Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
continuousarcasthe gantry rotates around the patient (volumetric modulated arc therapy;
VMAT). In all cases, the leaves of multileaf collimators enter the field or retract
dynamically during treatment to deliver the desired amount of radiation to tissues
withinthetarget.Verytightlyconformingradiationdistributionscanbeobtainedwiththis
approach.However,thetime requiredto plantreatments islengthened, andthe durationof
dailytreatmentsmayalsobelengthened.
Figure 5.9 Dose distribution obtained using intensity-modulated radiation therapy
(IMRT) to treat the pelvic lymph nodes after hysterectomy. In this case, each of seven
fieldswasmodulatedtoobtainadistributionthatcoveredtheiliacandpresacrallymphnodes
whilesparingbowelin the centralpelvisfromhighdose.Asomewhatlarger volume receives
low-doseradiationthanwithstandardtechniques,andtheverytightdosedistributionrequires
anaccurateunderstandingofanatomy,tissuesatrisk,andinternalorganmotion.
QualityassuranceisverydemandingforIMRTbecausethefieldsarelessreadilyvisualized
than static radiation fields. In the past 15 years, the use of IMRT and other highly
conformal radiation techniques has increased dramatically. In many cases, these
techniquescanbeusedtoreducethedosedeliveredtonormaltissuesduringacourseof
radiation therapy. The opportunities for error have also increased; unlike traditional
treatments that were based on relatively simple, empirically tested field shapes and
distributions,IMRTplansareentirelydependentontheclinician’sunderstandingofthe
target volume and tissues at risk. If the clinician misses or fails to correctly designate
tissuesatriskfordisease,thecomputerizedinverseplanningprocessislikelytocreateaplan
thatexcludesareas ofpossibletumorinvolvementor overtreatscriticalstructures.Because
thedoseofradiationfallsoffrapidlyoutsidethedesignatedtargetvolume,IMRTplans
requireahighdegreeofconfidenceinthedistributionofdisease,aclearunderstanding
ofinternalorganmotion,andmeticulouspatientimmobilization.
Becausethereareasyetfewlevel-1dataconfirmingthebenefitofIMRTintreatmentof
gynecologic neoplasms, payers may consider the treatment experimental and decline
payment of this relatively costly approach. However, an expanding body of evidence has
increasedtheacceptedindicationsforIMRT.In2018,Kloppetal.(86)reportedresultsofa
prospectivetrial randomizing patients who requiredpostoperative pelvic RTbetween
IMRT and “standard” conformal pelvic RT using a 4-field technique. In that study,
patients who had treatment with IMRT had significantly less gastrointestinal and
urinarytoxicity.RecentreportssuggestthatIMRThasalsomadeitpossibletosafelydeliver
highdoses(i.e.,≥60Gy)tositesofextensivenodaldisease,potentiallyimprovingthechance
forcure(20,87). Although IMRT is also useful as a boost technique for advanced central
diseaseinselectedcases,brachytherapyispreferredinmostcasesbecauseitusuallypermits
deliveryofhighercentraldoseswithoutexceedingnormaltissuetolerance.
Brachytherapy
Brachytherapy is a highly specialized form of treatment that is particularly critical to the
successfulmanagement ofvaginal andcervical cancers.Surveysindicatethatpatients who
are treated for cervical cancer in small, nonacademic radiation oncology facilities are less
likelytoreceivebrachytherapyandaremorelikelytohaveunacceptablyprolongedtreatment
coursesthanarepatientstreatedinlargeacademiccenters(88,89).Gynecologiconcologists
who are counseling newly diagnosed patients should always ascertain the level of
specialized experience and adequacy of resources before referring patients who may
requirebrachytherapytoaradiationoncologist.
IntracavitaryTreatment
Anytreatment thatinvolvesplacementof radioactive sourceswithin an existing body
cavity is termed intracavitary treatment. The most common gynecologic applications
involve placement of intrauterine or intravaginal applicators that are subsequently loaded
withencapsulated radioactive sources (e.g.,
137
Csor
192
Ir)(Table5.2). Applicator systems
varyintheirappearanceandconfiguration,butthoseusedforradicaltreatmentofcervicalor
uterinecancertendtohaveseveralfeaturesincommon.Theseapplicatorsusuallyconsistof
ahollowtube,or tandem, andsomeform of intravaginalreceptacle for additionalsources.
The greatest variation between systems is in the vaginal applicators, which differ in their
shape,theorientationofsources,andthepresenceorabsenceofshielding(68).
