Radiation Oncology A Physicist’s-Eye View - Michael Goitein.pdf - radioterapia - cassandracross

1. R ADIATION IN THE T REATMENT OF C ANCER

Introduction ............................................................................................1

Types of Radiation Used in the Treatment of Cancer.............................2

Why Does Radiation Work?....................................................................3

A Single Treatment Beam .......................................................................4

Multiple Treatment Beams......................................................................6

The Volume Effect...................................................................................7

Intensity-Modulated Radiation Therapy (IMRT)...................................8

Treatment Design and Delivery..............................................................9

Safety.......................................................................................................10

Summary ...............................................................................................11

I NTRODUCTION

The prognosis for someone diagnosed with cancer is not as dire as is

commonly believed. Many cancers, such as early stage cancer of

the larynx, childhood leukemia, and Hodgkin’s disease, are highly

curable. Unfortunately, others, such as pancreatic cancer, have a poor

prognosis. The curability of most cancers lies somewhere between

these extremes. *

Early in its development, a malignant tumor is generally well

localized. As most cancers develop, they tend to spread to neigh-

boring lymph nodes and, as metastases, to noncontiguous organs.

When the disease is localized, a local treatment such as surgical

excision or radiation therapy is indicated. When the tumor is in-

accessible or is intimately entwined with a vital anatomic structure,

* Much of the material in this chapter is adapted with permission of the

American Institute of Physics from the article of the same title which

appeared in the September 2002 issue of Physics Today (pp. 34 to 36) by

Boyer AL, Goitein M, Lomax AJ and Pedroni ES.

Tumor and normal tissue delineation .......................................................9

Dose prescription ......................................................................................9

Treatment planning and evaluation.........................................................10

Dose delivery...........................................................................................10

1. Radiation in the Treatment of Cancer

or when regional spread has occurred, surgery may not be a viable

option, and radiation therapy will then be the preferred approach.

Distant metastases can, for the most part, only be treated through the

use of systemic approaches such as chemotherapy, immunotherapy,

or, more futuristically, molecular targeting. Combination therapy –

the use of two, or even three, of the approaches just described – is

commonly undertaken to manage optimally the local and proven or

likely systemic components of the disease. An important rationale for

improving local therapy is the observation that the longer a patient

has a viable malignant tumor, the more likely that a metastatic “break

out” of that cancer will occur – which generally badly compromises

the outcome of treatment. Thus “local control” of tumors is necessary

for achieving long-term survival.

Overly aggressive surgery or very high doses of radiation and/or

chemotherapy can eradicate a cancer with high probability – but, at

the cost of causing unacceptable morbidity. Thus, the art of cancer

treatment is in finding the right balance between tumor cure and

injury to normal tissues . Much of the motivation for improving the

technology of radiation therapy stems from the desire to reduce the

probability of morbidity – which in turn may allow higher doses to be

delivered to the tumor with an associated increase in tumor control

probability.

T YPES OF R ADIATION U SED IN THE T REATMENT OF C ANCER

Research in physics has contributed directly and indirectly to cancer

therapy over the past century. Only months after their discovery by

Röntgen in 1895, X-rays were employed to treat a patient with breast

cancer. At present, the most commonly employed radiotherapy

treatment employs a beam of high-energy X-rays (often described as a

photon beam ) generated external to the patient and directed toward

the tumor. Machines containing radioactive 60 Co sources are also still

in active use in many parts of the world.

Other forms of radiation which have been used in radiation therapy

are: electron beams; implanted or inserted radioactive sources (

β,

emitters are used); neutrons; pi-mesons; protons; and

heavier charged ions such as 12 C and 20 Ne. The bulk of the material

in this book relates to the use of external beam therapy using photons.

External beam therapy with protons is discussed in Chapters

10 and 11.

and even

Why Does Radiation Work?

W HY D OES R ADIATION W ORK ?

Radiation can cause lethal damage to cells, mainly by forming highly

reactive radicals in the intracellular material that can chemically break

bonds in DNA, causing a cell to lose its ability to reproduce. The

higher the dose, the greater the probability of sterilizing cells. Such

damage is experienced both by the malignant cells one is trying to

eradicate, and by the cells in the healthy tissues that receive radiation

even though one would wish to spare them. There are two elements

to the strategy for maintaining the functional competence of the

irradiated normal tissues and organs.

First, there appears to be a small and favorable difference between

the radiation response of normal and malignant cells that allows

preservation of the normal cells that permeate the tumor, and of the

for this difference are complex, not fully understood, and even

controversial. The difference is probably due less to differences in

intrinsic cellular radiosensitivity than to differences in the genetic

machinery activated by radiation, in DNA repair kinetics, and in the

mechanisms of cell repopulation – and is counterbalanced by tumor-

protective factors such as the substantially greater resistance to

radiation of cells in regions of low oxygen tension such as are often

found in tumors. To further the differential effect, the dose is usually

delivered in small daily increments, termed fractions. This strategy is

generally thought to improve substantially the therapeutic advantage

as compared with radiation delivered in a single application. Con-

sequently, in conventional radiotherapy, about 30 to 40 daily

fractions of approximately 2 Gy each are used. 2 These fractions are

typically delivered once a day, with a weekend break, so that a course

of radiotherapy will typically last from 5 to 8 weeks. Treatment may

also be accelerated, for example, by delivering two fractions per day,

or by delivering higher doses per fraction with fewer fractions.

1 One generally defines as the target a volume that includes demonstrable

disease, possible subclinical extension of that disease (delineating this is

one of the radiation oncologist’s arts), and a safety margin for organ and

patient motion and technical uncertainties. This is termed the planning

target volume (PTV) as more fully described in Chapter 3.

2 There are particular clinical situations, usually involving relatively small

target volumes, in which far fewer fractions, sometimes only one, are

employed.

nearby tissues that are included in the target volume. The reasons

1. Radiation in the Treatment of Cancer

The second element of the strategy for minimizing the probability of

normal tissue injury involves the reduction of the dose delivered

to normal tissues that are spatially separated from the tumor. This

involves manipulating various properties of the therapy beams, as will

now be discussed.

A S INGLE T REATMENT B EAM

Figure 1.1 shows a modern radiation therapy machine. X-rays are

produced when electrons, accelerated in a linear accelerator, strike a

thick high atomic number target, with the X-rays being then shaped

by a contoured flattening filter that makes uniform the otherwise

forward-peaked X-ray flux. The accelerator, beam transport system,

and beam-shaping devices (inset) are all mounted on a gantry which

can rotate a full 360

Figure 1.1. A typical modern linear accelerator. Images courtesy of Varian

around the patient. The patient lies on a couch

that can move in all three translational directions and can rotate about

a vertical axis passing through the gantry’s isocenter. The shaped

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