Associazione Italiana di Fisica In Medicina Centro di … · 3 Associazione Italiana di Fisica In Medicina Centro di Cultura Scientifica “A. Volta” Scuola Superiore di Fisica

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Associazione Italiana di Fisica In MedicinaCentro di Cultura Scientifica “A. Volta”

Scuola Superiore di Fisica in Medicina “P. Caldirola”(Direttore della Scuola: A. Torresin)

Coordinatore del Corso: C. Marchetti

Impiego di sistemi HDRP. Montemaggi, U.O. Radioterapia Osp. Mariano Santo Cosenza

Como – Novembre 2001

Clinical Practice of Brachytherapy:High Dose Rate Systems Utilisation

Paolo Montemaggi, M.D.Head of Radiotherapy

Regional Cancer Center - Palermo


HDR systems in Brachytherapy

• Contents– Introduction– Physics and dosimetry– Radiobiology– Technical aspects– Clinical indications– Conclusions



• Brachytherapy is a radiotherapy technique whichallows the delivery of a high radiation dose to thetarget with a relatively small dose to thesurrounding normal structures

• The clinical use of brachytherapy has beenhistorically limited by problems of dose analysisand staff safety related to the physiccharacteristics of 226Ra



• After a period of relative decline, brachytherapy grewnewly in interest with the introduction in the clinicalpractice of the 226Ra substitutes which allowed a widerspectrum of clinical use

• 226Ra substitutes did impulse also to the designing anddeveloping of remote after loading systems with thepossibility of a different dose/time relationship (low LDRor high HDR dose rate)



• Differences in LDR and HDR brachytherapyhave been extensively evaluated, and a series ofcriteria have been proposed for a properselection in clinical practice

• Aim of these presentation will be the evaluationof the rationale of the use of HDR brachytherapylooking at its physic, radiobiologic, clinical andpractical characteristics




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• HDR brachytherapy is a brachytherapy technique inwhich the dose/rate is higher than 300 cGy/minute

• The activity of the source should be high enough toallow the required magnitude of the dose rate

• HDR systems were initially designed to utilize aminiaturized 60Co source (Cathetron), but nowadaysthey more frequently use a 192Ir miniaturized source

• Almost all the LDR after remote loading machines havebeen modified to be suitable for the HDR techique



• HDR brachytherapy is feasible in an outpatient bases,but requires shilded rooms

• The room shielding should be evaluated both on thesource activity and the number of treatments for theradiation safety of the surrounding environment

• For HDR units using 192Ir typical shielding requirementsare 5 to 7 cm of lead or 35 to 50 cm of concrete

• Because the radiation is uncollimated, all the directionsmust be similarly shielded



• The activity of the source should be checked when thesource is loaded into the unit

• The dose distribution of the HDR brachytherapyimplants is based on the source step by stepmovements along the active line

• However, the current calculation algorytms do not takeinto account this step by step movement

• The error which can be so produced will rarely behigher than 2% of the obtained dose distribution



• Rules for active lines number, length andspacing as used in LDR brachytherapy systemsmight need some modifications

• HDR after loading units are equipped withspecific dosimetry softwares allowing the socalled “dose optimization”

• These softwares in principle allow smallerimplants than those based on traditional LDR



• HDR after loading units softwares have thepossibility of manipulating the dose distrubutionby controlling the dwell time at each dwellposition

• Optimization based on dwell time is howeverlimited in its ability to alter the dose distribution

• There are two classes of optimizationalgorythms



• Dose point optimization– The clinical problem is seen as needing to achieve a

desired dose at defined points• Geometric optimization

– The implanted catheters or needles are assumed topermeate a target volume and the idea is to use thesource locations themselves to drive the solutionwithout the introduction of separate dose points

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• The optimization process should not beconsidered as a way to “correct” the implant.There is no way to make “good” an implanttechnically not properly done.