Table5.2IsotopesUsedinGynecologicOncology
Mostoftheintracavitaryapplicatorsinusetodaycanbeseentofallintooneoftwomajor
groups, each descended from applicators developed in the 1930s in the dominant
brachytherapy centers of Paris and Stockholm. Applicators that arose from the Paris
systemweredesignedtoplacethesourcesatleast1cmfromthevaginalsurfaceinthe
centerofcylindricalorovoid“colpostats”;thisarrangementleveragedtheinversesquare
lawtoallowdeliveryofarelativelyhighdosetodeeptissueswithoutoverdosingthevaginal
surfaceandadjacentcriticalstructures.
Oneapplicatorin this group that is commonly used to treatintactcarcinomasof the
cervixistheFletcher–Suit–Delclossystem.Importantcharacteristicsofthissystemarethe
arrangement of vaginal sources perpendicular to the tandem, and the presence of internal
shieldingthatreducesthedosetotherectumfromthevaginalsourcesbyasmuchas25%.
TheFletcher–WilliamsonapplicatorissimilartotheFletcher–Suit–Delclosapplicatorbutis
adaptedforusewithasteppingsourceof
192
Ir(68).Other“Fletcher-type”applicatorsystems
havebeendevelopedthathaveunshieldedovoids.
Thesecondgroupofapplicators,descendedfromtheStockholmsystem,usedapplicators
that placed sources very close to the cervix and vaginal surface. Most of the early
versions of this applicator type were abandoned because of high complication rates.
However,in recent years, these applicators have gained in popularity, with the most
common version being the ring applicator. The improved anatomy achieved with
chemoradiation and the advent of image-based therapy have made these applicators much
safer than earlier versions and their ease of use has made them one of the most common
applicatorsusedforcervicalcancerbrachytherapy.However,thepositionofthesourcesdoes
limittheamountofactivitythatcansafelybeplacedinthevaginaanddecreasesthedepthof
radiationpenetration.Forthisreason,clinicianswhofavorthisarrangementareincreasingly
adding interstitial needles to achieve better coverage of parametrial tissues. The “Vienna
applicator”isoneofthesetypesofhybridapplicators.Otherapplicatorsystems,suchasthe
Delclos dome cylinder, were designed specifically for treatment of the vaginal apex after
hysterectomy(68,90).
Figure 5.10 illustrates a typical pear-shaped isodose distribution produced by a line of
intrauterine sources and vaginal colpostats loaded with an
192
Ir stepping source.
Intracavitarybrachytherapyisusefulinthetreatmentofgynecologiccancersbecauseit
allowsaveryhighdoseofradiationtobedeliveredtoasmallvolumesurroundingthe
applicator (i.e., the cervix, vagina, paracervical tissues) without excessive treatment of
normaltissuesthataremoredistantfromthesources. Becauseof therapid changein dose
overshortdistances,accuratepositioningoftheintracavitaryapplicatorandsourcesisvery
important.Packingorretractionofthebladderandrectumcansignificantlyreducethedose
toportionsoftheseorgansbydistancingthemfromthevaginalsources.
Tominimizetheexposureofmedicalpersonneltoradiation,modernapplicatorsystems
are loaded with radioactive sources after adequate positioning is confirmed with
anterior–posterior and lateral x-rays of the pelvis or tomographic imaging. In most
cases, remote afterloading devices are used to automatically retract sources from the
applicatortoalead-linedsafewhensomeoneentersthepatient’sroom,furtherreducingthe
radiationexposuretovisitorsandmedicalpersonnel.
DoseRate
In the past, most brachytherapy was delivered at a low-dose rate (LDR), most
commonly40to60cGyperhour,using
137
Cssourcesthatweremanuallyinsertedinto
the applicators. Low-dose rate brachytherapy takes maximum advantage of the dose-rate
effect described above, differentially sparing late-responding normal tissues as compared
with acutely responding tissues and tumor cells. The dose of LDR intracavitary therapy
neededtoradicallytreatcervicalcancerisusuallydeliveredin72to96hoursduringoneor
twohospital admissions. Although someinvestigatorstried to reducetheduration of these
treatmentsbydoublingthedose rate (from approximately 40 cGy per hour to 80 cGy per
hour),thelimitedclinicaldataonthisapproachsuggestthatdoublingthedoserateresultsin
alessfavorabletherapeuticratio(91).
