Multidisciplinary Management of the Locally Advanced Unresectable Non-Small Cell Lung Cancer

수술 불가능한 국소 진행 비소세포성 폐암의 집합적 요법

  • Cho, Kwan-Ho (Research Institute and Hospital, National Cancer Center)
  • Published : 2004.03.01

Abstract

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development on distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases,, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach Improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of locally advanced NSCLC continues to evolve. The current issues in the multidisciplinary management of locally advanced NSCLC will be reviewed in this report.

비소세포성 폐암에서 국소 진행성 병변(병기 3)이 3분의 1을 차지한다. 이 중 완전 절제가 가능한 소수의 환자를 제외하고 대부분의 환자에서 근치적 방사선치료가 전통적으로 시행되어 왔다. 하지만 근치적 방사선치료 후 장기 생존율은 극히 불량하고, 대개의 경우 원격 전이 또는 국소 재발로 사망하게 된다. 지난 20년간, 집합적 요법으로 국소 진행성 비소세포성 폐암 치료효과의 향상이 있었다. 그중 화학방사선요법이 가장 흔히 사용되었고, 화학요법과 방사선치료를 병용하는 순서에 따라 다음 두 가지 기본적 방법이 있다. 즉, 순차적 요법과 동시 요법이 그것이다. 순차적 병용 요법은 유도 화학요법 완료 후 방사선 치료를 진행하는 순서로 주로 시행되었다. 근거로는 방사선 치료전 유도 화학요법 사용 으로 종양의 크기를 줄여 국소제어율을 높이고, 보이지 않는 미세 전이 병변을 제거하여 원격 전이를 감소시키는 데 있다. 방사선 단독 치료와 비교하여 순차적 화학방사선요법으로 중앙생존기간과 장기생존율의 향상을 보고한 여러 연구가 있다. 재발 양상을 분석한 보고에 따르면, 방사선치료 단독과 비교하여 순차적 병용요법이 원격전이율은 감소시키나, 국소 재발률에는 영향이 없었다. 화학요법과 방사선치료를 동시 시행하는 동시병용요법에 대한 많은 보고가 있다. 근거로는 화학요법을 방사선과 동시 투여함으로써 화학요법에 의한 종양세포 방사선 감작효과를 기대할 수 있고, 순차적요법과 비교하여 전체 치료기간을 단축하여 국소제어율을 향상시킬 수 있다. 기대했던 대로 동시 병용요법 후 국소 제어율 향상과 이로 인한 생존율 증가가 관찰되었다. 하지만 방사선 치료 단독과 비교하여 원격 전이율에는 차이가 없었고, 이는 급성 부작용, 특히 급성 식도염 위험을 줄이기 위해 대다수의 연구에서 관찰되듯이 화학요법의 강도를 줄인 때문으로 생각된다. 상기한 바와 같이 집합적 치료가 방사선 단독 요법과 비교하여 생존율의 향상에 기여하였고, 현재 새 표준 치료로 정착되었으나, 이의 치료효과는 아직도 실망스러우며, 최적 치료 개발을 위한 연구는 계속되어야 한다. 본 보고에서 국소 진행 비소세포성 폐암에서 집합적 치료에 대한 현 논점을 검토하고자 한다.

Keywords

References

  1. Facts and figures. In: Global action against cancer. WHO 2003 publications
  2. Jemal A, Murray T, Samuels A, et al. Cancer Statistics, 2003. CA Cancer J Clin 2003;53:5-26, 2003 https://doi.org/10.3322/canjclin.53.1.5
  3. Cancer statistics in Korea, 2001. Cancer registration and biostatistics branch, National Cancer Center
  4. Perez CA, Pajak TF, Rubin P, et al. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group. Cancer 1987;59:1874-1881 https://doi.org/10.1002/1097-0142(19870601)59:11<1874::AID-CNCR2820591106>3.0.CO;2-Z
  5. Sandler HM, Curran WJ Jr, Turrisi AT 3rd . The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1990;19(1):9-13 https://doi.org/10.1016/0360-3016(90)90127-6
  6. Arriagada R, Le Chevalier T, Quoix E, et al. ASTRO (American Society for Therapeutic Radiology and Oncology) plenary: Effect of chemotherapy on locally advanced nonsmall cell lung carcinoma: a randomized study of 353 patients. GETCB (Groupe d'Etude et Traitement des Cancers Bronchiques), FNCLCC (Federation Nationale des Centres de Lutte contre le Cancer) and the CEBI trialists. Int J Radiat Oncol Biol Phys 1991;20(6):1183-1190 Nationale des Centres de Lutte contre le Cancer) and the CEBI trialists. Int J Radiat Oncol Biol Phys 1991;20(6):1183-1190
  7. Arriagada R, Le Chevalier T, Rekacewicz C, et al. Cisplatin-based chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC): late analysis of a French randomized trial [Abstract]. Proc Am Soc Clin Oncol 1997;16
  8. Cox JD, Azarnia N, Byhardt RW, Shin KH, Emami B, Pajak TF. A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with Radiation Therapy Oncology Group stage III non-small-cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11. JCO 1990;8:1543-1555
  9. Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in nonsmall-cell lung cancer: a randomised multicentre trial. CHART Steering Committee Lancet 1997;19;350(9072):161-165
  10. Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 1990;323:940-945 https://doi.org/10.1056/NEJM199010043231403
  11. Dillman RO, Herndon J, Seagren SL, et al. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J Natl Cancer Inst 1996;88:1210-1215 https://doi.org/10.1093/jnci/88.17.1210
  12. Sause WT, Scott C, Taylor S, et al. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperativ Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable nonsmall-cell lung cancer. J Natl Cancer Inst 1995;87:198-205 https://doi.org/10.1093/jnci/87.3.198
  13. Sause W, Kolesar P, Taylor S IV, et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000;117:358-364 https://doi.org/10.1378/chest.117.2.358
  14. Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 1991;83:417-423 https://doi.org/10.1093/jnci/83.6.417
  15. Le Chevalier T, Arriagada R, Quoix E, et al. Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung carcinoma. Lung Cancer 1994;10(Suppl 1):S239-S244
  16. Schaake-Koning C, vanden Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 1992;326:524-530 https://doi.org/10.1056/NEJM199202203260805
  17. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyperfractionated radiation therapy with or without concurrent low-dose, daily carboplatin/etoposide for stage III non-small cell lung cancer: a randomized study. J Clin Oncol 1996;14:1065-1070
  18. Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:2692-2699
  19. Curran W Jr, Scott C, Langer C, et al. Phase III comparison of sequential vs. concurrent chemoradiation for patients (pts) with unresected stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410 [Abstract]. Proc Am Soc Clin Oncol 2000;19:484a:1891
  20. Clamon G, Herndon J, Cooper R, Chang AY, Rosen-man J, Green MR. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lun cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17(1):4-11
  21. Komaki R, Scott C, Ettinger D, et al. Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04. Int J Radiat Oncol Biol Phys 1997;38(1):149-155 https://doi.org/10.1016/S0360-3016(97)00251-4
  22. Byhardt RW, Scott C, Sause WT, et al. Response, toxicity, failure patterns, and survival in five Radiation Therapy Oncology Group (RTOG) trials of sequential and/or concurrent chemotherapy and radiotherapy for locally advanced non-small-cell carcinoma of the lung. Int J Radiat Oncol Biol Phys 1998;42:469-478 https://doi.org/10.1016/S0360-3016(98)00251-X