Hong Kong J. Dermatol. Venereol. (2009) 17, 79-86

Review Article

Current tools of radiation therapy in treatment of skincancer

WK Yeung , NM Luk , KH Yu

The mainstay treatment of non-melanoma skin cancer is surgery. However, radiotherapy is an effectivetreatment alternative in some clinical situations. The current tools of radiation therapy in treating skincancer include low-energy X-ray, electron beam therapy and brachytherapy. This review article providesan overview of these treatment techniques.

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Keywords: Non-melanoma skin cancer, radiation therapy

Department of Clinical Oncology, Prince of WalesHospital, Hong Kong

WK Yeung, FHKAM(Rad), FRCRKH Yu, FHKAM(Rad), FRCR

Dermatology Research Centre, The ChineseUniversity of Hong Kong, Hong Kong

NM Luk, FRCP(Edin), FHKAM(Medicine)

Correspondence to: Dr. WK Yeung

Department of Clinical Oncology, Prince of WalesHospital, 30-32 Ngan Shing Street, Shatin, N.T., HongKong

Introduction

The majority of non-melanoma skin cancer is well-differentiated epithelial carcinoma, either basal

cell carcinoma or squamous cell carcinoma.Nowadays, most of these skin cancers can becured by a wide variety of treatment modalities.Other than surgery, radiation therapy plays animportant role in the treatment of skin cancers.

The choice of radiotherapy is dependent on severalfactors, such as size, location, histopathologicaltype of the tumour, the condition and preferenceof patients, and the local availability of certaintreatment modalities. The main advantage ofradiotherapy is the possibility to treat the tumourand the area of subclinical spread with a safetymargin without substantial damage to normaltissue. Hence anatomical mutilation can beminimized. The better cosmetic outcome ofradiotherapy make it a good therapeutic choicefor skin tumours involving nasal ala, inner or outer

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canthus of eyes, pinna of ears, oral commissureand philtrum of lip. However the disadvantagesinclude the inability to check the treatment marginsand requirement of multiple treatment sessionsin order to achieve a good cosmetic outcome.

The current available tools of radiotherapy for skincancer include low-energy X-ray beam, electronbeam, and brachytherapy. The choice of thesetechniques depends on the tumour characteristics,the availability of machines and expertise.

Low-energy X-ray therapy

There is a spectrum of low-energy X-ray which isuseful for treating superficial skin cancer. Thisincludes the range from 5-20 kV (Grenz X-R) to200-400 KV (orthovoltage). The commonestX-ray used in our clinical practice is the superficialX-ray, with the range of energy between 60-100 kV.

Low-energy X-ray is usually generated from aX-ray tube, in which an electric current runs acrossa electric potential (defined by its voltage) in avacuum tube, and hits a metallic target (theanode), normally tungsten, thereby gives rise to aconcentrated beam of photon (electromagneticwave). The energy of photon beam is related tothe electric potential and the characteristic of themetallic target. Different combinations of electricpotential and metallic target may give rise tophoton beam with different penetrative power. Itis the energy of the photon produced thatdetermines how deep X-ray can penetrate theskin tissue. The penetrative power of X-ray is

represented by the half-value layer (HVL). This isdefined by the thickness of material, eitheraluminum (Al) or copper (Cu) which can reducethe intensity of beam by half (Table 1). Forexample, 100 kV superficial X-ray with HVL of2 mm Al can treat skin tumour of up to 3-4 mmin thickness.

The beam penetrative profile of low energy X-rayhas the characteristic of high energy deposit atthe surface and a rapid drop of intensity afterentering the skin tissue for a few millimeters. Thepenumbra of the beam which is defined by thedistance between the 90% and the 50% isodoseline (IL) at the surface level is also narrow. Thatmeans the physical margin to be considered fora skin tumour is narrow, usually just 2-3 mm.Moreover, the shielding for blocking ofunnecessary irradiation to normal tissue is lessdemanding. Usually a lead shield of 1 mm isenough to shield off the irradiation. Thus, low-energy X-ray has good physical advantage intreating skin tumour near the eyes (Figures 1-7).The shaping of irradiation field is also convenientand requires only a thin lead shield. The radiationprotection requirement of the treatment room isalso easily achieved.