Figure 5.10 Reconstructed coronal and sagittal MRI views through the approximate
center of the uterus with a Fletcher–Williamsonapplicator in place. Numbers represent
the total doses delivered during a 48-hour pulsed–dose-rate treatment. Note the high dose
delivered to the central cervical tumor and the rapid fall-off of dose close to the sources.
Althoughlateralstructuresreceiveamuchlower doseofradiation,the obturatornodalregion
(visible at the edge of the coronal view) received approximately 5 Gy from this first of two
plannedimplants.Thisdosemustbeconsideredin planning boosts that may be requiredfor
anyinvolvednodesinthisregion.
Inthepast30years,theadventofcomputer-controlledremoteafterloadinghasmadeit
possibleto deliverbrachytherapytreatmentsathigh-dose rates (in minutes rather than
hours).HDRtreatmentmayofferpracticaladvantagesforthepatientbecauseitistypically
performedonanoutpatientbasis,althoughmoreapplicationsareusuallyrequired.Withthis
technique,asingleveryhighactivitysourceof
192
Irisremotelyinsertedintotheintracavitary
applicator.Accordingtothetreatmentplan,duringeachtreatmentthesourceisadvancedin
individual“steps”todeliverradiationthroughoutthetreatmentvolume.Becauseofthehigh
activityofthesource(usuallyabout10Ci),treatmentmustbedeliveredinaheavilyshielded
room,andstrictsafetyandqualityassurancestandardsmustbemet.
HDRtherapyhasgainedsteadilyinpopularityoverthepast20yearsandisnowused
formostintracavitaryradiationtherapy.Thisispartlybecauseofthepracticaladvantages
forphysicianswhocentermostoftheirpracticeinanoutpatientsettingbutinterruptionsin
thesupplyofcesiumsourcessuitableforLDRgynecologicbrachytherapyalsoplayedarole
inthisevolution.Some cliniciansremainedreluctantto changetoHDRtherapybecauseof
thetheoreticalradiobiologicdisadvantagesoflarge-fractionirradiationandtheabsence
ofwell-controlledrandomized clinicaltrials comparingHDRandLDRregimens(92).
However, practical considerations have led most radiation oncologists to move to HDR
brachytherapy.
Inrecentyears,twofactorshavehelpedtoalleviateseveraloftheearlyconcernsaboutHDR
brachytherapy. First, the standard use of concurrent chemotherapy has meant that
tumorsaremuchsmalleratthetimeofbrachytherapy,typicallyimprovingthegeometry
ofintracavitaryplacements(andthereforetheratioofdosetotumorandnormaltissues).In
addition,theadventofimage-guidedbrachytherapytechniqueshavemadecliniciansmore
conscious and better able to address the potential exposure of normal tissues to large
fractionaldosesofradiation.
AnalternativetoHDRtherapythatisused insomelargecentersinEuropeandtheUnited
Statesispulsed–dose-rate(PDR)brachytherapy.Withthisapproach,treatmentisgivenin
intermittentpulses,usingasinglesteppingsourceof
192
Ir,which issimilarto,butlowerin
activity than, the source used for HDR brachytherapy. If treatment is delivered in hourly
pulsesof 40 to 50 cGy, the tissuesparingshould be nearly identical tothatachieved with
LDRbrachytherapy.
PDR holds several advantages over true LDR brachytherapy. The sources are readily
obtainable,patientsareabletoreceivenursingcareandhavevisitorsastheywishduringthe
intervalsbetweenpulses,andthesteppingsourcemethodpermitssomewhatmoreflexibility
in treatment planning. The equipment can be used for either interstitial or intracavitary
brachytherapy, and because the applicators are identical to those used for HDR
brachytherapy,clinicianswhochoosetohavebothoptionsavailabletotheirpatientsrequire
onlyonesetofapplicators.
IntracavitaryBrachytherapyRadiation-DosePrescription
Several methods are currently used to specify the dose of radiation delivered with
intracavitary brachytherapy, although these practices are currently in a state of rapid
evolution.
DoseSpecificationUsingReferencePoints
Inthepast,intracavitaryradiationdoseswereusuallyspecifiedatreferencepointsthatwere
localized on orthogonal x-rays taken with the applicator in place. This two-dimensional
approachdidnotrequireadvancedimaging,frequentlyunavailableinlow-resourcesettings,
butoftenledtoinaccurateestimatesofthetrueradiationdosedeliveredtotumorandcritical
structures.
