Journal of Breast Cancer ISSN J Breast Cancer 2007; June 10 (2): ORIGNAL ARTICLE 조기유방암환자에서 CMF 항암제와방사선동시치료의독성 염차경ㆍ김현아 1 ㆍ문병인ㆍ최국진ㆍ최금자ㆍ

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1 Journal of Breast Cancer ISSN J Breast Cancer 2007; June 10 (2): ORIGNAL ARTICLE 조기유방암환자에서 CMF 항암제와방사선동시치료의독성 염차경ㆍ김현아 1 ㆍ문병인ㆍ최국진ㆍ최금자ㆍ서현숙 2 ㆍ최혜영 3 이화여자대학교의과대학외과학교실, 2 방사선종양학과학교실, 3 영상의학과학교실, 1 원자력병원외과 Toxicity of Concurrent Adjuvant CMF Chemotherapy and Radiotherapy in Patients with Early Breast Cancer Cha-Kyong Yom, Hyun-Ah Kim 1, Byung-In Moon, Kuk-Jin Choe, Kum-Ja Choi, Hyun-Suk Suh 2, Hye-Young Choi 3 Departments of Surgery, 2 Therapeutic Radiology & Oncology and 3 Radiology, College of Medicine, Ewha Womans University, Seoul; 1 Department of Surgery, Korea Cancer Center Hospital, Seoul, Korea Purpose: Many patients with early stage breast cancer are currently being treated with both adjuvant chemotherapy (CT) and radiotherapy (RT). We performed this study to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5-fluourouracil (CMF) CT and RT for treating early breast cancer patients. Methods: Between January 2000 and December 2005, 97 patients with stage I or II invasive breast carcinoma were treated with breast-conserving surgery, and they received 6 monthly cycles of classic oral chemotherapy with CMF. Within day 7 of cycle 1, the patients started 3 dimensional conformal RT (3DCRT) with a stadard dose, followed by a boost. We used the Common Terminology Criteria for Adverse Events v 3.0 to score the level of acute toxicity for CT. The adverse effects of RT were graded according to the Radiation Therapy Oncology Group criteria. Results: The mean age of the patients was 45.8 yr (range: 30-64). The most common toxicity was nausea and leukopenia. The dose of chemotherapy was reduced to 80% of the planned dose for 6.2% of the patient. CT was disrupted for 4.1% of the patients. RT was not disrupted for any patient. Grade 3 and 4 neutropenia occurred in 41 (42.3%) patients, but only one patient needed hospitalization due to fever. Grade 3 skin lesions developed during or shortly after RT in 10.7% of the patients. Radiation penumonitis was noted in 15.5% of the patients. The median follow-up time was 38 