Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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The Results and Prognostic Factors of Postoperative Radiation Therapy in the Early Stages of Endometrial Cancer

초기 자궁내막암의 수술 후 방사선치료의 결과와 예후인자

  • Lee, Kyung-Ja (Department of Radiation Oncology, School of Medicine, Ewha Womans University)
  • 이경자 (이화여자대학교 의학전문대학원 방사선종양학교실)
  • Published : 2008.09.30
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Abstract

Purpose: To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial cancer, pelvic control, and overall survival rate was free of severe toxicity when pelvic radiation therapy or vaginal brachytherapy was performed. In the high-risk group, pelvic control rate was excellent, but the survival rate was poor due to distant metastases, in spite of the pelvic radiation therapy. The combined modality of chemotherapy and radiation therapy is recommended for high-risk groups. For the intermediate-risk group, a prospective randomized study is required to compare the efficacy between whole pelvic radiation therapy and vaginal brachytherapy.

목 적: 본 연구는 자궁내막암 병기 $1{\sim}2$ 환자에 수술 후 방사선치료의 결과와 예후인자를 분석하여 향후 치료원칙을 결정하는 데 도움을 얻고자 시행하였다. 대상 및 방법: 1991년 1월부터 2005년 12월까지 이화여자대학교 의과대학부속병원에서 자궁내막암으로 진단받고 수술 후 방사선치료를 받은 병기 $1{\sim}2$환자를 대상으로 후향적 분석을 하였다. 전체 환자는 35명이었으며 17명은 자궁절제술과 양측 난소제거술을 시행하였고 18명은 완전한 수술적 병기의 수술을 시행하였다. 골반강 방사선치료를 받은 환자는 17명, 질강내근접치료를 받은 환자는 12명, 골반강 방사선치료와 질강내근접치료를 받은 환자는 6명이었다. 결 과: 추적기간의 중앙값은 54개월이었다. 전체 환자의 5년 생존율은 91.4%, 무병생존율은 81.7%이었다. 저위험군, 중간위험군, 고위험군의 위험군에 따른 5년 생존율은 각각 100%, 100%, 55.6%이었으며 무병생존율은 각각 100%, 70.0%, 45.7%이었다. 국소재발된 환자는 없었으며 5명(14%)에서 원격전이가 발생하였으며 호발부위는 폐, 뼈, 간, 부신, 전복강의 순이었다. 원격전이에 대한 단변량 통계분석에 따르면 위험군, 조직학적 세포형태와 조직학적 등급이 유의성이 있었으며, 다변량 통계분석에 따르면 조직학적 세포형태로서 유두형, 장액형, 그리고 투명세포암은 자궁내막양암과 샘암편평암에 비하여 원격전이율이 높고 생존율이 낮았다. 골반강 방사선치료에 의한 후유증은 장염이 30%에서 나타났으며 다음으로 직장염이었으나 대부분 등급 $1{\sim}2$로 등급 $3{\sim}4$의 후유증은 발생하지 않았다. 결 론: 수술 후 골반강 방사선치료 혹은 질강내근접치료를 시행한 자궁내막암 병기 $1{\sim}2$환자들의 경우 저위험군과 중간위험군은 국소제어율과 생존율이 높았으나, 고위험군은 골반강 방사선치료를 시행하여 국소제어율은 높으나 원격전이율이 높고 생존율이 낮았다. 따라서 고위험군은 방사선치료와 동시에 항암화학요법이 요구된다. 중간 위험군의 더 효율적인 치료를 위하여 많은 환자를 대상으로 골반강 방사선치료와 강내근접치료를 비교하는 전향적 무작위연구가 필요하다.