The dosage of radiation therapy is defined by theenergy deposit per unit mass of tissue across thebeam. One Gray (Gy) is defined as one joule perkilogram. One Gray has 100 centi-Grays (cGyor Rad). The dosage has to be prescribed at acertain isodose level. Usually the prescription levelis at the 80-100% IL. However, there is anotherschool of thought, using 50% IL (i.e. half-value

Table 1. The characteristics of low-energy X-ray with different energy

Radiation Operating Typical Approximate HVL water or HVL in HVL intherapy potential measured average soft tissue cortical bone leadunit (kV) HVL energy (keV) (cm) (cm) (cm)Grenz rayGrenz rayGrenz rayGrenz rayGrenz ray 5-20 0.03 mm Al 7 0.04 0.004 −

Superficial XSuperficial XSuperficial XSuperficial XSuperficial X-ray-ray-ray-ray-ray 60-100 2 mm Al 30 1.8 0.3 0.002

Orthvoltage XOrthvoltage XOrthvoltage XOrthvoltage XOrthvoltage X-ray-ray-ray-ray-ray 200-400 3 mm Cu 150 5.0 2.5 0.03

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Figure 1 & 2. A patient with basal cell carcinoma at the inner canthus of right eye was in preparation forsuperficial X-ray therapy. Right internal eye shield was inserted.

Figure 3 & 4. Superficial X-ray therapy: patient wearing the cobex cast, with lead cut-out, and wax-jig mountedon it.

Figure 5. Superficial X-ray therapy: patient in thetreatment room of superficial X-ray.

Figure 6. Superficial X-ray therapy: the treatment headmounted on the patient.

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level) for dose prescription. This may give rise tohigher dose to the surface but lower dose to theunderlying normal tissue, sacrificing the dosehomogeneity in the tumour tissue. The choice ofenergy of X-ray is determined so that theprescription level (e.g. the 80-90% IL) can coverthe tumour depth with biological margin.

To allow for normal tissue repair, and hence lessnormal tissue late toxicity, multiple fractionationof the treatment course is necessary. The balancebetween advantage of multiple fractionations anddisadvantage of multiple visits has to beconsidered in our clinical practice, especially forold and fragile patients. The conventional dosefractionation in treating tumour is usually 66 Gyin 2 Gy per fraction, 5 fractions per week. Thisfractionation may not be suitable for old patients.So various schemes of dose fractionation are beingused among different countries and centres. Thereis intention to treat large sized tumour with moretotal dose. However, there is no consensus howhigh the dose has to be given.

Electron beam therapy

The electron beam in clinical use nowadays canbe generated in a linear accelerator which mostlyhas its second treatment mode of high energy

(Mega-volt) photon beam. High energy photonbeam is used to treat deep tumour, but electronbeam can be used to treat superficial tumour, likeskin tumour. The electron beam generated in thelinear accelerator is produced by an electriccurrent passing through a high energy potentialin a vacuum tube. The electrons are acceleratedby the microwave field. The energetic electronsare then directed by magnets in the treatmenthead to generate a concentrated beam.

Because of the rapid fall-off of energy depositwhen an electron enters tissue, the clinically usefulelectron beam has to be higher in energy (4-20Mega-volts) compared with low energy X-ray (kilo-volt). The useful energy range of electron beamin treating skin tumour is between 4-6 Mega-volts.

The dose profile of an electron beam in the tissueis very different from those of low-energy X-ray.The maximum energy deposit of an electron isnot at the surface, but at few mm beneath thesurface. However, it has a good distance of doseplateau, giving rise to a better dose homogeneityin the treatment depth. Its sharp dose fall-off isalso advantageous in giving lower doses to theunderlying tissue. When electron beam isemployed to treat superficial disease like skintumour, a bolus of tissue has to be added on thetreatment surface so as to achieve the maximumdose deposit at the surface level. Usually this tissuebolus is made of wax. The thickness of this bolusis critical for the clinical outcome.

The penumbra of an electron beam is largecompared with those of X-ray beam, usually8-10 mm width at the surface level. Moreoverconstriction of the high isodose level occurs at thedeeper tissue level (Figure 8). This implies a largerphysical margin has to be considered for thetreatment of tumour, compared to low energyX-ray. This limits its use in treating tumour nearcritical organ like the eyes.

