Number of liver metastatic nodules affects treatment options for pulmonary adenocarcinoma patients with liver metastases
Introduction
The most common extra-pulmonary sites of distant metastasis in non-small cell lung cancer (NSCLC) patients are the brain, bone, adrenal gland and liver [1]. The incidence of liver metastasis (LM) at the time of initial diagnosis of NSCLC is only 3.8%, and 95% of patients have involvement of more than 1 extra-hepatic organ [2]. The presence of LM is an independent prognostic factor for shorter survival in NSCLC patients; their median overall survival (OS) is only 4.2 months [3], [4], [5].
Treatment of NSCLC with chemotherapy has a response rate of about 20–30% [6], [7]. Patients with an epidermal growth factor receptor (EGFR) somatic mutation had a response rate of over 60% when treated with EGFR tyrosine kinase inhibitors (TKIs) [8], [9], [10]. Resection of a solitary metastatic lesion in the brain or the adrenal gland is becoming the standard of care and can achieve a significant survival benefit [11], [12], [13], [14]. Many published case reports suggest that lung cancer patients with LM may achieve long-term survival after metastatectomy, but determining which patients are likely to benefit from such an intervention is difficult [15], [16], [17], [18]. Surgical resection of LM in NSCLC is rare, since the majority of patients are not candidates for operation. Non-surgical alternatives, such as radiofrequency ablation (RFA), are more suitable for these patients because the procedures are generally less invasive, and lead to limited morbidity and speedier recovery [19], [20].
Continuation of EGFR-TKI plus local therapy for patients who develop oligometastases during EGFR-TKI treatment was suggested recently [21], [22]. However, the effect of EGFR mutation status and local therapy after LM development is unclear. Therefore, we conducted this retrospective study to examine a large cohort of consecutive patients with LM from pulmonary adenocarcinoma to determine which patients may benefit from combined local therapy for LM lesions and systemic therapy.
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Patients and LM lesions
We reviewed the chart records of 673 pulmonary adenocarcinoma patients who had EGFR mutation testing and received treatment at Veterans General Hospital, Taipei (VGH-TPE) from September 2006 to June 2011. Those who had other prior or concurrent malignancies were excluded. Patients who developed LM diagnosed with contrast-enhanced computed tomography (CT) during the disease course were identified. The timing of LM was categorized as synchronous and metachronous. Synchronous LM was defined as LM
EGFR mutation status and LM nodule characteristics
Eighty-five of the 673 patients who had EGFR examined had LM at any point during the disease course. All 85 patients were ethnic Chinese. The median age at LM diagnosis was 62.8 ± 13.6 years. LMs were synchronous with the primary lung cancer diagnosis in 29 (34.1%) patients and metachronous in 56 (65.9%). Synchronous LM was more common in the EGFR-mutated patients than in the wild-type patients (50.0% vs. 23.5%, P = 0.019). The median time from initial lung cancer diagnosis to the first LM
Discussion
This retrospective study found that patients with an EGFR mutation tended to have synchronous LM, and had longer OS after the development of LM (6.0 vs. 2.9 months, P = 0.002). Patients with fewer LM nodules had better OS (7.6 vs. 2.9 months, P < 0.001), and had less extra-hepatic organ metastasis (2.3 vs. 3.2, P = 0.003). Fifty-six patients in our cohort (65.9%) had ≦5 LM nodules; long-term survival (23.1 vs. 7.9 months, P = 0.035) could be achieved if they received RFA in addition to systemic therapy.
Conflict of interest statement
We declare no conflict of interest for all the authors and that the grant provider had no influence on the design and outcome of the study, on its analysis or on the content of this article.
Acknowledgements
This work was supported by grants from the Department of Health of the Republic of China, grant number DOH100-TD-C-111-007, and Taipei Veterans General Hospital, grant number VGH-101C-019. This work was presented as a poster abstract at the 15th World Conference on Lung Cancer, 27–30 October 2013 in Sydney.
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