Rectal Bleeding and Its Management after Irradiation for Cervix Cancer

자궁경부암 환자에서 방사선치료 후에 발생한 직장출혈과 치료

  • Chun Mison (Department of Radiation Oncology, School of Medicine, Ajou University) ;
  • Kang Seunghee (Department of Radiation Oncology, School of Medicine, Ajou University) ;
  • Kil Hoon-Jong (Department of Radiation Oncology, School of Medicine, Ajou University) ;
  • Oh Young-Taek (Department of Radiation Oncology, School of Medicine, Ajou University) ;
  • Sohn Jeong-Hye (Department of Radiation Oncology, School of Medicine, Ajou University) ;
  • Jung Hye-Young (Department of Preventive Medicine and Public Wealth, College of Medicine, Yonsei University) ;
  • Ryu Hee Suk (Department of Gynecology Oncology, School of Medicine, Ajou University) ;
  • Lee Kwang-Jae (Department of Gastroenterology, School of Medicine, Ajou University)
  • 전미선 (아주대학교 의과대학 치료방사선과학교실) ;
  • 강승희 (아주대학교 의과대학 치료방사선과학교실) ;
  • 길훈종 (아주대학교 의과대학 치료방사선과학교실) ;
  • 오영택 (아주대학교 의과대학 치료방사선과학교실) ;
  • 손정혜 (아주대학교 의과대학 치료방사선과학교실) ;
  • 정혜영 (연세대학교 의과대학 예방의학교실) ;
  • 유희석 (아주대학교 의과대학 산부인과학교실) ;
  • 이광재 (아주대학교 의과대학 소화기내과학교실)
  • Published : 2002.12.01

Abstract

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

목적 : 자궁경부암의 경우 종양에 충분한 양의 방사선을 조사하기 위해서는 직장도 고선량의 방사선을 받게 된다. 이로 인해 직장염을 비롯한 만성부작용이 발생하며 직장 출혈 빈도를 $5\~30\%$ 보고하고 있다. 저자는 완치 목적의 방사선치료를 받은 자궁경부암 환자들을 대상으로 직장 출혈 빈도와 그와 관련된 위험인자들을 분석하고 치료 방법을 살펴보고자 한다. 대상 및 방법 : 1994년 9월과 1999년 12월 사이에 방사선 단독치료를 받은 213명의 자궁경부암 환자를 대상으로 하였다. 90명이 외부 방사선치료의 일부를 하루 2회씩 받았다(변형된 다분할 방사선치료). 자궁주위조직의 외부 방사선량은 총 $51\~59\;Gy$였고 근접방사선치료로 A점에 총 $28\~30\;Gy$ (4 Gy씩 7회 혹은 5 Gy씩 6회)를 조사하였다. 직장에 조사된 선량은 ICRU 38에서 정한 위치와, 모의촬영필름에서 바리움에 의해 구분되는 직장 앞쪽 벽의 한 점을 선정하여 계산하였다. 직장출혈의 정도는 LENT/SOMA에 따라 분류하였다. 추적관찰 기간은 $12\~86$개월(중앙값 39개월)이었다. 결과 : 27명$(12.7\%)$의 환자에서 직장출혈이 발생하였다(등급 2와 3:각각 16명과 2명, $8.5\%$). 이들 중에서 추적관찰 기간동안 질-직장루 또는 폐쇄로 진행된 경우는 없었다 발생시기는 대부분의 환자에서$(92.6\%)$ 치료 종료 후 2년 이내였다(중앙값 16개월). 단변량분석에서 위험인자로 icruCRBED (직장이 받은 총 생물학적 동등선량), 자궁주위조직의 방사선량, 및 병기였다. icruCRBED가 100 미만인 경우와 100 이상인 경우 $4.2\%$$19.7\%$, 자궁주위조직에 대한 조사선량 55 Gy 미만과 그 이상인 경우가 $5.1\%$$22.1\%$, 병기 II 이하인 경우와 III 이상인 경우가 $10.5\%$$31.8\%$였다. 다변량분석에서는 icruCREED 만이 유의하였다(0=0.0432). 등급 1 출혈은 자연적으로 소실되거나(3명) $1\~2$개월의 sucralfate 관장으로 멈추었다. 등급 2의 환자 6명은 $1\~2$개월 동안 sucralfate 관장으로 출혈의 빈도와 양이 줄어들었고 이 중 4명은 전기응고술을 추가로 시행하였다. 다른 9명은 전기응고술을 먼저 시행하였다(4명; sucralfate 관장 병행). 모두 $3\~10$개월 내에 정지되었다. 등급 3의 출혈은 잦은 전기응고술과 수혈을 요하였다. 결론 : 본 연구에서 중등도 이상의 직장출혈빈도가 $8.5\%$로 타 문헌에서 보고된 빈도와 유사한 결과였다. 직장에 조사된 총 생물학적 동등선량이 100 Gy 이상인 경우에 직장출혈이 유의하게 증가하므로, 치료계획시 생물학적 동등선량을 고려함으로써 휴유증 감소에 도움이 될 것으로 생각된다. 직장출혈이 발생한 환자에서 조기에 적극적으로 치료를 시행함으로써 출혈로 인한 불편함을 신속하게 해결하고 이로 인한 심리적 불안감을 해소할 수 있으며 나아가 삶의 질 향상에도 도움을 줄 수 있을 것으로 판단된다.

