www.practicalradonc.org

Practical Radiation Oncology (2014) xx, xxx–xxx

Original Report

Surface mold brachytherapy for nonmelanomaskin cancer: Canadian patterns of practiceJim N. Rose MD a,⁎, Pierre-Yves McLaughlin MD a, Timothy P. Hanna MD a,David D'Souza MD b, Ranjan Sur MD c, Conrad B. Falkson MBChB a

aCancer Centre of Southeastern Ontario, Kingston, Ontario, CanadabLondon Regional Cancer Centre, London, Ontario, CanadacJuravinski Cancer Centre, Hamilton, Ontario, Canada

Received 1 October 2013; revised 10 December 2013; accepted 12 December 2013

AbstractPurpose: We sought to describe the use of surface mold brachytherapy (SMBT) for nonmelanomaskin cancer in Canada.Methods and Materials: A list of Canadian Association of Radiation Oncologists membership andprovincial registries were used for a preliminary survey to identify radiation oncologists andphysicists involved in the practice of SMBT. A detailed survey was sent electronically toindividuals involved in treating with SMBT.Results: Of 41 centers in Canada, 39 responded, with 7 centers indicating use of SMBT. Sevenradiation oncologists and 5 physicists from 6 of 7 treating centers responded to the detailed survey,with an overall 75% individual response rate (12/16). General agreement was found regardingindications for SMBT which included irregular or curved surfaces, avoidance of deep structures,and requirement for small fields. There was consensus regarding some contraindications for SMBTsuch as tumor depth and size. Hypofractionated schedules were used in 5 of 6 centers and dosesranged from 50 Gy in 5 fractions once per week to 30 Gy in 10 fractions twice a day over 5 days.The most common dosimetric parameters for plan evaluation included D90, D95, D100, andmaximum skin dose.Conclusions: A minority of Canadian centers practice SMBT. In centers practicing SMBT, generalagreement exists on general indications for its use. Given the wide variation in dose andfractionation used and the rarity of the indication a phase 2 Canadian protocol would be invaluable.© 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

This study was presented as an oral presentation at the 27th CanadianAssociation of Radiation Oncologists Annual Scientific Meeting,Montreal, September 18-21, 2013.

Conflicts of interest: None.⁎ Corresponding author. Department of Oncology, Cancer Centre of

Southeastern Ontario, 25 King St West, Kingston, ON, Canada K7L 5P9.E-mail address: jrose2007@gmail.com (J.N. Rose).

1879-8500/$ – see front matter © 2014 American Society for Radiation Oncohttp://dx.doi.org/10.1016/j.prro.2013.12.003

Introduction

Nonmelanoma skin cancer (NMSC) is the most commonmalignancy in Caucasian populations.1 An estimated 2.1million people in the United States receive treatment forNMSC each year, and the incidence of NMSC has beenincreasing over the past 40 years at an annual rate of2.4%.2,3 By virtue of its commonality, NMSC constitutes asignificant cost to the North American society.4

logy. Published by Elsevier Inc. All rights reserved.

2 J.N. Rose et al Practical Radiation Oncology: Month 2014

The choice of therapy considers tumor size andlocation, patient age and performance status, time, cost,cosmesis, functional outcome, and patient preference.Treatments include curettage, cryotherapy, electrodesic-cation, chemotherapy, immunomodulators, photodynamictherapy, surgery, or radiation therapy.5,6 Radiation therapymay be used as primary treatment, especially fornonsurgical candidates or areas where cosmesis orfunction after surgery would be suboptimal. Investigatorshave reported 5-year local control rates of 92%-96% forT1 NMSC treated with superficial x-ray therapy, electrons,and megavoltage radiation therapy.7-12

Surface mold brachytherapy (SMBT) is a less wellcharacterized form of radiation therapy that has been usedto treat NMSC using a variety of dose and fractionationschedules.13-17 Guix et al17 used polymethyl methacrylatemolds built over plaster molds to treat 117 patients withmostly small facial NMSC with high-dose-rate (HDR)SMBT to 60-80 Gy in 33-40 fractions. They reported a 5-year disease-free survival of 98% and good or excellentcosmesis in 98%.Maroñas et al14 have recently reported on51 patients with facial NMSC treated with hypofractio-nated schedules (35-57 Gy in 5-18 fractions). Theyreported 5 recurrences with good or very good cosmesisin all patients and no bone or cartilage necrosis.Brachytherapy has been endorsed as a treatment optionfor NMSC by a number of groups18-21; however, very fewdetails regarding the optimal dose, fractionation, andtreatment technique are included. We are not aware ofany guidelines for curative surface mold brachytherapy forNMSC at the time this study was submitted for publication.The purpose of this study is to determine the patterns ofpractice for curative surface mold brachytherapy of NMSCacross Canada.

