Elsevier

Lung Cancer

Volume 82, Issue 1, October 2013, Pages 95-102
Lung Cancer

Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): Patient outcomes and prognostic factors

https://doi.org/10.1016/j.lungcan.2013.07.023Get rights and content

Abstract

Objectives

Metastatic non-small cell lung carcinoma (NSCLC) generally carries a poor prognosis, and systemic therapy is the mainstay of treatment. However, extended survival has been reported in patients presenting with a limited number of metastases, termed oligometastatic disease. We retrospectively reviewed the outcomes of such patients treated at two centers.

Materials and methods

From September 1999–July 2012, a total of 61 patients with 1–3 synchronous metastases, who were treated with radical intent to all sites of disease, were identified from records of two cancer centers. Treatment was considered radical if it involved surgical resection and/or delivery of radiation doses ≥13 × 3 Gy.

Results

Besides the primary tumor, 50 patients had a solitary metastasis, 9 had two metastases, and 2 had three metastases. Locations of metastases included the brain (n = 36), bone (n = 11), adrenal (n = 4), contralateral lung (n = 4), extra-thoracic lymph nodes (n = 4), skin (n = 2) and colon (n = 1). Only one patient had metastases in two different organs. Median follow-up was 26.1 months (m), median overall survival (OS) was 13.5 m, median progression free survival (PFS) was 6.6 m and median survival after first progression (SAFP) was 8.3 m. The 1- and 2-year OS were, 54% and 38%, respectively. Significant predictors of improved OS were: smaller radiotherapy planning target volume (PTV) (p = 0.004) and surgery for the primary lung tumor (p < 0.001). Factors associated with improved SAFP included surgery for the primary lung tumor, presence of brain metastases, and absence of bone metastases. No significant differences in outcomes were observed between the two centers.

Conclusion

Radical treatment of selected NSCLC patients presenting with 1–3 synchronous metastases can result in favorable 2-year survivals. Favorable outcomes were associated with intra-thoracic disease status: patients with small radiotherapy treatment volumes or resected disease had the best OS. Future prospective clinical trials, ideally randomized, should evaluate radical treatment strategies in such patients.

Introduction

Almost half of patients diagnosed with non-small cell lung carcinoma (NSCLC) have distant metastases at presentation [1], [2]. Metastatic NSCLC is generally associated with a poor prognosis, and systemic therapy is the cornerstone of treatment. A number of randomized clinical trials have established a response rate of 20–30% to platinum based chemotherapy-schedules with a median survival in the order of 8–11 months [3], which is significantly better than after supportive care alone. However, sub-groups of patients with specific molecular characteristics and a better prognosis are being identified [4]. In addition, several retrospective reports have suggested that selected patients who present with only a limited number of metastases, so-called oligometastatic disease, may also have a better-than-expected survival [5].

The term oligometastasis and its significance were described by Hellman and Weichselbaum in 1995 [6], but efforts to cure patients with metastatic disease predate this by many years [7], [8]. Nonetheless, literature on outcomes in NSCLC patients with oligometastases is largely based on retrospective, single institution series and typically describes the outcomes with surgical treatment. Most reports have included patients with both synchronous and metachronous oligometastases, and have predominantly focused on brain or adrenal metastases [9]. More reports have emerged in recent years on treatment of metastases at other sites, and using other treatment modalities [10], [11], [12], [13], [14]. This growing body of data has been recognized in the recent ESMO guidelines (2012), which recommend consideration of radical treatment as an option for selected patients with a solitary metastasis [3]. Nonetheless, level 1 evidence supporting improved OS after aggressive treatment is lacking, apart from resection or stereotactic ablation of a single brain metastasis [15], [16] and there is limited information on outcome for the specific group of patients presenting with NSCLC and synchronous oligometastases.

The purpose of the present study was to add to the existing literature by evaluating outcomes in patients treated in routine clinical practice (i.e. outside clinical trials), who were diagnosed with NSCLC and 1–3 synchronous metastases at presentation, and had all sites of disease treated with radical intent. The goals of this study were to assess survival outcomes and determine predictors of survival, and to better guide clinical care and the design of future clinical trials.

Section snippets

Materials and methods

This analysis was performed at the VU University medical center (VUmc), the Netherlands, and in the London Regional Cancer Program (LRCP), Canada. Data was pooled from these 2 large comprehensive cancer centers in order to increase the power and generalizability of the study. At both centers, details of all patients with NSCLC who had been radically treated between September 1999 and July 2012, were retrospectively identified using an institutional database, with subsequent review of individual

Results

In the period September 1999–July 2012 a total of 61 patients met the inclusion criteria. In total, these patients accounted for 74 metastases located at 7 different body sites. More than 70% of the patients were treated after 2009. Thirty-six of these patients were treated in the VUmc in the Netherlands, and 25 patients were treated at the LRCP in Canada. Baseline patient and tumor characteristics, for all patients and stratified by cohort, are summarized in Table 1. Seventy-nine percent of

Discussion

This two-center pooled retrospective analysis of patients undergoing radical treatment for NSCLC and 1 to 3 synchronous metastases found that over 80% of the treated patients had a solitary metastasis, most often located in the brain. Radical treatment resulted in a median overall survival of 13.5 months and a median PFS of 6.6 months. Significantly, the major predictors of OS were the extent or resection of intra-thoracic disease: a PTV ≥639 cc, and the absence of surgery as part of the

Conclusion

Radical treatment of selected NSCLC patients presenting with 1–3 synchronous metastases can result in favorable 2-year survival. Patients with resected intra-thoracic disease had the best prognosis, and patients treated with radiotherapy who had a large primary PTV had the worst prognosis. Prospective clinical trials, ideally randomized, should evaluate the role of radical treatment strategies in patients with oligometastases.

Funding

No funding was received for this study.

Conflict of interest statement

MD and BS have received travel support and honoraria from Varian Medical Systems and Brainlab. SS has received speakers honoraria from Varian Medical Systems, and is also a member of the Trial Management Group for a phase III study in lung cancer sponsored by Lilly Oncology. All the other authors declare that they have no conflict of interest.

Acknowledgement

Dr Palma is the recipient of a Clinician-Scientist Grant from the Ontario Institute for Cancer Research, funded through the Government of Ontario.

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