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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
Postoperative irradiation improves locoregional control and survival in several settings
important to gynecologic oncologists. In vulvar cancer, postoperative pelvic and groin
irradiationreducestheriskofgroinrecurrenceandimprovesthesurvivalrateofpatientswith
multiple positive inguinal nodes (18). In endometrial cancer, postoperative pelvic
irradiationreducestheincidenceofpelvicrecurrenceinpatientswithhigh-riskdisease(6–8).
In cervical cancer, postoperative pelvic irradiation reduces the incidence of pelvic
recurrenceinpatientswithlymphnodeinvolvementandin thosewithhigh-risk featuresin
theprimarytumor(3).
CombinationApproaches
Combinedsurgeryandradiationtherapyisoptimizedwhenthetreatmentplanexploits
the complementary advantages of the two treatments. This requires close cooperation
betweenspecialists at the time ofthepatient’sinitial evaluation. Becausethemorbidity of
combinedtherapyis oftengreaterthanthatof single-modalitytherapy,combinedtreatment
shouldusuallybe limited to situations in whichacombined approach is likely to improve
survival, permit organ preservation, or significantly reduce the risk of local recurrence
comparedwiththeexpectedresultsfromtreatmentwitheithermodalityalone.
PhysicalPrinciples
IonizingRadiationsUsedinTherapy
Ionizingradiationslie on the high-energy portion of the electromagneticspectrumandare
characterizedbytheirabilitytoexcite,orionize,atomsinanabsorbingmaterial.Thedecay
of radioactive nuclei can produce several types of radiation, including uncharged
gamma(γ)rays,negativelychargedbetaparticles(electrons),positivelychargedalpha
particles (helium ions), and neutrons. The resulting ionizing radiations are exploited
therapeuticallyinbrachytherapytreatments,using
226
Ra,
137
Cs,
186
Ir,andotherisotopes, or
toproduceteletherapybeams(e.g.,60Co).The average energyof thephotonsproduced by
thedecayofradioactivecobaltis1.2millioneV(MeV).
Most external beam therapy is delivered via linear accelerators that produce photon
beams (x-rays) by bombarding a target such as tungsten with accelerated electrons.
Varying the energy of the accelerated electrons produces therapeutic x-rays of different
energies.X-raysandγ-raysarebothcomposedofphotonsanddifferonlyinthatx-raysare
producedbyextranuclearforcesandγ-raysareproducedbyintranuclearforces.
InteractionsofRadiationWithMatter
X-raysandGamma-rays
Photonsinteractwithmatterbymeansofthreedistinctmechanisms:thephotoelectric
effect,Comptonscatter,andpairproduction.
The photoelectric effect is most important at energies used for diagnostic purposes.
AbsorptionbythephotoelectriceffectisproportionaltoZ3,whereZistheatomicnumberof
theabsorbingmaterial.Thiseffect is responsible for the increased absorption of bone that
provides contrast between bone and soft tissue with diagnostic x-ray beams of 250 kV or
less.However,theincreasedboneabsorption,highskindose,andpoorpenetrationwithsuch
beams make them unsuitable for most modern therapeutic applications. Superficial
kilovoltageradiation beams, delivered usingatransvaginal cone, are occasionallyusedfor
patients with large bleeding exophytic tumors to achieve hemostasis before definitive
treatment(83).
Modern therapeutic beams of 1 to 20 megavolts (MV) produce photons that interact
withtissuesprimarilybyComptonscatter.Inthisprocess,incidentphotonsinteractwith
looselybound outer-shell electrons,ejectingthem from the atom. Boththephoton and the
electrongoontointeractwithotheratoms,causingadditionalionizations.Compton-scatter
absorptionisindependentofZbutvariesaccordingtothedensityoftheabsorbingmaterial.
Thisaccountsforthepoorcontrastofradiationportalverificationfilms.
Photons that are absorbed by Compton scatter produce an increasing number of scattered
electronsandionizationsastheypenetratebeneaththesurfaceofanabsorbingmaterial.This
creates a build-up region just below the surface that is responsible for the skin-sparing
characteristic of modern high-energy beams (Fig. 5.6). The maximum dose from a
megavoltagebeamisreachedat 0.5to3cmbelow theskin surface,depending onthe
photonenergy.Atgreaterdepths,thedosedecreasesatafairlyconstantratethatisrelatedto
thebeamenergy.Thegreaterskin-sparingeffectsandpenetrationofbeamswithenergiesof
15MVorgreatermakesuchbeamsparticularlyusefulforpelvictreatment.
