ground drawing known as “Etominja” (Plate XXXVII), which is
constructed in a similar way. Some of the latter (e.g. the “walk-about”
of the “Tjilba Purra Altjerra Knaninja”) are very large; others, as for
instance that connected with the “Erriakutta” or yelka ceremony, are
constructed over the entire surface of mounds which cover many
square feet of ground.
 Having briefly reviewed the different methods of art production in
vogue in Australia, we shall proceed to consider a number of the
designs in greater detail, deduce their origin, trace their evolution,
and, where possible, give their interpretation. It will be realized at the
outset that some of the designs are crude in the extreme, whilst
others are undeniably shapely and quite up to the standard of an
average European’s artistic proficiency. The latter remarks apply
best to actual representations of natural forms. It must be
remembered that the artistic reproductions an aboriginal makes are
invariably from memory; the primitive artist never draws with a model
in front of him. If we were to ask a number of Europeans to draw, say
a horse from memory, there is no doubt we should receive a great
variety of results in response to our request. So, among the
aboriginal artists, there is a great diversity of talent which is more
individual than tribal.
If, for instance, we study the different attempts at representing the
form of one of the most familiar subjects we could ask an aboriginal
to experiment upon—the ubiquitous kangaroo —we should find by
comparison of the productions placed before us, a very marked
difference in quality. Compare, for instance, the two pictures of
kangaroo on Plate XLVII. They are the works of men of the same
tribe, are all similarly drawn, and come from the same locality. Yet, in
the upper picture, the outline and proportions of the two animals are
so incorrect that it is very doubtful whether many people not
acquainted with the locality would guess what animal the pictures
are intended to represent. In the lower picture, however, anybody
acquainted with the shape of a kangaroo would have no hesitation in
pronouncing his diagnosis. The characteristic attitude, the large tail,
the disproportion between the front and hind limbs, and the shape of
the head are quite true enough to nature to permit of correct
identification.
Fig. 26. Carving depicting a quarrel between a man and his gin. Arunndta tribe (×
1/2). Tracing.

The three designs are all drawn in charcoal, the figures in the first
two cases being outlined with a white pipe-clay line, and in the
second case with one of yellow ochre. If we wish to go one better
still, we need only study the pipe-clay drawing on bark by a native of
the Katherine River district shown on Plate XLIX, 1—a very
creditable picture of a dead kangaroo.
Some of the designs one meets with are so accurately drawn that
a scientific determination of the species becomes possible. Look for
a moment at the fish, portrayed in pipe-clay, shown in Plate XLVIII.
The piscine nature of the form, here depicted on rocks, is not only
apparent, but it is possible to say with some certainty that the two
shown swimming belong to the Toxotes, which are commonly called
Archer Fish. The form shown in Plate XLIX, 4, is unquestionably
meant to be one of the Therapon species. Both kinds of fish are
known to be living in the Katherine River, not far from the site at
which these pictures were drawn.
 But if, on the other hand, some of the designs are so poor as to be
barely recognizable or even quite unrecognizable by us, how does
the aboriginal manage? When the artist is present, he can explain.
But he is not always available!
If, by way of illustration, we were asked to say definitely what the
meaning of the central figure on Plate L, 1, was we should in all
probability want to know more about it before committing ourselves.
But an aboriginal can give us a correct reply immediately. The
locality at which the photograph was obtained is north of the
Musgrave Ranges in central Australia. But that does not give us any
clue. After studying the picture more closely, we might be able to
distinguish the outline of a quadruped, the four legs being shown,
one behind the other, in a row, and a big head on the right-hand side,
in a position suggesting that the animal is feeding. But these are
characteristics common to many animals!
So far, therefore, we have seen nothing to suggest the class of
animal we are dealing with. When we look again, we might note that
there is a crude image of a human being shown on the back of the
animal; and behind this is a structure which might stand for a saddle.
We guess the answer and claim that the group is a very poor
drawing of a man on horseback.
But there are other animals a man could ride! And when we look
again, we observe that the second leg of the animal, counting from
the right, has a peculiar enlargement attached to its lower end. That
structure is the key to the riddle; it represents the track of the animal!
Those familiar with the great beast of burden, now used extensively
in central Australia, will recognize the two-toed spoor of a camel.
This method of pictorial elucidation is by no means exceptional.
We have already noticed something similar in the ancient carvings at
Port Hedland, where the human foot-print is added to disperse any
doubt which may be entertained in so far as the correct interpretation
of the figure is concerned. A similar device is well exemplified in the
accompanying sketch of an ochre drawing of a human form from the
Glenelg River district in the northern Kimberleys of Western Australia
(Fig. 15). In the carving of an emu from the King Sound district,
which is reproduced in Plate XLII, 2, we noticed the same sort of
thing.

