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