Radiation Oncology: An Evidence-Based Approach

658 Pages·2008·14.116 MB·English

by  Molls, M., Heilmann, H.-P

I
Contents
MEDICAL RADIOLOGY
Radiation Oncology
Editors:
L.W. Brady, Philadelphia
H.-P. Heilmann, Hamburg
M. Molls, Munich
C. Nieder, Bodø
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III
Contents
J. J. Lu · L. W. Brady
(Eds.)
Radiation Oncology
An Evidence-Based Approach
With Contributions by
A. A. Abitbol · R. R. Allison · B. Amendola · M. F. Back · J. J. Beitler · M. Biagioli · E. B. Butler
J. S. Butler · L. W. Brady · M. Chadha · A. Y. Chen · W-J. Chng · W. H. Choi · H. T. Chung
J. S. Cooper · B. R. Donahue · S. Fu · H. A. Gay · I. C. Gibbs · S. C. Han · L. B. Harrison
G. F. Hatoum · J. M. Herman · D. Hristov · K. Hu · B. J. Huth · A. J. Khan · F-M. Kong
L. Kong · K. LaFave · E. M. Landau · K. M. Lee · N. Lee · Y. Li · J. J. Lu · A. M. Markoe
V. K. Mehta · S. Mutyala · R. Ove · A. C. Paulino · T. M. Pawlik · J. A. Peñagarícano
C. L. Perkins · V. Ratanatharathorn · S. G. Soltys · M. M. Spierer · C. Takita · B. S. Teh
B-C. Wen · A. H. Wolfson · X. Wu · L. Xing · T. E. Yaeger · Q. Zhang · Z. Zhang
Foreword by
L.W. Brady · H.-P. Heilmann · M. Molls · C. Nieder
Introduction by J. J. Lu and L.W. Brady
With 150 Figures in 219 Separate Illustrations, 176 in Color and 147 Tables
123
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IV
Contents
Jiade J. Lu, MD, MBA Luther W. Brady, MD
Associate Professor and Consultant Hylda Cohn/American Cancer Society
Department of Radiation Oncology Professor of Clinical Oncology, and
National University Cancer Institute of Singapore Professor, Department of Radiation Oncology
National University Health System Distinguished University Professor
National University of Singapore Drexel University, College of Medicine
5 Lower Kent Ridge Road Broad & Vine Sts., Mail Stop 200
Singapore 119074 Philadelphia, PA 19102-1192
Singapore USA
and
Distinguished Clinical Professor
Department of Radiation Oncology
Cancer Hospital of Fudan University
270 Dong An Road
Shanghai 200232
P. R. China
Medical Radiology · Diagnostic Imaging and Radiation Oncology
Series Editors:
A. L. Baert · L. W. Brady · H.-P. Heilmann · M. Knauth · M. Molls · C. Nieder
Continuation of Handbuch der medizinischen Radiologie
Encyclopedia of Medical Radiology
ISBN 978-3-540-77384-9 e-ISBN 978-3-540-77385-6
DOI 10.1007 / 978-3-540-77385-6
Medical Radiology · Diagnostic Imaging and Radiation Oncology
Library of Congress Control Number: 2008922317
(cid:164) 2008, Springer-Verlag Berlin Heidelberg
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V
Contents
Foreword
For the past ten years there have been signifi cant scientifi c advances in biological sci-
ences and healthcare. At the same time, there has been increased accountability and,
in some instances, attempts to ration services as a mechanism to accomplish this.
Although arbitrary clinical practice guidelines have been published, more rational
bases to defi ne optimal healthcare should be based on the identifi cation of innovative
approaches, outcome analysis in properly designed clinical trials, and careful assess-
ment of current practice based on solid and creditable clinical research and evidence
based decision making in medicine. The growth in basic and translational research
data offers a guide to medical practice and is essential for the clinician to appraise and
use published evidence for medical decisions. Evidence based medicine exemplifi es
the effect of teaching clinicians to evaluate research data by methodologic standards
and to critically appraise published evidence from both a scientifi c and sociocultural
perspective. Physicians are trained to maintain high standards of critical conscious-
ness in methodologic domains, but not necessarily in the broader historic sociocultural
domains surrounding them.
It is important for those practicing evidence based medicine to take full advantage
of their encounters with patients, where the questions and answers that may arise can
lead to providing the patient with the best available medical care. Appropriate and
relevant clinical questions relate to the patient and the problem, to intervention, to a
comparison intervention, and to outcome.
The present volume is specifi cally aimed at the utilization of evidence based medi-
cine in outcome from radiation oncology. It stands as a signifi cant and important stan-
dard by which all programs in management can be judged.
