online ML Comm Head and Neck Korean J Otorhinolaryngol-Head Neck Surg 2016;59(3):222-8 / pissn 2092-5859 / eissn 2092-6529 http://dx.doi.org/10.3342/kjorl-hns.2016.59.3.222 Treatment Outcomes and Prognostic Factors of Nasopharyngeal Carcinoma Woo Sung Park, Sun Wook Kim, Yong Bae Ji, Chang Myeon Song, Chul Won Park, and Kyung Tae Department of Otorhinolaryngology-Head and Neck Surgery, Hanyang University College of Medicine, Seoul, Korea 비인강암의치료성적및예후인자 박우성 김선욱 지용배 송창면 박철원 태경 한양대학교의과대학이비인후 - 두경부외과학교실 Received July 8, 2015 Revised August 31, 2015 Accepted September 10, 2015 Address for correspondence Kyung Tae, MD Department of Otorhinolaryngology- Head and Neck Surgery, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea Tel +82-2-2290-8585 Fax +82-2-2293-3335 E-mail kytae@hanyang.ac.kr Background and ObjectivesZZNasopharyngeal carcinoma is an uncommon disease that is usually found in the advanced stage becuase its anatomical location makes early detection difficult. Radiation therapy or concurrent chemoradiation therapy is mainstay for treatment of nasopharyngeal carcinoma. We evaluated clinical characteristics and treatment outcomes of nasopharyngeal carcinoma and assessed prognostic factors related to survival. Subjects and MethodZZWe retrospectively reviewed medical records of 87 patients who were treated for nasopharyngeal carcinoma from 1994 to 2013. Clinical characteristics, pathologic type, stage, treatment modality, recurrence and survival were investigated. ResultsZZThe mean follow-up period was 66.7 (12-232) months. Recurrence rates were not significantly different between the radiation therapy group and combined chemoradiation groups in the early stage (27.3% vs. 21.6%, p=0.644) and the advanced stage (21.4% vs. 31.3%, p=0.496). Five-year overall survival and disease free survival rate was 74.0% and 58.9%, respectively. Five-year overall survival rate of the combined chemoradiation therapy group was significantly lower than that of the radiation therapy group (64.4% vs. 94.1%, p=0.001). Distant metastasis was significantly correlated with survival in multivariate analysis. ConclusionZZIn this study, the five-year overall survival rate was better in the radiation therapy group than in the combined chemoradiation group. This might be related to the fact that advanced stage disease was more common in the combined chemoradiation group. Further studies with larger study samples and longer follow-up are necessary to verify these results and determine optimal modalities for the treatment of nasopharyngeal carcinoma. Korean J Otorhinolaryngol-Head Neck Surg 2016;59(3):222-8 Key WordsZZChemotherapy ㆍ Concurrent chemoradiation ㆍ Nasopharyngeal carcinoma ㆍ Prognosis ㆍ Radiation therapy. 