• Optimization may, however, help to get a more“sophisticated” evaluation of the obtained dosedistribution and to taylor the dose distribution tothe target






• From a radiobiologic point of view, HDR mightbe considered in some way similar to thehypofractionation of the external beam

• That, if we come to consider the LDR standardtreatment scheme (60 Gy in 6 to 7 days at 40 to60 cGy/h) as a reference schedule

• In this respect we may be brought to fear ahigher rate of complications with HDR



• Lukily enough, however, the clinical experience withHDR brachytherapy has shown that fear unrealistic

• Rates of side effects have been similar with HDR andLDR, as well as similar have generally been the rates ofdisease local control

• The definition of criteria to calculate the equivalence ofHDR and LDR given doses remains of paramountimportance

• In the clinical practice, most of the radiation oncologistsconsider the Linear Quadratic model (LQ) as aneffective model to find the sought equivalence



Linear quadratic model for brachytherapy• The LQ equation for N equal exposures, each of

duration t, with correction for repopulation duringthe course of the irradiation in overall treatmenttime T (days) is:

-lnS = N[α(Rt)+Gβ(Rt)2] – 0.693T/Tpot

where Tpot is the potential doubling time of cells (indays) and 0.693 is ln2



• The equation leads to the formula for thebiologically effective dose (BED), also referred toas the Extrapolated Response Dose (ERD)

-lnS/α = BED = NRt[1+G · Rt/(α/β)] – 0.693T/αTpot

where the parameter α/β represents the curviness ofthe log cell survival curve

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• The a/b ratio is an intrinsic characteristic of tissue anddiffers in normal and neoplastic tissues, related to thecapability of biologic damage repair. Largely used arethe values– 10 for acute responding tissues (tumors)– 3 for late responding tissues (normal)

• Calculation should be made using the value for tumors,to avoid underdosage

• The BED for normal tissues will be evaluated andweighted afterward



• A new unit can be defined: Linear Quadratic EquivalentDose (LQEQ), once again expressed both for α/β 3and 10

• As a rule of thumb, LQEQ may be calculated dividing,for instance, the Gy3 BED by 1.67 for normal tissues,giving an extimate of the risk for late normal tissuescomplications

• As an example, in GYN HDR brachytherapy, the Gy3BED to the rectum should not exceed 100 Gy to be onthe safe side



• In HDR brachytherapy, where fraction time is soshort that negligeable repair occurs during eachexposure but the interval is long enough forcomplete repair to occur, G = 1

• In LDR Brachytherapy at a costant dose rate, thevalue of G is:

G = 2/µt · [1-(1-eµt/ µt)]where µ is the repair rate costant.



• Typical values for µ used in the literature for LQmodel calculations arefor late responding normal tissuesµ = 0.46 h-1 (t/2 = 1.5 h)

for tumorsµ = 0.46 – 1.4 h-1 (t/2 = 1.5 – 0.5 h)



• The BED is essentially a bioeffect dose, which takesinto account all the parameters of the treatment (doserate, dose per fraction, time per fraction and intervalbetween fractions)

• It can be used to convert LDR regimens to HDRschedule. However, it has to be carefully used by theexpert hands of a knowledgeable radiation oncologistunderstanding the radiobiologic principles on whichLDR and HDR equivalence is based



• In brachytherapy, normal tissue cells are closedto tumor cells; dose per fraction of HDR for LDRequivalence is low and several fractions areneeded

• LQ model calculations show that to replace a 60Gy LDR implant at 0.5 Gy/h 13 fractions of HDRat 3.5 Gy/fraction might be required.

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• All the above described methods of calculationand the consequently derived treatmentschedule suggestions, should be carefullyevaluated and weigthed on the bases of thepersonal and istitutional experience of theradiation oncologist. On the other hand, a closecooperation with physicists will guarantee aproper and correct utilization of the mathematicmodel






• HDR brachytherapy allows the same range ofapplications as LDR from a technical point of view

• It may therefore be used as– Contact– Intracavitary– Interstitial– intraluminal

brachytherapy.