The higher penetrative power of electron beamgenerated in the linear accelerator implies thicker

Figure 7. Patient with basal cell carcinoma just aftersuperficial X-ray therapy.

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shielding for adjacent normal tissue and for fieldshaping. The shielding is made of lead of morethan 5 mm in thickness, usually custom-made toconform to the shape of tumour. This results indifficulty in making an internal shield like internaleye shield or intranasal shield. For superficialX-ray, an internal eye shield can be inserted underlocal anesthetic eye-drops, just like wearing acontact lens (Figure 9). This can shield off anyunnecessary radiation from the eye. For electrontherapy, this shielding device is insufficient to shieldoff the unwanted radiation from the eyes. This isthe technical difficulty encountered in treating skincancers near the periorbital region with electrontherapy (Figures 10-14).

Radiobiological effectiveness of an electron isless than that of X-ray. The factor of radiobiologicaleffectiveness compared with X-ray is estimatedat about 0.9. This may imply the total doseprescribed should be higher in using electronbeam. However, the clinical significance of this isnot certain in the literature.

The dose is usually prescribed at 90% or at themaximum dose level (100% IL). The choice of

Figure 8. The depth isodose distribution of a 6 MeVelectron. This shows the dose profile after the electronbeam enter the surface of a phantom. The field size isdefined by the 50% isodose line. The distance betweenthe 50% isodose and 90% isodose is increasing alongthe depth. This means the effective treatment widthwill constrict when the beam penetrates deeper.

Figure 9. Internal eye shields of various size forsuperficial X-ray therapy.

Figure 10. A patient with basal cell carcinoma overleft nasal ala, before radiotherapy.

Figure 11. A patient with basal cell carcinoma overthe nose for electron beam therapy with treatment cast,bilateral eye trimmers, wax-bolus and jig.

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energy and the thickness of bolus are determinedso that 90% IL will cover the tumour depth withbiological margin. The dose fractionation and totalprescribed dose of electron beam in treating skincancer is similar to those of low-energy X-ray.

Because of the high radiation protectionrequirement, the availability of an electron beamequipped with linear accelerator is mainly confinedto hospital based radiation oncology centres.Together with the consideration of cost-effectiveness of a linear accelerator which can alsobe used in treating other visceral tumours, electronbeam therapy is still a major tool used in thehospital based cancer centres.

Brachytherapy

The use of brachytherapy in treating skin tumouris becoming less popular after the developmentof modern X-ray tube. However its importance inclinical practice cannot be underestimated.

Brachytherapy is also a short distance radiationtechnique. It employs radioactive materials togenerate radiation particles, either photon orelectron. The commonly used radioactivesubstance has been changed from radium in theold days to cesium-137, and finally to iridium-192

nowadays. These radioactive sources are appliedclose to or deep into the tumour, so as to give ahigh local dose to the tumour, whilst sparing theadjacent normal tissue. The radioactive source canbe put into a surface mould in order to be appliedclosely to the tumour surface (surface mouldbrachytherapy). Alternatively, the radioactivesource can be inserted deep into the tumour(interstitial brachytherapy). Brachytherapy hasbeen evolving from low-dose rate in the past tohigh-dose rate now. The technique of loading theradioactive source has also changed from pre-loading (the applicator and the radioactive sourceare inserted together) to afterloading (theapplicator is inserted before the source). Withcomputerization, dose optimization can be

Figure 12. Electron beam therapy: with the gantryhead over the patient.

Figure 13. Electron beam therapy: the lead insertmounted on the gantry head.

Figure 14. Electron beam therapy: the gantry headover the patient on treatment table.

Radiation therapy in treatment of skin cancer 85

performed by a planning system so as to givebetter dose conformity to the tumour shape. Theafterloading technique has also improved so thatthe radioactive source can be inserted by remote-control using computerized electronic systemrather than by manual loading. This means thatthe radiation exposure to the medical personnelis minimized.

The clinical useful energy of the photon emittedfrom the radioactive source in brachytherapy is inthe range of kilovoltage (e.g. 370 kV from Ir-192).This therapeutic photon is similar to the photonfrom low-energy X-ray tube. It also has the similarphysical advantage like rapid fall-off of dose. Thismakes brachytherapy very suitable for treating skincancer.