서론 비인강암은비인두의상피세포에서발생하는악성종양으로발생빈도는국지적으로달라중국남부, 타이완, 싱가포르등지에서발생빈도가높다. 중국일부지방에서는인구 100000 명당 26.8명에달하는유병률을보이는반면, 1) 세계대부분의다른지역에서는인구 100000명당 1명이하의유병률을보이 는드문질환으로, 다른인종에비해아시아계에서유병률이높다. 2) 국내에서는전체악성종양의약 0.2% 를차지하며인구 100000명당 5.6명의유병률을보이며, 남성에서여성보다약 3 배가량많이발생하는것으로조사되었다. 3) 비인강암은두경부영역의다른암종과는병기결정, Ebstein-Barr virus(ebv) 와의관련성, 치료방법등에서차이를 222 Copyright 2016 Korean Society of Otorhinolaryngology-Head and Neck Surgery
Treatment Outcomes of Nasopharyngeal Carcinoma Park WS, et al. 보이는질환으로, 경부또는전신전이가조기에발생하는비교적공격적인두경부암이다. 4) 원발부위의해부학적위치상조기발견이어려워진행된상태로늦게진단되는경우가많아예후가좋지않으며, 해부학적위치상수술적접근이어렵고방사선치료반응이좋아일차적인치료로서방사선치료가많이선택된다. 5) 방사선치료후 5년생존율은 32~62% 정도로보고되고있지만, 6) 국소재발과원격전이가흔하다. 최근에는동시항암화학방사선치료 (concurrent chemoradiation therapy) 로좋은치료결과를얻었다는보고들이있으며, 7-11) 반면에치료결과에유의한차이를얻지못했다는보고들역시있다. 12,13) 저자들은비인강암환자를대상으로, 임상양상을알아보고여러치료방법에따른치료성적을비교하고자하였으며, 이를통해우리나라비인강암환자에서의예후인자및임상적특성을파악하여향후치료에도움을얻고자본연구를시행하였다. 대상및방법 1994년부터 2013년까지비인강암으로진단받고치료받은 139명의환자중의무기록을통한조사가가능하였고최소추적관찰기간이 12개월이상이었던 87명의의무기록을후향적으로조사하였다. 환자의나이및성별, 주증상등의임상적특성, 병리학적소견, 병기와치료방법, 치료의결과및예후인자등을분석하였다. 병리학적분류는 WHO 분류를이용하였으며, 병기는 7th AJCC 분류에의한 TNM 병기를적용하였다. 병기에따른재발률및재발양상과구제치료의방법에대해조사하였고, 단독방사선치료군과여러방사선항암화학병합요법군등의치료방법에따른생존율과재발률및생존율과연관된인자를분석하였다. 또한 AJCC 분류에따라 I/II 병기의조기암과, III/IV 병기의진행암으로나누어치료법에따른재발률을비교하였다. 생존율분석을위해 Kaplan-Meier 법을이용하였으며, 치료방법별환자군의특성비교를위하여 Mann-Whitney U test 및 chi-square test를이용하였다. 각예후인자별생존율차이의유의성확인을위해 Log-Rank법및 Cox regression analysis법을이용하였으며, 환자군간치료법선택및치료법에따른재발률의차이비교를위해 Pearson s chi-square test 를이용하였다. 통계학적인분석은 SPSS(version 22.0 for windows; SPSS Inc., Chicago, IL, USA) 를사용하여유의수준이 0.05 미만인경우를통계학적으로유의한것으로판정하였다. 결과 전체대상환자 87예의임상적, 병리적특징을 Table 1에요약하였다. 평균연령은 51.3 세였으며, 평균추적관찰기간은 66.7 (12~232) 개월이었다. 성별은남 : 녀가 58:29으로남성이많았다. 원발부위는비인두의측벽 (Rosenmuller fossa) 이 63예 (72.4%) 로가장많았다. 병리조직학적분류상미분화암 (WHO type III) 이 67예 (77.0%) 로가장많았으며, 병기별분포는제I, 제II, 제III, 제IV 기가각각 7예 (8.0%), 34예 (39.1%), 23예 (26.4%), 23예 (26.4%) 의분포를보였다. 비인두조직에서 EBV 감염여부에대한검사는 10예에서시행하였으며, 6예 (60.0%) 에서양성소견을보였다. AJCC 병기와 M 분류에서방사선단독치료군과병합치료군간에유의한차이를보였다 (Table 1). 내원당시호소한주증상으로는경부종괴가 50예 (57.5%) 로가장많았으며, 이충만감또는이통이 18예 (20.7%), 코막힘또는코피가 14예 (16.1%), 안구운동마비또는안면감각마비등의중추신경계증상이 4예 (4.6%) 에서관찰되었다. 초치료로는총 87예중 36예에서방사선단독치료를시행하였다. 51예에서병합치료를시행하였는데, 34예에서동시항암화학방사선치료를, 5예에서유도항암화학요법후방사선치료를, 12예에서유도항암화학요법후동시항암화학방사선치료를시행하였다. 방사선치료로는원발부위의병소크기및전이된경부림프절의위치등을고려한통상적방사선조사치료를시행하였다. 전체환자군에게조사된방사선량의평균은 6810 cgy였으며, 방사선단독치료군 (6789±354 cgy) 과항암화학방사선병합치료군 (6826±361 cgy) 간의방사선조사량에유의한차이는없었다 (p=0.466). 