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      Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer

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          Abstract

          Purpose

          To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database.

          Patients and Methods

          Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection. Overall survival (OS) of patients receiving CT versus CRT was compared by using the log-rank test, Cox proportional hazards regression, and propensity score matching.

          Results

          A total of 8,637 patients were identified, among whom 3,775 (43.7%) received CT and 4,862 (56.3%) received CRT. The odds of receiving CRT decreased with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < .01). Use of CRT was associated with increased OS compared with CT on univariable and multivariable analysis (median OS, 15.6 v 9.3 months; 3-year OS, 22.0% v 6.3%; log-rank P < .001; Cox P < .001). Propensity score matching identified a matched cohort of 6,856 patients and confirmed a survival benefit associated with CRT (hazard ratio, 0.52; 95% CI, 0.50 to 0.55; P < .001). Subset analysis of CRT treatment sequence showed that patients alive 4 months after diagnosis derived a survival benefit with concurrent CRT over sequential CRT (median OS, 17.0 v 15.4 months; log-rank P = .01).

          Conclusion

          In elderly patients with limited-stage small-cell lung cancer, modern CRT appears to confer an additional OS advantage beyond that achieved with CT alone in a large population-based cohort. Our findings suggest that CRT should be the preferred strategy in elderly patients who are expected to tolerate the toxicities of the combined approach.

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          Most cited references19

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          A meta-analysis of thoracic radiotherapy for small-cell lung cancer.

          In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined-therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/- SD) was 5.4 +/- 1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients: the relative risk of death in the combined-therapy as compared with the chemotherapy group ranged from 0.72 for patients less than 55 years old (95 percent confidence interval, 0.56 to 0.93) to 1.07 (0.70 to 1.64) for patients over 70. Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials.
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            The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer.

            Small cell lung cancer (SCLC) is usually classified using the limited and extensive definition. The tumor, node, metastasis (TNM) classification should also be applicable to SCLC, but it has only been reported in small surgical series. The current analysis looks to the impact of the TNM system on the clinical staging of SCLC and of the new International Association for the study of Lung Cancer (IASLC) proposals. Using the IASLC database, survival analyses were performed for clinically staged patients. Prognostic groups were compared, and the new IASLC TNM proposals were applied to this population and to the Surveillance, Epidemiology, and End Results (SEER) database. The IASLC database contained 12,620 eligible cases of small cell histology. TNM staging was available for 8088 patients. Survival was directly correlated to both T and N category. Differences were more pronounced in patients without mediastinal or supraclavicular nodal involvement. Stage grouping using the sixth edition of TNM also differentiates survival except between IA and IB. Patients with pleural effusion regardless of the cytology have an intermediate prognosis between limited and extensive disease. The IASLC proposals for the seventh edition of the TNM classification also apply to this series of SCLC and to the SEER database. TNM staging is recommended for SCLC, and stratification by stage I-III should be incorporated in clinical trials of early-stage disease. Further studies are needed to clarify the impact of pleural effusion and the extent of N3 disease.
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              Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis.

              Our main purpose was to determine whether the addition of thoracic radiation therapy to systemic chemotherapy improves 2-year survival, improves local (intrathoracic) tumor control, and affects treatment-related mortality in patients with limited-stage small-cell carcinoma of the lung. Eleven randomized trials addressing this issue were identified using a computerized literature search (Medline and Cancerline) and by polling senior investigators in the field. A meta-analysis was then performed and the results of the trials were analyzed in two ways, the odds ratio (OR) (Peto) method and the risk difference method (Dersimonian and Laird). The overall OR for benefit of thoracic radiation on 2-year survival (ie, the odds of surviving 2 years among patients allocated to radiation compared with the odds of surviving 2 years among patients allocated to control) is 1.53 (95% confidence interval [CI], 1.30 to 1.76; chi 2 = 12.76; P less than .001). The risk difference method showed that radiation therapy improved 2-year survival by 5.4% (95% CI, 1.1% to 9.7%). Local control results were available for only nine studies, the OR for treatment benefit is 3.02 (95% CI, 2.80 to 3.24; chi 2 = 101.48; P less than .0001), and intrathoracic tumor control was improved by 25.3% (95% CI, 16.5% to 34.1%). The OR for excess treatment-related deaths in the thoracic radiation-treated patients was 2.54 (95% CI, 1.90 to 3.18; chi 2 = 8.24; P less than .01). The risk difference for treatment-related deaths was 1.2% (95% CI, -0.6% to 3.0%). This meta-analysis shows a small but significant improvement in survival and a major improvement in tumor control in the thorax in patients receiving thoracic radiation therapy. However, this is achieved at the cost of a small increase in treatment-related mortality.
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                Author and article information

                Journal
                J Clin Oncol
                J. Clin. Oncol
                jco
                jco
                JCO
                Journal of Clinical Oncology
                American Society of Clinical Oncology
                0732-183X
                1527-7755
                20 December 2015
                19 October 2015
                19 October 2015
                : 33
                : 36
                : 4240-4246
                Affiliations
                [1]All authors: Yale University School of Medicine, New Haven, CT.
                Author notes
                Corresponding author: Roy H. Decker, MD, PhD, Department of Therapeutic Radiology, Yale University School of Medicine, 20 York St, New Haven, CT 06510; e-mail: roy.decker@ 123456yale.edu .
                Article
                24270
                10.1200/JCO.2015.62.4270
                4678178
                26481366
                87d5c90c-f989-4922-bd15-396c70c003e9
                © 2015 by American Society of Clinical Oncology

                Creative Commons Attribution Non-Commercial No Derivatives 3.0 License: http://creativecommons.org/licenses/by-nc-nd/3.0/us/

                History
                Categories
                Thor4
                Thor5
                Thor6
                Thor11
                ORIGINAL REPORTS
                Thoracic Oncology

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