Methods and materials

An initial national brachytherapy survey22 was sent toall radiation oncologists practicing in Canada as listed inthe Canadian Association of Radiation Oncologistsdirectory and provincial physician registries. The aim ofthis initial survey was to determine the characteristics ofthe workforce across Canada in all areas of brachytherapy.Out of 41 centers in Canada, we received responses from39 centers. Seven centers indicated that they utilize SMBTfor skin cancer. Follow-up communication was used toidentify radiation oncologists and medical physicists fromthese centers who have used SMBT for NMSC. Radiationoncologists were invited to respond to a 23-item electronicquestionnaire (in both official languages, English andFrench) designed to inquire about the indications, dose,fractionation, and technical details of curative intentSMBT for NMSC. Medical physicists were invited torespond to a 16-item electronic questionnaire (in bothofficial languages, English and French) designed to

inquire about the technical details of curative intentSMBT for NMSC. An e-mail message with a link to thequestionnaire was sent to all participants on November 29,2012 with 2 follow-up emails sent prior to study closure onJanuary 15, 2013. Questionnaires were analyzed by centerand where responses within a center did not agree, bothresponses were included. Biologically effective dose(BED) was calculated using the following equation:

BED ¼ n� d 1þ d= α=βð Þ½ �;where n = number of fractions, d = dose per fraction, α/β =8.5 (tumor control), and α/β = 3 (late normal tissue).23

Results

Seven centers across Canada indicated that theypractice surface mold brachytherapy for curative treatmentof NMSC and we received responses from 6. Out of8 treating radiation oncologists and 8 physicists polled,responses were obtained from 7 and 5, respectively.

Radiation oncologists who practice SMBT were askedto report the number of patients per year that theypersonally treat with SMBT, electrons, MV photons,superficial x-ray, or orthovoltage techniques. The mediannumber of patients treated per year was highest forelectrons or MV photons (10, interquartile range [IQR] 0-25) followed by SMBT (7, IQR 1-10) and superficial ororthovoltage (5, IQR 0-28).

All respondents were asked whether they wouldrecommend surface mold brachytherapy as a first linetreatment for selected NMSC. Of radiation oncologists,71% responded yes, with 2 respondents stating that theywould not because orthovoltage is available at their center.All physicists polled stated they would recommend surfacemold brachytherapy as a first line treatment for selectedNMSC.

Table 1 shows radiation oncologist perceptions of thecontraindications for curative surface mold brachytherapyof NMSC. There was a consensus that previous surgery ortopical therapy and histologic subtype (ie, nodular vsinfiltrative basal cell carcinoma) were not contraindica-tions. There was less agreement about which factorsconstituted relative or absolute contraindications.

All centers reported using iridium (Ir-192) catheter-based high-dose-rate brachytherapy for their surface moldsand computed tomography imaging to contour a clinicaltarget volume (CTV). As shown in Table 2, a variety ofdoses, fractionation schedules, and prescription points areused. Three out of 6 of responding centers prescribe to anisodose line covering the CTV while 2/6 centers prescribeto either the surface or a depth of 5 mm. Hypofractionatedschedules are most commonly used (5/6 centers) withtwice a day fractionation used by half of the respondingcenters. Table 3 shows the biologically effective dose for

Table 1 Importance of tumor and treatment factors amongradiation oncologists as contraindications to surface moldbrachytherapy

Factors Contraindication

None Relative Absolute

Tumor factorsSize 2 4 0Depth 0 4 2Location 3 2 1Perineural invasion 4 1 1Lymphatic invasion 4 2 0Vascular invasion 4 2 0Degree of differentiation 5 1 0Histological subtype (ie,nodular vs infiltrative BCC)

6 0 0

Clinical appearance 5 1 0Treatment factorsPrevious radiation therapy 3 2 1Previous surgery 6 0 0Previous topical therapy 6 0 0

BCC, basal cell carcinoma, number of respondents = 6.

Table 3 Biologically effective dose (BED) for commondose schedules for nonmelanoma skin cancer

Total dose(Gy)

No. offractions

Dailyfraction size

BED8.5Gy BED3Gy

20 1 20 67.1 15330 3 10 65.3 13035 5 7 63.8 116.740 10 4 58.8 93.350 20 2.5 64.7 91.760 30 2 74.1 100

Surface brachytherapy: Canadian practice 3Practical Radiation Oncology: Month 2014

common dose and fractionation schedules used for EBRTfor NMSC.

