DOI: 10.3857/jkstro.2008.26.4.222 항문암의방사선치료시방사선조사기법에따른회음부피부독성 연세대학교의과대학연세암센터방사선종양학교실 유세환ㆍ성진실ㆍ금웅섭 목적 : 항문암의방사선치료는급성부작용을많이동반하므로다양한치료기법이적용되어왔다. 본원에서시행된항문암방사선치료를회음부피부반응의측면에서검토하여최적의방사선치료기법을모색하고자하였다. 대상및방법 : 1990년부터 2007년까지항문암으로근치적항암화학방사선치료를마친환자 35명을대상으로방사선조사방법및관련된임상적자료들을이용하였다. 방사선치료는원발병소, 영역림프절및서혜부림프절이치료범위에포함된상태로 1.8 Gy 씩 41.4 45 Gy 조사후원발병소또는전이성림프절에추가조사하는것을원칙으로하였다. 방사선조사기법은조사부위및조사수에따라 4가지로분류하였으며각기법에따른회음부급성피부반응및치료중지기간간의관련여부를알아보았다. 결과 : 방사선치료중 28명 (80.0%) 의환자에서 2등급이상의방사선피부염이발생하였고 10명 (28.6%) 이 3등급이상의방사선피부염을보였다. 4가지방사선조사기법중원발병소와영역림프절에대한 3면 X-선및양측서혜부림프절에대한전자선조사군과 electron thunderbird 군에서방사선피부염이동반된환자수가상대적으로적었으며치료중지기간이각각 8.2±10.2 일, 5.7±5.7 일로써다른치료기법보다적었다. 방사선치료종료후 1개월시점에서 27명 (77.1%) 의환자에서완전관해를보였으며 5년생존율은 67.7% 이었다. 결론 : 항문암의방사선치료에있어방사선조사방법및범위가치료순응도에영향을미칠수있으며, X-선의회음부조사범위를줄이는방법이회음부의심각한방사선피부염을감소시킴으로써환자의치료순응도를높이는데있어적절할것으로생각된다. 핵심용어 : 항문암, 방사선치료, 피부반응 서 1974년이후항문암에대한항암방사선치료의효과와안정성이밝혀져오면서 1~3) 대부분의환자에서수술없이항암화학방사선치료로좋은치료성적을거두고있으나, 방사선치료시원발병소, 영역림프절뿐만아니라양측서혜부림프절까지치료범위에포함시키게되어회음부피부반응등의부작용발생가능성이높으며이것이치료를어렵게만드는문제로남아있다. 일반적으로방사선치료시급성피부반응을일으키는위험인자로는총방사선선량, 회당방사선선량, 방사선의종류, 조사부위의해부학적구조, 방사선치료기법, 항암약 이논문은 2008 년 9 월 29 일접수하여 2008 년 11 월 13 일채택되었음. 책임저자 : 성진실, 연세대학교의과대학연세암센터방사종양학교실 Tel: 02)2228-8095, Fax: 02)312-9033 E-mail: jsseong@yuhs.ac 론 물치료와의병행여부등을들수있다. 특히항문암등회음부조사가불가피한암을방사선으로치료할경우접힌부위의피부깊이차이에의한볼루스효과로급성피부반응이일어나기쉬우며해부학적특성상세균성감염의가능성이높아치료기간연장의주된원인이된다. 4) 거의대부분의환자에서회음부피부염등급성부작용이발생한것으로보고되었으며피부염의정도도 3등급이상인경우가많았는데 5,6) 이로인한치료기간연장으로치료효과에도부정적인영향을미치는것으로보고되었다. 7~9) 최근전산화단층촬영모의치료에의한 3차원입체조형방사선치료가보편화되면서치료계획시회음부주위의열점을줄이는것이가능해졌지만여전히제약이있다. 본연구의목적은항문암환자에대한방사선치료에서각각의방사선치료기법이회음부피부염을일으키는정도를피부독성으로인한치료중지기간과연관지어알아봄으로써적절한선량분포를얻을수있는최적의방사선치료기법을모색해보고자하는데있다. - 222 -
유세환외 2 인 : 항문암의방사선치료시방사선조사기법에따른회음부피부독성 대상및방법 1990년 1월부터 2007년 8월까지연세의료원암센터에서항문암으로항암화학방사선치료를받은환자를대상으로후향적분석을하였다. 동시항암화학치료를하지않았거나처음부터원격전이가확인된경우, 재발하여처음으로방사선치료를한경우, 치료중에치료를그만둔경우, 방사선치료방법이매우예외적인극소수에해당하는경우를제외하여총 35명의환자를분석대상으로하였다. 29명의환자가 5-Fluorouracil (750 or 1,000 mg/m 2, daily on days 1 to 5 and days 29 to 33)/Cisplatin (75 or 100 mg/m 2, on day 2 and day 30) 으로항암화학치료를받았고나머지 6명의환자에대해서는 5-Fluorouracil 단독, 5-Fluorouracil/Carboplatin 또는 5-Fluorouracil/Cisplatin/Carboplatin으로치료하였다. 연령, 성별, 병기, 시행된방사선치료기법, 치료반응, 방사선피부염, 치료중지기간등을조사하였다. 병기의분류는 AJCC (American Joint Committee on Cancer, 6 th ed., 2002) 기준을따랐다. 방사선치료는고에너지선량가속기를이용하여모든치료에있어서원발병소및영역림프절과서혜부림프절이치료범위에포함되도록하였다. 기본적으로 6 MV, 10 MV 의 X-선이사용되었고양측서혜부림프절의경우전자선전면조사를추가하기도하였다. 