Keywords

References

  1. 2002 Annual Report of the Korea Central Cancer Registry
  2. Creasman WT, Morrow C, Bundy B, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group study. Cancer 1987; 60:2035-2041 https://doi.org/10.1002/1097-0142(19901015)60:8+<2035::AID-CNCR2820601515>3.0.CO;2-8
  3. International Federation of Gynecology and Obstetrics. Annual report on the results of Treatment in gynecologic cancer. Int J Genecol Obstet 1989;28:189-190 https://doi.org/10.1016/0020-7292(89)90482-7
  4. Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I & II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 1991;40:55-65 https://doi.org/10.1016/0090-8258(91)90086-K
  5. Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol 1980;56:419-427
  6. Grigsby PW, Perez CA, Kutten A. Clinical stage I endometrial cancer; prognostic factors for local control and distant metastasis and implications of the new FIGO surgical staging system. Int J Radiat Oncol Biol Phys 1992;22:905-911 https://doi.org/10.1016/0360-3016(92)90786-H
  7. Kucera H, Vavra N, Weghaupt K. Benefit external irradiation in pathologic stage I endometrial carcinoma; a prospective clinical trial of 605 patients who received postoperative vaginal irradiation and additional pelvic irradiation in the presence of unfavarable prognostic factors. Gynecol Oncol 1990;38:99-104 https://doi.org/10.1016/0090-8258(90)90018-G
  8. Roberts JA, Brcenetto VL, Keys HM, et al. A phase III randomized study of surgery vs surgery plus adjunctive radiation therapy in intermediate-risk endometrial carcinoma. Gynecol Oncol 1998;68:135
  9. Lin LL, Mutch DG, Rader JS, Powel MA, Grigsby PW. External radiotherapy versus vaginal brachytherapy for patients with intermediate-risk endometrial cancer. Gynecol Oncol 2007;196:215-220
  10. Fanning J. Long-term survival of intermediate risk endometrial cancer (Stage IG3, IC, II) treated with full lymphadenectomy and brachytherapy without teletherapy. Gynecol Oncol 2001;82:371-374 https://doi.org/10.1006/gyno.2001.6276
  11. Nelson G, Randall M, Sutton G, et al. FIGO stage IIIC endometrial carcinoma with metastases confined to pelvic lymph nodes. analysis of treatment outcomes, prognostic variables and failure patterns following adjuvant radiation therapy. Gynecol Oncol 1999;75:211-214 https://doi.org/10.1006/gyno.1999.5569
  12. Greven KM, Corn B, Lanciano RM, Case D, Randall ME. Pathologic stage III endometrial carcinoma: Pathologic stage III endometrial carcinoma: significance of extrauterine sites. Radiat Oncol Invest 1996;4:122-128 https://doi.org/10.1002/(SICI)1520-6823(1996)4:3<122::AID-ROI4>3.0.CO;2-#
  13. Grigsby EW, Perez CA, Kuske RR, Kao MS, Galakatos AE. Results of therapy analysis of failures and prognostic factors for clinical and pathologic stage III adenocarcinoma of the endometrium. Gynecol Oncol 1987;27:44-57 https://doi.org/10.1016/0090-8258(87)90229-0
  14. Hendrickson M, Ross J, Eifel P, Martinez A, Kempson R. Uterine papillary serous carcinoma. a highly malignant form of endometrial adenocarcinoma. Am J Surg Path 1982;6:93-108 https://doi.org/10.1097/00000478-198203000-00002
  15. Webb GA, Lagos MD. Clear cell carcinoma of the endometrium. Am J Obstet Gynecol 1987;156:1486-1491 https://doi.org/10.1016/0002-9378(87)90021-4
  16. Potish RA, Twiggo LB, Adcock LL, et al. Para-aortic lymph node radiotherapy in cancer of the uterine corpus. Obstet Gynecol 1985;654:251
  17. Jolly S, Vargus C, Kumar T, et al. Vaginal brachytherapy alone; an alternative to adjuvant whole pelvic radiation for early stage endometrial cancer. Gynecol Oncol 2005;97:887-892 https://doi.org/10.1016/j.ygyno.2005.02.021
  18. Ny TY, Perrin LO, Nicklin JL, Cheuk R, Crandon AJ. Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 2000;79:490-494 https://doi.org/10.1006/gyno.2000.6005
  19. Petereit DG, Tannehil SP, Grosen EA, Hartenbach EM, Schink JC. Outpatient vaginal cuff brachytherapy for endomtrial cancer. Int J Radiat Oncol Biol Phys 1999;9:456-462
  20. Chada M, Nanavati PJ, Lia P, Fanning J, Macobs A. Pattern of failure in endometrial carcioma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 1999;75:103-107 https://doi.org/10.1006/gyno.1999.5526
  21. Alektiar KM, Venkatramen E, Barakat RR. Intravaginal brachytherapy alone for intermediate-risk endometrial cancer. Int J Radiat Oncol Biol Phys 2005;62:111-117 https://doi.org/10.1016/j.ijrobp.2004.09.054
  22. Creutzberg CL, van Putten WL, Koper PC, et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomized trial. Post Operative Radiation Therapy in Endometrial Carcinoma. (PORTEC) Study Group. Lancet 2000;355:1404-1411 https://doi.org/10.1016/S0140-6736(00)02139-5
  23. Scholten AN, van Putten WL, Beerman H, et al. Postoperative radiotherapy for stage I endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys Biol 2005;63:834-838 https://doi.org/10.1016/j.ijrobp.2005.03.007
  24. Editorial. GOG99: Ending the controversy regarding pelvic radiotherapy for endometrial cancer. Gynecol Oncol 2004;92:740-743 https://doi.org/10.1016/j.ygyno.2004.01.009
