Elsevier

Clinical Lung Cancer

Volume 15, Issue 5, September 2014, Pages 346-355
Clinical Lung Cancer

Original Study
An Individual Patient Data Metaanalysis of Outcomes and Prognostic Factors After Treatment of Oligometastatic Non–Small-Cell Lung Cancer

https://doi.org/10.1016/j.cllc.2014.04.003Get rights and content

Abstract

Introduction/Background

An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC.

Materials and Methods

After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively).

Results

Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002), and adenocarcinoma histology (P = .036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%).

Conclusion

Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment.

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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