동시항암화학방사선치료의경우, 항암제로는 cisplatin 을사용하였으며, 100 mg/m 2 를 3주마다투여하는방법이나 (18 예 ) 매주 30 mg/m 2 씩을투여하는방법 (16 예 ) 이사용되었다. 유도항암화학요법으로는 cisplatin 70 mg/ m 2, docetaxel 70 mg/m 2, 5-fluorouracil 800 mg/m 2 를 3주간격으로 2회투여하는방법 (12예 ) 또는 cisplatin 60 mg/m 2 와 5-fluorouracil 1000 mg/m 2 를 3주간격으로 2회투여하는방법이 (5예) 사용되었으며, 이후방사선치료또는동시항암화학방사선치료를시행하였다. 유도항암화학요법후동시항암화학방사선치료를하는경우에는방사선치료와동시에동시에 docetaxel 20 mg/m 2 와 cisplatin 20 mg/m 2 를일주일에 1회투여하였다. I, II 병기와 III, IV 병기로나누어병기에따른치료법을비교해보았을때, I, II 병기에서는방사선단독치료가 53.7% (22/41) 에서, 병합치료가 46.3%(19/41) 에서시행되었으며, III, www.jkorl.org 223
Korean J Otorhinolaryngol-Head Neck Surg 2016;59(3):222-8 IV 병기에서는각각 30.4%(14/46) 와 69.6%(32/46) 에서시행되어, 진행암에서항암화학방사선병합치료의비율이높았다 (p=0.028)(table 2). 추적관찰기간중총 23명에서재발하여 27.6% 의재발률을보였으며, 초치료에따라서는방사선단독치료군은 25%(9/36), 병합치료군은 27.5%(14/51) 에서재발하였다 (p=0.798). 또한 I, II 병기의조기암과 III, IV 병기의진행암으로나누어치료방법에따른재발률을비교하였으며, 방사선단독치료군과병합치료군으로나누어보았을때, I, II 병기와 III, IV 병기모두에서치료법에따른재발률의유의한차이는없었다 (p=0.644, p=0.496). 방사선단독치료, 동시항암화학방사선치료, 유도항암화학요법후방사선치료및유도항암화학요법후동시 항암화학방사선치료군의네군으로나누어비교해보았을때 도, 조기암군과진행암군모두에서재발률의차이는유의하지 Table 2. Treatment modality for nasopharyngeal cancer according to AJCC stage Stage I/II (%) Stage III/IV (%) p Radiation only 22 (53.7) 14 (30.4) 0.028 Combined therapy 19 (46.3) 32 (69.6) CCRT 14 (34.1) 20 (43.5) IC+RT 2 (4.9) 3 (6.5) IC+CCRT 3 (7.3) 9 (19.6) Total (n=87) 41 (100) 46 (100) CCRT: concurrent chemoradiation, IC+RT: induction chemotherapy followed by radiation therapy, IC+CCRT: induction chemotherapy followed by CCRT Table 1. Clinicopathologic characteristics of nasopharyngeal cancer 224 Characteristics No. of patients Total (n=87) Radiation only (n=36) Combined therapy (n=51) p value Age (years) 51.3±13.9 (range, 12-89) 53.5±15.2 (15-89) 49.8±12.9 (12-73) 0.415 Follow up (months) 66.7±49.9 (range, 12-232) 85.4±61.5 (14-232) 53.4±34.7 (12-139) 0.018 Sex 0.166 Male 58 (66.7%) 27 31 Female 29 (33.3%) 9 20 Primary site of tumor 0.603 Rosenmuller fossa 63 (72.4%) 25 38 Central, posterior wall 24 (27.6%) 11 13 Histology* 0.734 WHO type I 7 (8.0%) 2 5 WHO type II 13 (14.9%) 5 8 WHO type III 67 (77.0%) 29 38 AJCC stage 0.038 I 7 (8.0%) 6 1 II 34 (39.1%) 16 18 III 23 (26.4%) 7 16 IV 23 (26.4%) 7 16 T classification 0.256 1 28 (32.2%) 15 13 2 35 (40.2%) 14 21 3 14 (16.1%) 3 11 4 10 (11.5%) 4 6 N classification 0.103 0 25 (28.7%) 16 9 1 33 (37.9%) 12 21 2 22 (25.3%) 6 16 3 7 (8.0%) 2 5 M classification 0.038 0 80 (92.0%) 36 44 1 7 (8.0%) 0 7 EB virus 0.429 Positive 6/10 3/4 3/6 Negative 4/10 1/4 3/6 *WHO type I: keratinizing squamous cell carcinoma, WHO type II: nonkeratinizing squamous cell carcinoma, WHO type III: undifferentiated carcinoma. EB: Ebstein-Barr
