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Page 1: Dose rate in brachytherapy using after-loading machine: Pulsed or high-dose rate?

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Cancer/Radiothérapie 18 (2014) 437–440

Disponible en ligne sur

ScienceDirectwww.sciencedirect.com

eview

ose rate in brachytherapy using after-loading machine: Pulsed origh-dose rate?

ébit de dose en curiethérapie avec projecteur de source : débit pulsé ou hautébit ?

.-M. Hannoun-Lévia,∗,1, D. Peiffertb,1

Département de radiothérapie oncologie, centre Antoine-Lacassagne, université Nice-Sophia, 33, avenue de Valombrose, 06000 Nice, FranceDépartement de radiothérapie oncologie, institut de cancérologie de Lorraine Alexis-Vautrin, 6, avenue de Bourgogne,4500 Vandœuvre-lès-Nancy, France

a r t i c l e i n f o

eywords:rachytherapyigh-dose rateulsed-dose ratefter-loading machine

a b s t r a c t

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end ofindustrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiationoncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Twotypes of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate orhigh-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-doserate brachytherapy, based on biological, technological, organizational and financial considerations.

© 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. Allrights reserved.

ots clés :uriethérapieaut débit de doseébit de dose pulsé

r é s u m é

Depuis février 2014, il n’est plus possible d’utiliser des sources radioactives d’iridium 192 de bas débit dedose du fait de l’arrêt de la production industrielle des sources d’IRF1 et d’IRF2. Le groupe de curiethérapiede la Société francaise de radiothérapie oncologique a recommandé de passer des fils d’iridium aux

rojecteur de sourceprojecteurs de sources. Actuellement, deux types de projecteurs de source sont disponibles selon le débitde dose utilisé : pulsé ou haut débit. Dans cet article, nous proposons une analyse comparative entre lacuriethérapie de débit pulsé et celle de haut débit de dose, selon des critères biologiques, technologiques,organisationnels et financiers.

© 2014 Société française de radiothérapie oncologique (SFRO). Publié par Elsevier Masson SAS. Tous

. Introduction

Brachytherapy is a very efficient weapon against cancer and cane described by the “3S system”. Indeed, brachytherapy is an irra-iation technique, which allows delivering a smart dose, in a small

olume, during a short time. The smart dose is due to the intrinsicose escalation linked to the hyperdose volumes within the clini-al target volume, leading to increase the chance of local control.

∗ Corresponding author.E-mail address: [email protected]

J.-M. Hannoun-Lévi).1 The authors are members of the Brachytherapy Group of the French society of

adiation oncology (Société francaise de radiothérapie oncologique).

http://dx.doi.org/10.1016/j.canrad.2014.07.156278-3218/© 2014 Société française de radiothérapie oncologique (SFRO). Published by E

droits réservés.

A small volume is due to the important dose fall-off outside of theclinical target volume, which protects organs at risk from radiationinjuries and consequently, decreases the risk of side effects. A shorttime is due to the possibility to deliver a higher dose per fractiondecreasing the overall treatment time and consequently, allowinga more comfortable/convenient/cost-effective treatment.

Since February 2014, it is no longer possible to use low-dose rate192 iridium wires due to the end of industrial production of IRF1and IRF2 sources. The Brachytherapy Group of the French societyof radiation oncology (GC-SFRO) has recommended switching from

iridium wires to after-loading machines [1]. Currently, two types ofafter-loading machines are available, based on the dose rate used:pulsed-dose rate and high-dose rate. In this article, we propose acomparative analysis between pulsed-dose rate and high-dose rate

lsevier Masson SAS. All rights reserved.

Page 2: Dose rate in brachytherapy using after-loading machine: Pulsed or high-dose rate?

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38 J.-M. Hannoun-Lévi, D. Peiffert / Ca

rachytherapy, based on biological, technological, organizationalnd financial considerations.

. Biological approach

Even if the biological effects of pulsed-dose rate brachytherapyre not strictly stackable to those observed after low-dose raterachytherapy, the former gets closer to latter than to high-ose rate brachytherapy. The results of the comparative studiesainly performed for cervical cancer confirm that there is no

ignificant difference (with even a small advantage for high-doseate) between low- and high-dose rate brachytherapy [2–5].urrently high-dose rate brachytherapy for cervical cancer isonsidered by the American Brachytherapy Society as the goldtandard technique [6]. However, trying to compare low- andigh-dose rate brachytherapy is confronted to an important biasecause the dose rate is not the only difference between the twoechniques. Indeed, dose distribution optimization is possibleith high-dose rate brachytherapy by playing with the dual timeositions of the source, while this type of optimization is notossible with the low-dose rate technique. This optimization caneeply impact the clinical outcome independently of the dose ratesed. A French multicentric study confirmed that pulsed-dose raterachytherapy improved local control with half the toxicitybserved with low-dose rate brachytherapy [7]. Currently, theres no comparison (randomized or not) between pulsed- andigh-dose rate brachytherapy performed for cervical cancer, so itemains difficult to precisely analyse the hypothetical differenceetween the two techniques only based on the difference of theose rate (both techniques allowing the dose optimization byodifying the time of stepping source).The definition of the optimal dose prescription scheme for

igh-dose rate brachytherapy represents another important issue:hich dose per fraction? Which fractionation? Which total dose?