서혜부림프절을치료범위에포함시키게되어전반적으로조사부위가커지게되었고이에따른부작용을최소화하는과정에서새로운조사기법이시도되어왔으며, 조사부위및조사문수그리고사용된방사선의종류에따라 4가지로분류하였다. 1군 (Technique 1) 은전면과후면을동일한범위의 X-선만으로조사한방법으로서각각의 X-선조사시모두원발병소, 영역림프절, 양측서혜부림프절, 넙다리뼈머리부분이포함된방법이며총 8명이이에해당되었다. 10) 2군 (Technique 2) 은부분적으로소장에대한조사를제한할수있는방법이며원발병소와영역림프절을후면과양측의 3면 X-선조사 ( 후면은 6 MV, 양측면은 10 MV가주로사용됨 ) 와양측서혜부림프절에대한전자선조사 ( 주로 9 MeV) 를시행한경우로 13명이이방법으로치료를받았다. 3군 (Technique 3) 은부분투과차폐물을사용한 2면평행조사법 (photon thunderbird technique with partial transmission block) 이라할수있으며모두 7명이시행받은방법으로전후면을 X-선으로조사를하되원발병소와영역림프절은전후면조사에서모두포함되지만양측서혜부림프절과넙다리뼈머리등은전면조사범위에만포함되면서 전면조사시부분투과차폐물 (partial transmission block) 을사용한 X-선조사를추가하여, 원발병소에지나치게많은선량이들어가지않으면서양측서혜부림프절에충분한선량이조사되도록한방법이다. 11,12) 4군 (Technique 4) 은 electron thunderbird technique이라불리는방법으로기본적으로 3군과동일한 X-선전후면조사범위를가지지만전면조사시사용된부분투과차폐물 X-선대신양측서혜부림프절에대한전자선조사를통하여이부분에충분한선량이조사되도록한방법이며총 7명이이에해당되었다. 12,13) 상기의치료기법으로일일조사선량 1.8 Gy로일주일에 5회시행하여 41.4 45 Gy 까지조사한후원발병소또는전이성림프절에다수의조사문으로추가조사하여총선량 54 Gy 까지치료하는것을원칙으로하였으며환자의개별특성에따라치료일정및선량에약간의변화를주었다. 최근에시행한환자일수록전산화단층촬영영상을이용한치료계획을하였는데 1군에서 1명, 2군에서 8명, 3 군에서 0명, 4군에서 7명이전산화단층촬영에의한 3차원적치료계획으로치료되었다. 환자들의연령분포는 29세에서 76세로중앙값은 58세였으며, 성비는 13 대 22로여성이더많았다. 병리조직상편평상피세포암이 33명, 선암이 2명이었다. 병기별로는 stage I 2명, stageii 12명, stageiiia 7명, stageiiib 14명의분포였고총조사선량의중앙값은 54 Gy (45 64.8 Gy) 이었다 (Table 1). 동일한환자에대하여전산화단층촬영영상과 Pinnacle 3 Table 1. Patient Characteristics according to Each Technique Group Characteristics Age (year) Median Range Gender Male Female Cell type Squamous cell carcinoma Adenocarcinoma Stage I II IIIA IIIB Overall patients (n=35) 58 29 76 13 22 33 2 2 12 7 14 Irradiation technique (%) 1 (n=8) 2 (n=13) 3 (n=7) 4 (n=7) 52 44 75 3 (37.5) 5 (62.5) 7 (87.5) 12 (92.3) 7 (100) 1 (12.5) 3 (37.5) 1 (12.5) 4 (50.0) 58 33 69 6 (46.1) 7 (53.9) 1 (7.7) 1 (7.7) 4 (30.8) 2 (15.4) 6 (46.1) 58 29 76 3 (42.8) 4 (57.2) 2 (28.6) 3 (42.8) 2 (28.6) 64 42 67 1 (14.3) 6 (85.7) 7 (100) 1 (14.3) 3 (42.8) 1 (14.3) 2 (28.6) - 223 -
Fig. 1. Isodose curves of each technique group were described. The thick lines around the anal canal, regional lymph nodes and both inguinal lymph nodes are 90 107% isodose curves of prescribed dose. (A) Technique 1 contains up to both inguinal lymph nodes and femur head with parallel anteroposterior posteroanterior (AP PA) photon fields. (B) Technique 2 covers pelvic area with posterior right left 3 photon field and both inguinal electron boost. (C) Technique 3 is photon thunderbird technique with partial transmission block. (D) Technique 4 is electron thunderbird technique. Table 2. Dermatitis Scale Associated with Radiation: Common Terminology Criteria for Adverse Events version 3.0 Grade 1 2 3 4 5 Sign Faint erythema or dry desquamation Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site Death (Philips Medical System, Milpitas, USA) 을이용하여 4가지방사선치료기법에대한선량분포를재현하여나타내었다 (Fig. 1). 회음부에대한방사선피부염은 NCI (National Cancer Institute) 의 Common Terminology Criteria for Adverse Events (CTCAE) v3.0을참고하였고 (Table 2), 각군간의회음부피부염빈도비교에는 chi-square test를, 치료중지기간비교에는 ANOVA를사용하였으며생존분석에는 Kaplan- Meier 방법을이용하였다. 결과치료에따른독성으로인하여 3명의환자에서처음의치료기법으로 41.4 Gy까지유지하지못하고조기에추가치료방법으로전환하는경우가있었으나대부분의환자는처음의치료기법으로 41.4 45 Gy까지치료를받았으며진단당시의병기가높았을경우 54 Gy 조사이후에도잔존병소가크게남아있어 64.8 Gy까지추가조사한경우 - 224 -
유세환외 2 인 : 항문암의방사선치료시방사선조사기법에따른회음부피부독성 Table 3. Acute Perineal Dermatitis and Factors about Treatment Compliance according to Each Technique Group Irradiation technique (%) 1 (n=8) 2 (n=13) 3 (n=7) 4 (n=7) p-value Radiation dermatitis Grade 1 Grade 2 Grade 3 or more Interruption period (day) No interruption 2 (25.0) 4 (50.0) 2 (25.0) 20.8±13.6 1 (12.5) 2 (15.4) 8 (61.5) 3 (23.1) 8.2±10.2 7 (53.8) 4 (57.1) 17.0±15.0 1 (14.2) 5.7±5.7 0.359 0.038 0.046 도있었다. 방사선치료중 28명 (80.0%) 의환자에서 2등급이상의방사선피부염이발생하였고 10명 (28.6%) 이 3등급이상의방사선피부염을보였다. 각군의회음부방사선피부염과전체치료기간, 치료연장일수및치료연장유무등을 Table 3에나타내었다. 3등급이상의방사선피부염은 1군에서 25.0%, 2군에서 23.1%, 3군에서 57.1%, 4군에서 14.2% 발생하였다 (p=0.359). 회음부피부독성으로인한치료중지기간은 1군에서 20.8±13.6일, 2군에서 8.2±10.2일, 3군에서 17.0±15.0일, 4군에서 5.7±5.7일이었으며 (p=0.038) 치료중지기간이없었던환자의비율은 1군 12.5%, 2군 53.8%, 3군 0.0%, 4군 42.9% 이었다 (p=0.046). 치료반응은방사선치료종료 1개월시점에시행한이학적검사또는전산화단층촬영검사상종양의크기변화로확인하였으며, 치료반응은모두부분관해이상이었다. 완전관해는 1군 5명 (62.5%), 2군 13명 (100%), 3군 4명 (57.1%), 4군 5명 (71.4%) 의분포를나타내었다. 중앙추적관찰기간은 55개월이었으며전체환자의 5년생존율은 67.7% 이었다. 고안및결론방사선치료기간을줄이고자하는노력으로써치료범위를최소화하여체적효과에의한부작용을줄이고자하는노력이있었다. 전통적으로시행되어왔던조사부위를줄여환자의치료순응도를높이고자하였으며비록치료부위가감소하였지만전반적인치료성적은전통적인치료방법과비교하였을때큰차이가없는것으로보고된바있다. 14) Vuong 등은 3차원입체조형기법을항문암의방사선치료에적용하여이것이환자의치료순응도와치료성적에있어전통적인기법보다나은결과가나올수있음을보고하였다. 15) 이경우전통적인치료기법은기본적으로휴지기를갖는것을전제로하였고국소제어및생존 율에서기존의방사선조사문의수를세분화하고그크기를줄인 3차원입체조형기법이우수함을나타내었다. 병기에따라서혜부림프절의일부를치료범위에서제외하고자하는시도가있었으며 16) 대체로 T1, T2 이내의낮은병기와 N1 이하의림프절전이일경우서혜부림프절을치료범위에서제외하였는데양측서혜부림프절을모두치료범위에포함시키는선택적방사선조사기법과비교하여치료성적에큰차이가없었다. 하지만, 실제환자를치료함에있어치료실패의가능성을최소화하기위해많은경우에낮은병기에서도선택적서혜부림프절조사가시행되고있다. Vuong 등이제시한 3차원입체조형조사방법이전통적인조사방법에비해급성회음부피부염을줄이는데는우수하지만 17,18) 이경우선택적서혜부림프절조사량을 30 Gy 미만으로제한하였으므로 17) 본연구에서시행된방사선치료와직접적인비교는어렵다. 항문암의방사선치료에서원발병소, 영역림프절및양측서혜부림프절을모두포함하여하나의조사문으로조사할경우, 그리고전면, 후면조사와같이조사문의수가적고단순할경우회음부주변의볼루스효과에의한영향을제어하기어렵고넓어진조사범위만큼 3단계이상의광범위한회음부피부염이발생하기쉽다. 반면 Vuong 등이제시한 3차원입체조형기법의경우조사문의크기가상대적으로작고조사문수가많아회음부주변의볼루스효과를제어하기가용이하지만조사문간의교차부위에대한보다정밀한접근이요구되는단점이있다. 본연구에서는대부분의환자가 40 Gy 이상의선택적서혜부림프절조사를받았는데향후회음부방사선피부염과관련하여적절한선량및조사문크기에대한추가적인연구가필요하리라고본다. 대부분의환자에서원발병소에대한방사선선량은국소제어를위해 54 Gy 이상조사되었고이는국소적인방사선피부염을동반할수밖에없다. 방사선치료중치료중단은 41.4 45 Gy 조사후원발병소또는전이성림프 - 225 -
절에다수의조사문으로추가조사를하는시기가아닌처음의치료기법으로치료하는도중인경우가대부분이었다. 아직원발병소주변의회음부에처방선량 50 Gy 이상의고선량이조사가되지않아야할시기로방사선피부염에의한치료기간연장이방사선조사범위의크기와이에따른회음부열점과관계가있음을나타내준다. 항문암치료환자의치료순응도를높이기위하여항암화학치료의일정에변화를주고자하는노력이있었다. 동시항암화학방사선치료를하는것이어려울경우에한하여환자의연령및전신상태등을고려하여약제의종류와용량에변화를주기도하였으며, 19,20) 일부연구에서방사선치료기간중항암화학치료를하는것대신선행화학요법을시도한경우가있었고, 21,22) 낮은병기의경우국소절제만시행하고방사선치료만시행하는등 23) 방사선치료가항암화학치료와동시에시행되지않도록하는방안에대한모색이있었다. 이경우치료에의한독성은감소하겠지만치료성적에대한영향을확실히제시하지는못하고있다. 항암화학치료의독성과관련하여 T1 이나조기 T2에서추가적인항암제의사용이필요하지않음을보고한경우도있었다. 24) 동시항암화학방사선치료를하는경우독성에대한문제가있지만몇몇환자에서심각한회음부피부독성없이예정대로치료를마친경우가있으므로방사선조사기법에따라이러한독성을극복할수있을것으로생각된다. 치료중지기간은 1군이 20.8±13.6일로가장많았으며이는어느정도예상된결과로대부분 3차원입체조형치료장비가도입되기이전의비교적정밀하지못한방법에의한것이었고넙다리뼈머리까지포함하는넓은범위의전후면조사로인한넓은범위의회음부조사로회음부주변볼루스효과의영향을많이받기때문인것으로생각된다. 2군의경우치료중지기간이 8.2±10.2일로비교적적은것은조사문크기가상대적으로작아회음부주변볼루스영향을상대적으로덜받기때문인것으로생각되며 4군의경우치료중지기간이 5.7±5.7일로적은편이었는데이는비록적은수의환자군이기는하나주로전산화단층촬영모의치료에기반한치료기법이적용되어회음부주변열점을최소화할수있었기때문으로생각된다. 선량학적관점에서 3군의선량균일성이 4군의그것보다낫다고결론내려진연구결과가있었다. 12) 그러나이것을실제임상에적용할경우장기별선량분포를함께고려해야하기때문에좋은선량균일성이좋은치료성적을보장하는것은아니며환자의전신상태및부작용등을종합적으로판단해야할것이다. 실제로선량균일성이우수한것으로나타난 3군에서치료순응도가가장떨어졌다는 것은방사선치료의선량학적접근시보다다각적인접근이필요함을나타내준다. 과거력상골반부위에수술을받았을경우소장을비롯한하부소화관의부작용이문제가될수있으므로소장의일부를조사범위에서제외할수있는 2군의방법이적합하겠다. 25) 단, 2군의경우다른기법과달리장골림프절에대한일련의고른방사선조사가되지못하는단점이있으므로향후항문암환자의방사선치료시보다세분화된접근을하여적절한치료기법을선택하는것이필요할것이다. 항문암의방사선치료시고려해야할점으로선량분포, 조사부위의깊이, 치료부위, 에너지등이있겠으며, 결국최적의항문암방사선치료는원하는부위에균일한선량분포를이루고회음부피부염등부작용및치료중지기간을최소화하는것이다. 2군에서는원발병소와서혜부림프절에이르는경로가차단되어있고 4군은전자선을함께사용하게되어선량분포의균일성에서 X-선만사용했을때보다조금떨어진다. 12) 그러나 3단계이상의방사선피부염은상대적으로적었고치료중지기간도적었다. 급성피부반응의관점에서 X-선의회음부조사범위를줄이고전자선으로서혜부림프절을조사하거나전산화단층촬영모의치료를이용하는방법이회음부주변볼루스효과영향을줄이고환자의치료순응도를높이는데있어적절할것으로생각된다. 본연구에서는대상환자수가적고각군환자들의회음부에조사된 x-ray 의조사범위에관한세부적인분석이없었으나향후이부분에대항보완이필요하겠으며조사문크기나조사문간교차의영향을덜받고불필요한회음부선량을줄이며동시통합추가 (simultaneous integrated boost) 기법에의해방사선치료기간의단축도가능한시스템개발이필요할것이다. 참고문헌 1. Nigro N, Vaitkevicius V, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974;15:354-356 2. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: Results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15: 2040-2049 3. Chung WK, Kim SK, Lee CG, Seong J, Kim GE. Concurrent chemoradiotherapy results in patients with anal cancer. J Korean Soc Ther Radiol 1994;12:99-107 4. Vuong T, Franco E, Lehnert S, et al. Silver leaf nylon - 226 -
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Abstract Perineal Skin Toxicity according to Irradiation Technique in Radiotherapy of Anal Cancer Sei Hwan You, M.D., Jinsil Seong, M.D., Ph.D. and Woong Sub Koom, M.D. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea Purpose: Various treatment techniques have been attempted for the radiotherapy of anal cancer because of acute side effects such as perineal skin reactions. This study was performed to investigate an optimal radiotherapy technique in anal cancer. Materials and Methods: The study subjects included 35 patients who underwent definitive concurrent chemoradiotherapy for anal cancer in Yonsei Cancer Center between 1990 and 2007. The patients clinical data, including irradiation technique, were reviewed retrospectively. The primary lesion, regional lymph nodes, and both inguinal lymph nodes were irradiated by 41.4 45 Gy with a conventional schedule, followed by a boost does to the primary lesion or metastatic lymph nodes. The radiotherapy technique was classified into four categories according to the irradiation field and number of portals. In turn, acute skin reactions associated with the treatment interruption period were investigated according to each of the four techniques. Results: 28 patients (80.0%) had grade 2 radiation dermatitis or greater, whereas 10 patients (28.6%) had grade 3 radiation dermatitis or greater during radiotherapy. Radiation dermatitis and the treatment interruption period were relatively lower in patients belonging to the posterior-right-left 3 x-ray field with inguinal electron boost and in patients belonging to electron thunderbird techniques. The interruption periods were 8.2±10.2 and 5.7±7.7 for the two technique groups, respectively. Twenty-seven patients (77.1%) went into complete remission at 1 month after radiotherapy and the overall 5 year survival rates were 67.7%. Conclusion: Field size and beam arrangement can affect patients' compliance in anal cancer radiotherapy, whereas a small x-ray field for the perineum seems to be helpful by decreasing severe radiation dermatitis. Key Words: Anal cancer, Radiotherapy, Skin reaction - 228 -