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pissn : 1226-4962 eissn : 2233-9841 Original Article J Korean Bone Joint Tumor Soc 2013; 19: 50-55 http://dx.doi.org/10.5292/jkbjts.2013.19.2.50 www.kbjts.or.kr 천골및골반골에발생한거대세포종에대한동맥색전술치료의효용성분석 Analysis for Usefulness of Arterial Embolization on Sacral and Pelvic Giant Cell Tumors 김승현 윤길성 조용진 신규호 서진석 * 양우익 연세대학교의과대학정형외과, * 영상의학과, 병리학과 목적 : 천골및골반골에발생한거대세포종에대한동맥색전술의효용성을규명하고자하였다. 대상및방법 : 1996년 12월부터 2008년 5월까지연속적동맥색전술을시행한 9예를대상으로그임상결과및동맥색전술에대한거대세포종의치료반응성을후향적으로분석하였다. 결과 : 9예중 6예에서거대세포종이진행되어연속적동맥색전술은천골및골반골거대세포종치료에있어서효과적인치료방법은아닌것으로나타났다. 5예의경우에서는수술, 방사선치료등의추가적인치료를시행했음에도불구하고거대세포종이진행되었다. 9예중 3예에서거대세포종의호전및완치소견을보여, 카이제곱검정을통해이와관련된인자들에대해분석하였다. 첫혈관조영술시행시거대세포종양의영양혈관수가 6개미만인경우 (p=0.048), 측부순환의개수가 3개미만인경우 (p=0.048) 만이동맥색전술에대한치료반응성과연관이있는것으로나타났으며, 첫동맥색전술시행후잔존종양염색유무와반복시행횟수는연관이없었다. 결론 : 천골및골반골거대세포종의치료에있어서연속적동맥색전술은일반적으로사용될수있는효과적인치료방법은아니나, 첫혈관조영술시행시종양의혈관분포가적은경우에한해서시행한다면좋은치료결과를기대할수있다. 색인단어 : 천골, 골반골, 거대세포종, 동맥색전술 서 론 거대세포종은양성종양이나, 매우침습적인임상경과를보이며심지어는폐전이를일으키기도한다. 1,2) 천골및골반골에서발생하는거대세포종의발생률은매우낮으나, Turcotte 등의보고에따르면천골에서발생하는거대세포종의비율은전체거대세포종의 8% 를차지하며, 이는대퇴골원위부, 경골근위부, 요골원위부에발생한경우에이어 4번째로높은비율이다. 3) 거대세포종의표준치료는수술이다. 과거에는수술방법에따라재발률이약 40% 까지높게보고되어왔으나, 4,5) 최근에는초고속버링 (high speed burring), 과산화수소, 아르곤레이저 (argon la- 접수일 2013 년 11 월 1 일심사수정일 2013 년 11 월 22 일게재확정일 2013 년 11 월 26 일교신저자신규호서울시서대문구연세로 50, 연세대학교의과대학정형외과 TEL 02-2228-2189, FAX 02-363-1139 E-mail qshin@yuhs.ac ser), 전기소작 (electric cauterization), 골시멘트충전술 (polymethyl methacrylate; PMMA) 등의보조요법들의도입으로병소내소파술후에도 10% 이하의재발률이보고되고있다. 6) 하지만천골및골반골에발생한거대세포종의표준치료에는아직이견이많다. 이는해부학적특성상, 과도한출혈, 감염, 신경학적손상의위험이높고재건술시행이어려우며, 7-9) 재발률이다른부위에서보다높게보고되고있어, 4,10) 수술의효용성이사지에발생한거대세포종에비해많이떨어지기때문이다. 이런이유로, 천골및골반골거대세포종의수술외대체치료법과 (alternative treatment) 보조치료법들이 (adjuvant treatment) 많이보고되어왔다. 방사선치료, 11,12) 동맥색전술, 13-16) 파골세포억제제, 17-19) 등이대표적이나, 방사선치료의경우는이차성악성신생물 (secondary malignant neoplasm) 발생, 동맥색전술의경우는낮은성공률, 파골세포억제제의경우는빈약한전향적무작위임상시험 (prospective randomized clinical trial) 결과가거대세포종치료에사용되기에제한요소로작용하고있다. 이런상황에서, 본연구는연속적동맥색전술을이용한천골 대한골관절종양학회지 : 제19권제2호 2013 Copyrights 2013 by The Korean Bone and Joint Tumor Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