months. There was no local recurrence and 2 (2.08%) distant metastases during follow-up. Conclusion: From the results of our study, we conclude that the concurrent administration of adjuvant CMF CT and RT is associated with a low risk of serious toxicity and this is an acceptable adjuvant regimen for patients with early stage breast cancer. (J Breast Cancer 2007;10:147-52) Key Words : Concurrent, CMF chemotherapy, Radiotherapy, Toxicity 중심단어 : 동시성, CMF 항암화학요법, 방사선치료, 독성 서 진단기술이발달하고건강에대한관심도가증가함에따라조 책임저자 : 문병인 서울시양천구목동 911-1, 이화여자대학교의과대학외과 Tel: , Fax: mbit@ewha.ac.kr 접수일 : 2007 년 1 월 16 일게재승인일 : 2007 년 4 월 9 일 * 본연구내용은 2004 년 10 월제 56 차추계대한외과학회에서구연되었음. 론 기에유방함을발견하여유방보존수술을받게되는환자도증가하고있다. 유방보존술은조기유방암의표준치료법으로인정되어왔으며, 유방보존수술후국소재발을감소시키고생존율을향상시키기위한보조적치료로항암화학요법 (Chemotherapy) 과방사선요법 (Radiotherapy) 을시행하고있다. 그러나, 수술후항암화학치료와방사선치료의적절한치료시작시기와그순서는아직확실하게정립되지않고있다.(1-4) 두보조요법의치료방법은연속적 (sequential), 동시 (concurrent), 또는교차적 147

2 148 Cha-Kyong Yom, et al. (alternating) 으로일명 sandwich therapy의방법, 즉항암요법의과정중간에방사선치료를행하는것으로계획할수있다. 대부분의센터에서는부작용의범위와크기를제한하기위해서연속적치료법을선호해왔다.(5) 하지만항암화학요법이후로방사선치료가늦어진다면국소재발의위험이증가할것이며, 방사선치료후로항암화학치료가늦어질경우는전신전이의가능성이높은것으로알려져있다.(6-10) 이처럼방사선요법이지연되는것보다는항암화학요법이지연될때더심각한결과를나타낼수있으므로항암화학요법이후로방사선요법시행하는연속적치료방법이일반적이었다.(11) 이론적으로는이두가지치료를동시에시행하는것이유방암의국소재발과전신전이를감소시킬수있는가장효과적인방법이라고기대할수있으나, 이경우급성독성이증가할가능성이있다.(12-14) 이러한급성독성의발생을피하기위하여두가지보조요법을동시에시행할경우항암제를표준용량보다감량하여투여하는경우가많은데이러한항암제의감량투여는미세병소에대한치료효과가감소시킨다.(7) 또한방사선조사량을감량하여치료를시행하는경우도마찬가지로국소재발에대한위험도를고려해야한다. 따라서본연구는수술후보조치료를시행함에있어최대의효과를얻고부작용을증가시키지않는최적의치료양식을알아보기위하여유방보존수술을받은조기유방암환자들을대상으로표준용량의 cyclophosphamide, methotrexate, and 5-flououracil (CMF) 항암제치료와표준조사량의방사선치료를동시에시행한경우의급성독성의발생에대해임상결과를비교분석하였다. 방법 병변으로부터 2 cm 의절제연을확보하여수술을시행하였고, 병변절제연의음성여부는수술중에동결절편을통해확인하였다. 동결절편시행시병변절제연에서암세포나비정형세포가남아있는경우추가절제를실시하고다시위의과정을반복하여절제연이동결절편상정상세포소견을보일때까지위의과정을반복한후수술을종결하였다. T1 에해당하는 2 cm 이하의작은병변일경우나수술전방사선검사에서액와부전이가의심되지않는환자에서는감시림프절생검을확인하여전이음성인경우액와부림프절절제를생략하였다. 감시림프절은수술전콜로이드방사성동위원소 (colloidal radioisotopes) 를유륜하주입 (subareolar injection) 하여림프신티그래피를시행하고수술중감마선검출기를이용하여탐색하였다. 종양의크기가큰경우, 초음파나 MRI 등수술전검사에서액와부림프절전이가의심되는경우와감시림프절생검에서양성을보인경우에는 level I과 level II 범위까지액와부림프절곽청술을시행하였다. 3. 항암화학요법항암요법은수술부위가회복되는수술후 3주에시작하는것을원칙으로하였다. Cyclophosphamide는 100 mg/m 2 를1-14 일경구투약하였고, methotrexate 40 mg/m 2 과 5-fluorouracil 600 mg/m 2 를 1일과 8일째정맥투여하여, 28 일간격으로 6회시행하였다. 