he biological models currently available to calculate the biolog-cal equivalent dose at 2 Gy (BED) between low- and high-doseate are not validated for doses per fraction higher than 8 Gy [8].ut, is the biological equivalent dose, derived from a mathemati-al model, the only one parameter to consider? What about moreragmatic parameters such as the “clinical equivalent dose” orhe “pathological equivalent dose”? Could the clinical equivalentose and/or the pathological equivalent dose contribute with theiological equivalent dose calculation to establish new protocolsoutinely applicable? Indeed, a total dose of 39 Gy delivered in 9ractions over 5 consecutive days leads to a rate of 92% of completeathological response observed on the hysterectomy specimenfter preoperative high-dose rate brachytherapy for high-risk T1B1quamous cell cervical cancers (size larger than 20 mm, vascularmboli) without urinary or digestive grade 2 or above toxicities9]. The calculated biological equivalent dose of this protocols 59 Gy for normal tissues (�/� = 3) and 47 Gy for the tumour�/� = 10), therefore, significantly lower compared to the classicalose of 60 Gy delivered by low-dose rate brachytherapy but giv-

ng (at least) equivalent pathological results. Based on the clinicalquivalent dose approach applied for lips cancers, Guinot et al.,etrospectively compared 99 patients treated with interstitial low-ose rate brachytherapy to 104 patients treated with high-doseate brachytherapy (no significant difference in terms of tumourtage between the two groups) [10]. The high-dose rate protocolas 40.5 Gy in 9 fractions over 5 consecutive days. With a median

ollow-up of 51 months for the high-dose rate group, the authorseported a local control rate higher than 90% in the low- and high-

ose rate treatment groups. In this study, the calculated biologicalquivalent dose of the delivered dose was 61 Gy for normal tissue�/� = 3) and 49 Gy for the tumour (�/� = 10). Then, it could be notecessary to absolutely reach the 60 Gy biological equivalent dose

Radiothérapie 18 (2014) 437–440

delivered by low-dose rate brachytherapy for achieving an equiva-lent clinical or pathological result by high-dose rate brachytherapy.

Equivalence of the dose between low- and high-dose rate wasalso investigated for prostate cancer with comparable clinical out-come observed between the two dose rates in terms of efficacy andtoxicity (an advantage for high-dose rate is even suggested) [11,12].American Brachytherapy Society (ABS) as well as Groupe Européende Curiethérapie of the European Society of Therapeutic RadiationOncology (GEC-ESTRO) reported numerous high-dose rate proto-cols used for prostate boost after a first course of external beamradiation therapy [13,14]. However, regarding patient comfort andorganizational considerations, a single fraction of 14 to 15 Gy isnow generally accepted. A prostate boost of 14 Gy in one fractionis used in the French phase III protocol GETUG-P05 randomizingfor intermediate risk prostate cancer, an external beam radiationtherapy boost versus a brachytherapy boost based on low-doserate (iodine seed implant) or high-dose rate. While high-dose ratebrachytherapy is now a well-established technique for the boost, itremains under evaluation in case of sole therapy with various doseprotocols using hypofractionated approach or single dose (around20 Gy) [8,11].

For breast cancer, no comparative analysis between low- andhigh-dose rate brachytherapy has been performed; however, theprotocol which delivers a total dose of 34 Gy in ten fractions (twicedaily) over five consecutive days (biological equivalent dose of42 Gy for �/� = 4) is used in the two phase III randomized trials ofpartial breast irradiation conducted by the National Surgical Adju-vant Breast and Bowel Project (NSABP) and the GEC-ESTRO [15,16].

3. Technological approach

Currently, there is no difference in terms of technical con-siderations for the implant between pulsed- and high-dose ratebrachytherapy, whatever the indication. Vectors (applicators,tubes, needles) are the same and after-loading machine are quitesimilar. Treatment planning systems can be used equally forprotocols, allowing the same optimization of the dose distribu-tion. However, for prostate cancer, high-dose rate brachytherapyenables intraoperative irradiation using a dedicated treatmentplanning system based on ultrasound imaging (such treatment isnot compatible with a pulsed-dose rate approach). For pulsed- andhigh-dose rate brachytherapy, postimplant imaging can be equallyused based on CT-scan or MRI.

Guedea et al. reported the results of a survey, which evaluatedbrachytherapy practices and resources in Europe [17]. A total of1121 radiotherapy centres from 41 countries were investigated.High-dose rate brachytherapy was the most commonly reportedtechnique (65% of centres), while most brachytherapy interven-tions were for gynaecological tumours (59% of all cases), prostate(17%), breast (9%), lung/bronchus (3%), and oesophagus tumours(2%). In France, 37 pulsed-dose rate after-loaders are implanted,representing almost 50% of the total number of pulsed-dose ratemachines in the world, while 50 high-dose rate after-loadersare regularly used (data provided by the French brachytherapyproviders). Unlike pulsed-dose rate, different radioactive sourcescan be used with high-dose rate, such iridium 192 or cobalt 60,giving comparable dose distribution [18].