Philadelphia Luther W. Brady
Hamburg Hans-Peter Heilmann
Munich Michael Molls
Bodø Carsten Nieder
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VII
Introduction
Introduction
Jiade J. Lu and Luther W. Brady
The practice of radiation oncology constantly involves decision making. Everyday,
r adiation oncologists are challenged with evaluating diagnostic and therapeutic
options for cancer patients, and making decisions together with patients to ensure
the best treatment of their disease. Historically, clinical experience and summarized
expert knowledge served as important bases of medical practice. The rationales of
medical decision making include those made in cancer management based largely on
pathologic and physiologic rationales. The ability of physicians to provide effective
medical care and rational decision making has long been assumed the valuable product
of experience and expertise. When personal experience or understanding is lacking,
clinicians usually turn to experts in the fi eld for their opinions, or seek knowledge from
textbooks.
While personal experience and expertise, as well as summarized knowledge, are
valuable in providing references for daily practice in medicine, experience gained
from physiologic/pathologic rationale-oriented practice faces several important pit-
falls. One of the most concerning issues is the reliability of such practice, and decisions
made according to the “obvious” situation according to our understanding of a disease
(the perception of a physician) may not produce an effective outcome. Consistency of
practice is another issue in empirical medicine, and close observation of the actual
practices has demonstrated that even experienced physicians are likely to be unsystem-
atic and inconsistent in medical decision making. Wide variations in patient care that
are not related to differences in patients’ preference, availability of treatment technol-
ogy, or specifi c individual scenarios are often observed.
A recent example that illustrates the insuffi ciency of the pathologic/pathologic ratio-
nale in decision making is the concurrent use of erythropoietin with radiation therapy.
It is well recognized that radiation is more effective against cancer cells with higher
oxygen concentration. It has been demonstrated that the treatment outcome in patients
with head and neck cancer or cervical cancer with high hemoglobin levels, for example,
are superior to those with severe anemia during radiation therapy. While the effi cacy
of erythropoietin has been repeatedly demonstrated in patients with cancer or chemo-
therapy-induced anemia, it is reasonable to postulate that an increased hemoglobin
level induced by erythropoietin may also improve outcome after radiation therapy.
Based on this rationale, clinical trials were initiated to study whether correction of
anemia during radiation therapy using certain drugs “should” improve the outcome.
However, to the surprise of most researchers, although a reliable rise in hemoglobin
concentration was observed with the use of medication, no benefi t in local control,
disease-free survival, and overall survival rates were observed when the medication
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VIII
Introduction
was used concurrently with radiation therapy. In actual fact, treatment of anemia using
erythropoietin during radiotherapy may impair tumor control, rather than improve
the effectiveness of radiation (Henke et al. 2003).
This example demonstrated the insuffi ciency of physiologic and pathologic reason-
ing to provide expected results, but also argued that experience and expertise were not
reliable for preventing the mistreatment of patients. Since the detrimental effects of the
medication on disease control was not always apparent immediately after the use of the
medication, a cause–effect relationship could not be readily established. Accumulated
experience in medical practice tends to be less systemic and may not be useful for rec-
ognizing cause–effect relationships typifi ed above, especially when the time interval
between the root cause and the effect is relatively protracted.
What Is Evidence-Based Medicine?
It is generally accepted that effective disease management and medical decision making
rely on the best available scientifi c evidence, in combination with the clinician’s expe-
rience and patients’ preferences. The most common question posed upon hearing the
term evidence-based medicine is: “Isn’t that what we always do?” Many physicians,
including radiation oncologists, may claim that clinical evidence is always incorpo-
rated in their practice. It is very true that much progress has been made in clinical
research, and that medical decision making based on the results of scientifi c studies
has increasingly prevailed; however, simply citing or using some research results is
insuffi cient for effective clinical decision making and, alone, is far from evidence-
based medical practice.
The Triad of Evidence-Based Medicine
Evidence-based medicine aims to utilize scientifi cally obtained evidence for medi-
cal practice and is defi ned as the conscientious, explicit, and judicious use of current
best evidence in making decisions about the care of individual patients (Sackett et
al. 1996). It involves integrating the best available scientifi c evidence from systematic
research on patients’ condition, value, and expectations, as well as the attending physi-
cian’s expertise in clinical decision making.
Although scientifi c evidence is one of the most important elements of evidence-
based medicine (and effective medical practice requires routine application of the best
evidence in patient care), a fundamental principle of evidence-based medicine is that
evidence alone, even when obtained through systemic and exhaustive research, is not
suffi cient for effective clinical decision making. Systemically reviewed clinical evi-
dence must be integrated with patients’ expectations and value, together with clinical
expertise. Effective decision making in medical practice requires the application of all
three elements of evidence-based medicine (Fig. 1).