  25. 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 adenocarcioma: a Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744-751 [Erratum in Gynecol Oncol 2004;94:241-242] https://doi.org/10.1016/j.ygyno.2003.11.048
  26. Kadar N, Malfetano JH, HOmesley HD. Determinats of survival of surgically staged patients with endometrial carcinoma histologically confined to the uterus: Implications for therapy. Obstet Gynecol 1992;80:655-659
  27. Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA 2006;295:389-397 https://doi.org/10.1001/jama.295.4.389
  28. Horowitz NS, Peters WA, Smith MR, Drescher CW, Atwood M, Mate TP. Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma. Obstet Gynecol 2002;99:235-240 https://doi.org/10.1016/S0029-7844(01)01672-6
  29. Alektiar KM, Venkatraman E, Baraket RR. Intravaginal brachytherapy alone for intermediate-risk endometrial cancer. Int J Radiat Oncol Biol Phys 2005;62:111-117 https://doi.org/10.1016/j.ijrobp.2004.09.054
  30. Weiss E, Hirnle P, Arnold-Botinger H, Hess CF, Bamberg M. Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy. Gynecol Oncol 1998;71:172-176 https://doi.org/10.1006/gyno.1998.5165
  31. Aalders J, Abeler V, Kolstad P. Recurrent adenocarcinoma of the endometrium; a clinical and histopathological study of 379 patients. Gynecol Oncol 1984;17:85 https://doi.org/10.1016/0090-8258(84)90063-5
  32. Creutzberg CL, van Putten WLJ, 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 Clinical Oncology 2004;22;123-1241
  33. PORTEC-2: Postoperative radiation therapy for endometrial carcinoma: a multicentric randomized phase III trial comparing external beam radiation and vaginal brachytherapy: Nederlands Trial Register http//www.trialreigster.nl/trialreg/admin/retview.asp? TC=332 Accessed September 9, 2005
  34. Lin LL, Mutch DG, Rader JS, Powell MA, Grigsby PW. External radiotherapy versus vaginal brachytherapy for patients with intermediate risk endometrial cancer. Gynecol Oncol 2007;106:215-220 https://doi.org/10.1016/j.ygyno.2007.03.024
  35. Kang MK, Huh SJ, Park W, et al. The results of postoperative radiotherapy for early sage endometrial carcinoma. J Korean Soc Ther Radiol Oncol 2006;24:116-122
  36. Lim P, Al Kushi A, Gilks B, Wong F, Aquino-Parsons C. Early stage uterine papillary serous carcinoma of the endometrium: effect of adjuvant whole abdominal radiotherapy and pathologic parameters on outcome. Cancer 2001;91:752-757 https://doi.org/10.1002/1097-0142(20010215)91:4<752::AID-CNCR1061>3.0.CO;2-E
  37. Sutton G, Axelrod JH, Bundy BN, et al. Adjuvant whole abdominal irradiation in clinical stage I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2006;100:349-354 https://doi.org/10.1016/j.ygyno.2005.08.037
  38. Hamilton CA, Liou WS, Osann K, et al. Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys 2005;63:839-844 https://doi.org/10.1016/j.ijrobp.2005.03.028
  39. NCCN Clinical Guidelines in Oncology. Uterine cancer V.2. 2008. National Comprehensive Cancer Network. www.nccn.org
  40. Descamp 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
  41. Lanciano RM, Com BW, Schultz DJ, Kramer CA, Rosenblum N, Hogan WM. The justification for a surgical staging system in endometrial carcinoma. Radiother Oncol 1993;28:189-196 https://doi.org/10.1016/0167-8140(93)90057-F
  42. Mayr NA, Wen BC, Benda JA, et al. Postoperative radiation therapy in clinical stage I endometrial cancer: corpus, cervical, and lower uterine segment involvement-Patterns of failure. Radiology 1995;196: 323-328 https://doi.org/10.1148/radiology.196.2.7617840
  43. Inoue Y, Obata K, Abe K, et al. The prognostic significance of vascular invasion by endometrial carcinoma. Cancer 1996;78:1447-1451 https://doi.org/10.1002/(SICI)1097-0142(19961001)78:7<1447::AID-CNCR11>3.0.CO;2-#
  44. Corn BW, Lanciano RM, Greven KM, et al. Impact of improved irradiation technique, age and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis. J Clin Oncol 1994;12:510-515 https://doi.org/10.1200/JCO.1994.12.3.510
  45. Nunns D, Williamson K, Swancy L, Davy M. The morbidity of surgery and adjuvant radiotherapy in the management of endometrial carcinoma. Int J Gynecol Cancer 2000;10:233-238 https://doi.org/10.1046/j.1525-1438.2000.010003233.x
  46. Creutzberg CL, van Putten WLJ, Koper PC, et al. The morbidity of treatment for patients with stage I endometrial cancer: Results from a randomized trial. Int J Radiat Oncol Biol Phys 2001;51:1246-1255 https://doi.org/10.1016/S0360-3016(01)01765-5
  47. Randall ME, Wilder J, Greven K, Raben M. Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma. Int J Radiat Oncol Biol Phys 1990;19:49-54 https://doi.org/10.1016/0360-3016(90)90133-5
  48. Irwin C, Levin W, Fyles A, Pintilie M, Manchul L, Kirkbride P. The role of adjuvant radiotherapy in carcinoma of the endometrium: Results of 550 patients with pathologic stage I disease. Gynecol Oncol 1998;70:247-254 https://doi.org/10.1006/gyno.1998.5064
  49. Greven KM, Lanciano RM, Herbert SH, Hogan PE. Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys 1991;21:919-923 https://doi.org/10.1016/0360-3016(91)90730-R
  50. Greven KM, Corn BW. Endometrial cancer. Curr Probl Cancer 1997;21:65-127 https://doi.org/10.1016/S0147-0272(97)80002-5