자궁내막암의 수술 후 방사선치료 결과에 영향을 미치는 예후인자

Prognostic Factors Influencing the Result of Postoperative Radiotherapy in Endometrial Carcinoma

  • 기용간 (부산대학교 의과대학 방사선종양학교실) ;
  • 권병현 (부산대학교 의과대학 방사선종양학교실) ;
  • 김원택 (부산대학교 의과대학 방사선종양학교실) ;
  • 남지호 (부산대학교 의과대학 방사선종양학교실) ;
  • 윤만수 (부산대학교 의과대학 산부인과학교실) ;
  • 이형식 (동아대학교 의과대학 방사선종양학교실) ;
  • 김동원 (부산대학교 의과대학 방사선종양학교실)
  • Ki Yong-Kan (Departments of Radiation Oncology and Pusan National University School of Medicine) ;
  • Kwon Byung-Hyun (Departments of Radiation Oncology and Pusan National University School of Medicine) ;
  • Kim Won-Taek (Departments of Radiation Oncology and Pusan National University School of Medicine) ;
  • Nam Ji-Ho (Departments of Radiation Oncology and Pusan National University School of Medicine) ;
  • Yun Man-Su (Obstetrics and Gynecology, Pusan National University School of Medicine) ;
  • Lee Hyung-Sik (Department of Radiation Oncology, Dong-A University School of Medicine) ;
  • Kim Dong-Won (Departments of Radiation Oncology and Pusan National University School of Medicine)
  • 발행 : 2006.06.01

초록

목적: 수술 후 보조적으로 방사선치료를 받은 자궁내막암 환자의 전체생존율, 무병생존율, 재발 부위 등을 분석하여 이와 관련된 예후인자를 알아보고자 하였다. 대상 및 방법: 1992년 4월부터 2003년 5월까지 부산대학교병원에서 수술 후 방사선치료를 받은 자궁내막암 환자 중 조직유형이 선암인 환자 54명을 대상으로 후향적 분석하였다. 전체 환자의 중앙 나이는 55세(35-76세)였고, 병기 분포는 FIGO 병기 I군이 34명(63.0%), 병기 II군이 8명(14.8%), 병기 III군이 12명(22.2%)이었다. 모든 환자는 수술 및 외부 방사선조사($41.4{\sim}54.0Gy$, 중앙값 50.4 Gy)를 받았고, 20명(전체 환자의 37.0%)의 환자에서 추가로 질내 근접치료($15.0{\sim}24.0Gy$, 중앙값 15.0 Gy)를 받았다. 전체추적기간은 $5{\sim}115$개월로 중앙추적기간은 35개월이었다. 분석 결과 유의 인자로 나타난 조직 분화도(histologic grade), 림프-혈관 침범(Iymphovascular space invasion), 그리고 자궁근 침범 정도(myometrial invasion depth)를 점수화(GLM 점수)하여 생존분석을 시행하였다. 생존분석은 Ka-plan-Meter 법을, 단변량 및 다변량 통계분석은 각각 log-rank 검정과 Cox 회귀분석을 사용했다. 결과: 전체 자궁내막암 환자의 5년 생존율은 87.7%였고, 5년 무병생존율은 87.1%였다. 단변량 통계분석에서는 조직분화도, 림프-혈관 침범, 그리고 자궁근 침범 정도가 전체생존율 및 무병생존율과 관련 있는 인자였고, 다변량 통계분석에서는 림프-혈관 침범이 무병생존율과 관련 있는 인자였다(p=0.0158). GLM 점수는 전체생존율 및 무병생존율과 의미 있는 관계를 나타냈고(각각 p=0.0090, p=0.0073), 원격재발에도 유의한 예후인자로 나타났다 (p=0.0132). 전체 환자 중 6명(11%)의 환자에서 재발을 보였고, 재발 부위는 대동맥 림프절 2명, 폐 2명, 쇄골상부 림프절 1명, 질 1명이었다. 결론: 수술 및 수술 후 방사선치료를 받은 자궁내막암 환자의 예후는 수술 후의 병리 소견과 밀접한 관계를 가지고 있다. 더 많은 연구를 통해 자궁내막암 환자의 예후인자를 체계화한다면, 병의 진행양상을 예견하고 대처하는데 도움이 될 것이다.