MostradiationoncologistsspecifiedtreatmentusingsomevariationoftheManchester
system,whichusestwoprimaryreferencepoints:
1. Point A—a point 2 cm lateral to the center of the tandem and 2 cm superior to the
vaginalfornixintheplaneoftheimplant(Fig.5.10).
2. PointB—apoint3cmlateraltopointA.
Although the doses from intracavitary and external beam radiation therapy may not be
biologicallyequivalent(particularlywithHDRtherapy),thesedosesarefrequentlysummed
todetermine thetotaldoses topointsAandB.The totaldosetopointA(fromexternal
beam and LDR or PDR intracavitary therapy) considered to be adequate to achieve
centraldiseasecontrolisusuallybetween75Gy(forsmallstageIB1cancers)and90Gy
(forbulkyorlocallyadvanceddisease).
However,PointA,with itsfixedgeometry,isonlyasurrogateanddoesnotaccurately
representthevaryinganatomyofindividualpatients.Prescriptionandtreatmentplanning
cannot be limited to specification of the dose to these reference points. Other factors that
shouldbeconsideredincludethefollowing:
1. The position and length of the intrauterine tandem, which influence the loadingof the
tandem
2. Thetypeandpositionofvaginalapplicators,whichinfluencetheloadingofthevaginal
applicators
3. Thequalityofthevaginalpacking
4. Thesizeofthecentraltumorbeforeandafterexternalbeamtreatment
5. Thevaginalsurfacedose(usuallylimitedto120to140cGy)
6. Theproximityofthesystemtothebladderandrectum
7. Thedoserate(orfractionsize)
A number of methods and reference doses have been described to estimate the maximum
dosetothe bladder and rectum onthebasis of orthogonal reference filmsoftheimplants.
Themostcommonmethodforspecifyingnormaltissuedosesistocalculatethedosesto
reference points defined by the International Commission on Radiation Units and
Measurements(93).Usingthismethod,thebladderreferencepointisplacedattheposterior
edgeofaFoleybulbfilledwith7ccofcontrastmaterialonalinedrawnfromthecenterof
theFoleybulbtotheclosestsourceinthevaginalapplicator;therectalpointislocated5mm
posteriortothevaginalapplicatororpacking(whicheverismostposterior)atthelevelofthe
vaginalsources.Three-dimensional reconstructionsofintracavitary placementssuggestthat
most methods that use orthogonal x-rays to estimate the dose to normal structures tend to
underestimatethetruemaximumdose(94).
Image-GuidedBrachytherapy
Overtheyears,clinicianshavebecomeincreasinglydissatisfiedwiththeinaccuraciesofdose
estimatesbasedonreferencepoints.Forthisreason,therehasbeenagrowingmovement
towardtheuse ofimage-guidedbrachytherapy,with treatmentplanningbasedonCT
orMRIimagesobtainedwiththeimplantinplace(Fig.5.11).Forthetreatmentofintact
cervical cancer, these methods have been standardized by the Groupe Européen de
Curietheérapie (GEC-ESTRO) working group and tested in several large international
retrospectiveandprospectivetrials(EMBRACE)(74,76).Theresultsofthesestudiessuggest
thatimage-guidedtreatmentplanningmethodsleadtohighlocalcontrolratesandrelatively
lowcomplicationrates.
Withthisapproach,ahigh-riskclinicaltargetvolume(HRCTV)isdesignatedconsisting
oftheentirecervixplusanymacroscopicresidualparacervicaltumorremainingafter
externalbeamtherapy(Fig.5.11).Itisgenerallyrecommendedthattheseregionsbetreated
toadoseof85to90Gy.
Regionsofinitialtumorextension,particularlyinthebodyoftheuterusorvaginamustalso
betreated,evenifthereisnoresidualdiseaseappreciatedonpre-brachytherapyexamination.
Three-dimensionalimage-guided techniques also permit much more precise estimates
ofthedosestotumorandcriticalstructures.Avarietyofmethodshavebeenproposedfor
reportingcriticalstructuredosesusingadvancedimaging.However,themethodthathasbeen
most actively studied involves calculation of the minimum dose (EqD2) to the most
irradiated 2-cc volume (D
2 cc
) of rectum, bladder, and sigmoid (76). Estimates of critical
structuredoses,particularlybladderdoses,tendtobemuchhigherwiththismethodthanwith
traditionalreferencepoints,suggestingthatthesetissuesmaytoleratehigherdosesthanwas
oncebelieved.CurrentGEC-ESTROrecommendationsaretolimittheD2ccdosesto<80Gy
tothebladderand65Gytotherectumalthoughsomewhathigherdoses(upto90Gyand75
Gy,respectively)maybeprescribedifnecessarytoachievetumorcontrol(76).