항암제치료의각주기마다전혈검사 (Complete blood count, CBC) 와간효소수치검사 (aspartate transminase & alanine transaminase) 를시행하였다. 항암제독성은 Common Terminology Criteria for Adverse Events v 3.0 (CTCAE) 을기준으로평가하였다. 1. 대상 2000년 1월부터 2005년 12 월까지이화여자대학교목동병원에서원발성유방암으로진단을받은환자중유방보존술을받은후항암화학요법과방사선치료를동시에시행한환자를대상으로시행하였다. 모든환자는수술후보조치료를시행하기전에항암화학요법과방사선치료의동시병용에대하여충분한설명을하였으며이에동의한환자들을대상으로치료를시행하였다. 대상환자의병기는 stage I, II로제한하였으며호르몬요법의시행여부에관계없이포함시켰다. 병리학적소견에서일반형침윤성관암종 (infiltrative ductal carcinoma, not otherwise specified) 과수질암종 (medullary carcinoma), 점액암종 (mucinous carcinoma) 등의특수형관암종이포함되었다. 2. 수술모든환자는유방보존수술을시행받았으며유방병변절제시 4. 방사선치료항암치료의첫 cycle 시작후일주일이내에방사선치료를시작하는것을원칙으로하였고, 모든환자에서모의치료 (Simulation) 및흉부컴퓨터단층촬영을시행하였으며, 치료는 3차원입체조형방법을변형하여한조사각 (beam angle) 에서의치료부위를여러개의분할조사야 (segmented field) 를나누어각각의선량을다르게하는변형된 3차원입체조형방법 (three dimensional conformal radiotherapy, 3DCRT) 을사용하였다. 방사선치료는림프절전이가없는경우에는유방에 50.4 Gy를 28 분할하여조사하였고, 림프절전이가있거나림프관침범양성인경우는유방과동측쇄골상부림프절 (supraclavicular node) 을포함하여 50.4 Gy를조사하였다. 이후두경우모두수술시삽입된클립과수술흉터를포함하여원발종양주위에 10 Gy 를 5회에걸쳐추가조사 (booster) 를시행하였다. 방사선성폐렴 (Radiation pneumonitis) 의평가는방사선치료종료 4주후흉부방사선촬영을

3 Toxicity of Concurrent CMF CT and RT 149 시행하여확인하였다. 방사선치료와관련된독성은 Radiation Therapy Oncology Group criteria (RTOG) 를사용하여평가하였다. 5. 통계학적분석 통계는 SPSS 11.5판을사용하여 Chi-square test를이용하였으며결과는 p 값이 0.05 이하일때통계적으로유의하다고판정하였다. 1. 환자의임상병리학적특징 결 총 97 명의환자가포함되었으며모든환자는여성이었다. 환자의연령, 병기, 림프절전이상태, 호르몬수용체, 조직형등은 Table 1에요약하였다. 모든환자들은유방보존술식을시행받았다. 수술중병변절제연의동결절편검사에서 66 명 (68.0%) 이음성을보여수술을종결하였으며, 나머지 31명 (32.0%) 의환자에서는동결절편상비정형세포나암세포가발견되어추가절제를시행하였고, 다시시행한절제연의동결절편검사상음성소견을보여수술을종결하였다. 절제연의영구조직검사결과에서는관상피내암이나침윤성관암의소견은없었으며 2예 (2.1%) 에서보통형 과 Table 1. Clinicopathologic characteristics of the patients No. of patients % Mean age 45.8±7.7 Age > Nodal status Negative Positive Mean no. of removed nodes 20.4±9.2 Stage I IIA IIB Histology Infiltrative ductal carcinoma, NOS Mucinous carcinoma Medullary carcinoma Malignant cystsarcoma phylloides Hormone receptor status ER (+) and/or PR (+) ER (-) and PR (-) Operation Wide excision with SNB with AND NOS, not otherwise specified; ER, Estrogen receptor; PR, Progesterone receptor; SNB, Sentinel node biopsy; AND, Axillary node dissection. 관상피증식증 (usual ductal hyperplasia, UDH) 이있었다. 2. 