51 천골및골반골거대세포종과동맥색전술 및골반골거대세포종치료의임상결과와동맥색전술에대한거대세포종의치료반응성을후향적으로분석하여동맥색전술의효용성을규명하고자한다. 대상및방법 1996년 12월부터 2008년 5월까지조직검사를통해병리학적으로거대세포종으로확진받은환자들중, 연속적동맥색전술을시행받은 9명의환자를대상으로연구를진행하였다. 본연구는본원의연구윤리심의위원회의승인받은절차및방법에따라진행되었다. 총 9예중 3예에대해서는동맥색전술만을시행하였으며, 3예에대해서는동맥색전술과방사선치료, 3예에대해서는동맥색전술, 방사선치료, 수술을시행하였다. 천골에발생한경우가 4예, 천장관절주위에발생한경우가 3예, 비구및좌골에발생한경우가각각 1예씩이었다. 성비는남성 5예, 여성 4예였다. 평균연령은 36.4세 (22-65세) 였으며, 평균추시기간은 43.8개월 (2.3-126개월) 이었다. 환자의의무기록, 진단이후총추시기간동안시행된단순방사선사진, 자기공명영상및혈관조영사진, 진단당시의혈청알칼리성인산분해효소와유산탈수효소수치를분석하였다. 모든통계분석은 SPSS를 (version 20.0, SPSS, Inc., Chicago, IL) 이용하여시행하였다. 동맥색전술반응성과연관된인자분석에는카이제곱검정 (χ 2 test) 을이용하였다. 모든카이제곱검정시유의확률은피셔의정확검정 (Fisher`s extract test) 을이용하여계산하였으며, 양측검정결과만유의한것으로간주하였다. 결과 1. 연속적동맥색전술치료의임상결과분석본연구에동록된환자들에이용된치료법들과임상결과들을요 약하였다 (Table 1). 총 9예중 6예에서거대세포종이진행되어연속적동맥색전술은천골및골반골거대세포종치료에있어서효과적인치료방법은아닌것으로나타났다. 5예의경우에서는수술, 방사선치료등의추가적인치료를시행했음에도불구하고거대세포종이진행되었다. 수술은변연부절제술 2예, 병소내소파술 1예가시행되었으며, 병소내소파술을시행받은 1예에서완치 (continuous disease free, CDF) 결과를보였다. 방사선치료는총 5예에서시행되었으나, 환자순응도문제로중도포기한 1예에서만거대세포종의호전 (stable disease, SD) 양상을보였다. 환자 7의경우는거대세포종치료기간중병발한위암으로사망하였다. 2. 거대세포종의동맥색전술에대한치료반응성분석각거대세포종의기질적특성, 첫혈관조영술시행시의종양혈관분포 (tumor vascularity), 및동맥색전술치료의반응결과를요약하였다 (Table 2). 총 3예에서동맥색전술에좋은반응을보였다. 거대세포종의평균크기는 9.6 cm (5-13 cm) 이었으며, Enneking 병기와 Campanacci 병기는모두 3이었다. 3예에서진단당시에이차성동맥류골낭종성변화가 (secondary aneurysmal bone cystic change) 관찰되었다. 종양혈관분포는영양혈관의개수와영양혈관이기시하는종말동맥 (end artery) 의개수로평가하였다. 영양동맥이기시하는종말동맥의개수는종양의측부순환 (collateral arterial supply) 개수로간주하였다. 환자 6의경우는골반내혈액공급을 (pelvic blood supply) 받지않아색전술을시행할수없었다. 각거대세포종의기질적특성, 종양혈관분포, 및골종양과연관된혈청표시자들중, 동맥색전술의치료반응성과연관있는인자들을규명하기위해카이제곱검정을이용하여분석하였다 (Table 3). 첫혈관조영술시행시거대세포종양의영양혈관수가 6개미만인경우 (p=0.048), 측부순환의개수가 3개미만인경우 Table 1. Treatments and Clinical Outcomes Patient Sex/age Location Embolization (number of times) Surgery Radiation (cgy) F/U Period (months) Clinical outcome 1 F/33 SI joint 4 - - 126.0 SD 2 M/33 Sacrum 6-27 112.0 SD 3 M/47 Acetabulum 4 Curettage - 51 CDF 4 M/38 Ischium 7 Excision 50.4 40.4 PD 5 F/40 SI joint 6 Excision 50.3 32.7 PD 6 M/50 Sacrum 3-49.6 15.47 DOC 7 F/22 Sacrum 4-50.4 8.14 PD 8 F/27 SI joint 2 - - 4.77 PD 9 M/65 Sacrum 3 - - 2.3 PD F/U, follow up; SI, sacroiliac; SD, stable disease; CDF, continuous disease free; PD, progression of disease; DOC, died of other cause.