Keywords

References

  1. Akine Y, Arimoto H, Ogino T, et aI. High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: early experience with 84 pationts. Int J Radiat Oncol Biol Phys 1988;14:893-898 https://doi.org/10.1016/0360-3016(88)90011-9
  2. Teshima T, Chatani M, Hata K, Inoue T. High-dose rate intracavitary therapy for carcinoma of the uterine cervix : II. Risk factors for rectal complication. Int J Radiat Oncol Biol Phys 1988;14:281-286
  3. Fu kk, PhiIIips TL. High-dose rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1990;19:791-796 https://doi.org/10.1016/0360-3016(90)90511-H
  4. Chen MS, Lin Hong CH, et aI. High-dose-rate afterloading technique in the radiation treatment of uterine cervical cancer : 399 cases and 9 years experience in Taiwan. Int J Radiat Oncol Biol Phys 1991;20:915-919 https://doi.org/10.1016/0360-3016(91)90185-7
  5. Orton CG, Seyedsadr M, Somnay A. Comparison of high and low dose rate remote afterloading for cervix cancer and the importance of fractionation. Int J Oncol Biol Phys 1991;21:1425-1434 https://doi.org/10.1016/0360-3016(91)90316-V
  6. Roman TN, Souhami L, Freeman CR, et aI. High dose rate afterloading intracavitary therapy in carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1991;20:921-926 https://doi.org/10.1016/0360-3016(91)90186-8
  7. Ha SW, Chung WK, Kin JH. Bowel complication after radiotherapy of uterine cervix carcinoma. J Korean Soc Ther Radiol 1992;10:237-245
  8. CIark BG, Souhami L, Roman TN, Evans MD, PIa C. Rectal complications in patients with carcinoma of the cervix treated with concomitant cisplatin and external beam irradiation with high dose rate brachytherapy : a dosimetric analysis. Int J Radiat Oncol Biol Phys 1994;28:1243-1250 https://doi.org/10.1016/0360-3016(94)90501-0
  9. Ogino I, Kitamura T, Okamoto N, et aI. Late rectal complication following high dose rate intracavitary brachytherapy in cancer of the cervix. Int J Radiat Oncol Biol Phys 1995;31:725-734 https://doi.org/10.1016/0360-3016(94)00547-8
  10. Wang CJ, Leung SW, Chen HC, et aI. High-dose-rate intracavitary brachytherapy (HDR-IC) in treatment of cervical carcinoma : 5-year results and implication of increased lowgrade rectal complication on initiation of an HDR-IC fractionation scheme. Int J Radiat Oncol Biol Phys 1997;38:391-398 https://doi.org/10.1016/S0360-3016(96)00624-4
  11. Uno T, Itami J, Aruga M, et aI. High dose rate brachytherapy for carcinoma of the cervix : Risk factors for late rectal complications. Int J Radiat Oncol Biol Phys 1998;40:615-621 https://doi.org/10.1016/S0360-3016(97)00849-3
  12. Chen SW, Liang JA, Yang SN, Liu RT, Lin FJ. The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose- rate brachytherapy. Int J Radiat Oncol Biol Phys 2000;47:955-961 https://doi.org/10.1016/S0360-3016(00)00559-9
  13. KiI HJ, Chun M, Kang S, et aI. Radiotherapy results in stage IIB uterine cervix cancer. J Korean Soc Ther Radiol Oncol 2001;19:345-352
  14. Chun M, Kang S, Ryu HS, et aI. Modified partial hyperfractionation in radiotherapy for bulky uterine cervical cancer : Reduction of overall treatment time. Int J Radiat Oncol Biol Phys 2000;47:973-977 https://doi.org/10.1016/S0360-3016(00)00539-3