Figure 5.11 Sagittal MRI showing the high-risk clinical target volume (HRCTV) and
normal tissue dose parameters as defined by GEC-ESTRO guidelines. Shaded areas
representthe 2-mLhigh-dose volumes for the bladder, rectum,andsigmoid. The associated
lines represent the isodose lines corresponding to the lowest doses within these 2-mL
volumes.(ReprintedwithpermissionfromEifelP,KloppAH.GynecologicRadiationOncology.
APracticalGuide,1sted.Philadelphia,PA:WoltersKluwer;2017:113–131.)
ConversionofDosesBetweenLDRandHDRBrachytherapy
ThetotalbrachytherapydosemustbereducedtoconvertfromLDRtoHDRregimens.
The appropriate dose and dose per fraction are based on calculations of the estimated
biologically effective dose (BED) for tumor and normal tissues. BED is derived from the
linear–quadraticformuladescribed earlier in this chapter and is equal to the total nominal
dose(nd)timestherelativeeffectiveness:BED=(nd)×(1+d/[α/β]),whered isthe dose
perfraction.Forexample,assumingα/βvaluesof10and3fortumorandfornormaltissues,
respectively,afractionationschemeinwhichatotaldoseof30Gyisgiveninfivefractions
of6Gyeachwouldresultin:
TumorBED=(30)×(1+6/10)=48Gy
10
NormaltissueBED=(30)×(1+6/3)=90Gy
3
Cliniciansoftenexpressthesedosesinthemorefamiliartermsoftheequivalentdoseat
2Gyperfraction,whichisequaltoBED/(1+2/[α/β]). Usingthis calculation,the above
examplewouldyieldequivalentdoses of40and54 Gy,respectively,fortumorandnormal
tissues. In other words, the effect on normal tissues is about 35% greater than would be
expected from the same tumor-effective dose given at 2 Gy per fraction or with LDR
brachytherapy(which,at40to45cGyperhour,hasaneffectsimilartothatofadosedivided
in2-Gyfractions).
This differential effect would make HDR unacceptable if the normal tissues received the
samedoseasthetumor.However,withgoodapplicatorpositioning,effectivepackingofthe
bladder and rectum, and optimal source positioning, the total dose and dose per fraction
delivered to normal tissues are usually considerably lower than those delivered to tumor,
makingitpossibletoachievearatiooftumoreffecttonormaltissueeffectthatissimilarto
whatisachievedwithLDRtherapy.Ifthetumorisverylargeorthevaginalanatomyis
unfavorable,thenominaldoses to tumorandnormaltissues may be similar; in these
cases, patients may be more effectively treated with LDR, PDR, or a larger than usual
numberofsmallerHDRfractions(93).
DosefractionationschemesusedforHDRtherapyshouldbedesignedtoproducetumor
control and complication rates approximately equivalent to those seen with LDR
therapy.TheoptimaldoseperfractionforHDRtherapyisunknownandisprobablypatient-
specificbut,ingeneral,increasingthenumberoffractionsandconcomitantlydecreasingthe
doseperfractiontendstoreducetheriskofmoderateandseverecomplications.
Themost common HDR regimens used fortreatmentofintactcervical cancerinthe
UnitedStatesinvolve4to6treatments,typicallydeliveredafter40 to45 Gyof pelvic
externalbeamirradiation,althoughtherehavebeenwidevariationsinthenumberof
fractions(2to13)andthedoseperfraction.Someoftheschemescommonlyusedinthe
UnitedStatesare4fractionsof7Gy,5fractionsof5.5to6Gy,and6fractionsof5Gy(94).
During the past 5 to 10 years, clinicians have begun to more effectively integrate
sophisticated imaging into the brachytherapy planning process. Most radiation therapy
simulatorsarenowbasedonCTratherthanfluoroscopicorplainimages.Manyfacilitiesuse
intraoperative ultrasonography to confirm correct positioning of applicators, and
increasinglyMRIisbeingusedtodelineatetargetvolumesandcriticalstructures(Fig.
5.11)(95).
Theextenttowhichtheseresourcesareexploitedinbrachytherapyplanningvariesbetween
facilities. At a minimum, ultrasonography, CT,or MRI should be used to rule out uterine
perforations, which, if undetected, frequently lead to life-threatening complications.
Clinicians are increasingly exploring the use of true three-dimensional image-guided