Trends in the outcomes for patients with limited stage small cell lung cancer: An analysis of the Surveillance, Epidemiology, and End Results database☆
Introduction
Twenty-five years ago clinicians and researchers were poised to make major advancements in the treatment of small cell lung cancer (SCLC). They had devised a unique staging system, established the effectiveness of multiple chemotherapeutic agents and radiation therapy, and even discovered the central nervous system sanctuary which required distinct treatment. Small cell lung cancer was being added to some lists of “curable cancers” [1]. Unfortunately, a recent analysis suggests that only modest improvements in survival have occurred since [2]. It should also be noted that over the past two decades the pace of investigation of treatments for SCLC has stalled. This is reflected by the declining number of SCLC abstracts submitted to the American Society of Clinical Oncology over the past 25 years [3]. The current slow pace of small cell lung cancer investigation is unfortunate as the estimated deaths from this disease are approximately 4% of all cancer mortality [4].
The initial breakthough in small cell lung cancer treatment occurred in the late 1960s with the recognition that small cell lung cancers were more responsive to available chemotherapeutic agents than an inert compound [5]. While encouraging results were achieved with chemoradiotherapy [6], the standard of care for limited stage (LS) SCLC was chemotherapy alone during the 1970s and early 1980s. As a result, the 1980s saw a flurry of clinical trials investigating chemoradiotherapy vs. chemotherapy alone in LS-SCLC. The publication of Cancer and Leukemia Group B (CALGB) trial 8083 [7] in the New England Journal of Medicine in 1987 showed a benefit in local control, failure-free survival, and overall survival with the addition of thoracic radiation combined with doxorubicin-based chemotherapy for patients with LS-SCLC. This trial initiated a shift in the standard of care for patients with LS-SCLC. Subsequently, two meta-analyses [8], [9] published in late 1992 comprising, 14 total trials, confirmed the benefit of thoracic radiotherapy by demonstrating a survival benefit of 5.4% for chemoradiotherapy over chemotherapy alone in the treatment of LS-SCLC. CALGB 8083 utilized doxorubicin-based chemotherapy; cisplatin plus etoposide was originally shown to be equivalent to doxorubicin-based chemotherapy in patients with extensive stage SCLC [10]. These results were extrapolated for the use in LS-SCLC without confirmation because of the compatibility with radiotherapy and a significantly better toxicity profile. Subsequent clinical trials did confirm the superiority of cisplatin–etoposide–radiotherapy regimen [11].
To determine if any trends exist in the outcomes of patients with LS-SCLC in the community, we used the Surveillance, Epidemiology, and End Results (SEER) database to examine survival after radiotherapy among this population. We hypothesized that clinical trials have impacted outcomes positively and this initiated the diffusion of definitive radiotherapy into the patterns of practice.
Section snippets
Methods
Data for this retrospective study was obtained from the National Cancer Institute’s SEER program using the 17-Registry 1973–2003 data set, November 2005 Submission, released May 2006. The SEER Program is the only comprehensive source of population-based information in the United States that includes stage of cancer at the time of diagnosis, first course of treatment, and patient survival data.
From the SEER database, we assembled a cohort of patients aged 21 years and older with pathologically
Statistical analysis
The chi-square test was used to compare the prevalence of covariates among patients who did and did not receive radiotherapy. Radiotherapy utilization was defined by the ratio (# of patients receiving radiotherapy)/(# of patients not receiving radiotherapy) for each year based on age (<60 years old, 60–69 years old, and ≥70 years old). These results were plotted for each year and fit with a first-order linear regression. Proportional hazards models were used to examine the adjusted association
Results
This analysis included 6271 patients; 3425 (55%) received radiotherapy while, 3846 (45%) did not receive radiotherapy. The median patient age at diagnosis within the cohort was 67 years (range = 27–97 years). The median follow-up for all patients was 1.2 years. Younger patients, non-Caucasian patients, patients with larger tumors, and patients with primaries located in the upper lobe or at the main bronchus had a higher frequency of radiotherapy use; females were more likely to receive
Discussion
The survival for patients with LS-SCLC has improved over the last 20 years. The hypothesis we investigated is that this increase in survival is secondary to the adoption of definitive chemoradiotherapy (over chemotherapy alone) as defined by the results of published multi-institutional clinical trials; however, this is difficult to prove. In our analysis, the positive outcomes appear to correlate with radiotherapy utilization. As a result, we feel our results suggest our hypothesis to be true.
Conclusion
Our results show a significant improvement in survival for patients with limited stage SCLC over the past two decades. We believe that this increase in survival was the result of clinical trials which investigated and subsequently defined chemoradiotherapy as the standard of care. In order to improve outcomes for patients with this disease, it is necessary that all eligible patients be offered participation in clinical trials. Such trials need to be designed reflecting the changing age of
Conflict of interest
No actual or potential conflict of interest exists connected to any of authors of this manuscript and its content.
Acknowledgements
Special thanks to Dr. Carolyn Ferree for her critical review of the manuscript and Dr. Feng-Ming (Spring) Phoenix Kong for her assistance in learning of current patterns of care. Brian E. Lally was supported by NIH grant T32CA113267, TRADONC fellowship.
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2019, Critical Reviews in Oncology/HematologyCitation Excerpt :As far as evidence from real-life experiences is concerned, a retrospective study including a cohort of 6271 limited stage SCLCs from the Surveillance, Epidemiology, and End Results (SEER) database reported in multivariate analysis female sex as a positive prognostic factor (HR = 0.91; 95% CI 0.87–0.96; p = 0.0007), whereas older age, African American race, and main bronchus location were all associated with a statistically significant increase in mortality hazard (Turrisi et al., 1999). A retrospective study investigating the role of chemo-radiotherapy on 8637 elderly patients (aged ≥ 70 years) with limited SCLC included female sex among factors associated with improved OS on univariate and on multivariate analysis (HR = 0.83; 95% CI 0.79-0.87; p = 0.001) (Lally et al., 2009). Another retrospective study on 179 limited SCLC treated with definitive chemo-radiotherapy in a real-life scenario showed that female gender was significantly associated with longer brain metastases free survival (p = 0.023) and a lower incidence of metachronous brain failure.
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This work was presented at the American Society for Therapeutic Radiology and Oncology 48th Annual Meeting held on 5–9 November 2006, in Philadelphia, PA.