Fig. 27. Ochre-drawing of spear-boomerang duel, Arunndta tribe (× 1/2). Tracing.

The cases before us are not accidental, but we have acquainted

ourselves with the recognized determinative system of Australian
pictographs which is quite analogous to that known to have been
practised by the ancient Egyptians. Consider, for instance, the
character signifying “to love”—a human figure in profile with one
hand lifted to the level of the mouth. The same figure, with a few
parallel wavy lines, signifying water, drawn against it, means no
longer “to love,” but “to drink.” The wavy lines in this instance are the
determinative. In the Australian illustrations given above, we have
selected samples which are easily followed, but there are many
cases where the reading would be quite impossible if it were not for
the presence of the little, subsidiary, determinative sketch.
In his endeavour to make the meaning of some of his designs
clear, a native often embodies as many features as possible, quite
regardless as to whether in reality they would all be visible in the one
plane he is drawing. In the picture of a crocodile appearing on a
boabab-nut from the Derby district in Western Australia, shown in
Fig. 16, it will be observed that the reptile, in spite of having its dorsal
surface represented, has its vent indicated. The long, slender muzzle
of this figure, by the way, makes it clear that the smaller species of
the two northern Australian crocodiles (C. Johnstoni) is intended.
The human figure, too, very often appears half in full and half in
profile.
The aboriginal is a keen observer, and takes careful note of many
things besides a kangaroo, a snake track, or other similar natural
objects which may lead him to his daily bread. When travelling in the
Buccaneer Archipelago in the far north-west I remember one of the
natives drawing my attention to a peculiar formation in the clouds,
and saying, in the Sunday Island dialect: “Arrar ninmiddi,” which
means, literally: “Cloud knee.” My instructor proceeded to draw the
extraordinary shape he could see with his finger upon the hatchway
of the pearling lugger we were sailing in, after which he completed
the figure of a man. I was struck with this man’s faculty of
observation, because the cloud effect he referred to was rather out
of the common and projected from a cirro-cumulus like the bent limb
of a swastica.
It is in this way that many inspirations come to the cave artist.
Repeatedly one has occasion to notice how a pre-existing feature or
defect in the rock face—a crevice, a floor, a concretion—becomes
the centre piece of a design drawn to suit it. The feature one finds
most commonly embodied in a cave drawing is a small hole. This
often figures in the place of an animal’s eye, or a hole into which a
snake is disappearing. A local bulge in the rock may also be taken in
as part of a design and represent portion of a head or body.
Not only does the artist embody suitable natural features in his
designs, but, conversely, he also applies his knowledge of form to
explain already existing phenomena in the world about him. The
embodiment of his artistic ideas in his poetical explanations of
Nature’s wonders plays, as might be expected, an important role in
his mythology. These remarks apply especially to any striking
characteristics in the sky. When among the tribes of the Musgrave
Ranges, I ascertained that the black-looking gap in the Milky Way,
close to the Southern Cross, which is commonly known as the Coal
Sack, was referred to as “Kaleya Pubanye,” that is, the “Resting
Emu.”

Fig. 28. Charcoal sketch of ceremonial dance, Pigeon Hole, Victoria River (× 1/6).
Tracing.

In the north of Australia, the Larrekiya, Wogait, and other tribes

have adopted a similar designation for a series of dark spaces along
the Milky Way. But they have extended the idea considerably in that
the Coal Sack represents only the head of a gigantic emu, the beak
of which is pointed towards the Musca constellation (i.e. towards the
south). A small star of the Southern Cross group very appropriately
stands for the eye of the bird; the nebulous effect usually
surrounding this star gives it an extra life-like appearance. The neck
is but faintly discernible near the head, but becomes clearly visible in
the neighbourhood of the nearer Pointer; it passes between the two
Pointers and curves slightly towards the constellation of Lupus.
Within the constellation of Norma, the dark space widens
considerably and represents the body of the emu. The blunt tail turns
sharply towards, and into, the constellation of Scorpio. A nebulous
patch lying practically on the point of junction between the imaginary
areas of Ara, Scorpio, and Norma affords a good division between
the legs of the bird, whilst another lying between μ and ζ of the
Scorpion group separates the tail. The lower portions of the legs are
not very clear, but some of the more imaginative natives maintain
that they can distinguish three toes on each extremity. There is no
doubt the primitive eye has herein discovered a striking similarity
between an optical phenomenon in the southern sky and a living
creature, which is of great importance in the hunting field, and at the
same time plays a prominent role in tribal folk-lore. They refer to this
emu by the name of “Dangorra.” Vide Fig. 17.