Treatment Outcomes of Nasopharyngeal Carcinoma Park WS, et al. 않았다 (p=0.816, p=0.441)(table 3). 재발부위는원발부위가 9예, 경부림프절재발이 8예, 원격전이가 8예였으며, 원격전이가나타난증례중새로이원격전이가나타난증례가 6예, 기존원격전이부위에서재발한증례가 2예있었다. 원발부위에재발한 9예에서는구제치료로항암화학요법 (4예), 내시경하비인두절제술 (2예), 방사선근접치료 (3예) 를시행하였으며, 경부림프절에재발한 8예중 2예에서경부림프절절제술을, 1예에서는경부림프절절제술및항암화학요법을시행하였으며, 나머지 5예에서는항암화학요법을시행하였다. 원격전이가있었던 8예에서는항암화학요법을시행하였으며, 폐에만전이가있었던 1예에서는수술적치료가병행되었다. 본연구대상군의 5년생존율과 5년무병생존율은각각 74.0% 와 58.9% 였으며 (Fig. 1), 5년생존율을조기암군 ( 병기 I, II) 과진행암군 ( 병기 III, IV) 에서비교하면각각 82.7% 와 75.3% 으로, 조기암군에서생존율이높았으나, 통계적으로유의하지는않았다 (p=0.160)(fig. 2). 치료법에따른생존율을보면, 방사선단독치료군에서는 96.7%, 병합치료군중에서는동시항암화학방사선치료, 유도항암화학요법후방사선치료, 유도항암화학요법후동시항암화학방사선치료군에서의 5년생존율은각각 79.1%, 33.3%, 23.1% 로, 방사선단독치료군과병합치료군사이에생존율의유의한차이가있었다 (p<0.001)(fig. 3). 생존율과관련된인자를분석하였을때, 단변량분석에서는경부림프절전이여부와원격전이여부가생존율과유의한상관성을보였고, 연령이나성별, AJCC 병기와 T 병기, 뇌신경침범증상등은통계학적으로유의하지않았다. 다변량분석에서는원격전이여부가유의하게생존율에영향을미치는것으로조사되었다 (Table 4). 고찰 비인강암은 40~50대에서가장많이발생하며, 남녀성비는 2.2~3.4:1 정도이다. 5) 비인강암은 WHO 분류에따라 WHO type I( 각화성편평세포암, keratinizing squamous cell carcinoma), WHO type II( 비각화성편평세포암, non-keratinizing Table 3. Recurrence rate of nasopharyngeal carcinoma according to stage and treatment modalities Tx. modality Stage I/II Stage III/IV No of cases Recurrence (%) p value No of cases Recurrence (%) p value Radiation only 22 6 (27.3) 0.644 14 3 (21.4) 0.496 Combined therapy 19 4 (21.6) 32 10 (31.3) CCRT 14 3 (21.4) 20 6 (30.0) IC+RT 2 0 (0) 3 0 (0) IC+CCRT 3 1 (33.3) 9 4 (44.4) CCRT: concurrent chemoradiation, IC+RT: induction chemotherapy followed by radiation therapy, IC+CCRT: induction chemotherapy followed by CCRT 1.0 1.0 0.8 0.8 Cumulative survival rate 0.6 0.4 Cumulative survival rate 0.6 0.4 0.2 0.2 Overall survival Stage I, II 0.0 Disease free survival 0.0 Stage III, IV 0.00 20.00 40.00 60.00 0.00 20.00 40.00 60.00 Time (months) Time (months) Fig. 1. 5-year overall survival and disease free survival. Fig. 2. 5-year overall survival according to AJCC stage (p=0.160). www.jkorl.org 225
Korean J Otorhinolaryngol-Head Neck Surg 2016;59(3):222-8 Cumulative survival rate 1.0 0.8 0.6 0.4 0.2 0.0 Treatment modality Radiation only CCRT IC+RT IC+CCRT 0.00 20.00 40.00 60.00 Fig. 3. 