Table 4 shows the dose–volume histogram (DVH)metrics used from plan evaluation at responding centers.Centers were asked to provide a number for each DVHmetric used. The letter Y indicates that the metric is usedbut no number was given. Overall, the DVH metrics usedto evaluate plans vary between centers. Half of centerspolled use either the D100, D95, minimum dose to the CTVor mean/median dose to the surface to evaluate targetcoverage. In terms of plan evaluation for maximal dosesthere was no agreement on the metrics used.

All respondents were asked to provide reasons forchoosing surface mold brachytherapy over external beamradiation therapy (EBRT, superficial x-ray, orthovoltage,electrons, or megavoltage photons) and vice versa. Asshown in Table 5, 7/12 respondents cited treatment ofirregular or curved surfaces as a reason for choosing surfacemold brachytherapy over EBRT. Avoidance of deep

Table 2 Technical details of surface mold brachytherapy at respon

Site CSD (cm) Dose Prescript

1 0.5-1.5 50 Gy/5#, once per wk (a) surfa2 1 30 Gy/10# BID in 5 d (a) 0.5 c3 0.5-1 30 Gy/10# BID in 5 d 100% ID4 0.5 60 Gy/30# daily surface5 0.5-0.8 (a) 40 Gy/10# BID in 5 d IDL cov

(b) 45 Gy/15# daily6 0.25 36 Gy/6# IDL cov

#, fraction; BED, biologically effective dose; BID, twice a day; CSD, catheterwk, week.

a Where responses at the same center differed between respondents, both

structures and requirement for small fields were alsocited as indications for surface mold brachytherapy versusEBRT (5/12 in each case). Four out of 12 respondentsstated they would choose surface mold brachytherapy overEBRT for frail patients or those for who live distant fromthe center. Conversely, reasons for choosing EBRT oversurface mold brachytherapy included deep or large tumors,tumors requiring nodal treatment, and certain locationssuch as head and neck, where standard fractionation ispreferred. A minority preferred EBRT to surface moldbrachytherapy because of the simplicity and greaterexperience with EBRT.

Discussion

At the time of publication, we were not able to identifyany reports of significant experience with SMBT forNMSC in North America. With this study, we sought todescribe the use of SMBT for curative treatment of NMSCin Canada.

We found that a minority of Canadian radiation therapycenters practice SMBT (7/39 responding centers) despite91% of centers in Canada having an HDR remoteafterloader.22 Among Canadian centers practicing SMBTfor NMSC, there are a variety of approaches being used.Twice daily fractionation has the advantage of decreasedoverall treatment time, which can benefit the frail or those

ding centers a

ion Point BED8.5Gy BED3Gy

ce (b) 0.5 cm depth 108.8 216m depth (b) IDL covering CTV 51.2 90L 51.2 90

74.1 100ering CTV 77.6 146.7

60.9 90ering CTV 61.4 108

to skin distance; CTV, clinical target volume; d, days; IDL, isodose line;

responses are listed.

Table 4 Dose–volume histogram metrics for surface mold brachytherapy plan evaluation used at responding sites

Target coverage

Site D100 D95 D90 Min doseto CTV

Min doseto surface

Mean/mediandose to surface

Depth of 90%isodose line

1 Y Y Y Y Y2 Y3 = 100% Y Y Y4 = 100% Y5 N 97% = 100% Y6 Y

Toxicity

Site V200 V150 V120 Max doseto surface

D0.1cc D1cc D2cc

1 Y2 Y3 = 0 Y b 120 %45 Y Y Y6 Y

DX, % of prescription dose received by X% of target; Dx cc, minimum dose in the most irradiated volume of X cc; Min, minimum; VX, volumereceiving dose of X% or more; Y, metric is used but no number was given.Blank cells indicate that metric is not used.

4 J.N. Rose et al Practical Radiation Oncology: Month 2014

who live distant from the treatment center. Three centers inCanada deliver 30-40 Gy prescribed at a nominal depthwith twice daily fractionation over 5 days. This approachhas been used by other practitioners of SMBT to treatNMSCs of the hand24 and ear25 although the doses usedwere greater than 40 Gy. A dose of 30 Gy in 5 fractionswas reported in 1 study,13 but only 2 patients were treatedwith this schedule. We were unable to find any other

Table 5 Reasons for choice of surface mold brachytherapyover EBRT and vice versa

Reasons for choosing SMBT over EBRT n = 12

Irregular or curved surface 7Avoid deep structures(ie, bone, locations such as hand)

5

Small fields required 5Unable to undergo protracted course ofradiation therapy

4

Would not choose SMBT over EBRT 2

Reasons for choosing EBRT over SMBT

Deep or large lesions, nodal treatment required 5Standard fractionation preferred due to OAR,location (head and neck)

2

More experience, simple technique,less resources needed

2

EBRT, external beam radiation therapy (orthovoltage, superficialx-rays, electrons, or megavoltage photons); OAR, organs at risk;SMBT, surface mold brachytherapy.

reports from the literature that use a 30 Gy in 10 fractionBID dose schedule. Hypofractionated schedules delivered2 to 3 days per week can also minimize treatment centervisits and have been reported.14,15 One Canadian centerreported delivering 50 Gy in 5 fractions delivered once aweek that is less common but a similar schedule has beenreported previously.13 Standard fractionation (60 Gy/30daily fractions) is used by 1 center in Canada. The largestpublished series of catheter-based SMBT16 used a similarschedule to treat 136 patients with 60-65 Gy in 33 to 36fractions with a boost to 75-80 Gy for lesions greater than4 cm. With a minimum follow up of 12 months, the localrecurrence rate was 2%.

This study has also found some consistency for theindications among users of SMBT for NMSC. Seven out of12 respondents cited irregular or curved surfaces as a reasonfor choosing SMBT over superficial or megavoltagephotons or electrons. The steep dose gradient displayedby brachytherapy facilitates treatment of superficial targetsand avoidance of deep organs at risk. This is reflected in oursurvey which found that SMBT is often chosen over otherradiation modalities to avoid deep structures. The highenergy of megavoltage photons and the need to account forlateral scatter of electrons may result in treatment of morenormal tissue than necessary compared with SMBT. In oursurvey, 5/12 respondents identified the requirement to treata small area as another indication for SMBT. Becausesmaller volumes of tissue can tolerate higher doses,hypofractionation with SMBT has been used to decreasethe number of treatments for the frail or those who livedistant from the treatment center. A minority (4/12) of

Surface brachytherapy: Canadian practice 5Practical Radiation Oncology: Month 2014

respondents did cite this as an indication for SMBT in thissurvey. The European Society for Radiotherapy andOncology guidelines state that brachytherapy can be usedas a boost for T2-T3 tumors after EBRT,21 a practice whichdoes not appear to be common among Canadians.

In this study, there was less agreement regarding thecontraindications for SMBT. The majority of respondentsindicated that tumor depth and size were either relative orabsolute contraindications. Other tumor factors such asperineural invasion and clinical appearance were not citedas contraindications by most. There was unanimousagreement in this survey that SMBT can be used afterprevious surgery or topical treatments. Recurrence afterprevious radiation therapy was felt to be either a relative orabsolute contraindication by half of respondents.

The strength of this study is that it is the first Canadianpublication regarding the use and practice of SMBT forNMSC. This study does have some limitations. It is not aformal audit of the practice of SMBT and may be subjectto recall bias. Although respondents from 7 out of 39responding cancer centers in Canada indicated that theypractice SMBT for NMSC at their center it is possible thatwe were not able to reach all potential practitioners. Thisstudy identified a relatively small number of respondentswho practice this technique across Canada. This indicatesrelatively little experience with SMBT across Canada andunderscores the need for published case series amongCanadians in this area.

From our survey of the Canadian patterns of practicefor SMBT for NMSC we can summarize a fewobservations based on survey responses.

1. The most commonly cited reason for using SMBTover EBRT was for targets overlying irregular orcurved surfaces. The next most common reasonswere when avoidance of deep structures was desired,or for treatment of small fields where other radiationtherapy modalities are not practical.

2. The most common reason cited for using EBRT overSMBT was for patients who have deep or largelesions or for whom nodal treatment is indicated.

3. All respondents considered depth as either a relativeor absolute contraindication to SMBT.

4. No respondent considered tumor size, lymphaticinvasion, vascular invasion, differentiation, histo-logic subtype, or clinical appearance as absolutecontraindications to SMBT

5. Previous surgery and previous topical therapy werenot considered contraindications to SMBT.

Conclusions

Canadian outcomes from SMBT for NMSC arelacking. Limited outcomes data from other countriessuggest excellent outcomes for HDR SMBT for

NMSC.13,14,17,24-27 These results should be confirmedfor the dose and fractionation used in a Canadian context,especially as they vary from common dose schedules in theliterature (ie, 30 Gy/10 fractions twice a day). Given thewide variation in dose and fractionation used withinCanada and the rarity of the indication, a phase 2 Canadianprotocol would be invaluable.

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