Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지
DOI QR코드

DOI QR Code

Results of Definitive Chemoradiotherapy for Unresectable Esophageal Cancer

절제 불가능한 식도암의 근치적 항암화학방사선치료의 성적

  • Noh, O-Kyu (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Je, Hyoung-Uk (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Kim, Sung-Bae (Department of Medical Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Lee, Gin-Hyug (Department of Gastroenterology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Park, Seung-Il (Department of Thoracic Surgery, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Lee, Sang-Wook (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Song, Si-Yeol (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Ahn, Seung-Do (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Choi, Eun-Kyung (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan) ;
  • Kim, Jong-Hoon (Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan)
  • 노오규 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 제형욱 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 김성배 (울산대학교 의과대학, 서울아산병원 종양내과) ;
  • 이진혁 (울산대학교 의과대학, 서울아산병원 소화기내과) ;
  • 박승일 (울산대학교 의과대학, 서울아산병원 흉부외과) ;
  • 이상욱 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 송시열 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 안승도 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 최은경 (울산대학교 의과대학, 서울아산병원 방사선종양학과) ;
  • 김종훈 (울산대학교 의과대학, 서울아산병원 방사선종양학과)
  • Published : 2008.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: To investigate the treatment outcome and failure patterns after definitive chemoradiation therapy in locally advanced, unresectable esophageal cancer. Materials and Methods: From February 1994 to December 2002, 168 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated by definitive chemoradiation therapy. External beam radiation therapy (EBRT) ($42{\sim}46\;Gy$) was delivered to the region encompassing the primary tumor and involved lymph nodes, while the supraclavicular fossa and celiac area were included in the treatment area as a function of disease location. The administered cone-down radiation dose to the gross tumor went up to $54{\sim}66\;Gy$, while the fraction size of the EBRT was 1.8-2.0 Gy/fraction qd or 1.2 Gy/fraction bid. An optional high dose rate (HDR) intraluminal brachytherapy (BT) boost was also administered (Ir-192, $9{\sim}12\;Gy/3{\sim}4\;fx$). Two cycles of concurrent FP chemotherapy (5-FU $1,000\;mg/m^2$/day, days $2{\sim}6$, $30{\sim}34$, cisplatin $60\;mg/m^2$/day, days 1, 29) were delivered during radiotherapy with the addition of two more cycles. Results: One hundred sixty patients were analyzable for this review [median follow-up time: 10 months (range $1{\sim}149$ months)). The number of patients within AJCC stages I, II, III, and IV was 5 (3.1%), 38 (23.8%), 68 (42.5%), and 49 (30.6%), respectively. A HDR intraluminal BT was performed in 26 patients. The 160 patients had a median EBRT radiation dose of 59.4 Gy (range $44.4{\sim}66$) and a total radiation dose, including BT, of 60 Gy (range $44.4{\sim}72$), while 144 patients received a dose higher than 40 Gy. Despite the treatment, the disease recurrence rate was 101/160 (63.1%). Of these, the patterns of recurrence were local in 20 patients (12.5%), persistent disease and local progression in 61 (38.1%), distant metastasis in 15 (9.4%), and concomitant local and distant failure in 5 (3.1%). The overall survival rate was 31.8% at 2 years and 14.2% at 5 years (median 11.1 months). Disease-free survival was 29.0% at 2 years and 22.7% at 5 years (median 10.4 months). The response to treatment and N-stage were significant factors affecting overall survival. In addition, total radiation dose (${\geq}50\;Gy$ vs. < 50 Gy), BT and fractionation scheme (qd. vs. bid.) were not significant factors for overall survival and disease-free survival. Conclusion: Survival outcome after definitive chemoradiation therapy in unresectable esophageal cancer was comparable to those of other series. The main failure pattern was local recurrence. Survival rate did not improve with increased radiation dose over 50 Gy or the use of brachytherapy or hyperfractionation.

목 적: 절제 불가능한 식도암에서의 근치적 동시항암화학방사선치료의 치료 성적과 재발 양상에 대해 알아보고자하였다. 대상 및 방법: 1994년 2월부터 2002년 12월까지 서울아산병원에서 절제불가능한 국소진행된 식도암으로 진단 받거나 내과적으로 수술이 불가능한 식도암으로 진단 받은 후 근치적 목적의 동시항암화학방사선치료를 시행 받은 168명을 대상으로 하였다. 방사선치료는 원발병소와 종격동, 그리고 원발병소와 림프절 전이의 위치에 따라 쇄골상부림프절과 복강림프절을 포함하여 $42{\sim}46\;Gy$의 외부방사선을 조사하였고, 이후 원발병소와 림프절 전이 부위에는 $54{\sim}66\;Gy$까지 추가 조사하였다. 분할조사 방법은 분할조사선량 $1.8{\sim}2\;Gy$씩 1일 1회 조사하거나, 1.2 Gy씩 1일 2회 조사하였다. 고선량률관내 방사선치료를 실시하는 경우에는 Ir-192를 이용한 고선량률 방식으로 3 Gy씩 $3{\sim}4$회 시행하였다. 항암치료는 5-FU와 cisplatin을 이용하여 동시항암화학방사선치료(5-FU $1,00\;mg/m^2$/day, days $2{\sim}6$, $30{\sim}34$, cispiatin $60\;mg/m^2$/day, days 1, 29)를 2주기 시행하고 방사선치료 후에 2 주기를 추가하여 시행하였다. 결 과: 분석 가능한 환자는 160명 이었으며, 추적관찰 기간은 1개월에서 149개월(중앙값 10개월)이었다. 환자의 AJCC 병기는 I, II, III, IV 기가 각각 5명(3.1%), 38명(23.8%), 68명(42.5%), 49명(30.6%)이었다. 26명(16.3%)의 환자에서는 $9{\sim}12\;Gy$의 추가 관내방사선치료를 시행하였다. 관내방사선치료를 포함하여 총 40 Gy 이상 조사받은 144명의 환자에서 외부 방사선조사량의 범위는 $44.4{\sim}66\;Gy$ (중앙값 59.4)이었고, 총 방사선 조사량의 범위는 $44.4{\sim}72\;Gy$ (중앙값 60)이었다. 분석가능한 160명의 환자 중에서 101명(63.1%)에서 재발하였으며, 재발 양상으로는 국소 재발이 20명(12.5%), 지속적 병변 또는 국소 진행이 61명(38.1%), 원격전이가 15명(9.4%), 국소재발과 원격전이가 함께 있는 경우가 5명(3.)%)이었다. 전체환자의 중앙생존기간은 11.1개월이었고, 2년 및 5년 전체생존율은 각각 31.8%, 14.2%이었다. 중앙무병 생존기간은 10.4개월이었고, 2년 및 5년 무병생존율은 각각 29.0%, 22.7%이었다. 항암화학방사선치료 후에 종양 반응 및 림프절 병기만이 전체생존율에 유의하게 영향을 미치는 예후인자였다. 방사선 조사량(${\geq}50$ Gy vs. < 50 Gy), 관내 방사선치료의 추가 유무, 분할조사(1회/day vs. 2회/day)에 따른 전체 생존율 및 무병생존율에 유의한 차이는 관찰되지 않았다. 결 론: 식도암에서 근치적 동시 항암화학방사선치료의 성적은 다른 연구 결과와 유사한 결과를 보였다. 동시 항암화학 방사선치료 후의 주된 재발 양상은 국소 재발이었다. 방사선 조사량의 증가(${\geq}50\;Gy$), 고선량률관내방사선치료 및 과분할조사법의 시행은 치료 성적을 향상시키지 못하였다.

Keywords

References

  1. Earlam R, Cunha-Melo JR. Oesophogeal squamous cell carcinoms: II. A critical view of radiotherapy. Br J Surg 1980;67: 457-461 https://doi.org/10.1002/bjs.1800670702
  2. Hennessy TP, O'Connell R. Surgical treatment of squamous cell carcinoma of the oesophagus. Br J Surg 1984;71: 750-751 https://doi.org/10.1002/bjs.1800711004
  3. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593-1598 https://doi.org/10.1056/NEJM199206113262403
  4. Smith TJ, Ryan LM, Douglass HO, et al. Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 1998;42:269-276
  5. Bedenne L, Michel P, Bouche O, et al. Randomized phase III trial in locally advanced esophageal cancer: radiochemotherapy followed by surgery versus radiochemotherapy alone (FFCD 9102). In, Proc ASCO; 2002
  6. Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005; 23:2310-2317 https://doi.org/10.1200/JCO.2005.00.034
  7. Ajani J, Bekaii-Saab T, D'Amico TA, Javle M. Clinical practice guideline in oncology: esophageal cancer. National Comprehensive Cancer Network 2006
  8. Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term followup of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 1999;281:1623-1627 https://doi.org/10.1001/jama.281.17.1623
  9. Minsky BD, Neuberg D, Kelsen DP, et al. Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 1999;43:517-523 https://doi.org/10.1016/S0360-3016(98)00463-5
  10. Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A Phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207). Cancer 2000;88:988-995 https://doi.org/10.1002/(SICI)1097-0142(20000301)88:5<988::AID-CNCR7>3.0.CO;2-U
  11. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20: 1167-1174 https://doi.org/10.1200/JCO.20.5.1167
  12. Fink U, Stein HJ, Wilke H, Roder JD, Siewert JR. Multimodal treatment for squamous cell esophageal cancer. World J Surg 1995;19:198-204 https://doi.org/10.1007/BF00308626
  13. Bedenne L, Michel P, Bouche O, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25:1160-1168 https://doi.org/10.1200/JCO.2005.04.7118
  14. Kim JH, Choi EK, Kim SB, et al. Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer. Int J Radiat Oncol Biol Phys 2001;50: 1-12 https://doi.org/10.1016/S0360-3016(01)01459-6
  15. Wang Y, Shi XH, He SQ, et al. Comparison between continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma. Int J Radiat Oncol Biol Phys 2002;54:131-136
  16. Ohtsu A. Chemoradiotherapy for esophageal cancer: current status and perspectives. Int J Clin Oncol 2004;9:444-450 https://doi.org/10.1007/s10147-004-0454-9
  17. Ohtsu A, Boku N, Muro K, et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 1999;17:2915-2921 https://doi.org/10.1200/JCO.1999.17.9.2915
  18. Lee JL, Kim SB, Jung HY, et al. Efficacy of neoadjuvant chemoradiotherapy in resectable esophageal squamous cell carcinoma-a single institutional study. Acta Oncol 2003;42: 207-217 https://doi.org/10.1080/02841860310010736
  19. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19:305-313 https://doi.org/10.1200/JCO.2001.19.2.305
  20. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462-467 https://doi.org/10.1056/NEJM199608153350702
  21. Bosset JF, Gignoux M, Triboulet JP, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 1997; 337:161-167 https://doi.org/10.1056/NEJM199707173370304
  22. Araujo CM, Souhami L, Gil RA, et al. A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagus. Cancer 1991;67:2258-2261 https://doi.org/10.1002/1097-0142(19910501)67:9<2258::AID-CNCR2820670908>3.0.CO;2-G
  23. Roussel A, Jacob JH, Haegele P, et al. Controlled clinical trial for the treatment of patients with inoperable esophageal carcinoma: a study of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Recent Results Cancer Res 1988; 110:21-29
  24. Slabber CF, Nel JS, Schoeman L, Burger W, Falkson G, Falkson CI. A randomized study of radiotherapy alone versus radiotherapy plus 5-fluorouracil and platinum in patients with inoperable, locally advanced squamous cancer of the esophagus. Am J Clin Oncol 1998;21:462-465 https://doi.org/10.1097/00000421-199810000-00008
  25. Nam TK, Nah BS, Chung WK, Ahn SJ, Song JY. Results of concurrent chemoradiotherapy and intraluminal brachytherapy in esophageal carcinoma-retrospective analysis with respect to survival. J Korean Soc Ther Radiol Oncol 2004;22: 25-32

Cited by

  1. 고령의 국소 진행된 식도암환자에서 동시 항암화학방사선치료 vol.27, pp.2, 2009, https://doi.org/10.3857/jkstro.2009.27.2.84