5-year overall survival according to the treatment modality (p<0.001). CCRT: concurrent chemoradiation, IC+RT: induction chemotherapy followed by radiation therapy, IC+CCRT: induction chemotherapy followed by CCRT. Table 4. Prognostic factors related to survival in nasopharyngeal cancer Factors Univariate Multivariate Age 0.166 Gender 0.163 Advanced stage (stage III, IV) 0.169 Advanced T classification (T3, T4) 0.233 Regional lymph node metastasis 0.040 0.097 Distant metastasis <0.001 <0.001 Pathologic type (WHO type I, II) 0.274 Cranial nerve symptoms* 0.128 *one or more cranial nerve symptom squamous cell carcinoma), WHO type III( 미분화암, undefferentiated carcinoma) 로분류되며, 빈도는 type III 가가장 많고 type I 이예후가가장나쁘다. 14) 본연구에서환자군의평 균연령은 51.3±13.9 세 (12~89) 였으며, 남녀성비는 2.1:1 로나타 나기존의보고와유사한양상을보였으며, 조직학적분류도 WHO type III 가가장많았다. Time (months) 대부분의비인강암환자의경우, 초기증상이경미하고, 발 현되는증상이다양하며경부림프절종창이나혈관운동성 비염, 감염성비부비동염등양성의비강질환과흡사한증상 을보이는경우가많아비인두검사를소홀히하는경우초기 에진단이어려울수있다. 진행된환자에서도병변이두개강 내로파급되어뇌신경증상이나두통같은신경학적증상을 보이는경우가많아두개내질환으로오인되는경우역시많 다. 본연구에서도비폐색이나코피, 이충만감등의코나귀의 증상으로병원을찾은경우가 32예 (36.8%) 였다. 이러한이유가초치료가늦어지고치료가어려워지는원인중의하나가되며, 특히비인강암의유병률이낮은대부분의지역에서문제점으로인식되고있다. 14) 비인두는수술로서접근하기어려운반면방사선치료에비교적잘반응하기때문에비인강암의치료에서방사선치료가주된역할을담당하고있다. 최근에는전산화단층촬영및자기공명촬영으로종양의국소침범부위를정확하게예측하는방사선치료의시뮬레이션기법의향상으로인해방사선치료후생존율이점차향상되고있으며, 15) 세기변조방사선치료 (intensity modulated radiation therapy) 의도입으로, 통상적방사선치료에비해높은치료성공률과생존율을얻었다는보고가있다. 16) 하지만진행된비인강암의경우단독방사선치료에의한성공률이높지않아선행항암화학치료후방사선치료나동시항암화학방사선치료등이시도되고있고, 이를통해더좋은치료결과를얻었다는연구들이있다. 8,9) 동시항암화학방사선치료와방사선단독치료의결과를비교한무작위 3상임상시험에서 3년생존율과무병생존율모두동시항암화학방사선치료가월등히높다고보고하였으며, 7) 또다른연구에서도동시항암화학방사선치료를받은환자군의생존율및국소치료율이방사선단독치료군에비해더높았다고보고하였다. 8) 동시항암화학방사선치료와방사선단독치료를비교한메타연구에서도생존율, 재발률, 원격전이에있어동시항암화학방사선치료가방사선단독치료보다좋은결과를보인다고보고하였다. 9) 조기암과진행암을나누어분석한다른연구에서도전체환자군을대상으로하면치료에따른무병생존율의통계학적차이는없으나, 진행암군에서만분석하면동시항암화학방사선치료군의무병생존율이유의하게높았다는보고가있다. 10) III/IV 병기의진행된비인강암만을대상으로동시항암화학방사선치료와방사선단독치료를비교한무작위전향적연구에서도동시항암화학방사선치료가항암제로인한부작용은있지만, 초기치료반응및생존율이통계적으로유의하게높다고보고하였다. 11) 유도항암화학요법의장점과동시항암화학방사선치료의장점을모두얻기위해시행하는유도항암화학요법후동시항암화학방사선치료후의치료성적을보고한연구에의하면, 질병특이생존율, 전체생존율과재발률에서모두좋은결과를얻었다는보고가있다. 17) National Comprehensive Cancer Network 의암치료지침은 T1 병기의림프절전이가없는비인강암의치료로는방사 226
Treatment Outcomes of Nasopharyngeal Carcinoma Park WS, et al. 선단독치료를, T2 병기이상및림프절전이가있는경우에는동시항암화학방사선치료또는유도항암화학치료후방사선치료를권고하였다. 18) 하지만항암제사용에따라구내점막염, 빈혈, 백혈구감소증, 또는위장관계합병증은증가하는데에반해, 동시항암화학방사선치료를함으로써얻는치료효과의상승에는의문을재기한연구결과들도보고되고있다. 348예를대상으로한무작위배정연구에서, 동시방사선항암화학치료군이 5년무병생존율과무진행생존율에있어방사선치료군에비해유의하게높은결과를보였지만, 치료에의한독성이나우발적원인에의한사망으로 5년생존율은차이가없었다고보고되었다. 12) 심지어 T4 병기의진행암환자만을대상으로세기변조방사선단독치료와동시항암화학방사선치료를비교한연구에서두군간재발률, 원격전이, 생존율에있어통계적으로유의한차이가없어세기변조방사선단독치료가진행암에서도시행될수있음을보여준연구도있다. 13) 본연구에서는각치료법에따른재발률의유의한차이는없었으며, 생존율의경우방사선단독치료군의 5년생존율이항암화학방사선병합요법군보다더높았는데, 이는대상환자군의수가많지않고항암화학방사선병합요법이주로진행암에서많이시행된결과에기인하리라사료된다. 비인강암의예후는다른두경부악성종양과마찬가지로병기가진행될수록좋지않다. 특히, 두개저나두개내침범, 뇌신경침범이있는경우와하부경부림프절에침범이있는경우예후가좋지않으며, 조직학적분류에따라 WHO type I이 II, III에비해좋지않은예후를보인다고알려져있다. 국내의한연구에서는비인강암이뇌신경을침범하여복시나연하장애등의증상을나타내는경우에는생존율에악영향을준다고보고하였으며, 연령이나성별, T 병기나 N 병기는예후와유의한연관이없었다고보고되었다. 