Pairproduction absorption is relatedtoZ2.In soft tissue, thistypeof absorption begins to
dominateonlyatphotonenergiesofmorethanapproximately30MeV,sopairproductionis
oflimitedimportanceinthecurrentradiationtherapyplanning.
ElectronsandOtherParticles
Severaltypesofparticle beamsareusedinradiationtherapy: electronbeams,proton
beams,andneutronbeams.
Electrons are very light particles. When they interact with matter, they tend to lose
mostoftheirenergyinasingleinteraction.Thedosefromanelectronbeamisrelatively
homogeneousuptoadepththatisrelatedtothebeam’senergy(Fig.5.6).Beyondthisdepth,
the dose decreases very rapidly to nearly zero. Electrons are used to treat relatively
superficial targets without delivering a significant dose to underlying tissues. The
approximatedepth(incentimeters)atwhichtherapidfalloffindoseoccurscanbeestimated
bydividingtheelectronenergyby3.
Protonsarepositively chargedparticlesthat aremuch heavierthan electrons.Protons
scatterminimallyastheyinteractwithmatter,depositincreasingamountsofenergyasthey
slow down, and then stop at a depth related to their initial energy. This results in rapid
depositionofmost oftheirenergyatdepth(called theBraggpeak),with asteep falloffin
dosetonearzeroshortlyafterthepeak.Modulatingtheenergycanspreadthispeakout.The
absenceofanexitdosemakesprotonbeamsidealforconformaltherapy,andinterestin
their use has increased as the cost of producing proton generators has become
somewhatmorereasonable.
The physics support, quality assurance, and clinical requirements needed to safely treat
patientswithprotonsarecomplex,highlyspecialized,andtimeconsuming.Insomedifficult
clinical situations (e.g., central nervous system tumors, some pediatric cancers), protons
clearly provide a dosimetric advantage over photons, but there are as yet no randomized
comparisons.Becausethedepthofpenetrationofprotonsishighlydependentonthedensity
of intervening tissue, the presence of variable gas-filled structures (e.g., bowel) in the
midpelvismaylimitapplicationsingynecologicradiationoncology.
Figure 5.6 Depth-dose curves for selected x-ray and γ-ray beams (top). As the energy
increases,thedepthofmaximumdose(D
max
orD
100
)increases.Forkilovoltagebeams,the
doseismaximumat the skin surface. With appositionally directed megavoltage beams (e.g.,
60
Co or 25-MeV photon beams), the maximum dose is reached at a depth beyond the skin
surface,producingskinsparing.High-energybeamsalsopenetratemoredeeply,makingthem
more useful for treatment of deep-seated pelvic tumors. Depth-dose curves for electron
beam fields of selected energies (bottom). The depth of maximum dose increases with
increasingenergy.Atdepthsjustbelowthemaximum,thedosefallsoffrapidly,sparingdeeper
tissues.
Neutrons are neutral particles that tend to deposit most of their energy in a single
intranuclearevent.Forthisreason, there is little or no repairable injuryandthereforeno
shoulderonthetumorcellsurvivalcurve.Thefalloffofaneutrondoseissimilartothatofa
photonbeam of4 to6 MV,butthe highrelative biologiceffectivenessof denselyionizing
neutronbeamsisofinteresttoclinicalinvestigators.Clinicalstudiesofneutrontreatments
inpatientswithcervicalcancerhavebeenplaguedbyhighcomplicationrates(84),and
currently,neutronsarerarelyifeverusedtotreatgynecologictumors.
MeasurementofAbsorbedDose
Absorbeddoseisameasureoftheenergydepositedbytheradiationsourceinthetarget
material.TheunitcurrentlyusedtomeasureradiationdoseistheGray(Gy),where1
Gyisequalto1Jouleperkilogram(J/kg)ofabsorbingmaterial.Beforetheearly1980s,
absorbeddosesofradiationweremeasuredinradians(rads),where1rad=1cGyand
1Gy=100rad.
The rate of decay of a sample of radioactive material (such as radium or cesium) is
referredtoastheactivityofthesampleandismeasuredincuries(Ci),where1Ci=3.7
×1010disintegrationspersecondand1mCi=10−3Ci.
Safe delivery of radiation depends on precise calibration of radiation source activities and
machineoutput. These are measured using sensitive ionization chambers in phantoms that
simulate tissue density. Periodic calibrations of equipment and sources are a vital part of
qualityassuranceinanyradiationoncologydepartment.
InverseSquareLaw
Thedoseofradiationfromasourcetoanypointinspacevariesaccordingtotheinverse
of the square of the distance from the source to the point (85). This relationship is
particularlyimportantforbrachytherapyapplications,becauseitresultsina rapidfalloffof
doseasdistancefromanintracavitaryorinterstitialsourceisincreased.