PLATE XLII
 1. Rock carvings, Flinders Ranges.

2. Emu design carved into the butt of a boabab tree, King Sound.

Fig. 29. Remarkable cave drawing, Glenelg River, N.W. Australia

As affording a means of comparison, a hunting scene is

reproduced carved upon the surface of a club by aborigines of
Victoria. The little group is composed of an aboriginal hunter who in
one hand is poising a spear and in the other is carrying a
boomerang; behind him are two emus standing in much the same
position as that assumed to be the case in the heavenly image just
described.
The Minning at Eucla recognize only the long neck of the emu in
the sky, and refer to it as “Yirrerri”; on the Nullarbor Plains the same
portion is looked upon as the heavenly tjuringa of the emu.

Fig. 30. Pictograph of lizard, natural and conventional form.

Speaking generally, there is perhaps no other creature living which

figures so frequently in aboriginal art, both on the cave wall and in
the dance, as the great struthious bird of Australia. This is no doubt
due in the first place to the admirable way in which it lends itself for
the purposes mentioned; its antics in the field suggest many tricks
for mimicry at a corrobboree, and its distinctive form supplies the
artist with a model which never fails to attract the attention of the
artistically inclined among his people. In Plate XLIX, 2, we have a
pipeclay drawing of an emu from the Katherine River which is rather
exceptional in that it shows the bird more en face than is usual; the
proportions are, on the whole, good, except that the head is screwed
upwards in a rather strange way. On a boomerang from Broome
(Fig. 18), we have a series of engraved emu pictures, all in profile,
and in different attitudes.
On the whole, an aboriginal’s pictures are flat and without
perspective. He takes the inspiration direct from nature and
reproduces the subject singly, and as a separate entity; a number of
such designs are drawn side by side with or without pictographic
sequence. But there are countless occasions upon which artists,
especially the more gifted, prefer to draw a real scene from life,
combining subject with action. Environment or surroundings rarely, if
ever, receive attention.
Take as a very simple illustration the lizard shown in the pipeclay
rock drawing from the Katherine River (Plate XLIX, 3). The general
shape of the body, together with the large and well-differentiated
head, strongly suggests a species of the large monitor which is
common throughout the district. The interesting feature about the
picture is, however, the life which is indicated by the fact that the
reptile is drawn in the act of shooting out a long, split tongue.

Fig. 31. Normal, conventional, and emblematic representations of turtle.

 Fig. 32. Normal, conventional, and emblematic representations of frog.

Again, in the charcoal sketch of two crows from the Pigeon Hole
district (Fig. 19), one bird is represented in an attentive attitude, as
though on the point of flying away, while the other is very
characteristically shown in the act of cawing.
One could produce an almost endless variety of decorated figures,
representing men and women performing at ceremonial dances and
corrobborees to illustrate the life and action which is embodied in
aboriginal art. In Fig. 20 a selected number of pipe-clay drawings
from the Humbert River, Northern Territory, have been grouped
together to serve this purpose.

Fig. 33. Normal, conventional, and emblematic representations of echidna.

The most interesting effects, however, are those brought about by

a combination of two or more figures. How different, for instance, the
two kangaroo shown together in Fig. 21 seem to those previously
discussed (Plate XLVII). These are charcoal drawings from Pigeon
Hole on the Victoria River, and in them the hopping movement of the
animals is indicated very clearly. The animal in the rear is in full
flight, as the erect position of the tail and the general holding of the
body betray; but the one in the lead is on the point of drawing up and
is turning its head back towards its mate.
How realistic, too, the little bark drawing is from east of Port
Darwin (Fig. 22), in which a bird of prey is shown mounted upon a
wallaby or kangaroo, with its claws and beak embedded in the flesh
of its victim.
 PLATE XLIII

1. Carved boabab nut, King Sound.

2. “Wanningi” from north-western Australia.

3. Slate scrapers used by the extinct Adelaide tribe for trimming skins.
 A neat pipe-clay drawing from the remote Humbert River district is
presented in Fig. 23. The group, which is three feet in length, is
composed of a central figure of a man who is holding one arm on
each side towards a dog, as if offering them something to eat or for
the purpose of patting them. The dogs seem to be giving their
attention to the man.

Fig. 34. Conventionalized “Ladjia” or yam Tjuringa pattern.

