Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Preliminary Results of Concurrent Chemotherapy and Radiation Therapy using High-dose-rate Brachytherapy for Cervical Cancer

자궁경부암에 항암화학요법과 동시 병용요법으로 외부 방사선조사와 고선량률 강내조사의 예비적 치료 결과

  • Lee, Kyung-Ja (Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University) ;
  • Lee, Ji-Hye (Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University) ;
  • Lee, Re-Na (Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University) ;
  • Suh, Hyun-Suk (Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University)
  • 이경자 (여자대학교 의과대학 방사선종양학교실) ;
  • 이지혜 (여자대학교 의과대학 방사선종양학교실) ;
  • 이레나 (여자대학교 의과대학 방사선종양학교실) ;
  • 서현숙 (여자대학교 의과대학 방사선종양학교실)
  • Published : 2006.09.30
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Abstract

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

목 적: 자궁경부암 환자에 항암화학요법과 동시에 외부 방사선조사와 고선량률의 강내조사를 시행하여 국소제어율, 생존율 및 독성을 후향적으로 분석하여 그 효과와 안전성을 알아보기 위한 연구이다. 대상 및 방법: 2001년 1월부터 2002년 12월까지 자궁경부암으로 진단받고 완치목적의 방사선치료가 필요한 30명의 환자를 대상으로 항암화학요법과 방사선조사를 동시에 시행하였다. 환자 나이의 중앙값은 58세($34{\sim}74$세)였다. 병리조직학적 소견은 29명이 편평상피세포암이고 1명은 선암이었다. FIGO 병기에 따라 IB 7명(23%), IIA 3명(10%), IIB 12명(40%), IIIA 3명(10%), IIIB 5명(17%)이었다. 외부 방사선조사는 골반강에 1회 180 cGy로 총 선량 $45{\sim}50.4\;Gy$ (중앙값: 50.4 Gy)를 시행하였다. 강내조사는 외부 방사선조사 41.4 Gy 조사 후 Ir-192를 이용한 고선량률로 point A에 1회 4 Gy를 주 2회 시행하여 총 $4{\sim}8$회 조사하여 $16{\sim}32\;Gy$ (중앙값 28 Gy) 조사하였다. Point A에 외부조사와 강내조사의 합산 선량의 생물학적 동등선량(biological effective dose, BED)은 $77{\sim}94\;GY_{10}$ (중앙값 $88\;Gy_{10}$)이었다. ICRU 38에 따른 직장의 선량은 $88{\sim}125\;Gy_3$ (중앙값 $109\;Gy_3$), 방광의 선량은 $91{\sim}123\;Gy_3$ (중앙값 $111\;Gy_3$)이였다. 항암제는 cisplatin ($60\;mg/m^2$)과 5-FU ($1,000\;mg/m^2$)를 외부 방사선조사와 동시에 시작하여 3주 간격으로 정맥 주입하였으며 총 $2{\sim}6$회(중앙값 5회) 시행하였다. 방사선조사 완료 후 4주에 진찰소견과 복부-골반 전산화단층촬영을 시행하여 관해정도를 관찰하였다. 추적기간은 $8{\sim}50$개월(중앙값 36개월)이었으며 국소제어율, 3년 생존율, 직장과 방광의 급성 및 만성 합병증을 관찰하였다. 결 과: 방사선조사와 항암화학요법을 동시에 시행하여 완전관해는 30명 중 28명으로 완전관해율은 93%였다. 3년 국소제어율은 87%, 전체환자의 3년 생존율은 93%, 무병생존율은 87%였다. 4명(13%)에서 국소실패를 보였고 1명(3%)에서 원격전이를 보였다. 치료 중 급성 합병증으로 11명(37%)에서 RTOG grade 1-2의 장염을 보였으며 1명은 대장의 천공이 발생하여 수술로 치유되었다. 12명(40%)에서 RTOG grade 1-2의 급성 방광염을 보였다. 3명(10%)에서 RTOG grade 1-2의 백혈구 감소증이 보였으며 1명에서 심한 백혈구 감소증(RTOG grade 4)이 나타났으나 회복되어 치료를 완료하였다. 만성 합병증으로 5명(15%)에서 RTOG grade 1-2의 만성 장염을 보였으며 별다른 치료 없이 지내고 있으며 1명(3%)에서 RTOG grade 2의 만성 방광염을 보였다. 그러나 치료에 의해 사망한 환자는 없었다. 결 론: 자궁경부암 환자에 항암화학요법과 동시에 외부 방사선조사와 고선량률의 강내조사를 시행한 결과 독성이 심하지 않고 국소제어율과 단기 생존율이 양호하여 안전하고 효율적인 치료방법으로 생각된다. 그러나 장기 생존율과 만성 합병증을 파악하기 위해서는 더 많은 환자를 대상으로 장기 추적관찰이 요구된다.