RadiationTechniques
Radiationtherapyisdeliveredinthreeways:
1. Externalbeamirradiation:X-raysare deliveredfroma sourceata distancefrom the
body(externalbeamtherapy).
2. Brachytherapy: Radiation sources are placed within or adjacent to a target volume
(intracavitaryorinterstitialtherapy).
3. Radioactivesolutions:Solutionsthatcontainisotopes(e.g.,radioactivecolloidalgoldor
radioactivephosphorus,P32) areintroducedintoacavity (e.g.,the peritoneum)totreat
thewallsofthecavity.
ExternalBeamIrradiation
Most curative gynecologic radiation treatments begin with a course of external beam
irradiation designed to include the primary site of disease and potential sites of regional
metastasis. The goal of external beam therapy is to sterilize disease in these sites while
deliveringaslittledoseaspossibletoadjacentnormaltissues.
ExternalBeamPlanning
Theprocessof externalbeam treatmentplanningbeginswith a simulation, usually a
dedicatedCTscanobtainedwiththepatientintheplannedtreatmentposition.Various
immobilization devices can be used to secure the patient in a consistent and reproducible
position. Using specialized software, relevant diagnostic imaging studies (contrast CTs,
MRIs,PETscans)can bedigitallyfused totheplanningCTtofacilitatedesignationofthe
targetsfortreatment.
Using these materials and information from clinical examination, pathology reports,
operative reports, and other diagnostic materials, the physician designates target
volumes, including sites of gross disease (gross target volume; GTV) and sites of
microscopicdisease (clinicaltarget volume; CTV) as well asnormal tissue structures
thatshouldbeavoided.Mostgynecologictreatmentsthatincludethevaginaoruterus
also require designation of an internal target volume (ITV) that takes into account
internal inter- and intratreatment movement of target tissues; this is particularly
important for the treatment of gynecologic cancers because changes in bladder and
rectal filling can cause marked shifts in the positions of the uterus and vagina. An
additional margin, usually 5 to 7 mm, is then added to each target volume to account for
potential day-to-day inaccuracies in the positioning of the patient; the resulting planning
targetvolumes(PTVs)areusedtogenerateatreatmentplan.
Oncethetargetvolumeshavebeendetermined,thepatient’sdigitalfilesaretransferredtoa
radiationtherapydosimetrist, whousesspecializedtreatmentplanning softwaretodesigna
treatmentplan.Thattreatmentplanmustthenbeapprovedbythephysicianandgoesthrough
rigorousqualityassurancebeforethefirsttreatmentisgiven.
CommonTermsandFactorsThatInfluencetheDeliveredDoseofRadiation
Several terms are commonly used to describe the dose distributions produced by external
beamirradiationoftissues.
Percentagedepthdose:thechangeindosewithdepthalongthecentralaxisofaradiation
beam(Fig.5.6).
D
max
:themaximumdosedelivered tothetreatedtissue.Withasingle appositionalphoton
beam,theD
max
islocatedatadistancebelowthetissuesurfacethatincreaseswiththeenergy
ofthephotonbeam(Fig.5.6).
Isocenter:apointwithinthepatientthatremainsafixeddistancefromtheradiationsource
asthetreatmentsource(gantry)isrotatedaroundthepatient(Fig.5.7).
Figure 5.7 Diagram of a therapeutic linear accelerator. Patients are positioned on the
treatment couch with a system of lasers that are aligned precisely with the center of the
radiationbeam.Collimatorsinthetreatmenthead,locatedonarotatinggantry,definethesize
androtationoftheradiationfield.Thetreatmentcouchcanalsoberotatedaroundthecentral
axisoftheradiationbeam.Beam-modifyingdevicessuchasshieldingblocksandwedgescan
be attached to a tray beneath the collimator (not shown). (Republished with permission of
McGrawHillLLC,fromKarzmarkCJ,NunanCS, TanabeE. Medical Electron Accelerators.
NewYork:McGraw-Hill;1993;permissionconveyedthroughCopyrightClearanceCenter,Inc.)
Sourcetoskindistance:thedistancebetweenthesourceofx-rays(e.g.,acobaltsourceor
thetargetinalinearaccelerator)andtheskinsurface.
Sourcetoaxisdistance:thedistancefromthesourceofx-raystotheisocenter.
Isodosecurve:alineorsurfacethatconnectspointsofequalradiationdose(Fig.5.8).
Dose–volume histogram: a histogram that relates radiation dose to the volume of tissue
irradiated.
Manyfactorsinfluencethedose distribution in tissue fromasingleexternalbeamof
photons.Theseincludethefollowing:
1. Theenergyofthebeam (determinedby its voltage).Higher-energyphotonbeams are
more penetrating than lower-energy beams. In other words, the dose of radiation
deliveredtodeeptissuesrelativetomoresuperficialtissuesisgreaterwithhigher-energy
beams.Higher-energybeamshavealargerbuildupregionthanlower-energybeams;this
resultsinarelativesparingoftheskinsurface,facilitatingirradiationofdeeptissues(Fig.
5.6).
2. Thedistancefromthesourcetothepatient.Asthesourcetoskindistanceincreases,
thepercentagedepth-doseincreases.
3. The size of the radiation field. The percentage depth-dose increases with increasing
fieldsizebecauseoftheincreasingcontributionofinternalscattertotheradiationdose.
Thiseffectisgreatestwithrelativelylow-energyradiationbeams.
4. Thepatient’scontourandtheangleofthebeam’sincidence.
5. Thedensityoftissuesinthetargetvolume(particularlyairvs.softtissue).
6. A variety of beam-shaping devices placed between the radiation source and the
patientthataltertheshapeordistributionoftheradiationdose.
Figure5.8Isodosedistribution for external beam irradiation of the pelvisusingan18-
MVbeam.A:Apairofparallelopposedanteriorandposteriorfields.B:Anterior,posterior,and
twolateralfields(four-fieldboxtechnique).Theheavyredisodoselinerepresentstheregionof
tissuetreatedto≥45Gy.
Modern linear accelerators permit many variations in these factors (Fig. 5.7). A rotational
gantry permits isocentric beam arrangements that maintain a fixed distance between the
beam’s source and a point within the patient. This facilitates accurate patient setup and
treatmentplanning.
ConventionalThree-DimensionalTreatmentPlanningApproaches
Mostradiation therapy treatmentplans combine twoormorebeams to createa dose
distributiondesignedtoaccomplishthreeobjectives:
(i) tomaximizethedoseofradiationdeliveredtothetarget;
(ii) to produce a relatively homogeneous dose within the volume of interest to
minimize hot or cold spots that would increase the risks of complications or
recurrence,respectively;
(iii) to minimize the dose delivered to uninvolved tissues, taking into account the
differenttolerancesofvariousnormaltissues.
Theoverallplanisoftendesignedtodeliverdifferentdosestoareasofgreaterorlesser
risk (e.g., gross vs. microscopic residual disease) by increasing (boosting) the dose to
areasatgreaterriskwithsmallertreatmentfieldsafterinitialdeliveryoftreatmenttoa
relatively large volume. Two opposing beams (e.g., anterior–posterior and posterior–
anterior) usually produce a relatively homogeneous distribution of dose within the
interveningtissuewithsomesparingoftheskinsurface.However,inmanycases,multiple
fieldsareusedto“focus”thehigh-doseregiontoconformmorecloselytoadeeptarget
volume(Fig.5.8).
Modern technology has made it possible to use computers to optimize the beam
arrangements that are requiredin treatment plans that incorporate many fields and
beam-shaping devices. These conformal treatment plans may provide a very tight
distributionofdosearoundthetargetvolume.Thesimplestformofconformaltherapyuses
fairly conventional beam arrangements, but exploits modern CT-based treatment-planning
techniques to more accurately define the targetvolumeandto design blocks that conform
closelytothatvolume.CTreconstructionspermitmoreaccurateshapingoffieldsthat
enter the patient from oblique angles. Multileaf collimators have computer-controlled
leavesthatcanformirregularlyshapedfields,replacinghand-loadedbeam-shapingdevices.
Becausethetherapistnolongerneedstoentertheroomtoreplaceblocksoneachfield,itis
possibletotreatpatientswithmorefieldsandmorecomplexbeamarrangementsinasingle
treatmentvisitofacceptableduration.
Intensity-ModulatedRadiationTherapy
IMRT(Fig. 5.9) is a form of highly conformal radiation therapy that uses complex
computeralgorithmstooptimizedeliveryofradiationfrommultiplebeamangles.The
physicianmust carefullycontour targetvolumesandall criticalnormal tissuestructures on
eachslice of a CTscan that is obtainedwhilethe patient is inthetreatment position. The
minimum and maximum acceptable doses of radiation to be delivered to each area are
specified.Inverseplanningtechniques(basedon thephysician’s designationof targets
and avoidance structures rather than specific radiation fields) are used to design an
optimized plan, which usually includes multiple irregularly shaped fields from each of
several (usually six to nine) beam angles. In other cases, treatment may be delivered in a
sequence of slices as the patient moves past a rotating source (tomotherapy) or in a