Two more charcoal drawings from Pigeon Hole, though roughly

sketched by the artist, depict very graphically scenes from the hunt.
In one (Fig. 24), the hunter is in the act of stalking a buffalo or
bullock with his spear held in readiness to throw, while in the other
the attitude of the hunter indicates that the spear has just been
thrown and is entering the body of the prey, a kangaroo (Fig. 25).
The carving of an Arunndta man, reproduced in Fig. 26, is most
effective. An angry husband has been caught by the artist in the act
of punishing his wife with a waddy. The placement of the legs of the
two persons indicates stability on the part of the man engaged in the
flagellation, and a swinging movement on the part of the woman who
is being held back by her hand.
 Fig. 35. A dog-track.

We have already seen the carved representations of two stages in

a stone-knife duel by an Arunndta tribesman (Fig. 4), and here, in
Fig. 27, an ochre drawing is reproduced which is, if anything, more
animated than any previously discussed. A spear-boomerang duel is
being fought, during which each of the combatants is protecting
himself with a shield. The artist has evinced considerable talent in
portraying the men just at the moment when both are bounding
through the air towards each other, the one on the left parrying his
opponent’s spear, while the other, on the right, is preparing to
receive the blow from the boomerang.

Fig. 36. A kangaroo-track.

One might now go a step further in analyzing aboriginal art. The

productions we have studied so far embody the ideas of form, life,
and action; and, it might be added, occasionally one finds a very fair
sense of composition as well. Such, indeed, might already be said to
be true of several of the pictures discussed above, but a finer
specimen lies before us in the charcoal drawing from Pigeon Hole
(Fig. 28). This faithfully portrays a scene from a gala ceremony, in
which the body of performers, fully “dressed” for the occasion, are
acting before the leader, who, in his turn, is being supported by two
others in the foreground. It must be admitted that the composition of
this group of figures is remarkably good, and, what is quite
exceptional, a very successful attempt has been made at
perspective. All figures are shown in different attitudes of dancing.
The impression this charcoal drawing gives one, at first glance, is
that of a rough sketch in crayon resembling the outline a European
artist might make on his canvas prior to starting upon the actual
painting.

Fig. 37. A rabbit track.

Leaving that section of aboriginal art which deals essentially with

designs copied directly from Nature in a sense more or less purely
artistic and æsthetic, we shall turn our attention to a few types which
are more specialized.

Fig. 38. Emu tracks.

From a study of his religious ideas, we have learned that the

aboriginal identifies himself with some mystic, natural creature or
object, which he adopts as his “totem.” It would only be reasonable
to expect, therefore, that some of the drawings represent these
objects; and that they are recognized by the natives as having
particular personal or family significance. Looked at from a modern
standpoint, these designs are really the equivalent of a family crest,
and are claimed only by those rightfully entitled to them. This
explanation must be given for many of the naturalistic designs
appearing on rocks, trees, grave posts, and personal belongings.
These “totemic” crests or symbols being hereditary, we have before
us a primitive form of heraldry, a conception we have already learned
to be covered by the word “Kobong,” originally introduced by Sir
George Grey from the north-west of Australia.
 Fig. 39. Pictographic
representation of nesting emu.

Fig. 40. A lizard track.

We have also ascertained that some of the central as well as

north-western tribes of Australia believe that the earliest tribal
ancestors originally were more animal than human in appearance,
and adopted the shape of a man only at a later period; that they can,
however, return to the animal form whenever they desire; and that
others remain semi-human. It is not surprising, therefore, to find
amongst their drawings and carvings representations which are
partly human and partly animal in outline; these are honest attempts
at perpetuating the traditional appearance of the ancestral beings of
the tribe. In the photograph attached hereto (Plate LI, 1), taken at
Forrest River, two pictures of such creatures are to be found which
are drawn in ochre. There were many others, from three to five feet
in length, reptilian in shape, some with human hands and feet, others
with hair shown upon the head, and in most of them the sex unduly
prominent. These remarkable designs are, therefore, not naturalistic,
but have been evolved on purely fictional or mythological lines,
based upon the tradition of the tribe and upon the imagination of the
artist.

Fig. 41. A snake or snake-track.