  15. InternationaI Commission of Radiation Units. Report 38 : Dose and volume specification for reporting intracavitary therapy in gynecology. Bethesda : Interntional Commission of Radiation Units, 1985
  16. LENT SOMA scales for all anatomic sites. Int Radiat Oncol Biol Phys 1995;31:1049-1091
  17. Kochhar R, PateI F, Dhar A, et aI. Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine pIus rectal steroids versus rectal sucralfate. Dig Dis Sci 1991;36:103-107
  18. Fischer L, Kimose HH, SpjeIdnaes N, Wara P. Late progress of radiation-induced proctitis, Acta Chir Scand 1990;156:801-805
  19. Lanciano RM, Martz K, Montana GS, Hanks GE. Influence of age, prior abdominal surgery, fraction size, and dose on compIications after radiation therapy for squamous cell cancer of the uterine cervix. A patterns of care study. Cancer 1992;62:2124-2130
  20. Teshima T, Hanks GE, Hanlon AL, Peter RS, SchuItheiss TE. Rectal bleeding after conformal 3D treatment of prostate cancer : Time to occurrence, response to treatment and duration of morbidity. Int J Radiat Oncol Biol Phys 1997;39:77-83 https://doi.org/10.1016/S0360-3016(97)00301-5
  21. SchoeppeI S, LaVigne M, MarteI MK, McShan D, Fraass B, Roberts J. Three-dimensional treatment planning of intracavitary gynecologic implants: analysis of ten cases and impIications for dose specification. Int J Radiat Oncol Biol Phys 1994;28:277-283 https://doi.org/10.1016/0360-3016(94)90168-6
  22. Kapp KS, StueckIschweiger GF, Kapp DS, HackI AG. Dosimetry of intracavitary placements for uterine and cervical carcinoma : Results of orthogonal film, TLD, and CT-assisted techniques. Radiother Oncol 1992;24:137-146 https://doi.org/10.1016/0167-8140(92)90372-2
  23. Pourquier H, Dubois JB, DeIard R. Cancer of the uterine cervix; Dosimetric guidelines for prevention of late rectal and rectosigmoid complications as a resuIt of radiotherapeutic treatment. Int J Radiat Oncol Biol Phys 1982;8:1887-1895
  24. Stryker JA, BarthoIomew M, VeIkIey DE, et aI. Bladder and rectal compIications following radiotherapy for cervix cancer. Gynecol Oncol 1988;29:1-11 https://doi.org/10.1016/0090-8258(88)90140-0
  25. Montana GS, FowIer WC. Carcinoma of the cervix : Analysis of bladder and rectal radiation dose and complications. Int J Radiat Oncol Biol Phys 1989;16:95-100 https://doi.org/10.1016/0360-3016(89)90015-1
  26. Perez CA, Breaux S, Bedwinek JM, et aI. Radiation therapy alone in the treatment of carcinoma of th uterine cervix. II. AnaIysis of compIicatons. Cancer 1984;4:235-246
  27. Esche BA, Crook JM, Horiot JC. Dosimetric methods in the optimization of radiotherapy for carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1987;13:1183-1192 https://doi.org/10.1016/0360-3016(87)90193-3
  28. Van Lancker M, Storme G. Prediction of severe late compIications in fractionated, high dose-rate brachytherapy in gynecological applications. Int J Radiat Oncol Biol Phys 1991;20:1125-1129 https://doi.org/10.1016/0360-3016(91)90214-O
  29. Shin KH, Huh SJ, Chie EK, et aI. Analysis of correlation between rectal complications and rectal dose following high dose rate intracavitary radiotherapy in patients with uterine cervix cancer : in vivo dosimetric analysis. Radiat Med 1999;17:289-293
