ALC  Vol.7 No.3 , September 2018
Outcomes and Prognostic Factors of Small Cell Lung Cancer: A Retrospective Study
Abstract: Background: Small cell lung cancer (SCLC) is a high grade neuroendocrine tumor, and has aggressive nature, so the majority of cases are presented with extensive disease. SCLC was staged into 2 categories: limited-stage disease (LS-SCLC) and extensive disease (ES-SCLC). Despite SCLC is sensitive to ra-diotherapy and chemotherapy, SCLC has high tendency for rapid dissemina-tion to regional and distant sites. Median survival time ranged from 2 - 4 months in patients with untreated SCLC. Multiagent chemotherapy was the primary treatment for SCLC. Aim of the work: This retrospective study was conducted to evaluate and analyze clinical features, treatment outcome, sur-vival and prognostic factors affecting survival in patients with SCLC presented to Clinical Oncology and Nuclear Medicine department, Chest department and Medical oncology unit in Mansoura Oncology Centre during the period from 2000-2015. Methods: Data of patients were collected from their files. The information obtained included demographic features, treatment received; its toxicity and outcome, survival and its prognostic factors. Demographic data were: age, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), smoking status, stage of disease. Data also included disease presentation and metastatic sites. Several factors affecting survival were analysed as age, sex, stage, PS, smoking status and LDH. Results: Sixty-three patients were enrolled in this study. Median age was 56.2 ± 6. Strong male predominance (92.1%) was observed; 84.1% of them were smoker. Thirty six patients (57.2%) were of ECOG-PS of 0 - 1. ES-SCLC was reported in 65% of cases and LDH was high (>1.5 xN) in 47.6%. The most common symptom was chest pain (38.1%) followed by cough (31.8%), weight loss (30%). Fifteen patients had single metastatic site (23.8%) and bone was the most common site of metastasis (reported in 8 patients) followed by brain, lung and liver. 2-year overall survival rate was 35% with median survival time of 14 months. On multivariate analysis, there were significantly higher survival in patients aged < 65 years (P = 0.03), female gender (P = 0.04), LD-SCLC (P = 0.03), good performance status (P = 0.04), low LDH level (P = 0.02) and non-smoker (P = 0.04). Conclusion: This clinico-epidemiologic study provides multiple prognostic factors that have important impact on survival as age, sex, LDH level, stage, smoking and performance status. Larger number of patients and prospective studies are needed to clarify more prognostic factor.
Cite this paper: Wahba, H. , El-Hadaad, H. , Anter, A. , Ahmad, M. and Ghazy, H. (2018) Outcomes and Prognostic Factors of Small Cell Lung Cancer: A Retrospective Study. Advances in Lung Cancer, 7, 21-31. doi: 10.4236/alc.2018.73003.

[1]   Jemal, A., Bray, F., Center, M.M., et al. (2011) Global Cancer Statistics. CA: A Cancer Journal for Clinicians, 61, 69-90.

[2]   Jett, J.R., Schild, S.E., Kesler, K.A., et al. (2013) Treatment of Small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 143, e400S-e419S.

[3]   Halperin, C.E., Wazer, D.E., Carlos, A.P., et al. (2013) Perez and Brady’s Principles and Rdiation Oncology. 6th Edition, Lippincott Wiliams and Wilkins, Philadelphia, 966 p.

[4]   Murray, N., Copy, P., Pater, J.L., et al. (1993) Importance of Timing for Thoracic Irradiation in the Combined Modality Treatment of Limited-Stage Small Cell Lung Cancer. The National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology, 11, 336-344.

[5]   Simon, G.R. and Turrisi, A. (2007) American College of Chest Physicians. Management of Small Cell Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). Chest, 132, 324S-339S.

[6]   Socinski, M.A., Smit, E.F., Lorigan, P., et al. (2009) Phase III Study of Pemetrexed plus Carboplatin Compared with Etoposide plus Carboplatin in Chemotherapy-Naive Patients with Extensive-Stage Small-Cell Lung Cancer. Journal of Clinical Oncology, 27, 4787-4792.