52 김승현 윤길성 조용진외 3 인 Table 2. Tumor Characteristics and Embolization-Responsiveness Tumor vascularity Response Residual tumor staining End artery for feeding artery arousing (Collateral supply) Number of end artery for feeding artery arousing (Collateral supply) Number of main feeding artery Aneurysmal cystic change Campanacci stage Size (cm) Patient 1 11 3 No 5 2 Superior gluteal a, L4 lumbar a Yes Yes 2 7 3 Yes 5 2 Iliolumbar a, L4 lumbar a Yes Yes 3 10 3 No 3 2 Inferior pudendal a, Inferior gluteal a No Yes Yes No 4 13 3 No 8 5 Superior gluteal a, Inferior gluteal a, Obturator a, Superficial femoral br, Deep femoral br 5 12 3 No 5 3 Superior gluteal a, Inferior gluteal a, L4 lumbar a Yes No 6 6 3 No 8 4 Iliolumbar a, Superior gluteal a, Inferior gluteal a, Obturator a Yes No 7 12 3 No 6 2 Superior gluteal a, Obturator a Yes No 8 5 3 No 7 3 Superior gluteal a, Obturator a, L4 lumbar a Yes No 9 10 3 Yes 6 3 I nternal iliac a, Iliolumbar a, Superior gluteal a No No a, artery; br, branch. (p=0.048) 만이동맥색전술에대한치료반응성과연관이있는것으로나타났다. 상기두인자에서의절단값들은 (cutoff value) 중위수를 (median value) 기준으로정하였다. 첫동맥색전술시행후잔존종양염색유무와반복시행횟수는연관이없었다. 흥미롭게도혈청알칼리성인산분해효소와유산탈수효소증가여부, 거대세포종양의이차동맥류성골낭종변화와같이종양의기질적특징에의해결정되는인자들은동맥색전술치료반응성과연관이없었다. 고찰 본연구에서연속적동맥색전술의성공률은 30.3% 로저조하다. 하지만, 본연구에서의저조한성적으로천골및골반골거대세포종치료에있어서동맥색전술의효용성을절하하기에는무리가있다. 실제로, 기존의문헌들은약 80% 의성공률을보고하였다. 13,14) 이런혼란스런결과속에서, 동맥색전술의치료성공률에대한고려못지않게동맥색전술의시행에대한정확한적응증에대한분석이천골및골반골거대세포종치료에있어서동맥색전술의효용성규명에중요할것으로생각된다. 천골및골반골거대세포종수술시가장큰위험인자는과도한출혈이며, 수술중출혈양이수혈에도불구하고환자의생명을위협할수있는경우도흔하다. 9) 특히병소내소파술을시행할경우과도한출혈의위험은더커진다. 이러한이유로, 수술중출혈양을줄이기위해수술전색전술을시행하는것이합리적인치료과정으로제안되었으며, 20) 수술전혈관조영술및색전술은수술전필수적인처치로시행되고있다. 따라서, 수술전시행한혈관조영술에서종양의혈관분포를자연스럽게알수있게된다. 본연구결과에따르면, 영양혈관수가 6개미만인경우이거나측부순환의개수가 3개미만인경우에는성공적인동백색전술결과를기대할수있으므로, 이에해당하는경우는수술을연기하고연속적동맥색전술시행을고려할수있을것이다. 즉, 수술전색전술시행이필수적인수술전처치과정이자, 동시에연속적동맥색전술시행가능성에대한실험연구 (pilot study) 가되는것이다. 이런알고리즘 (algorism) 을그림으로요약하였다 (Fig. 1). 연속적동맥색전술의성공을기대하기어려운거대세포종의경우는수술, 방사선치료, 파골세포억제제투여등을고려해야할것이다. 본연구의결과로유추할수있는새로운사실은동맥색전술의성공여부는종양의기질적특성보다는종양의혈관분포에더관계가깊다는것이다. 따라서, 이알고리즘은모든경우의천골및골반골거대세포종에대해적용가능하다는장점이있다. 본연구는 9예의작은표본크기로시행한후향적연구로결과의신뢰성에한계성이있다. 특히, 영양혈관개수와측부순환의개수에적용한절단값이다른표본들을대상으로유효하게적용될지는미지수이다. 따라서, 큰크기의표본에서의검증이반드

53 천골및골반골거대세포종과동맥색전술 Table 3. χ 2 Tests for Evaluating Associations between Clinical Factors and Embolization-Responsiveness Clinical factor Responsive n (%) Unresponsive n (%) p* Sex Male 2 (40.0) 3 (60.0) 1.000 Female 1 (25.0) 3 (75.0) Aneurysmal cystic change Yes 1 (50.0) 1 (50.0) 1.000 No 2 (28.6) 5 (71.4) ALP elevation Yes 1 (50.0) 1 (50.0) 1.000 No 2 (28.6) 5 (71.4) LDH elevation Yes 3 (60.0) 2 (40.0) 0.196 No 0 (0.0) 3 (100.0) Main feeding artery 6 0 (0.0) 5 (100.0) 0.048 <6 3 (75.0) 1 (25.0) End artery for feeding artery arousing 3 0 (0.0) 5 (100.0) 0.048 (Collateral supply) <3 3 (75.0) 1 (25.0) Residual tumor staining Yes 2 (28.6) 5 (71.4) 1.000 No 1 (50.0) 1 (50.0) Embolization 4 3 (50.0) 3 (50.0) 0.464 (number of times) <4 0 (0.00) 3 (100.0) *Calculated by Fisher s extract test. ALP, alkaline phosphatase; LDH, lactate dehydrogenase. Figure 1. Algorism for Selecting Treatment Modality on Sacral and Pelvic GCT. GCT, giant cell tumor. 