 From the consideration of these artistic effigies of their Demigods,
it is not a big step forwards which brings us face to face with the
sacred tribal drawings. During initiation ceremonies, especially of the
now practically extinct south-eastern tribes of Australia, gigantic
figures resembling a human being were moulded into the surface of
the ground and subsequently tinted with ochre, which were
supposed to conceal the Great Spirit or Deity, which, like the “Altjerra
Knaninja” of central Australia, watched over the proceedings as the
young men passed from a condition of adolescence to that of
permanent manhood; numerous carvings and ochre drawings were
also made upon the trunks of any trees nearby.
Not only during the initiation ceremonies are these practices
resorted to, but when a sacred observance is contemplated,
especially those having to do with the “totem,” elaborate designs are
painted in ochre upon the surrounding surfaces of rocks and trees
which depict an act connected with the traditional origin of the sacred
object.
A classical illustration is to be found in the MacDonnell Ranges, at
Emily Gap. According to Arunndta belief, it was at this spot that the
early semi-human ancestors of the witchedy grub or “Utnguringita”
alighted from Altjerringa. They brought with them large numbers of
the grub, which they cooked and ate. The territory dominated by
these ancient beings extended from Heavitree Gap to Emily Gap,
and across to Jessie Gap. On the western wall of the first-named
gap, known by the natives as “Ndariba,” an inclined slab of rock, not
high above the level of the sandy bed of the Todd River, contains a
series of peculiar concentric iron stains which are regarded as the
impressions of the stern of an Utnguringita Altjerra who sat there,
and, as he collected grubs, moved forwards. The Utnguringita came
into frequent conflict with the Dingo or “Knullia” people whose
country lay immediately west of Heavitree Gap, but, nevertheless,
they blessed the land with many eggs, which developed into larvæ
and supplied the tribe with food.
 Fig. 42. Human foot-prints and trail.

Eventually the Utnguringita ancestors returned to Altjerringa, but

they left a number of stone tjuringas in Emily Gap, which are
supposed to be occupied by the spirits whenever a sacred ceremony
is performed on the spot. On the eastern stony wall of this gap some
rather imposing designs are to be seen, which originally must have
occupied most of the area available. The drawings are very old; their
origin dating back long before the recollections of the present
generation. It is wonderful how well the work has withstood the
denuding action of the weather for so long. The natives tell you that
the old Altjerringa men applied the pigment to the rock and that they
mixed it with the “knudda” (fat) of the grubs. It is more likely that the
ochres were mixed with emu fat; in places the pigment seems as
though it were chemically combined with the rock, and it could only
be removed by chipping the surface. The designs in their present
condition (Plate LI, 2) consist of a series of parallel, vertical lines,
alternately coloured red and white, and capped by horizontal bands
of the same colours, the white of which containing three or four red
dots. What the original designs may have been like, it is now difficult
to say, but the natives maintain that they included the images of
some women they call “Aluggurra,” who were waiting at the foot of
the cliff while the men were concealing their tjuringas in the rocks
and nooks above. To the present day, the old men of the local
Arunndta group store their ceremonial objects in the same sanctuary,
thinking that the sacred figures on the wall will protect them from the
hands of inquisitive intruders.
There remains yet another class of ochre drawing which deserves
mention. I allude to the famous discovery of Sir George Grey in
1837. There is perhaps no other Australian drawing, old or modern,
which has been so freely discussed and criticized. During an
expedition in the northern Kimberleys of Western Australia, it was my
good fortune to re-discover several drawings of this type in
practically the same locality as that recorded by Sir George Grey,
near the Glenelg River. One figure was perfect, others were partly
obliterated or incomplete. The best design was in a cave near the
top of a prominent bluff the local Worora people call Berrial; it was
drawn in ochre upon a steep face of rock immediately under an
overhanging ledge of quartzite. The figure was unquestionably that
of a human being, although it measured fully nine feet in length. It lay
fully extended, upon its left side, with its arms placed straight against
its sides. It reminded one forcibly of a Buddha in a Ceylonese
temple. What made the figure seem un-Australian was that it was
clothed in a long, striped garment, resembling a priestly gown, from
which only the head, hands, and feet were excluded. A loosely-fitting
belt is also shown. As seems common to all these drawings, the
facial features are only indicated by the eyes and nose, the mouth
being omitted. Another characteristic, which is shared by all other
drawings, is that the head is surrounded by a number of peculiar,
concentric bands, through which, and from which, many lines
radiate, giving the structure the effect of a halo surrounding the head
of a saint. The picture bore an unmistakable likeness to the type
illustrated by Sir George Grey, and was drawn in red, brown, black,
and white. Vide Fig. 29 and Plate L, 2.

Fig. 43. “A man is tracking a rabbit.” Simple example of pictography.

There is no doubt about these curious drawings, now more or less

adopted by the local tribe, having originated under some exotic
influence. It is historically known that for centuries past excursions
have been made to the north of Australia by Macassans and other
eastern people, who may have been responsible for the first drawing
of a figure of so sacerdotal an appearance, which the aborigines
have since learned to copy so perfectly. It has also been speculated
that shipwrecked sailors might be responsible for the representation