  30. Cunningham DE, Stryker JA, VeIkIey DE, Chung CK. Routine cInical estimation of rectal, rectosigmoidal, and bladder doses from intracavitary brachytherapy in the treatment of carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1981;7:653-660 https://doi.org/10.1016/0360-3016(81)90381-3
  31. Huang EY, Lin H, Hsu HC, et aI. High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer. Gynecol Oncol 2000;79:406-410 https://doi.org/10.1006/gyno.2000.5997
  32. CoIwell JC, GoIdberg M. A review of radiation proctitis in the treatment of prostate cancer. J Wound Ostomy Continence Nurs 2000;27:179-187
  33. Kang S. Chun M, Hahm K, Oh YT, Kim JH, Park JH. The effect of Sucralfate on the reduction of radiation esophagitis : CIinical and Iaboratory data. J Kor Cancer Asso 2000;32:925-932
  34. Szabo S, Vattay P, Scarbrough E, FoIkman J. Role of vascular factors, including angiogenesis, in the mechanism of action of sucralfate. Am J Med 1991;91(2A):158S-160S
  35. Eastwood G. Epithelial renewal in protection and repair of gastroduodenal mucosa. J Clin gastroenterol 1991;13(suppl):S48-S53
  36. FoIkman J, Szabo S, Strovroff M, McNeiI P, Li W, Shing Y. Duodenal uIcer. Discovery of new mechanism and development of angiogenetic therapy that accelerates heaIing Ann Surg 1991;214:414-425
  37. Zahavi I, Avidor I, Marcus H, et aI. Effect of sucralfate on experimentaI colitis in the rat. Dis Colon Rectum 1989;32:95-98 https://doi.org/10.1007/BF02553817
  38. Kochhar R, Sriram PV, Sharma SC, GoeI RC, PateI F. Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension. Dig Dis Sci 1999;44:973-8 https://doi.org/10.1023/A:1026612731210
  39. ShipIey WU, Zietmen AL, Hanks GE, et aI. Treatment related sequelae following external beam radiation for prostste cancer : A review with an update in patients with stages T1 and T2 tumor. J Urol 1994;152:1799-1805
  40. Barbatzas C, Spencer GM, Thorpe SM, Sargeant LR, Bown SG, Carbatzas C. Nd-YAG laser treatment for bleeding from radiation proctition proctitis. Endoscopy 1996;28:498-500
  41. Donner CS. Pathophysiology and therapy of chronic radiation-induced injury to the colon. Dig Dis 1998;16:253-261 https://doi.org/10.1159/000016873
  42. Swaroop V, Gostout C. Endoscopic treatment of chronic radiation proctopathy. J CIin Gastroenterol 1998;27:36-40 https://doi.org/10.1097/00004836-199807000-00007
  43. Viggiano TR, ZigheIboim J, AhIquist DA, Gostout CJ, Wang KK, Larson MV. Endoscopic Nd : YAG laser coagulation of bleeding from radiation proctopathy. Gastointest Endosc 1993;39:513-517 https://doi.org/10.1016/S0016-5107(93)70161-3
  44. Jensen DM, Machicado GA, Cheng S, Jensen ME, Jutabha R. Randomized prospective study of endoscopic bipolar electrocoagulation and heater probe treatment of chronic rectal bleeding from radiation telangiectasia. Gastrointest Endosc 1997;45:20-25 https://doi.org/10.1016/S0016-5107(97)70298-0
  45. Jao SW, Beart RW, Gunderson LL. Surgical treatnent of radiation injuries of the colon and rectum. Am J Surg 1986;151:272-277 https://doi.org/10.1016/0002-9610(86)90086-3
  46. Babb RR. Radiation proctitis: a review. Am J Gastroenterol 1996;91:1309-1311