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IX
Introduction
Fig. 1. The triad Scientifi c
of evidence-based Evidence
medicine
Asking
Acquiring
Appraising
Applying
Auditing
Clinical Patient´s
expertise value
Hierarchy of Evidence
As scientifi c evidence plays a major role in the learning and practice of evidence-based
medicine, it is necessary to briefl y clarify the meaning of evidence in this context. The
Cambridge dictionary defi nes “evidence” as anything that helps to prove that some-
thing is or is not true. This simple defi nition can be applied to clinical evidence of
any specialty in medicine, including radiation oncology. Results obtained from basic
science, animal, translational, as well as clinical research can all be used as medical
evidence. Furthermore, observations made in the clinician's daily practice are also
considered clinical evidence.
However, not all evidence in medicine is created equal, and not all evidence can be,
or should be, used in decision making in patient care. The quality, i.e., the validity, rel-
evance, and importance of clinical evidence differ signifi cantly. Evidence-based medi-
cine seeks to assess the quality of scientifi c evidence relevant to the risks and benefi ts
of treatment (or in many cases, lack of treatment), with the purpose of improving the
health of patients by means of decisions that will maximize patients’ quality of life and
life span. Merely applying study results without critical appraisal may not only be less
useful, but potentially harmful or dangerous to patients.
Evidence used in any clinical decision making process can be categorized according
to its quality based on the probability of freedom from error, and is usually classifi ed
by critical appraisal. The following four aspects are the most basic of critical appraisal:
relevance, validity, consistency, and signifi cance of the results. The quality of evidence
can be differentiated according to those elements of quality.
In a simple sense, the quality of evidence, specifi cally its validity, can be differenti-
ated according to the nature of the evidence. For a specifi c topic, when all other factors
are equal, meta-analyses and systemic reviews based on r andomized clinical trials, as
well as well-designed and -powered randomized clinical trials, are usually of superior
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X
Introduction
quality than retrospective series. Figure 2 is a simplifi ed illustration of the quality of
clinical evidence. However, it is important to remember that quality also depends on
the relevance and importance of the evidence, and such factors depend largely on spe-
cifi c clinical scenarios.
Fig. 2. Hierarchy of
evidences
Systematic
reviews
and/or
e high-power
enc randomized controlled
vid trials (RCTs)
e
of
y
alit Low-power randomized trials
u
Q
Quasi-experimental studies
(e.g., prospective non-randomized studies)
Non experimental studies (e.g., retrospective series
Case Reports
The “5As” Practice of Evidence-Based Medicine
Radiation oncology is an ever-changing fi eld. With the development of new technology
and treatment techniques, the management of cancer using ionizing or particle radia-
tion is evolving on a monthly, if not daily, basis. Like any other forms of therapy, apply-
ing newly developed radiation techniques (such as imaging-guided radiation therapy
and particle therapy) or treatment strategies (such as combined chemoradiotherapy)
to a particular type of malignancy, or applying existing treatment techniques proven
for one type of disease to a different type of cancer, requires vigorous testing and veri-
fi cation before it can be called standard. As a result, the fi eld of radiation oncology is
fl ooded with publications and literature.
While it is encouraging to observe the exponential growth in scientifi c research
papers and literature published in this fi eld, it is important to recognize that evaluat-
ing and understanding the scientifi c evidence in order that one can utilize it in decision
making requires profi cient skills and knowledge of evidence-based medicine, as well
as suffi cient time and effort.
Scientifi c evidence is one of the three integral parts of evidence-based medical prac-
tice; thus, understanding and being able to apply pertinent and best-available evidence
for a particular clinical question is crucial in the practice of evidence-based medicine
in radiation oncology. To achieve this purpose, the following fi ve key steps (the “5As”
cycle) should be considered sequentially (Fig. 3):
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XI
Introduction
Frame patient scenario into a clinical question
Librarian Centred
Systematically retrieve best evidence available
Critically appraise evidence
Apply results to patient
Fig. 3. Five key steps of effective evi-
Evaluate decision making
dence-based medical practice. [From
UBC HEALTH LIBRARY (2008)]
1. Formulating a clinical question (Asking)
2. Acquiring relevant and complete information (Acquiring)
3. Critically appraising the quality (including validity and importance) of available
evidence, or identifying the lack of evidence (Appraising)
4. Applying the knowledge in the clinical management of patients (Applying)
5. Evaluating the results of practice (Auditing)
A Strategy of Learning and Clinical Practice
(Why Use Evidence-Based Medicine?)
Evidence-based medicine is probably more of a strategy of effective and effi cient med-
ical care than a scientifi c subject. The ultimate purpose of evidence-based medicine
by practicing the “5As” cycle is to improve the quality of care for patients. However,
clinical practice based on the essence of evidence-based medicine can also be used as
a strategy of continuing medical education and professional development. Inevitably,
physicians' knowledge deteriorates over time. The “5As” process of evidence-based
medicine emphasizes a structural, systemic, and strategic search for and evaluation
of evidence for questions encountered in daily clinical practice, to be used in decision
making in patient management. Through such a process, clinicians and other health-
care professionals continuously educate themselves and sharpen their knowledge.
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