A population-based comparative effectiveness study of chemoradiation regimens and sequences in stage III non-small cell lung cancer
Introduction
For locally advanced non-small-cell lung cancer (NSCLC) patients (i.e. stage IIIA/B), combined modality therapy (chemoradiation) is generally recommended [1]. Studies repeatedly demonstrated the benefit of chemotherapy over radiation alone, as well as the benefit of using a platinum-based agent, typically with a second agent, termed “platinum-based doublet therapy” [1], [2], [3]. Chemotherapy can be given in various sequences: before radiation (sequential), during radiation (concurrent-alone), before and during radiation (induction-concurrent), or during and after radiation (concurrent-consolidation). As for radiation therapy, generally treatment is 60–66 Gy in 2 Gy fractions, although hyperfractionated or accelerated courses are also being studied [4].
Controversies remain regarding the optimal choice for the sequence of chemotherapy [1], [5], [6]. Although there are randomized trials showing a lack of efficacy with consolidation after cisplatin-based chemotherapy [7], [8], [9], there are no randomized trials studying consolidation after carboplatin-based chemotherapy. Rather, evidence for consolidation after carboplatin-based chemotherapy has been limited to single-arm trials [10]. Using SEER-Medicare, we studied the use of platinum-based doublet therapies as well as chemoradiation sequences among elderly patients in the US.
Section snippets
Patient selection
Patients diagnosed with NSCLC from January 2002 to December 2009 were identified using Surveillance, Epidemiology, and End Results (SEER)-Medicare. SEER-Medicare is a linked dataset maintained by the National Cancer Institute and contains data from 17 registries accounting for approximately 28% of the US population [11]. The dataset contains demographic, clinical, pathological, outcomes, and Medicare insurance claims data [12]. Follow up was through December 2010.
The cohort included patients
Results
We identified patients with stage III NSCLC diagnosed 2002–2009 who were treated with a platinum-based doublet therapy and radiation (Fig. 1). The five most common chemoradiation regimens were: carboplatin-paclitaxel (1423 patients), cisplatin-etoposide (242 patients), carboplatin-docetaxel (186 patients), carboplatin-etoposide (59 patients), and carboplatin-gemcitabine (33 patients). From 2002 to 2009 cisplatin-etoposide increased from 8% to 17% (Fig. 2). The chemoradiation sequences were:
Discussion
For stage III NSCLC, chemoradiation is the standard treatment for the majority of patients with multi-station or bulky adenopathy. However, no standard chemoradiation regimen or sequence strategy has emerged despite decades of research. We analyzed patients diagnosed 2002–2009 using SEER-Medicare, allowing us to determine the variations in chemoradiation regimens and sequences and perform comparative effectiveness analyses. The most commonly utilized chemotherapy regimens consisted of
Conclusions
In summary, using SEER-Medicare we found that for patients with locally advanced NSCLC undergoing definitive chemoradiation survival outcomes are similar for carboplatin- or cisplatin-containing regimens, as long as consolidation chemotherapy is given for patients receiving carboplatin. Our data therefore support a personalized approach to use of consolidation chemotherapy based on the choice of drugs given during radiation.
Conflict of interest
BWL and MD have received research support from Varian Medical Systems. BWL has received research support from RaySearch Laboratories, and speaking honoraria from Varian Medical Systems. HAW has received research support from Novartis and Eli Lilly. JPH and MIP have no disclosures.
Funding
This work was supported by grants from Varian and the Stanford Society of Physician Scholars. The supporting institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Acknowledgements
This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services, Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database.
References (37)
- et al.
Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines
Chest
(2013) - et al.
How can we optimise concurrent chemoradiotherapy for inoperable stage III non-small cell lung cancer?
Lung Cancer
(2014) - et al.
Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature
J. Thorac. Oncol.
(2013) - et al.
A population-based comparative effectiveness study of radiation therapy techniques in stage III non-small cell lung cancer
Int. J. Radiat. Oncol. Biol. Phys.
(2014) - et al.
Population-based estimates of survival benefit associated with combined modality therapy in elderly patients with locally advanced non-small cell lung cancer
J. Thorac. Oncol.
(2011) - et al.
Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases
J. Clin. Epidemiol.
(1992) - et al.
Development of a comorbidity index using physician claims data
J. Clin. Epidemiol.
(2000) - et al.
Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates
Control. Clin. Trials
(2000) - et al.
Cisplatin vs. carboplatin-based chemoradiotherapy in patients >65 years of age with stage III non-small cell lung cancer
Radiother. Oncol.
(2014) - et al.
Randomized phase II study of concurrent cisplatin/etoposide or paclitaxel/carboplatin and thoracic radiotherapy in patients with stage III non-small cell lung cancer
Lung Cancer
(2012)
Patterns of tumor recurrence after definitive irradiation for inoperable non-oat cell carcinoma of the lung
Int. J. Radiat. Oncol. Biol. Phys.
The effect of radiotherapy dose on survival in stage III non-small-cell lung cancer patients undergoing definitive chemoradiotherapy
Clin. Lung Cancer
Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer
J. Clin. Oncol.
Concurrent chemoradiotherapy in non-small cell lung cancer
Cochrane Database Syst. Rev.
Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis
J. Clin. Oncol.
Emerging developments of chemoradiotherapy in stage III NSCLC
Nat. Rev. Clin. Oncol.
Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology
J. Clin. Oncol.
GILT—a randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer
Strahlenther. Onkol.
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