Elsevier

Clinical Oncology

Volume 33, Issue 3, March 2021, Pages 163-171
Clinical Oncology

Original Article
Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis

https://doi.org/10.1016/j.clon.2020.10.010Get rights and content

Highlights

  • Patients in this study had contemporary imaging with brain MRI and whole-body FDG-PET/CT.

  • Appropriate selection of patients presenting with solitary brain metastases for definitive treatment of the lung and brain was associated with a favourable 5-year overall survival.

  • Prolonged overall survival was also noted in those patients with >N1 disease.

  • Highlights the need for future prospective studies to guide the management of patients with oligometastatic NSCLC.

Abstract

Aims

At diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease.

Materials and methods

This retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors.

Results

Forty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS.

Conclusions

Definitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

Introduction

Non-small cell lung cancer (NSCLC) is the greatest cause of cancer-related death worldwide. About 10% of all patients with NSCLC have intracranial metastases and <1% have a synchronous solitary brain metastasis (SSBM) [1,2]. Recently, management of metastatic disease has altered significantly, with the development of targeted therapeutics and immunotherapies resulting in durable progression-free survival (PFS) and overall survival (OS). The oligometastatic paradigm is described as an intermediate metastatic state where tumours are limited in site and number [3]. The maximum number of oligometastases and organs is five and three, respectively, as agreed upon by the pan-European multidisciplinary consensus group and reported in the Journal of Thoracic Oncology in 2019 [4]. Synchronous oligometastases are those that are diagnosed ≤3 months of the primary; however, some publications recognise synchronous metastases ≤6 months. The Journal of Thoracic Oncology consensus on defining synchronous oligometastases stated that a uniform and reliable definition does not exist. Any metastatic disease diagnosed after these times are considered metachronous [1,5]. There is now published randomised phase II evidence showing that local treatment in oligometastatic NSCLC to the primary and metastatic sites is associated with long-term PFS and OS compared with standard of care [[6], [7], [8], [9]].

Appropriate selection of those patients with limited oligometastatic disease is essential if definitive treatment is to be effective. In the modern era, 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is recommended for assessing TNM status, excluding the brain. Use of FDG-PET/CT can potentially up- or downstage disease and therefore influence decisions regarding definitive treatment based on N-stage and the presence and number of distant (oligo)metastases. Staging with FDG-PET/CT is now regarded as the standard of care for the extracranial staging of NSCLC [9,10]. Brain magnetic resonance imaging (MRI) has a significantly higher sensitivity for the detection of brain metastases in asymptomatic or symptomatic patients compared with contrast-enhanced CT brain [2,9,[11], [12], [13], [14], [15], [16]]. Older retrospective evidence dates from the pre-FDG-PET/CT era and reports poor OS in patients with >N1 disease [[16], [17], [18], [19], [20], [21], [22], [23], [24]]. Despite the lack of randomised trial evidence, a survey of lung radiation oncologists suggested that most would elect to treat SSBM NSCLC with definitive therapy in the absence of other extrathoracic disease [9]. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease.

Section snippets

Materials and Methods

In this single institution multicampus retrospective study, eligible patients had histologically confirmed NSCLC and a SSBM (diagnosed within 2 months of the primary diagnosis) staged with FDG-PET/CT and received definitive treatment from 1 February 1999 to 31 December 2017. Patients were identified for potential inclusion through a search of a fully integrated electronic medical record institutional database. Patients were staged based on the UICC seventh edition TNM criteria. Patients were

Results

In total, 49 patients were eligible. The median age was 63 years (range 34–76). Thirty patients (61%) were male. The ECOG performance status was 0 in 19 (39%), 1 in 26 (5%) and 2 in four (8%) patients, respectively. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. Of the 49 patients, mutation status was tested/documented in nine tumours: four had EGFR mutations, five had KRAS mutations (Table 1, Supplementary Table S2). The median SSBM size was 20 mm (range 3–59 mm) with 43 (88%)

Discussion

The optimal treatment for NSCLC with a SSBM is not well defined. The oligometastatic paradigm challenges conventional thinking by describing a state where longer survival is more likely due to lower volume of disease. An accumulating volume of retrospective evidence suggests that long-term OS is possible in this cohort of patients when both the intracranial and intrathoracic disease are treated definitively [3,[16], [17], [18], [19], [20], [21], [22], [23], [24],27].

In our study, patients with

Conclusions

In this retrospective study, all of our patients were staged with FDG-PET/CT, which is a novel inclusion criterion compared with previous retrospective studies assessing this subset of patients with NSCLC. We have been able to show that when staged appropriately with FDG-PET/CT and MRI brain, patients with NSCLC and SSBM treated definitively had a favourable OS. This retrospective study supports oligometastatic prospective phase II and III trials, such as NRG-LU002, NRG-BR002, SABR-COMET-3 and

Conflicts of Interest

S. Siva receives personal fees and non-financial support from Astra Zeneca outside the submitted work. D. Ball receives personal fees from Astra Zeneca outside the submitted work.

Acknowledgement

Shankar Siva was supported by a National Health and Medical Research Council fellowship grant APP1122347, as well as a Peter MacCallum Discovery Partner Fellowship.

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