Evaluation of prognostic factors on survival in non-small-cell lung cancer patients treated with postoperative radiotherapy

Abstract

OBJECTIVES To investigate the prognostic factors on survival in nonsmall-cell lung cancer patients treated with postoperative radiotherapy. METHODS Sixty-five patients treated with a median dose of 59 Gy (50-66.6 Gy) between October 1995 and January 2005 were included in the study. Clinical and categorical variables were analyzed. RESULTS On multivariate analysis, presence of clinical N2 and brain metastasis at first relapse and absence of chemotherapy (p=0.02, p=0.004, p=0.004) had a negative impact on overall survival, while presence of pathological nodal involvement and absence of chemotherapy (p=0.02, p=0.04) were effective on disease-free survival. Regarding categorical variables, type of resection was found related with positive margin and N1, right-sided location with N1-e and N2, and systematic nodal dissection with N1. The number of involved lymph nodes was found related with N2 skip metastasis and involved N1-10 was related with N1-e. CONCLUSION Presence of metastatic lymph nodes was found to be a poor prognostic factor and delivery of chemotherapy was seen to positively affect overall and disease-free survival rates.

Keywords

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Postoperatif radyoterapi uygulanan küçük hücreli dışı akciğer kanserli olgularda sağkalım üzerine etkili prognostik faktörlerin değerlendirilmesi

Abstract

AMAÇ Postoperatif radyoterapi alan küçük hücreli dışı akciğer kanserli hastalarda sağkalım üzerindeki prognostik faktörler araştırıldı. GEREÇ VE YÖNTEM Ekim 1995-Ocak 2005 arasında 65 hasta ortanca 59 Gy (50-66.6 Gy) ile tedavi edildi. Klinik ve kategorik değişkenler incelendi. BULGULAR Çok değişkenli analizde; klinik N2 tutulumu, ilk nüksün beyin metastazı olması ve kemoterapi yokluğu (p=0.02, p=0.004, p=0.004) genel sağkalımı; patolojik lenf nodu tutulumu ve kemoterapi yokluğu (p=0.02, p=0.04) hastalıksız sağkalımı olumsuz etkilemiştir. Kategorik analizde; rezeksiyon tipi, pozitif cerrahi sınır ve N1 ile, sağ yerleşim, N1-e ve N2 ile sistematik nodal diseksiyon N1 ile ilişkili bulundu. Tutulmuş lenf nodu sayısı, N2 skip metastaz ile ve N1-10 tutulumu N1-e ile ilişkili bulundu. SONUÇ Metastatik lenf nodu varlığı kötü prognostik faktör olarak bulunmuş ve kemoterapi verilmesinin genel ve hastalıksız sağkalım oranlarını olumlu etkilediği görülmüştür.

Keywords

• Küçük hücreli dıflı akciğer kanseri, postoperatifradyoterapi, prognostik faktörler, sağkalım

References

1. 1. PORT Meta-Analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2003;(1):CD002142.
2. 2. Dinçbafl FÖ. Küçük hücreli d›fl› akci¤er kanserinde (KHDAK) radyoterapinin sa¤kal›ma ve yaflam kalitesine katk›s›. Dispne 2007;(2):38-45.
3. 3. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. The Lung Cancer Study Group. N Engl J Med 1986;315(22):1377-81.
4. 4. Van Houtte P, Rocmans P, Smets P, Goffin JC, L u s t m a n - M a r é c h a l J , Vanderhoeft P, et al. Postoperative radiation therapy in lung cancer: a controlled trial after resection of curative design. Int J Radiat Oncol Biol Phys 1980;6(8):983-6.
5. 5. Israel L, Bonadonna G, Sylvester R and Members of the EORTC Lung Cancer Group. Controlled study with adjuvant radiotherapy, chemotherapy, immunotherapy and chemoimmunotherapy in operable squamous cell carcinoma of the lung. In: Muggia FM, Rozencweig M, editors. Lung Cancer: progress in therapeutic research. New York: Raven Press; 1979. p. 443-52.
6. 6. Stephens RJ, Girling DJ, Bleehen NM, Moghissi K, Yosef HM, Machin D. The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party. Br J Cancer 1996;74(4):632-9.
7. 7. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998;352(9124):257-63.
8. 8. Machtay M, Lee JH, Shrager JB, Kaiser LR, Glatstein E. Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-smallcell lung carcinoma. J Clin Oncol 2001;19(19):3912-7.

9. 9. Bekelman JE, Rosenzweig KE, Bach PB, Schrag D. Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006;66(2):492-9.
10. 10.Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, et al. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. Eastern Cooperative Oncology Group. N Engl J Med 2000;343(17):1217-22.
11. 11. Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000;70(2):358-66.
12. 12.Bogart JA, Aronowitz JN. Localized non-small cell lung cancer: adjuvant radiotherapy in the era of e ffective systemic therapy. Clin Cancer Res 2005;11(13 Pt 2):5004s-5010s.
13. 13.Rea F, Marulli G, Callegaro D, Zuin A, Gobbi T, Loy M, et al. Prognostic significance of main bronchial lymph nodes involvement in non-small cell lung carcinoma: N1 or N2? Lung Cancer 2 0 0 4 ; 4 5 ( 2 ) : 2 1 5 - 2 0 .
14. 14.Sen S. Prognosis of non-small cell lung cancer. Turkiye Klinikleri J Surg Med Sci 2006;2(12):52-7.
15. 15.Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111(6):1710-7.
16. 16.Okada M, Sakamoto T, Nishio W, Uchino K, Tsubota N. Characteristics and prognosis of patients after resection of nonsmall cell lung carcinoma measuring 2 cm or less in greatest dimension. Cancer 2003;98(3):535-41.
17. 17.Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metasta- sis in resected lung cancer. J Thorac Cardiovasc Surg 1978;76(6):832-9.
18. 18.American Thoracic Society. Medical section of the American Lung Association. Clinical staging of primary lung cancer. Am Rev Respir Dis 1983;127(5):659-64.
19. 19.Riquet M, Manac’h D, Le Pimpec-Barthes F, Dujon A, Chehab A. Prognostic significance of surgicalpathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg 1999;67(6):1572-6.
20. 20.Izbicki JR, Passlick B, Pantel K, Pichlmeier U, Hosch SB, Karg O, et al. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial. Ann Surg 1998;227(1):138-44.
21. 21.Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg 1998;22(3):290-5.
22. 22.Should subcarinal lymph nodes be routinely examined in patients with non-small cell lung cancer? The Lung Cancer Study Group. J Thorac Cardiovasc Surg 1988;95(5):883-7.
23. 23.Yano T, Fukuyama Y, Yokoyama H, Kuninaka S, Terazaki Y, Uehara T, et al. Long-term survivors with pN2 non-small cell lung cancer after a complete resection with a systematic mediastinal node dissection. Eur J Cardiothorac Surg 1998;14(2):152-5.
24. 24.Yano T, Yokoyama H, Inoue T, Asoh H, Tayama K, Ichinose Y. Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes. J Thorac Cardiovasc Surg 1994;107(6):1398- 402.
25. 25.Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer 2002;36(1):1-6.
26. 26.Osaki T, Nagashima A, Yoshimatsu T, Tashima Y, Yasumoto K. Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer 2004;43(2):151-7.
27. 27.Okada M, Sakamoto T, Yuki T, Mimura T, Nitanda H, Miyoshi K, et al. Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors. J Thorac Cardiovasc Surg 2005;129(4):825-30.
28. 28.Prenzel KL, Mönig SP, Sinning JM, Baldus SE, Gutschow CA, Grass G, et al. Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer. J Surg Oncol 2003;82(4):256-60.
29. 29.Sayar A, Turna A, Kiliçgün A, Solak O, Urer N, Gürses A. Prognostic significance of surgical-pathologic multiple-station N1 disease in non-small cell carcinoma of the lung. Eur J Cardiothorac Surg 2004;25(3):434-8.
30. 30.Marra A, Hillejan L, Zaboura G, Fujimoto T, Greschuchna D, Stamatis G. Pathologic N1 nonsmall cell lung cancer: correlation between pattern of lymphatic spread and prognosis. J Thorac Cardiovasc Surg 2003;125(3):543-53.
31. 31.Bradley JD, Paulus R, Graham MV, Ettinger DS, Johnstone DW, Pilepich MV, et al. Phase II trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage II and IIIA non-small-cell lung cancer: promising long-term results of the Radiation Therapy Oncology Group-- RTOG 9705. J Clin Oncol 2005;23(15):3480-7.
32. 32.Ademuyiwa FO, Johnson CS, White AS, Breen TE, Harvey J, Neubauer M, et al. Prognostic factors in stage III non-small-cell lung cancer. Clin Lung Cancer 2007;8(8):478-82.
33. 33.Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 2001;18(4):243-59.
34. 34.Rades D, Setter C, Schild SE, Dunst J. Effect of smoking during radiotherapy, respiratory insuffic i e n c y, and hemoglobin levels on outcome in patients irradiated for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2008;71(4):1134-42.
35. 35.Kelsey CR, Light KL, Marks LB. Patterns of failure after resection of non-small-cell lung cancer: implications for postoperative radiation therapy volumes. Int J Radiat Oncol Biol Phys 2 0 0 6 ; 6 5 ( 4 ) : 1 0 9 7 - 1 0 5 .
36. 36.D a u t z e n b e rg B, Arriagada R, Chammard AB, Jarema A, Mezzetti M, Mattson K, et al. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d'Etude et de Tr a i t e m e n t des Cancers Bronchiques. Cancer 1999;86(2):265- 7 3 .
37. 37.Trodella L, Granone P, Valente S, Valentini V, Balducci M, Mantini G, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol 2002;62(1):11-9.
38. 38.Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatinbased adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350(4):351-60.
39. 39.Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA nonsmall-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006;7(9):719-27.
40. 40. http://www.nccn.org.