Elsevier

Lung Cancer

Volume 67, Issue 2, February 2010, Pages 221-226
Lung Cancer

Prognostic factors for limited-stage small cell lung cancer: A study of 284 patients

https://doi.org/10.1016/j.lungcan.2009.04.006Get rights and content

Abstract

Combined modality therapy is the standard care for limited stage-small cell lung cancer (LS-SCLC) and has led to a significant improvement in patients’ survival. This study sought to investigate and define the importance of prognostic effects of known and controversial factors especially the impact of smoking status and treatment strategies. A total of 284 patients with LS-SCLC were diagnosed and prospectively followed from 1997 to 2008 at Mayo Clinic; their characteristics and survival outcome were assessed on the basis of age, gender, smoking history, performance status (PS), tumor recurrence or progression, and treatment using Cox proportional hazards models. Our main results are as follows: (1) Although neither smoking status (former or current smokers) nor intensity (pack-years smoked) at the time of SCLC diagnosis were significant survival predictors, compared to continued smokers (who never quit smoking), patients who quit at or after diagnosis cut the risk of death by 45% (HR = 0.55, 95% CI 0.38–0.79); patients who quit before lung cancer diagnosis also experienced survival benefit (HR = 0.72, 95% CI 0.52–1.00). (2) Thoracic radiotherapy and platinum-based chemotherapy could significantly improve survival but the timing (within or after one month of diagnosis) of starting chemotherapy or radiation therapy did not. (3) After adjusting for other known factors, a lower PS did not predict poorer survival, suggesting that PS should not be the only factor for making treatment decisions. In conclusion, this study demonstrated the negative impact of continued cigarette smoking on survival; therefore, clinicians and all care providers should strongly encourage smoking cessation at diagnosis of LS-SCLC.

Introduction

Approximately 30–40% of small cell lung cancer (SCLC) is limited-stage SCLC (LS-SCLC) at first clinical presentation. The median ranges of survival for LS-SCLC are from 15 to 20 months. In the last few decades, a modest yet significant improvement of the survival rate of LS-SCLC has been shown in North America and other countries [1], [2], [3], [4]. Some prognostic factors such as age, gender, smoking status, or different strategies of combined chemoradiotherapy have been studied in LS-SCLC, but the role of some of these factors in predicting patients’ survival remains controversial. Although a personal history of cigarette smoking has been associated with decreased overall survival among patients receiving treatment for non-small cell lung cancer [5], [6], only a few studies have reported the impact of smoking status after diagnosis and/or during treatment on survival in patients with SCLC. Videtic et al. [7] showed that LS-SCLC patients who continued to smoke during treatment had poorer survival rates than those who quit smoking; however, the authors failed to provide quantitative information on smoking history and to demonstrate any dose-response effect of smoking, such as quantification of cigarette use at the onset of therapy and the duration of smoking cessation in the patients who were not smoking at the time of diagnosis. Two earlier studies on SCLC used mixed, limited- and extensive-stage SCLC (ES-SCLC) populations and provided conflicting conclusions. Johnston-Early et al. [8] showed worse survival with continuation of smoking while Bergman and Sorenson [9] reported no difference in survival. Thus, a firm conclusion could not be drawn on whether and at what magnitude smoking status carries a prognostic effect among LS-SCLC patients.

Another issue the current study sought to clarify is the timing of combined modality therapy. Although unequivocal data support the benefit from combined modality therapy for LS-SCLC patients’ survival, the optimal timing to start chemoradiotherapy is still controversial. An early trial by the CALGB compared chemotherapy alone vs. TRT (50 Gy) with either cycle 1 or 4. The arms containing TRT were superior to the chemotherapy alone arm. The difference was statistically significant for delayed (cycle 4) TRT but not for early TRT (p = 0.082) [10]. In contrast, the National Cancer Institute of Canada (NCIC) reported TRT (40 Gy) initiated with either the second or sixth cycle of chemotherapy and showed a survival advantage for early vs. late TRT (five-year survival rate of 20% vs. 11%, respectively; p = 0.008) [11]. In an attempt to replicate the NCIC trial using the identical inclusion and exclusion criteria, Spiro et al. [12] failed to show a benefit for early vs. late TRT. In addition, several meta-analyses addressing the timing of TRT suggested a modest benefit of early vs. delayed TRT [13]. It also seems that the benefit of early concurrent chemoradiotherapy may be maximized by more intensified TRT delivered with uncompromised doses of chemotherapy.

In this study, we performed a retrospective cohort study of LS-SCLC patients at Mayo Clinic, Rochester, Minnesota. We analyzed the association of LS-SCLC with multiple factors including age, sex, smoking status at time of diagnosis, smoking cessation, performance status (PS), and treatment regimens, to determine which of these factors has an independent impact on survival and to determine the magnitude of the impact.

Section snippets

Study cohort and data collection

From January 1997 to December 2007, a total of 1124 patients with a pathologically confirmed diagnosis of SCLC at Mayo Clinic were enrolled and actively followed. Only patients who provided informed consent as approved by the Mayo Clinic Institutional Review Board were included in this study. Two hundred eighty-four LS-SCLC cases were identified in this cohort. Detailed procedures of patient enrollment, diagnosis, data collection, and follow-up have been described in a previous publication [14]

Basic characteristics and univariate analysis

The demographics and clinical information of 284 LS-SCLC patients were summarized in Table 1. Sex difference of each variable was compared and none was statistically different. In univariate survival analysis of all factors in Table 1, age, smoking cessation, recurrence or progression, early radiation, chemotherapy started after one month of diagnosis, concurrent chemoradiotherapy, PCI, platinum-based chemotherapy, and combined chemotherapy were all significantly associated with post diagnosis

Discussion

In our analysis of 284 LS-SCLC patients, multiple factors were associated with the survival of LS-SCLC. Younger age, female, smoking cessation at or after diagnosis, and combined modality treatment had favorable impact on survival, while recurrence/progression during treatment universally indicated very poor prognosis. Most of these were consistent with previous reports and provided additional evidence to support the benefit of current combined modality therapy. However, we also found that the

Conclusion

This study provides strong evidence for multiple prognostic factors including epidemiology, clinical features, and treatment in LS-SCLC; whereas, the majority of the literature focused on one or a few aspects only. Although neither smoking status (former or current smokers) nor intensity (pack-years smoked) at the time of SCLC diagnosis was significant survival predictors, compared to continued smokers (who never quit smoking), patients who quit at or after diagnosis cut the risk of death by

Conflict of interest

None.

Acknowledgements

We would like to thank Susan Ernst, M.A., for her technical assistance with the manuscript.

Funding: This work was partially funded by NIH grants, R01 CA 80127, 84354, and 115857 and Mayo Clinic institutional funds.

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