Prev ious l y, the p lann ing techn ique o fbrachytherapy was developed according to majorguidelines, the Manchester’s system and the Parissystem. With the computerization of planningtechnique, the planning can be easily achievablewith dose optimization. In treating skin tumourover an uneven surface contour, the mould canbe customized to the surface of tumour. Themodern planning technique can create a gooddosimetry so as to conform to the tumour shape.A good example is the treatment of large sizedperineal extramammary Paget’s disease by mouldbrachytherapy technique (Figure 15).1

The current trend of brachytherapy is movingtowards remote-control afterloading high doserate technique with a computerized planningsystem. The radioactive source is stored in aradiation protected safe. During treatment, theradioactive source can be delivered automaticallyto the applicator through the connecting channelsby an electronic device with remote-control(Figures 16-17). For mould brachytherapy, theapplicator (surface mould) is placed onto thepatient’s tumour with accurate localization qualitycontrol. The applicator is usually composed ofmultiple catheters, which are arranged in paralleland are equally separated from each other,

Figure 15. Mould brachytherapy for a perinealextramammary Paget's disease: a cobex cast withmultiple catheters embedded in wax. The radioactivesource will run through multiple catheters on the castduring treatment.

embedded in some tissue equivalent material likewax or silicone. The radioactive source will runthrough these catheters inside the mould duringtreatment. The radioactive source is a point sourcepropelled by an electronic controlled metallic wire.It will move in steps into each dwelling positionalong the catheters for a pre-planned period oftime (dwelling time). The dwelling time of theradioactive source at each position will affect thedose contribution at the site. The summation ofthe dose contribution from all dwelling positionswill give the overall dosimetry to the tumour. Thecomplicated calculation can be performed by thecomputer.

When the high dose rate brachytherapy systemwas introduced, there was criticism on itsradiobiological disadvantage. The late toxicityfrom high dose rate radiation was expected to belarger. However, with more knowledge onradiobiology, this late toxicity can be reduced bymultiple fractionations. Subsequent clinicalexperience has proven that it is a good treatmenttechnique with late toxicity comparable to that oflow dose rate technique.

The disadvantage of brachytherapy in treating skincancer is its cost-effectiveness. It is quite time-

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Figure 17. The head of the afterloader with multiplechannels through which the radioactive source will bedelivered to the patient.

Figure 16. A high dose rate afterloading brachytherapymachine: the afterloader.

consuming in preparing a mould brachytherapywhich not only involves medical physician, but alsomould laboratory technician, radiation therapistsand oncologists. With equivalent clinical results,other alternative treatment like low-energy X-rayand electron therapy are usually preferred byclinicians. However, brachytherapy is moreeffective in treating large sized superficial skintumour with uneven contour in which otheralternatives cannot achieve a good clinical andcosmetic result.

Conclusion

In management of skin tumours, despitecontroversy exists, electron beam therapy seems tobe inferior to superficial X-rays in some studies.2,3

In contrast, Tapley and Zablow, using electronbeam therapy, achieved similar results assuperficial X-rays.4,5 For skin tumours located atsome areas, e.g. around the eyes, superficialX-ray is definitely superior to electron beam interms of applicability. The importance ofbrachytherapy in treating skin tumour cannot beneglected. With the evolution of radiation therapytechnique, radiation is still playing a role as analternative in treating skin tumours.

References

1. Luk NM, Yu KH, Yeung WK, Choi CL, Teo ML.Extramammary Paget’s disease: outcome ofradiotherapy with curative intent. Clin Exp Dermatol2003;28:360-3.

2. Lovett RD, Perez CA, Shapiro SJ, Garcia DM. Externalirradiation of epithelial skin cancer. Int J Radiat OncolBiol Phys 1990;19:235-42.

3. Brady LW. External irradiation of epithelial skin cancer(editorial). Int J Radiat Oncol Biol Phys 1990;19:491-2.

4. Tapley Ndu V, Fletcher GH. Applications of the electronbeam in the treatment of cancer of the skin and lips.Radiology 1973;109:423-8.

5. Zablow AI, Eanelli TR, Sanfilippo LJ. Electron beamtherapy for skin cancer of the head and neck. HeadNeck 1992;14:188-95.