[7]   Simon, G.R. and Wagner, H. (2003) American College of Chest Physicians. Small cell Lung Cancer. Chest, 123, 2571S.

[8]   Souhami, R.L., Geddes, D.M., Spiro, S.G., et al. (1984) Radiotherapy in Small Cell Cancer of the Lung Treated with Combination Chemotherapy: A Controlled Trial. British Medical Journal (Clinical Research Ed.), 288, 1643-1646.

[9]   Warde, P. and Payne, D. (1992) Does Thoracic Irradiation Improve Survival and Local Control in Limited-Stage Small-Cell Carcinoma of the Lung? A Meta-Analysis. Journal of Clinical Oncology, 10, 890-895.

[10]   Arriagada, R., Pignon, J.P., Ihde, D.C., et al. (1994) Effect of Thoracic Radiotherapy on Mortality in Limited Small Cell Lung Cancer. A Meta Analysis of 13 Randomized Trials among 2,140 Patients. Anticancer Research, 14, 333-335.

[11]   Kallianos, A., Rapti, A., Zarogoulidis, P., et al. (2013) Therapeutic Procedure in Small Cell Lung Cancer. Journal of Thoracic Disease, 5, S420-S424.

[12]   Ganti, A.K., West, W.W. and Zhen, W. (2013) Current Concepts in the Management of Small Cell Lung Cancer. Indian Journal of Medical Research, 137, 1043-1051.

[13]   Zhu, H., Zhou, Z., Wang, Y., et al. (2011) Thoracic Radiation Therapy Improves the Overall Survival of Patients with Extensive-Stage Small Cell Lung Cancer with Distant Metastasis. Cancer, 117, 5423-5431.

[14]   Yee, D., Butts, C., Reiman, A., et al. (2012) Clinical Trial of Post-Chemotherapy Consolidation Thoracic Radiotherapy for Extensive-Stage Small Cell Lung Cancer. Radiotherapy and Oncology, 102, 234-238.

[15]   Socha, J. and Kepka, L. (2012) Prophylactic Cranial Irradiation for Small-Cell Lung Cancer: How, When and Whom? Expert Review of Anticancer Therapy, 12, 505-517.

[16]   Seute, T., Leffers, P., Ten Velde, G.P., et al. (2004) Neurologic Disorders in 432 Consecutive Patients with Small Cell Lung Carcinoma. Cancer, 100, 801-806.

[17]   Patel, S., Macdonald, O.K. and Suntharalingam, M. (2009) Evaluation of the Use of Prophylactic Cranial Irradiation in Small Cell Lung Cancer. The Cancer, 115, 842-850.

[18]   Slotman, B., Faivre-Finn, C., Kramer, G., et al. (2007) Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer. The New England Journal of Medicine, 357, 664-672.

[19]   Schild, S.E., Foster, N.R., Meyers, J.P., et al. (2012) Prophylactic Cranial Irradiation in Small-Cell Lung Cancer: Findings from a North Central Cancer Treatment Group Pooled Analysis. Annals of Oncology, 23, 2919-2924.

[20]   Eisenhauer, E.A., Therasse, P., Bogaerts, J., et al. (2009) New Response Evaluation Criteria in Solid Tumors: Revised RECIST Guideline (Version 1.1). European Journal of Cancer, 45, 228-247.

[21]   Siegel, R., Naishadham, D. and Jemal, A. (2013) Cancer Statistics, 2013. CA: A Cancer Journal for Clinicians, 63, 11-30.

[22]   Maestu, I., Pastor, M., Gómez-Codina, J., et al. (1997) Pretreatment Prognostic Factors for Survival in Small-Cell Lung Cancer: A New Prognostic Index and Validation of Three Known Prognostic Indices on 341 Patients. Annals of Oncology, 8, 547-553.