항암요법독성 수술부위상처치유지연등의문제로수술후평균 26.6일에항암요법을시작하였다. 가장흔히발생한부작용은오심으로 49 예 (50.5%) 에서나타났으며, 구토가 26예 (26.8%) 였고, 식욕부진이 22예 (22.7%), 이밖에도탈모증이나타난경우가 15 예 (15.5%), 변비를호소하는경우가 12 예 (12.4%), 두통이 11 예 (11.3%) 에서나타났다. 수액치료등보조적치료가필요한 Grade 3 증상은 5예 (5.2%) 에서만관찰되었다 (Table 2). Grade 3의호중구감소증이 41예 (42.3%) 에서나타났으나, 증상이동반되어입원이필요한경우는 2예 (2.1%) 뿐이었다. Grade 3 이상으로 aspartate transminase (AST) 가증가한경우는 1예 (1.03%) 였고 alanine transaminase (ALT) 는 3예 (3.1%) 였다. Grade 4의 AST, ALT증가는 1예로 B형간염보균자에서나타났으며, 5일간입원하여보존적치료후회복되었다. 이밖에호중구감소증을제외한모든경우에있어서 Grade 4의손상은나타나지않았다. Grade 4의호중구감소증이나타난환자는 11 예 (11.3%) 로이중열성호중구감소증 (febrile neutropenia) 으로입원치료를요하는환자는 1 예 (1.03%) 뿐이었다 (Table 3). 항암화학요법중부작용으로치료가지연된경우는 43예 (43.8%) 로이중39예 (39.8%) 가호중구감소증이그원인이었으며모두 7일정도경과관찰후회복되었으며 Grade 3 이상의호중구감소증에서는과립세포군촉진인자 (Granulocye-colony stimulating factor, G-CSF) 를사용하여백혈구수치가정상화된후항암요법을시작하였다. 항암제용량을감량한경우는 6예 (6.2%) 였으며, 이중용량의 80% 미만으로투여한예는없었다. 항암화학요법을중단한경우는 4예 (4.1%) 로우울증 (major depression) 으로중단한 1예, 항암요법에의한어지러움 (dizziness) 으로낙상한경우에서어지러움이지속되어항암요법을중단한 1예, Grade 4의백혈구감소증에서 1예, 항암요법후발생한급성백혈병의 1예등모두 4예 (4.1%) 에서항암요법을중단하였다. Table 2. Chemotherapy related toxicity, n (%) Grade Adverse event Anorexia 11 (11.3) 8 (8.2) 3 (3.1) 0 Nausea 37 (38.1) 11 (11.3) 1 (1.03) 0 Vomiting 16 (16.5) 9 (9.3) 1 (1.03) 0 Diarrhea 3 (3.1) Constipation 8 (8.2) 4 (4.1) 0 0 Headache 11 (11.3) Stomatitis 5 (5.2) 3 (3.1) 0 0 Alopecia 11 (11.3) 4 (4.1) 0 0

4 150 Cha-Kyong Yom, et al. Table 3. Chemotherpy related hematologic toxicity, n (%) Table 4. Radiation related toxicity, n (%) Grade Adverse event Grade Adverse event Leukocyte abnormality 16 (16.5) 54 (55.7) 27 (27.8) 0 ANC abnormality 14 (14.4) 34 (35.1) 30 (30.9) 11 (11.3) AST abnormality 58 (59.8) 5 (5.2) 0 1 (1.03) ALT abnormality 60 (61.9) 15 (15.5) 2 (2.06) 1 (1.03) ANC, absolute neutrophil count; AST, aspartate transminase; ALT, alanine transaminase. 3. 방사선요법독성 항암요법을시작후평균 5.8 일이내에방사선요법을시작하였다. 방사선의평균조사량은 60.1 Gy ( 범위 : Gy) 였고, 평균분할횟수는 32회 ( 범위 : 28-33회 ) 였으며각각의분할조사량은 1.9 Gy였다. 병변부위의유방에방사선치료를시행한환자는 59 명 (60.8%) 이었고, 쇄골상부를포함하여방사선치료를받은환자는 38명 (39.2%) 이었다. RTOG의기준으로방사선치료를받은부위의피부손상정도를평가한결과에서 Grade 3의손상은 9예 (9.3%) 에서관찰되었고, 대부분 Grade 2 이하의경미한발적정도만나타났으며 (Table 4), 방사선치료의부작용으로인하여방사선투여가중지된경우는없었다. 