Keywords

References

  1. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and par-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137-1143 https://doi.org/10.1056/NEJM199904153401501
  2. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144-1153 https://doi.org/10.1056/NEJM199904153401502
  3. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin vs. hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 1999;17:1339-1348 https://doi.org/10.1200/JCO.1999.17.5.1339
  4. Wong LC, Ngan HY, Cheung AN, et al. Chemoradiation and adjuvant chemotherapy in cervical cancer. J Clin Oncol 1999; 17:2055-2060 https://doi.org/10.1200/JCO.1999.17.7.2055
  5. Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer. An update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol 2004;22: 872-880 https://doi.org/10.1200/jco.2004.22.14_suppl.872
  6. Green JA, Kilwan JM, Tierney JF, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 2001;258:781-786
  7. Lukka H, Hirte H, Fyles A, et al. Concurrent cisplatinbased chemotherapy plus radiotherapy for cervcial cancer - a meta-analysis. Clin Oncol 2002;14:203-212 https://doi.org/10.1053/clon.2002.0076
  8. Lunciano R, Calkins A, Bundy BN, et al. Randomized comparison of weekly cisplatin or protracted venous infusion of fluorouracil in combination with pelvic radiation in advanced cervix cancer: a Gynecologic Oncology Group study. J Clin Oncol 2005;23:8289-8295 https://doi.org/10.1200/JCO.2004.00.0497
  9. Fletcher GH. Textbook of radiotherapy. 3rd ed. Philadelphia, PA; Lea & Febier, 1980:720-773
  10. Horiot JC, Pigneux J, Pourquier H, et al. Radiotherapy alone in carcinoma of the intact uterine cervix according to G.H Fletcher guideline: a French cooperative study of 1,983 cases. Int J Radiat Oncol Biol Phys 1988;14:605-611 https://doi.org/10.1016/0360-3016(88)90080-6
  11. Perez CA, Camerl HM, Kuske RR, et al. Radiation therapy alone in the treatment of carcinoma of the uterine cervix: a 20-yr experience. Gynecol Oncol 1986;23:127-140 https://doi.org/10.1016/0090-8258(86)90216-7
  12. Strauss HG, Kuhnt T, Laban C, et al. Chemoradiation in cervical cancer with cisplatin and high-dose-rate brachytherapy combined with external beam radiotherapy: results of a phase-II study. Strahlenther Onkol 2002;178:378-385 https://doi.org/10.1007/s00066-002-0956-1
  13. Souhami L, Seymour R, Roman R, et al. Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1993;27:871-878 https://doi.org/10.1016/0360-3016(93)90462-5
  14. Tod M, Meredith W. A dosage system for use in the treatment of cancer of the uterine cervix. Br J RadioI 1938;11:809-824 https://doi.org/10.1259/0007-1285-11-132-809
  15. International Commission on Radiation Units and Measurements. Dose and volume specification for reporting intracavitary therapy in gynecology. ICRU Rep. vol. 38. Washington; ICRU, 1985
  16. Folwer JF. The linear-quadratic formula and program in fractionated radiotherapy. Br J Radiol 1989;62:679-694 https://doi.org/10.1259/0007-1285-62-740-679
  17. NCI Clinical Announcement: Concurrent chemoradiation for cervical cancer. Washington, DC; United States Department of Public Health, February 1999
  18. Peters WA, Liu PY, Baret RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000; 18:1606-1613 https://doi.org/10.1200/JCO.2000.18.8.1606
  19. Lanciano R. Optimizing radiation parameters for cervical cancer. Semin Radiat Oncol 2000;10:36-43 https://doi.org/10.1016/S1053-4296(00)80019-3
  20. Bastin KT, buchler DA, Stitt JA, et al. Resource utilization: high dose rate versus low dose rate brachytherapy for gynecologic cancer. Am J Clin Oncol 1993;16:256-263 https://doi.org/10.1097/00000421-199306000-00013
  21. Stitt JA, Fowler JF, Thomadsen BR, et al. High-doserate intracavitary brachytherapy for carcinoma of the cervix: the Madison System: I. Clinical and radiobiological considerations. Int J Radiat Oncol Biol Phys 1992;24:335-348 https://doi.org/10.1016/0360-3016(92)90690-J
  22. Wright J, Jones G, Whelan T, et al. Patient preference for high-or low-dose-rate brachytherapy in carcinoma of the cervix. Radiother Oncol 1994;33:187-194 https://doi.org/10.1016/0167-8140(94)90353-0
  23. Nag S, Erickson B, Thomadsen B, et al. For the American Brachytherapy Society. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2000; 48:201-211 https://doi.org/10.1016/S0360-3016(00)00497-1
  24. Petereit DG, Pearcey R. Literature analysis of high dose rate brachytherapy fractionation schedules in the treatment of cervical cancer: Is there an optimal fractionation schedule? Int J Radiat Oncol Biol Phy 1999;43:359-366 https://doi.org/10.1016/S0360-3016(98)00387-3
  25. Clark BG, Souhami L, Roman TN, et al. The prediction of late rectal complications in patients treated with high-doserate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1997;38:989-993 https://doi.org/10.1016/S0360-3016(97)00074-6
  26. Clark BG, Souhami L, roman TN, et al. Rectal complications in patients with irradiation with high-dose-rate brachytherapy: a dosimetric analysis. Int J Raddat Oncol Biol Phys 1994;28:1243-1250 https://doi.org/10.1016/0360-3016(94)90501-0
  27. Toita T, Kakinohna Y, Ogawa K, et al. Combination external beam radiotherapy and high-dose-rate intracavitary brachytherapy for uterine cervical cancer: analysis of dose and fractionation schedule. Int J Radiat Oncol Biol Phys 2003;56: 1344-1353 https://doi.org/10.1016/S0360-3016(03)00288-8
  28. Orgino I, Kitamura T, Okamoto N, et al. Late rectal complication following high-dose-rate intracavitary brachytherapy in caner of the cervix. Int J Radiat Oncol Biol Phys 1995;31 :725-734 https://doi.org/10.1016/0360-3016(94)00547-8
  29. Toita T, Moronmizato H, Ogawa K, et al. Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy for uterine cervical cancer. Gynecol Oncol 2005;96:665-670 https://doi.org/10.1016/j.ygyno.2004.11.046