• From a technical point of view, we must keep inmind that dosimetry systems used for LDR arenot per se valid also in HDR

• Previsional planning is possible with HDR, but,even if it migth be done according to the generalrules of some LDR dosymetric system, theobtained results may even largely vary



• In some ways, the quality of the implant and of the dosedistribution the implant will allow, are more dependingon the dosymetry software than the LDR implants do

• Optimization in fact plays a relevant role and may helpin tayloring the dose distribution to the target

• However, one has to remember that there is no way tomake good a badly designed or carried out implant

• The radiation oncologist training for HDR can not avoida solid expertise of LDR



• Several aspects of HDR have played animportant role on the rapid spread of thistechnique

• First of all, patients can be treated as oupatienteven for interstitial brachytherapy

• The treatment time is very short allowing a largernumber of patients to be treated,

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• From an economic point of view, the increase ofnumber of the treatable patient and thepossibility of an outpatient based treatment, bothcontribute to a more favorable ratio betweeninvestments and revenues, even taking intoaccount the initial cost of the brachytherapy unit,including the room shielding, the need for sourcereplacement and the cost of the disposablematerial to be used






• HDR and LDR are generally both suitable for allthe clinical indications of brachytherapy

• It is however possible to define criteria which willallow a selection of clinical situations selectivelysuitable for each one of the two techniques



• Neither the number of patients which can betreated nor the economic advantages, mayinduce the radiation oncologist to use the HDR ifnot properly indicated for a specific clinicalsituation

• Even if HDR and LDR are generally overlapping,criteria should be defined to identify selectivearea of application



• Clinical indications for HDR brachytherapy may bedivided in three categories:– Cases where LDR is preferable– Cases of overlapping indication– Cases of HDR selective indication

• The availbility of only HDR unit in a radiotherapy center,may allow violations of the proposed criteria, provided apersonal and istitutional expertise in brachytherapy

• Radiotherapy facility devoted to a brachytherapypractice, should have both HDR and LDR or PDRsystem



• Cases where LDR is preferable

– Intracavitary brachytherapy for cervix cancer

– Interstitial brachytehrapy for oral cavity

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• Cases of overlapping indications– Breast cancer boost after external radiotherapy– Oropharynx– Anorectal cancer– Intracavitary for endometrium and vagina– GYN interstitial brachytherapy– Soft tissue sarcomas



• Cases of selective indications

– Intraluminal brachytherapy for oesophagus– Intraluminal brachytherapy for bile duct– Intraluminal brachytherapy for pancreas– Intravascular brachytherapy to prevent restenosis

after balloon angioplastic


Brachytherapy Boost in BreastCancer

Fig. 1A Como – Novembre 2001


Fig. 1B





Fig. 3B

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Fig. 4B





Fig. 5B


epitelioma del labbro


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guancia


piani


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tonsilla


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guancia


piano


rec. Endometrio


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cervice

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piani


utero


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epitelioma


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Como – Novembre 2001 Como – Novembre 2001



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• HDR brachytherapy is a valid brachytherapytechnique which can be used either as analternative to or instead of LDR brachytherapy

• HDR radiobiology is an important element of thetreatment planning and safety and should bewell known and carefully used by the radiationoncologist



• LQ is an effective model for calculating doseequivalence between HDR and LDRbrachytherapy

• Technical aspects and economic considerationstend to privilege HDR from a practical point ofview

• These aspects can not be in any waysubstituting the carefull clinical evaluation



• Criteria to select specific indications for eitherone of the two brachytherapy techniques shouldbe clearly identified and followed

• So far, non differences of relevance have beenshown in clinical results and side effectsbetween HDR and LDR when properly used inexpert hands

Documents

Associazione Italiana di Fisica In Medicina Centro di … · 3 Associazione Italiana di Fisica In Medicina Centro di Cultura Scientifica “A. Volta” Scuola Superiore di Fisica