단순흉부촬영으로확인된방사선성폐렴 (radiation pneumonitis) 은 15 예 (15.5%) 로보고 되었고, 이중쇄골상부를포함하여방사선조사를받은환자가 11 예 (11.3%) 로대부분을차지하였으며, 경미한기침이나객담을동반하여마취성진해제 (narcotic antitussive) 를투여한경우는 4 예 (4.1%) 가있었으나, 호흡곤란또는스테로이드나산소치료를필 요로하는 Grade 2 이상의부작용을동반한경우는없었다 (Table 4). 방사선유도성식도염 (radiation induced esophagitis) 이의심되어스테로이드치료를받은환자가 1 예 (1.03%) 보고되었다. 4. 추적관찰 1예에서이민으로인해추적소실되어총 96 명의추적관찰결과, 추적관찰기간의중간값은 38 개월 ( 범위 : 19-74개월 ) 로추적기간내에국소재발은없었으며원격전이는 2예가보고되었다. 추적기간동안 94명 (97.9%) 의환자가생존하였으며, 사망한경우는원격전이에서보고된 2예 (2.08%) 로 Stage I 환자에서수술 14 개월후, 폐전이및뇌전이발견되고 24 개월에사망한경우와, 마찬가지로 Stage I 환자에서수술 42 개월후, 폐, 간전이가발견되고 62 개월에다발성전신전이로사망한경우였다. 고 조기유방암환자에서유방보존수술후 CMF 항암요법과방 찰 Kin toxicity, n (%) 63 (64.9) 25 (27.8) 9 (9.3) 0 (0.0) Radiation peumonitis, 11 (11.3) 4 (4.1) 0 (0.0) 0 (0.0) n (%) 사선치료의동시시행에대한시도가이미여러연구에서보고되었지만대부분은항암요법의기간내에방사선치료의기간이어느정도중복 (overlap) 되는경우를동시치료로간주하였거나, 또는항암제나방사선조사량을감량하여동시치료를시행한경우가대부분이었다. 본연구에서는항암치료의시작 7일이내에방사선치료를시작하여 6회의항암요법기간내에방사선치료를완결하였기때문에좀더엄격한의미에서동시성치료방법 (concurrent therapy) 이라고할수있으며, 또한, 치료용량의감량없이표준용량의 4주간격경구 CMF 항암요법과표준조사량의방사선치료를시행하여결과를분석하였으므로더욱의미가있다고볼수있다. 본연구결과에따르면호중구감소증으로항암화학요법이지연된경우가 39.8% 에서보고되었지만, 모두보존적치료로회복되어전체치료주기에큰영향을미치지않고치료를완결할수있었으며, 또한, Grade 4 이상의독성은 12 예 (12.06 %) 에서보고되었으나항암요법을중단한경우는 4예 (4.1%) 에서만보고되었다. 항암제독성으로인하여항암제용량을감량하여투여한경우가 6.2% 이었으나대부분의환자가표준용량을투여하였다. CMF 단독요법에서의결과를비교해보면 Tada 등 (15) 의자료에서호중구감소증등의부작용으로 1주일이상항암요법이지연된경우가 54.2% 였고, 이중 20.8% 에서는 28일이상항암요법이지연되었으며, 29.2% 에서용량을감량하였다. 모발손실 (hair loss) 에서도본연구에서는 15.4% 에서모발손실이있었으나 CMF 단독요법에서는오히려 31.8% 나보고되어동시성치료의안전성을뒷받침하고있다. 본연구에서는방사선성폐렴의빈도가 15.5% 로비교적높게나타났으나대부분증상없이지나간경미한정도로전체치료에는영향을주지않았다. Kimsey 등 (16) 은유방보존술후방사선요법시방사선조사후 2-6개월이지나면약 1% 정도에서폐렴증상이나타난다고하였으며, Taghian 등 (17) 은특히 taxane계열의약물요법을병용했을경우방사선폐렴의빈도가 10% 이상에서나타나지만증상의발현은방사선요법과약물요법의시행순서와무관하다고보고하였다. 수술후액와부위의재발위험이높은경우, 즉림프절피막이침윤되었거나불완전하게절제되었을경우에는방사선치료시액와부위를포함하여치료하고액와에서 4개이상의림프절전이가발견되었거나액와첨부에전이가된경우에는쇄골상부림프절을치료하는것으로알려져있다.(18)

5 Toxicity of Concurrent CMF CT and RT 151 Lingos 등 (19) 은 CMF 항암요법과쇄골상부를포함한방사선치료를동시에시행할경우폐렴 (pneumonitis) 의위험률이증가한다고하였다. 본연구에서는쇄골상부를포함하여방사선치료를시행한경우 38 예중 11예 (28.9%) 에서방사선성폐렴이보고되었으며, 병변부위의유방에만방사선조사를시행한경우에는 59예중 4예 (6.8%) 에서방사선성폐렴이확인되어쇄골상부를포함하여방사선조사를시행할경우방사선성폐렴의빈도가유의하게증가하는소견을보였다 (p=0.003). I-II기유방암환자를대상으로표준용량의 CMF 항암화학요법과동시에방사선요법을감량하여시행하였던다른연구에서 53 개월의추적기간동안국소재발은 4%, 원격전이는 18% 로보고되었으며,(4) 본연구에서는 50% 의수술이 2003년도이후에시행되었기때문에 5년생존율을비교하기에는무리가있지만, 38 개월의짧지않은추적관찰기간동안 97.9% 의생존율과, 2.08 % 의원격전이, 0% 의국소재발의탁월한결과를보이고있다. 