14) 그러나다른연구는 T 병기에따라생존율의유의한차이가있으며, 조직학적유형은 WHO type III에서가장좋은예후를보이나, N 병기, 연령, 성별은생존율과관련이없다고보고하였다. 19) 또한, 전신상태및면역기능의차이, 치료에대한적극성의차이등으로인해연령이예후와관련된다는보고도있다. 20) 본연구에서조기암군과진행암군간의생존율을비교해본결과통계적유의성은없었으나조기암군에서생존율이높은경향을보였으며, 성별이나연령모두생존율과통계학적으로유의한차이는없었다. 뇌신경증상유무에따라서도통계학적으로유의한차이가없었으며, 원격전이여부가생존율과통계학적으로유의한연관이있었다. 본연구의단점으로는, 첫째, 후향적연구로연구대상의선택에편견이있을수밖에없으며, 둘째, 여러치료방법에따른 분류로인하여치료분류대상군의종류는많고각대상군의 환자수가비교적적고, 또한비교되는대상군들의집단이균 일하지못하다는점등이있는데, 향후이런단점을보완하기 위한추가연구가반드시필요하리라생각된다. 결론적으로, 비인강암의치료에서치료방법에따른재발률 의유의한차이는없었으나, 5 년생존율은항암화학방사선 병합요법군이방사선단독치료군보다낮았고, 이는진행암군 에서항암화학방사선병합요법을시행한경우가더많았기 때문으로사료된다. 또한, 원격전이여부가비인강암의생존 율에유의한영향을미치는예후인자로확인되었다. 향후비 인강암의치료성적을향상시키고재발또는생존과관련된 예후인자를확실히규명하기위해서는더많은환자를대상 으로한전향적인연구가필요할것으로사료된다. REFERENCES 1) Forman D, Bray F, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M. Cancer incidence in five continents, Vol. X. Lyon: IARC Scientifi Publications;2014. p.953-55. 2) Wang Y, Zhang Y, Ma S. Racial differences in nasopharyngeal carcinoma in the United States. Cancer Epidemiol 2013;37(6):793-802. 3) Korean Central Cancer Registry, National Cancer Center. Annual report of cancer statistics in Korea in 2012. Sejong: Ministry of Health and Welfare;2014. 4) Teo P, Shiu W, Leung SF, Lee WY. Prognostic factors in nasopharyngeal carcinoma investigated by computer tomography--an analysis of 659 patients. Radiother Oncol 1992;23(2):79-93. 5) al-sarraf M, McLaughlin PW. Nasopharynx carcinoma: choice of treatment. Int J Radiat Oncol Biol Phys 1995;33(3):761-3. 6) Kim KH, Sung MH, Chang SO, Byun SW, Lee DH, Kim JY. Combination of chemotherapy and radiation therapy for nasopharyngeal cancer. Korean J Otolaryngol 1996;39(1):69-74. 7) Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16(4):1310-7. 8) Venkitaraman R, Ramanan SG, Vasanthan A, Sagar TG. Results of combined modality treatment for nasopharyngeal cancer. J Cancer Res Ther 2009;5(2):102-6. 9) Zhang L, Zhao C, Ghimire B, Hong MH, Liu Q, Zhang Y, et al. The role of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma among endemic population: a meta-analysis of the phase III randomized trials. BMC Cancer 2010;10:558. 10) Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, et al. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 2002;20(8):2038-44. 11) Kong F, Cai B, Lin S, Zhang J, Wang Y, Fu Q. Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma: a prospective study. J BUON 2015;20(1):206-11. 12) Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2010;102(15):1188-98. www.jkorl.org 227
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