[23]   Bharti, M.K., Chauhan, A., Kaushal, V., et al. (2011) Characteristics, Treatment Patterns and Outcomes of Patients with Small Cell Lung Cancer. A Retrospective Analysis, 2, 2206-2210.

[24]   Tsao, A.S., Liu, D., Lee, J.J., et al. (2006) Smoking Affects Treatment Outcome in Patients with Advanced Non-Small Cell Lung Cancer. Cancer, 106, 2428-2436.

[25]   Videtic, G.M., Stitt, L.W., Dar, A.R., et al. (2003) Continued Cigarette Smoking by Patients Receiving Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer Is Associated with Decreased Survival. Journal of Clinical Oncology, 21, 1544-1549.

[26]   Govindan, R., Page, N., Morgensztern, D., et al. (2006) Changing Epidemiology of Small-Cell Lung Cancer in the United States over the Last 30 Years: Analysis of the Surveillance, Epidemiology and End Results Database. Journal of Clinical Oncology, 24, 4539-4544.

[27]   Vallieres, E., Shepherd, F.A., Crowly, J., et al. (2009) International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals Regarding the Relevance of TNM in the Pathologic Staging of Small Cell Lung Cancer in the Forthcoming (Seventh) Edition of the TNM Classification of Lung Cancer. Journal of Thoracic Oncology, 4, 1049-1059.

[28]   Luan, Z., Wang, Z., Huang, W., et al. (2015) Efficacy of 3D Conformal Thoracic Radiotherapy for Extensive-Stage Small-Cell Lung Cancer: A Retrospective Study. Experimental and Therapeutic Medicine, 10, 671-678.

[29]   Unalmus, D., Yasar, Z., Buyuksirin, M., et al. (2015) Clinical Features and Outcomes of Patients with Small Cell Lung Carcinoma; Retrospective Analysis. Acta Medica Anatolia, 3, 47-50.

[30]   Hanna, N., Bunn Jr., P.A., Langer, C., et al. (2006) Randomized Phase III Trial Comparing Irinotican/Cisplatin with Etoposide/Cisplatin in Patients with Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer. Journal of Clinical Oncology, 24, 2038-2043.

[31]   Frülh, M., De Ruysscher, D., Popat, S., et al. (2013) ESMO Guidelines Working Group: Small-Cell Lung Cancer (SCLC): ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Annals of Oncology, 24, vi99-vi105.

[32]   Noda, K., Nishiwaki, Y., Kawahara, M., et al. (2002) Irinotican plus Cisplatin Compared with Etoposide plus Cisplatin for Extensive Small-Cell Lung Cancer. The New England Journal of Medicine, 346, 85-91.

[33]   Natale, R.B., Lara, P.N., Chansky, K., et al. (2008) SO124: A Randomized Phase III Trial Comparing Irinotican/Cisplatin (IP) with Etoposide/Cisplatin (EP) in Patients with Previously Untreated Extensive Stage Small Cell Lung Cancer (E-SCLC). Journal of Clinical Oncology, 26, 7512.

[34]   Lee, J.H., Kim, S.H., Kim, S.Z., et al. (2009) Retrospective Analysis of Chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer. The Journal of the Korean Society for Therapeutic Radiology and Oncology, 27, 133.

[35]   Nathan, R., Foster, M.S., Sumithera, J., et al. (2009) Prognostic Factors Differ by Tumor Stage for Small Lung Cancer. Cancer, 15, 2721-2731.

[36]   Cerny, T., Blair, V., Anderson, H., et al. (1987) Pretreatment Prognostic Factors and Scoring System in 407 Small-Cell Lung Cancer Patients. International Journal of Cancer, 39, 146-149.

[37]   Souhami, R.L., Bradbury, I., Geddes, D.M., et al. (1985) Prognostic Significance of Laboratory Parameters Measured at Diagnosis in Small Cell Carcinoma of the Lung. Cancer Research, 45, 2878-2882.