유방보존술후유방내에서재발할때에는약 65-80% 에서원발병소가있었던주변에서발생하며유방절제후병리소견에서도대부분의다발성병소가원발병소주변 2 cm 이내에서발견되고있기때문에유방전체에방사선조사를한후추가방사선량을절제병소중심으로조사하면유방내국소재발률을감소시킬수있다고한다. 그러나이러한추가방사선조사로인해유방연조직의섬유화, 부종, 경화등이심해질수있고미용적효과가감소되는부작용을초래하기도한다.(18) 본연구에서는모든환자에서추가방사선치료를시행하였으나이로인해심각한부작용이나타난경우는없었으며, 이러한결과는방사선치료시에변형된 3차원입체조형방법 (3DCRT) 을사용하여일반적인 3DCRT 보다환자의유방의크기및모양의차이에따라발생할수있는치료범위내불균질선량 (dose heterogenity) 을줄이고폐및주위정상조직으로들어가는방사선량을최소화한것에기인한다고할수있다. 본연구에서는포함되지않았지만, 유방보존수술에있어서미용적인측면에대한평가는매우중요하며간과되어서는안된다. 이미여러연구에서 CMF 항암요법과방사선치료의동시시행이연속적치료보다미용적인치료결과에악영향을미친다고보고하고있고, Abner 등 (20) 은표준용량의 CMF 와방사선치료를동시에시행할경우미용적결과가악화된다는보고를하였다. 하지만이러한견해는일반적인것이아니며좀더체계적이고이상적인판단기준으로평가하는것이필요하다. 항암화학요법과방사선치료의동시시행의큰장점은치료기간을단축시켜환자에게편의를제공하여치료에대한환자순응도 (compliance) 를높일뿐만아니라, 환자가수술이전의일상생활로돌아갈수있는시간도빨라진다는것이다. 그러므로환자의사회적단절 (social disruption) 에대한두려움도감소될수있다. 이밖에도치료적측면에서의이점은두치료요법에대한저항성의기전이다를때, 항암요법에저항성이있는세포 (chemoresistant cells) 가방사선치료에의해제거될수있으며, 마찬가지로방사선요법에저항성이있는세포 (radioresistant cells) 가항암치료에의해제거될수있는가능성이있다는것이다.(21) 따라서항암치료와방사선치료의동시시행은 cell killing을증가시키고이러한경우연속적인치료 (sequencial treatment) 보다동시치료 (concurrent treatment) 가국소재발에있어서큰효과를나타낸다는사실은이미두경부암을포함한여러부위에서입증되었다.(22, 23) 결론유방보존수술후표준용량의 CMF 화학요법과방사선치료의동시시행은뚜렷한독성의증가없이치료기간을단축시킬수있는안전하고적합한 (feasible) 방법으로, 국소재발의빈도를감소시키고원격전이를방지하는치료적이점뿐아니라, 일상생활로의조기복귀를가능하게하여삶의질을향상을가능하게한다는점에서조기유방암환자의안전하고효과적인치료방법이라고할수있으며앞으로조기유방암환자들에게표준치료요법 (Standard therapy) 으로권장할만하다. 참고문헌 1. Harris JR, Halpin-Murphy P, McNeese M, Mendenhall NP, Morrow M, Robert NJ. Consensus statement on postmastectomy radiation therapy. Int J Radiat Oncol Biol Phys 1999;44: Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337: Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Eng J Med 1997;337: Dubey A, Recht A, Come SE, Gelman RS, Silver A, Harris JR, et al. Concurrent CMF and radiation therapy for early stage breast cancer: results od a pilot study. Int J Radiat Oncol Biol Phys 1999;45: Fiets WE, van Helvoirt RP, Nortier J, van der Tweel I, Struikmanse H, Acute toxicity of concurrent adjuvant radiotherapy and chemotherapy (CMF or AC) in breast cancer patients: a prospective, comparative, non-randomised study. Eur J Cancer 2003;39:

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy