Original StudyAn Individual Patient Data Metaanalysis of Outcomes and Prognostic Factors After Treatment of Oligometastatic Non–Small-Cell Lung Cancer
Introduction
Non–small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide.1 Approximately half of all patients with NSCLC present with metastatic disease at the time of diagnosis, and the predominant pattern of failure in patients with localized NSCLC is distant metastatic spread.2, 3 Platinum-based doublet chemotherapy can improve quality of life and extend survival, but the prognosis of patients with metastatic NSCLC remains extremely poor, with median survival ranging from 8 to 11 months.4 However, the identification of molecular biomarkers and advances in targeted systemic therapies have transformed the management of metastatic NSCLC, resulting in a subgroup of patients who can enjoy significantly longer treatment responses and prolonged survival.5, 6, 7
Hellman and Weichselbaum proposed the existence of the oligometastatic state in 1995, a state of limited systemic metastatic burden, in which eradication of “oligometastases” with local ablative therapies could be curative in select patients.8, 9 In light of the prolonged disease control that can be achieved with the use of targeted agents, and of evidence that suggests that the predominant pattern of failure after systemic treatment is local, there has been increasing interest in the incorporation of local ablative treatments into the management of metastatic NSCLC.10, 11
There are emerging reports in the literature that suggest that the oligometastatic state might exist in NSCLC, in which select patients with limited metastatic disease can achieve long-term survival when treated with locally ablative therapies, such as surgery or radiotherapy (RT), to eliminate all sites of metastatic disease.12, 13, 14, 15, 16 Whether the oligometastatic state truly exists in NSCLC is unclear, because no NSCLC-specific randomized trials in this specific patient population have been completed. In a recent systematic review of the literature, including 49 publications reporting on 2176 oligometastatic patients, survival outcomes were highly variable, with most patients progressing locally or distantly within 1 year of treatment, and the available evidence was insufficient to permit the accurate delineation of factors predictive of long-term survival.17 Therefore, the goal of this metaanalysis was to determine if long-term survivors exist after ablative treatment of oligometastases in NSCLC, and to develop a predictive model for identification of oligometastatic NSCLC patients who are most likely to achieve long-term survival.
Section snippets
Materials and Methods
A systematic review was conducted to identify articles published in the MedLine and EMBASE databases between 1985 and July 2012, and reporting on NSCLC patients with 1 to 5 synchronous metastases (diagnosed at the same time as the primary tumor) or metachronous metastases (diagnosed ≥ 2 months after the primary tumor) and a controlled primary tumor (defined as previous or current treatment of the primary lung tumor with curative-intent primary RT, stereotactic ablative RT (SABR)/stereotactic
Results
Data were available on 757 patients from 20 independent data sources (Table 1). All datasets were previously reported either entirely, or in part, in the context of 18 reports13, 14, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 and 2 abstracts.33, 34, 35 The final composite data set included patients treated at centers in Europe (n = 497; 65.7%), Asia (n = 125; 16.5%), North America (n = 82; 10.8%), and Australia (n = 53; 7.0%). Baseline tumor, patient, and treatment characteristics
Discussion
This large, individual patient data metaanalysis for patients with oligometastatic NSCLC demonstrated a favorable 5-year OS (29.4%), far superior to the average 5-year OS (2%) for stage IV NSCLC,37 suggesting that this highly favorable subset of metastatic NSCLC patients might benefit from more ablative therapies. Although technically having stage IV disease, these patients represented a select population with favorable, less traditionally-used risk factors, including a median age of 61 years,
Conclusion
In this highly select population of stage IV NSCLC patients, based on our proposed risk stratification scheme, the longest survivals were observed in patients with metachronous metastases (low-risk group: 5-year OS, 47.8%). Patients with synchronous metastases and N0 disease (intermediate-risk group) had a 5-year OS of 36.2%, and patients with synchronous metastases and N1/N2 disease had the poorest survivals (high-risk group: 5-year OS, 13.8%).
These findings suggest that patient selection is
Disclosure
The authors have stated that they have no conflicts of interest.
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