4. Organizational approach

While the organizational management of pulsed-dose rate

brachytherapy is very close to low-dose rate brachytherapy interms of treatment delivery and nursing care, high-dose ratebrachytherapy is comparable to linear accelerator treatments, withone or two teams of dedicated technicians, a devoted bunker and
Page 3: Dose rate in brachytherapy using after-loading machine: Pulsed or high-dose rate?

J.-M. Hannoun-Lévi, D. Peiffert / Cancer/R

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[6] Viswanathan AN, Beriwal S, De Los Santos JS, Demanes DJ, Gaffney D, HansenJ, et al. American Brachytherapy Society consensus guidelines for locallyadvanced carcinoma of the cervix. Part II: high dose rate brachytherapy.Brachytherapy 2012;11:47–52.

ig. 1. Pragmatic medicoeconomic analysis comparing pulse-dose rate (PDR) versusigh-dose rate (HDR) brachytherapy.

pecific patient schedules, especially in case of bifractionated irra-iations. For brachytherapy that needs hospitalization (mainly forelvic implants), the high-dose rate procedure can be performedhile the patient remains in a standard, non-shielded room, allow-

ng visits and consequently, decreasing the loneliness sensationue to the treatment itself. Furthermore, nursing care is simpli-ed because of the absence of radioprotection procedures. Withulsed-dose rate brachytherapy, the patient must stay in a shieldedoom.

Specifically in case of head and neck implants, the mandibu-ar/maxillary lead shield protection is placed only during the few

inutes of the irradiation (mainly twice daily), leading to betterreatment compliance for the patient and subsequently, potentialecrease of the risk of bone necrosis.

While ambulatory treatments are not possible with pulsed-doseate brachytherapy, the high-dose rate technique allows outpatientrocedure, contributing to a palpable quality of life improvementy avoiding hospitalization. It could be mainly the case for breast,kin, lips and soft tissue sarcoma implants.

. Potential financial impact

When choosing between pulsed- or high-dose rate after-loadingachines, a simple analysis can be performed: considering the

reatment of five patients during five consecutive days in a ded-cated brachytherapy unit, in case of a pulsed-dose rate procedure,ve after-loader machines and five shielded rooms will be neces-ary; however, for the high-dose rate technique, only one machineill be used without any dedicated shielded rooms (Fig. 1). In addi-

ion, only one iridium radioactive source will be changed everymonths for the high-dose rate procedure, instead of five in casef the pulsed-dose rate approach.

Furthermore, the radioprotection conditions offered by high-ose rate brachytherapy allow the hospital converting the shieldedoom dedicated to brachytherapy into a standard room for moreeneral treatments.

. Potential technological evolution

The end of low-dose rate 192 iridium wires production repre-ents a new step in the technological evolution of brachytherapy.urrently, both pulsed- and high-dose rate after-loader machinesllow continuing the practice of brachytherapy. However, due to

ifferent technological features, different fractionation and theirotential impact on quality of life and economical resources, it isighly recommended for each treatment centres to evaluate theiresults. In this context, the Antoine-Lacassagne Cancer Centre

adiothérapie 18 (2014) 437–440 439

switched from low- to high-dose rate brachytherapy in 2004.Since this date, we have treated almost one thousand patients andstep-by-step, like many other centres, we evaluated and publishedour dosimetric and clinical results, mainly for cervical, prostate,and breast cancers, but also for less frequent lesions such penileand anal canal tumours1 [9,19–21].

Regarding the technological evolution of brachytherapy, it isalso important to pay attention to other procedure, which couldrepresent a new solution for brachytherapy. Indeed, electronicbrachytherapy, based on a miniaturized linear accelerator deliver-ing 50 kV photons, can offer new opportunities to do brachytherapywith less radioprotection constraints if the technical features ofthese new devices remain compatible with all the BT indication,which is currently not the case due to the too large size of the source(5 mm in diameter including the cooling system) [22].

7. Conclusion

After the end of low-dose rate 192 iridium wires production,the Brachytherapy Group of the SFRO proposed to use pulsed-or high-dose rate after-loader machines to replace low-dose ratebrachytherapy. It is currently debatable to promote one techniqueor the other due to the lack of rigorous comparison and in France,the main objective at this time is to be able to continue the practiceand the development of brachytherapy around the country. How-ever, for the centres that did not make the choice between pulsed-or high-dose rate techniques, it appears crucial to integrate in thetreatment equation classically based on efficacy and toxicity, a thirdvariable, which is the economic impact. Indeed, even if pulsed-doserate brachytherapy brings some theoretical radiobiological advan-tages over high-dose rate brachytherapy, is this option still valuableregarding cost-effectiveness considerations [23]? Finally, the evo-lution of brachytherapy has to be analysed also in the context of theglobal technological evolution of radiation therapy. Brachytherapyremains a key weapon against cancer, and ethical and new method-ological approaches will help promoting and defining the place ofthis irradiation technique in the landscape of cancer treatment [24].

Disclosure of interest

The authors declare that they have no conflicts of interest con-cerning this article.

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