시필요할것으로판단된다. 또, 혈관조영술결과분석이이차원방사선사진으로시행되었기때문에, 삼차원적공간관계를갖는혈관분포가얼마나정확하게분석됐는지에대한고려도필요할것이다. 결론 요약하자면, 천골및골반골거대세포종의치료에있어서연속적동맥색전술의성공률에대한상반된결과들이있지만, 본연구에 서제시한알고리즘과같이정확한적응증에해당하는경우에만한정적으로사용한다면, 동맥색전술은천골및골반골거대세포종의치료에있어서유용한치료법이될것이다. 참고문헌 1. Wülling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. The nature of giant cell tumor of bone. J Cancer Res Clin Oncol. 2001;127:467-74.

54 김승현 윤길성 조용진외 3 인 2. Cheng JC, Johnston JO. Giant cell tumor of bone. Prognosis and treatment of pulmonary metastases. Clin Orthop Relat Res. 1997;(338):205-14. 3. Turcotte RE, Sim FH, Unni KK. Giant cell tumor of the sacrum. Clin Orthop Relat Res. 1993;(291):215-21. 4. Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106-14. 5. Kivioja AH, Blomqvist C, Hietaniemi K, et al. Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years. Acta Orthop. 2008;79:86-93. 6. Balke M, Schremper L, Gebert C, et al. Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol. 2008;134:969-78. 7. Wanebo HJ, Koness RJ, Turk PS, Cohen SI. Composite resection of posterior pelvic malignancy. Ann Surg. 1992;215:685-93; discussion 693-5. 8. Guo W, Sun X, Zang J, Qu H. Intralesional excision versus wide resection for giant cell tumor involving the acetabulum: which is better? Clin Orthop Relat Res. 2012;470:1213-20. 9. Guo W, Ji T, Tang X, Yang Y. Outcome of conservative surgery for giant cell tumor of the sacrum. Spine (Phila Pa 1976). 2009;34:1025-31. 10. Leggon RE, Zlotecki R, Reith J, Scarborough MT. Giant cell tumor of the pelvis and sacrum: 17 cases and analysis of the literature. Clin Orthop Relat Res. 2004;(423):196-207. 11. Feigenberg SJ, Marcus Jr RB, Zlotecki RA, Scarborough MT, Berrey BH, Enneking WF. Radiation therapy for giant cell tumors of bone. Clin Orthop Relat Res. 2003;(411):207-16. 12. Caudell JJ, Ballo MT, Zagars GK, et al. Radiotherapy in the management of giant cell tumor of bone. Int J Radiat Oncol Biol Phys. 2003;57:158-65. 13. Hosalkar HS, Jones KJ, King JJ, Lackman RD. Serial arterial embolization for large sacral giant-cell tumors: mid- to longterm results. Spine (Phila Pa 1976). 2007;32:1107-15. 14. Lackman RD, Khoury LD, Esmail A, Donthineni-Rao R. The treatment of sacral giant-cell tumours by serial arterial embolisation. J Bone Joint Surg Br. 2002;84:873-7. 15. Lin PP, Guzel VB, Moura MF, et al. Long-term follow-up of patients with giant cell tumor of the sacrum treated with selective arterial embolization. Cancer. 2002;95:1317-25. 16. Martin C, McCarthy EF. Giant cell tumor of the sacrum and spine: series of 23 cases and a review of the literature. Iowa Orthop J. 2010;30:69-75. 17. Cornelis F, Truchetet ME, Amoretti N, et al. Bisphosphonate therapy for unresectable symptomatic benign bone tumors: A long-term prospective study of tolerance and efficacy. Bone. 2013;58C:11-6. 18. Chaudhary P, Khadim H, Gajra A, Damron T, Shah C. Bisphosphonate therapy is effective in the treatment of sacral giant cell tumor. Onkologie. 2011;34:702-4. 19. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901-8. 20. Thangaraj R, Grimer RJ, Carter SR, Stirling AJ, Spilsbury J, Spooner D. Giant cell tumour of the sacrum: a suggested algorithm for treatment. Eur Spine J. 2010;19:1189-94.

Original Article pissn : 1226-4962 eissn : 2233-9841 J Korean Bone Joint Tumor Soc 2013; 19: 50-55 http://dx.doi.org/10.5292/jkbjts.2013.19.2.50 www.kbjts.or.kr Analysis for Usefulness of Arterial Embolization on Sacral and Pelvic Giant Cell Tumors Seung Hyun Kim, Gil Sung Yoon, Yong Jin Cho, Kyoo-Ho Shin, Jin-Suck Suh*, and Woo-Ick Yang Departments of Orthopedic Surgery, *Radiology and Research Institute of Radiological Science, Pathology, Yonsei University College of Medicine, Seoul, Korea Purpose: The purpose of this study is to determine the usefulness of arterial embolization on sacral and pelvic giant cell tumor (GCT). Materials and Methods: We retrospectively reviewed the medical records of 9 patients who had undergone serial arterial embolization between December 1996 and May 2008. We analyzed the clinical outcomes and therapeutic responsiveness of arterial embolization on sacral and pelvic GCT. Results: Six of 9 cases showed progression of disease (PD) status, even if 5 cases showed PD status despite of additional treatments including surgery and radiation, implying that serial arterial embolization on sacral and pelvic GCT is not effective. Three of 9 cases showed stable disease (SD) or continuous disease free (CDF) status and we analyzed associated factors with these good responses for embolization by χ 2 test. The number of feeding vessels under six (p=0.048) and the number of collateral arterial supply under three (p=0.048) in the first angiogram showed significant relationships with good response for embolization, while remaining tumor staining by contrast after the first embolization and repeated embolization times were not significant. Conclusion: Although serial arterial embolization is not an effective modality on sacral and pelvic giant cell tumors, it may be a pilot modality under narrow indication of tumors with poor vascularity at first angiogram. Key words: sacrum, pelvic bone, giant cell tumor, arterial embolization Received November 1, 2013 Revised November 22, 2013 Accepted November 26, 2013 Correspondence to: Kyoo-Ho Shin Department of Orthopedic Surgery, Yonsei University College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea TEL: +82-2-2228-2189 FAX: +82-2-363-1139 E-mail: qshin@yuhs.ac The Journal of the Korean Bone and Joint Tumor Society Vol. 19, No. 2 (December 2013) Copyrights 2013 by The Korean Bone and Joint Tumor Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.