[38]   Onoda, N., Nehmi, A., Weiner, D., et al. (2001) Nicotine Affects the Signaling of the Death Pathway, Reducing the Response of Head and Neck Cancer Cell Lines to DNA Damaging Agents. Head Neck, 23, 860-870.

[39]   Dasgupta, P., Kinkade, R., Joshi, B., et al. (2006) Nicoyine Inhibits Apoptosis Induced by Chemotherapeutic Drugs by Up-Regulating XIAP and Surviving. Proceedings of the National Academy of Sciences of the United States, 103, 6332-6337.

[40]   Heeschen, C., Jang, J.J., Weis, M., et al. (2001) Nicotine Stimulates Angiogenesis and Promotes Tumor Growth and Atherosclerosis. Nature Medicine, 7, 833-839.

[41]   Mousa, S. and Mousa, S.A. (2006) Cellular and Molecular Mechanisms of Nicotine’s Pro Angiogenesis Activity and Its Potential Impact on Cancer. Journal of Cellular Biochemistry, 97, 1370-1378.

[42]   Zhang, Q., Tang, X., Zhang, Z.F., et al. (2007) Nicotine Induces Hypoxia-Inducible Factor-1 Alpha Expression in Human Lung Cancer Cells via Nicotine Acetylcholine Receptor-Mediated Signaling Pathways. Clinical Cancer Research, 13, 4686-4694.

[43]   Chen, J., Jiang, R., Garces, Y.I., et al. (2010) Prognostic Factors for Limited-Stage Small Cell Lung Cancer: A Study of 284 Patients. Lung Cancer, 67, 221.

[44]   Bergman, B. and Sorenson, S. (1988) Smoking and Effect of Chemotherapy in Small Cell Lung Cancer. European Respiratory Journal, 1, 932-937.

[45]   Kuo, H.Y., Lin, Z.Z., Yang, Y.Y., et al. (2012) Survival of Patients with Small Cell Lung Carcinoma in Taiwan. Oncology, 82, 19-24.

[46]   Sculier, J.P., Chansky, K., Crowly, J.J., et al. (2008) The Impact of Additional Prognostic Factors on Survival and Relationship with the Anatomical Extent of Disease Expressed by the 6th Edition of the TNM Classification of Malignant Tumors and the Proposals for the 7th Edition. Journal of Thoracic Oncology, 3, 457-466.

[47]   Gaspar, L.E., McNamara, E.J., Gay, E.G., et al. (2012) Small Cell Lung Cancer: Prognostic Factors and Changing Treatment over 15 Years. Clinical Lung Cancer, 13, 115-122.

[48]   Albain, K.S., Crowley, J.J., LeBlank, M., et al. (1990) Determinants of Improved Outcome in Small Cell Lung Cancer: An Analysis of the 2,580-Patients Southwest Oncology Group Data Base. Journal of Clinical Oncology, 8, 1563-1574.

[49]   Spiegelman, D., Maurer, L.H., Ware, J.H., et al. (1989) Prognostic Factors in Small-Cell Carcinoma of the Lung: An Analysis of 1,521 Patients. Journal of Clinical Oncology, 7, 344-354.

[50]   Ramlov, A., Tietze, A., Khalil, A.A., et al. (2012) Prophylactic Cranial Irradiation in Patients with Small Cell Lung Cancer. A Retrospective Study of Recurrence, Survival and Morbidity. Lung Cancer, 77, 561-566.

[51]   Aynaci, O., Canyilmaz, E., Serdar, L., et al. (2016) Survival and Prognostic Factors in Limited Stage Small Cell Lung Cancer: A Retrospective Study from Northeast Turkey. Journal of Cancer Research and Therapeutics, 12, 238-243.

[52]   Pijls-Johannesma, M., De Ruysscher, D., et al. (2007) Timing of Chest Radiotherapy in Patients with Limited Stage Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancer Treatment Reviews, 33, 461-473.