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1 대한방사선종양학회지 2005;23(3):143~156 처방선량 및 치료기법별 치료성적 분석 결과에 기반한 자궁경부암 환자의 최적 방사선치료 스케쥴 :, Tel: 02) , Fax: 02) gekim@yumc.yonsei.ac.kr

2 대한방사선종양학회지 2005;23(3):143~156

3 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식

4 대한방사선종양학회지 2005;23(3): Fig. 1. Two standard protocols for combination of EBRT and ICR in Yonsei University Medical center. External RT on whole pelvis 1.8 Gy/d; External RT midline shielding Gy/d; External RT parametrial boost 2.0 Gy/ d; HDR-ICR 5 Gy to point A/ fr. * * * A B Fig. 2. Localization of Rectal ( ) and bladder point ( ). These figures are the examples showing that the distances from R & Vpoint to tandem (source) can be largely different according to anatomical configuration of an individual patient. On ICR plan that prescribes 5 Gy to point A, the absorbed radiation doses delivered to R & V-point are 2.5 Gy & 4.1 Gy in patient A, 4.5 Gy, 3.5 Gy in patient B, respectively. 여 사용하였다. 직장과 방광에 조사되는 방사선선량을 낮 Total Dose, 이하 MTD), 전골반조사선량과 강내근접치료선 추기 위해서 대부분의 환자에서 질 내 gauze packing을 시 량을 단순히 더하여 누적방사선총선량(Accumulated Total 행하였다. 결과적으로 치료계획 상 얻어진 R-Point 및 Dose, 이하 ATD)으로 하였다. 통상적으로 한 번에 V-Point 선량은 환자에 따라 큰 차이를 보였다. Simulation Gy씩 조사하는 외부방사선조사와 한 번에 3 7 Gy씩 조사 film상 R-Point 및 V-Point의 위치를 Fig. 2에서 보여주고 있 하는 내부방사선치료법의 분할선량 차이에서 기인할 수 다. 있는 종양 및 정상 조직에 대한 영향의 차이를 극복하기 위해 각각의 분할선량의 크기를 고려하여 생물학적으로 동 3. 처방 선량 및 생물학적 유효선량 등한 영향을 미친다고 간주할 수 있는 객관적인 환산된 방 처방선량은 다음과 같이 세분하여 조사하였다. 우선 전 사선 선량인 생물학적유효선량(Biologically Effective Dose, 골반에 조사된 방사선 선량을 전골반조사선량(Whole Pelvis BED)을 적용하였다. 특히 이 BED는 종양조직과 만성반응 Dose, 이하 WPD), 전골반조사선량에다가 조사영역축소법 조직에 대한 효과를 모두 반영할 수 있기 때문에 적정 조 (cone down)을 시행하여 골반벽으로 침윤된 종양 혹은 육 사선량을 평가하는데 매우 유용한 도구라고 생각된다. α/ 안 골반림프절 전이에 대해서 추가 조사된 방사선량을 β비를 종양은 10, 만성반응조직은 3으로 하여 BED를 계 합한 선량을 외부방사선총선량(External Total Dose, 이하 산하였다. ETD), 전골반조사 중 중앙차폐를 시작한 선량을 중앙외부 접치료선량의 합산 선량을 BED로 환산한 값을 α/β비에 19) 중앙외부방사선량과 Point A에 처방된 강내근 방사선량(Midline Block Dose, MBD), 중앙차폐선량과 강내 따라 각각 중앙유효선량-Gy10 (Midline BED Gy10, 이하 MD- 근접치료선량을 단순히 더하여 중앙방사선총선량(Midline BED Gy10) 및 중앙유효선량-Gy3 (Midline BED Gy3, 이하

These figures are the examples showing that the distances from R & Vpoint to tandem (source) can be largely different according to anatomical configuration of an individual patient.

5 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식

6 대한방사선종양학회지 2005;23(3):143~156

7 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식

8 대한방사선종양학회지 2005;23(3):143~156

9 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식

10 대한방사선종양학회지 2005;23(3):143~156

11 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식 Point A

12 대한방사선종양학회지 2005;23(3):143~156 Remote afterloading with intracavitary applicators. Radiology 1964;83: A new remotely controlled unit for the treatment of uterine carcinoma. Lancet 1965;18: Treatment of carcinoma of the uterine cervix by remotely afterloading intracavitary radiotherapy with high dose rate: a comparative study with a low-dose system. Int J Radiat Oncol Biol Phys 1983;9: High-dose rate and low-dose rate intracavitary therapy for carcinoma of the uterine cervix. Cancer 1993;72: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 1994;28: High-dose-rate versus low-dose-rate intracavitary brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1990;19: High and low dose-rate brachytherapy for cervicalcarcinoma. Acta Oncol 1998;37; Literature analysis of high dose

Int J Radiat Oncol Biol Phys 1983;9:351-356 High-dose rate and low-dose rate intracavitary therapy for carcinoma of the uterine cervix. Cancer 1993;72:2409-2414 Low dose rate vs.

13 조재호 외 10인:자궁경부암의 방사선치료에 있어서 최적선량분할방식 rate brachytherapy fractionation scheduled in the treatment of cervical cancer : is there an optimal fractionation schedule? Int J Radiat Oncol Biol Phys 1999;43: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 2000;48: Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1995;32: The adverse effect of treatment prolongation in cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32: The influence of treatment time on outcome for squamous cell cancer of the uterine cervix treated with radiation: a patternsof-care study. Int J Radiat Oncol Biol Phys 1993;25: Fractionated high-dose-rate brachytherapy in the management of uterine cervical cancer. Yonsei Med J 2002;43: Treatment of carcinoma of the uterine cervix with high-dose-rate intracavitary irradiation using Ralstron. J Korean Soc Ther Radiol Oncol 1990;8: Treatment for uterine cervical cancer using high-dose-rate Co-60 sources. J Korean Soc Ther Radiol Oncol 1983;1: High versus low dose rate intracavitary irradiation for adenocarinoma of the uterine cervix. Jpn J Clin Oncol 2001;31: Late rectal complication in patients with high dose rate brachytherapy for stage IIB carcinoma of the cervix. J Korean Soc Ther Radiol Oncol 1996;14:41-52 Optimum dose combination of external radiation and high dose rate ICR in FIGO IB uterine cervical cancer. J Korean Soc Ther Radiol Oncol 1996;14: The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989;62: 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: Late rectal complication following high dose rate intracavitary brachytherapy in cancer of the cervix. Int J Radiat Oncol Biol Phys 1995;31: The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1997;38: High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications. Int J Radiat Oncol Biol Phys 2001;50: Comparative study of reference points by dosimetric a- nalyses for late complications after uniform external radiotherapy and high-dose-rate brachytherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2004;60:

Int J Radiat Oncol Biol Phys 2000;48:201-211 Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy.

14 대한방사선종양학회지 2005;23(3):143~156 Optimum Radiotherapy Schedule for Uterine Cervical Cancer based-on the Detailed Information of Dose Fractionation and Radiotherapy Technique Departments of Radiation Oncology, Preventive Medicine and Public Health, and Pathology, Yonsei University Medical School, Seoul, Korea Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and A total external beam radiotherapy (EBRT) dose of Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of Gy (Median 36.0) of EBRT in 495 patients, while in the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ( / =10) and late-responding tissues ( / =3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED Gy 3 and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED Gy 3 and rectal complications and between V-BED Gy 3 and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED Gy 10, and the treatment duration. Results: The overall complication rate for RTOG Grades 1 4 toxicities was 33.1%. The 5-year actuarial pelvic control rate for all 743 patients was 83%. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to Gy 10 (median 93.0) for tumors and from 93.6 to Gy 3 (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED Gy 3) and bladder point BED (V-BED Gy 3) were Gy 3 (range ) and Gy 3 (range: ), respectively. MD-BED Gy 3 showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED Gy 3 had a very strong association (p= ), and was more predictive of rectal complications than A-BED Gy 3. B-BED Gy 3 also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences in tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered. Cervix cancer, Fractionation, High dose rate brachytherapy

$It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation.$

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( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy