Saadet TOKLUOĞLU, Arife ULAŞ, Fatma TÜRKÖZ PAKSOY, Ayşe DURNALI GÖK, Erkan ARPACI, Ahmet BİLİCİ, Necati ALKIŞ

Prognostic factors affecting survival in patients with operable non-small cell lung cancer: Single center experience and review of the literature

Giriş: Erken evre akciğer kanserli hastalar kürabl olabilmesine rağmen, prognoz sınırlı olup, 5-yıllık sağkalım oranları % 40-65 arasında değişmektedir. Bu çalışmada, cerrahi uygulanmış küçük hücreli dışı akciğer kanserli hastalarda klinikopatolojik özellikler, tedavi yanıtları ve prognostik faktörler araştırılmıştır. Yöntemler: 19992009 yılları arasında takip edilen 738 küçük hücreli dışı akciğer kanseri tanılı hastanın verileri retrospektif olarak incelenerek, cerrahi uygulanmış 80 hasta çalışmaya dahil edildi. Bulgular: Hastaların 71i erkek ve 9u kadın olup, ortanca yaş 55 yıl (39-71) idi. Yüzde 46.3ü yassı hücreli ve % 35i adenokarsinomaydı. Hastaların 31i Evre I, 30u evre II ve 19u evre IIIAydı. Adjuvan radyoterapi hastaların % 46sına, kemoterapi ise % 50.7sine uygulanmıştı. Ortanca takip süresi 34.2 ay (12-132), 5-yıllık genel sağkalım % 45.5, 5-yıllık hastalıksız sağkalım oranı ise %32.8 bulundu. Performans durumu (p= 0.024), tümör boyutu (p= 0.015), nodal tutulum (p= 0.015) ve anemi varlığı (p= 0.001) genel sağkalımı etkileyen prognostik faktörler iken, evre (p= 0.005), anemi varlığı (p= 0.007) ve histopatolojik tipin adenokanser olmasının (p< 0.001) hastalıksız sağkalım üzerine etkili olduğu görüldü. Sonuç: Opere edilmiş, küçük hücreli dışı akciğer kanserli olgularda performans durumu, evre, anemi varlığı ve nodal tutulum sağkalımı etkileyen faktörlerdir.

Opere küçük hücreli dışı akciğer kanserli hastalarda sağkalım üzerine etkili faktörler: Tek merkez deneyimi ve literatürün gözden geçirilmesi

Objective: Although early-stage lung cancer patients are curable, the prognosis is limited and the 5-year survival rates range from 40 to 65 percent. In this study, clinicopathologic features, treatment responses and prognostic factors of non-small cell lung cancer patients treated with surgery were investigated. Methods: Seven-hundred-thirty-eight non-small cell lung cancer patients diagnosed and followed up between the years of 1999 and 2009 were evaluated retrospectively. Eighty patients who underwent surgery were included in the study. Results: There were 71 male and 9 female patients with the median age of 55 years (range, 39 to 71). Forty-six-point-three percent of the patients had squmous cell cancer and 35 % had adenocarcinoma. Thirty-one patients had stage I, 30 had stage II and 19 had stage IIIA disease. Forty-six percent of the patients had adjuvant radiotherapy and 50.7% had adjuvant chemotherapy. The median follow-up time after diagnosis was 34.2 months (range, 12 -132), the 5-year overall survival and the 5-year disease free survival rates were 45.5% and 32.8%, respectively. Performance status (p=0.024), tumor size (p=0.015), lymph node involvement (p=0.015) and anemia (p=0.001) were the prognostic factors associated with the overall survival. Stage (p=0.005), anemia(p=0.007) and adenocarcinoma subtype (p< 0.001) significantly affected the disease free survival. Conclusion: The performance status, stage, nodal involvement, presence of anemia are the prognostic factors affecting the survival in patients with non- small cell lung cancer.

PDF

___

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2010. Cancer J Clin 2010; 60:277- 300.
2. Spiro SG, Porter JC. Lung cancer-Where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 2002;166:1166-96.
3. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997; 111:1710-7.
4. Martini N, Burt ME, Bains MS, et al. Survival after resection of stage I and II nonsmall cell lung cancer. Ann Thorac Surg 1992;54: 460-5.
5. Smit EF, Groen HJM, Splinter TAW, et al. New prognostic factors in resectable non small cell lung cancer. Thorax 1996; 51: 638-46.
6. Graziano SL. Non-small cell lung cancer: clinical value of new biological predictors. Lung Cancer 1997; 17:S37-S58.
7. Graziano SL, Tatum AH, Newman NB, et al. S. The prognostic significance of neuroendocrine markers and carcinoembryonic antigen in patients with resected stage I and II non-small cell lung cancer. Cancer Res 1994; 54: 2908-13.
8. Strauss GM. Prognostic markers in resected non-small cell lung cancer. Hematol Oncol Clin North Am 1997; 11: 409-34.
9. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2: 706-14
10. Groome PA, Bolejack V, Crowley JJ, et al. The IASLC Lung Cancer Staging Project: Validation of the Proposals for Revision of the T, N, and M Descriptors and Consequent Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol 2007; 2: 694.
11. Travis WD, Brambilla E, Muller-Hermlink HK, Harris CC (eds). World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press. Lyon 2004.
12. Oken MM et al. Toxicity and response criteria of the Eastern Coooperative Oncology Group. Am J Clin Oncol 1982;5: 649-55.
13. Van Rens MTM, de la Riviere AB, Elbers HRJ, van den Bosch JMM. Prognostic assessment of 2,361 patients who underwent pulmonaryresection for non-small cell lung cancer, stage I, II, and IIIA. Chest 2000;117:3749.
14. Al-Kattan, E Sepsas, E R Townsend, S W Fountain Factors affecting long term survival following resection for lung cancer. Thorax 1996; 51: 1266-9.
15. Pfannschmidt J, Muley T, Bulzebruck H, Hoffmann H, Dienemann H.Prognostic assessment after surgical resection for non small cell lung cancer experience in 2083 patients. Lung Cancer 2007; 55:371-7.
16. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: A meta-analysisusing updated data on individual patients from 52 randomized clinical trials. BMJ 1995;311:899-909.
17. Scagliotti GV, Fossati R, Torri V, et al. (ALPİ) Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell Lung cancer. J Natl Cancer Inst 2003;95:1453-61.
18. Arriagada R, Dunant A, Pignon JP, et al. Update IALT: Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010;28:35-42.
19. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719-27.
20. Vincent MD, Butts C, Seymour L, et al. Updated survival analysis of JBR.10: A randomized phase III trial of vinorelbine/cisplatin versus observation in completely resected stage IB and II non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27:382s.
21. Strauss GM, Herndon JE, Maddaus MA, et al. Adjuvant Paclitaxel Plus Carboplatin Compared With Observation in Stage IB Non-Small-Cell Lung Cancer: CALGB 9633. J Clin Oncol. 2008 Nov 1; 26(31): 5043-51.
22. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26: 3552-9.
23. Scott WJ, Howington J, Feigenberg S, et al. Treatment of non-small cell lung cancer stage I and II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132:234S-242S.
24. Trodella L, Granone P, Valente S, 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;62:11-9.
25. National Comprehensive Cancer Network (NCCN) guidelines. NCCN 2012 (Available at http: // www.nccn.org/professionals/physician/guidelines.accessed on 2012).
26. Kwiatkowski DJ, Harpole Jr DH, Godleski J, et al. Molecular Pathologic Substaging in 244 stage I non-small cell lung cancer patients: Clinical Implications. J Clin Oncol 1998; 16: 2468-77.
27. Paesmans, M, Sculier JP, Libert P, et al. Prognostic factors for survival in advanced nonsmall cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1052 patients. J Clin Oncol 1995; 13:1221-30.
28. Wertzel H, Siebert H, Lange W, et al. Results after surgery in stage-I bronchogenic carcinoma. Thoracic Cardiovasc Surg 1998; 46: 365-9.
29. Jazieh AR, Hussain M, Howington JA et al. Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer. Ann Thorac Surg 2000; 70: 1168-71.
30. Wigren T. Confirmation of a prognostic index for patients with inoperable non-small cell lung cancer. Radiother Oncol 1997; 44: 9-15.
31. Alexiou C, Onyeaka CV, Beggs D et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg 2002; 21: 319-25.
32. Radzikowska E, Glaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases Ann Oncol. 2002;13:1087-93.
33. Cerfolio RJ, Bryant AS, Scott E, et al. Women with pathologic stage I, II, and III nonsmall cell lung cancer have better survival than men. Chest 2006; 130:1796.
34. Schwartz AG, Wenzlaff AS, Prysak GM, et al. Reproductive factors, hormone use, estrogen receptor expression and risk of non small cell lung cancer in women. J Clin Oncol 2007; 25: 5785.
35. Schwartz AG, Prysak GM, Murphy V, et al. Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex. Clin Cancer Res 2005; 11:7280-7.
36. Abdul R. Jazieh et al. Prognostic Factors in Patients With Surgically Resected Stages I and II Non-Small Cell Lung Cancer. Ann Thorac Surg 2000; 70:1168-71.
37. Lopez-Encuentra A. Comorbidity in operable lung cancer: A multicenter descriptive study on 2992 patients. Lung Cancer 2002;35: 263-9.
38. Yovino S, Kwok Y, Krasna M, Bangalore M, Suntharalingam M. An association between preoperative anemia and decreased survival in early stage non-small-cell lung cancer patients treated with surgery alone. Int J Radiat Oncol Biol Phys 2005; 62: 143843.
39. Paul I, Lappin TR, Maxwell P, Graham AN. Pre-operative plasma erythropoietin concentration and survival following surgery for non-small cell lung cancer. Lung Cancer 2006; 51: 32934
40. Mandrekar SJ, Schild SE, Hillman SL, et al. A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer 2006;107:781-92.
41. Ferrigno D, Buccheri G. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients. Monaldi Arch Chest Dis. 2003; 59:193-8.
42. Shinkai T, Eguchi K, Sasaki Y, et al. A prognostic-factor riskindex in advanced non- small-cell lung cancer treated with cisplatin-containing combination chemotherapy. Cancer Chemother Pharmacol 1992;30:1-6.
43. Hoang T, Xu R, Schiller JH, et al. Clinical model to predict survival in chemonaive patients with advanced non-smallcell-lung cancer treated with third-generation chemotherapy regimens based on Eastern Cooperative Oncology Group data. J Clin Oncol. 2005; 23:175-83.
44. Ichinose Y, Kato H, Koike T, et al. Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials. Lung Cancer 2001;34: 29-36.
45.Andre F, Grunenwald D, Pignon JP, et al. Survival of patients with resected N2 nonsmall-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 2000;18: 2981-9.
46. Harpole DH, Herndone JE, Young WG, et al. Stage I nonsmall cell lung cancer: a multivariate analysis of treatment methods and patterns of recurrence. Cancer 1995; 76:787-96.
47. Thomas PA, Piantadosi S. Postoperative T1N0 non-small cell lung cancer: squamous versus non-squamous recurrences. J Thorac Cardiovasc Surg 1987; 94:349-54.
48. Alexiou C, Onyeaka CV, Beggs D et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg 2002; 21:319-25.
49. Ferguson MK, Wang J, Hoffman PC, Haraf DJ, Olak J, Masters GA, Vokes EE. Sexassociated differences in survival of patients undergoing resection for lung cancer. Ann Thorac Surg 2000; 69:245-50.