Purpose: This study was performed to determine the prognostic factors influencing relapse pattern, overall and disease-free survival in patients treated with postoperative radiotherapy for endometrial carcinoma. Materials and Methods: The records of 54 patients with endometrial adenocarcinoma treated postoperative radiotherapy at Pusan National University Hospital between April 1992 and May 2003 were reviewed retrospectively. Median age of the patients was 55 (range $35{\sim}76$). The distribution by surgical FIGO stages were 63.0% for 0Stage I, 14.8% for Stage II, 22.2% for Stage III. All patients received postoperative external radiotherapy up to $41.4{\sim}54Gy$ (median: 50.4 Gy). Additional Intravaginal brachytherapy was app led to 20 patients (37.0% of all). Median follow-up time was 35 months ($5{\sim}115$ months). Significant factors of this study: histologic grade, Iymphovascular space invasion and myometrial invasion depth were scored (GLM score) and analyzed. Survival analysis was peformed using Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. Results: 5-year overall and disease-free survival rates were 87.7% and 871%, respectively. Prognostic factors related with overall and disease-free survival were histologic grade, Iymphovascular space invasion and myometrial invasion according to the univariate analysis. According to the multivariate analysis, Iymphovascular space invasion was associated with decreased disease-free survival. GLM score was a meaningful factor affecting overall and disease-free survival (p=0.0090, p=0.0073, respectively) and distant recurrence (p=0.0132), which was the sum of points of histologic grade, Iymphovascular space Invasion and myometrial invasion. Total failure rate was 11% with 6 patients. Relapse sites were 2 para-aortic Iymph nodes, 2 lungs, a supraclavicular Iymph node and a vagina. Conclusion: The prognosos in patients with endometrial carcinoma treated by postoperative radiotherapy was closely related with surgical histopathology. If further explorations confirm the system of prognostic factors in endometrial carcinoma, it will help us to predict the progression pattern and to manage.

키워드

참고문헌

  1. Jemal A, Murray T, Samuels A, et al. Cancer statics, 2004. CA Cancer J Clin 2004;54:8-29 https://doi.org/10.3322/canjclin.54.1.8
  2. Ministry of Health and Welfare, R.O.K. 2002 Annual Report of the Korea Central Cancer Registry 2003
  3. Berek JS, Haker NF. Practical gynecologic oncology. 3rd ed. Philadelphia; Lippincott Williams, Wilkins, 2000:407-455
  4. Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 2006;24: 36-44 https://doi.org/10.1200/JCO.2004.00.7617
  5. Zanio RJ, Kurman RJ, Diana KL, Morrow CP. Pathologic models to predict outcome for women with endometrial adenocarcinoma. Cancer 1996;77:1115-1121 https://doi.org/10.1002/(SICI)1097-0142(19960315)77:6<1115::AID-CNCR17>3.0.CO;2-4
  6. Amant F, Cadron I, Fuso L, et al. Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer. Gynecol Oncol 2005;98:274-280 https://doi.org/10.1016/j.ygyno.2005.04.027
  7. Scholten AN, Cresutzberg CL, Noordijk EM, Smit VT. Long-term outcome in endometrial carcinoma favors a two-instead of a three-tiered grading system. Int J Radiat Oncol Biol Phys 2002;52:1067-1074 https://doi.org/10.1016/S0360-3016(01)02710-9
  8. Briet JM, Hollema H, Reesink N, et al. Lymphovascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol 2005;96:799-804 https://doi.org/10.1016/j.ygyno.2004.11.033
  9. Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium. Gyecol Oncol 1991;40:55-65 https://doi.org/10.1016/0090-8258(91)90086-K
  10. Lurain JR, Rice BL, Rademaker AW, Proggensee LE, Schink JC, Miller DS. Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Obstet Gynecol 1991;78:63-69
  11. Jereczek-fossa B, Badzio A, Jassem J. Surgery followed by radiotherapy in endometrial cancer: analysis of survival and pattern of failure. Int J Gynecol Cancer 1999;9:285-294 https://doi.org/10.1046/j.1525-1438.1999.99038.x
  12. Descamps P, Calais G, Moire C, et al. Predictors of distant recurrence in clinical stage I or II endometrial carcinoma treated by combination surgical and radiation therapy. Gynecol Oncol 1997;64:54-58 https://doi.org/10.1006/gyno.1996.4511
  13. Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma. Gynecol Oncol 2004;94:241-242 https://doi.org/10.1016/j.ygyno.2004.04.002
  14. Aalders JG, vd Syde R, Poppema S, Szabo BG, Janssens J. Prognostic factors and changing trends in the treatment of Stage I endometrial cancer: a clinical and histopathological study of 182 patients. Int J Radiat Oncol Biol Phys 1984;10: 2083-2088 https://doi.org/10.1016/0360-3016(84)90206-2
  15. Kuten A, Grigsby PW, Perez CA, Fineberg B, Garcia DM, Simpson JR. Results of radiotherapy in recurrent endometrial carcinoma: a retrospective analysis of 51 patients. Int J Radiat Oncol Biol Phys 1989;17:29-34 https://doi.org/10.1016/0360-3016(89)90366-0
  16. Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC, et al. Outcome of high risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the postoperative radiation therapy in endometrial carcinoma trial. J Clin Oncol 2004;22:1234-1241 https://doi.org/10.1200/JCO.2004.08.159
  17. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study. J Clin Oncol 2004;22:3902-3908 https://doi.org/10.1200/JCO.2004.02.088
  18. Thigpen JT, Brady MF, Alvarez RD, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the gynecologic oncologic group. J Clin Oncol 1999;17:1736- 1744 https://doi.org/10.1200/JCO.1999.17.6.1736
  19. Lentz SS, Brady MF, Major FJ, Redi GC, Soper JT. Highdose megesterol acetate in advanced or recurrent endometrial carcinoma: a gynecologic oncologic group study. J Clin Oncol 2004;14:357-361