Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis

Fujimoto, Daichi; Ueda, Hiroyuki; Shimizu, Ryoko; Kato, Ryuichi; Otoshi, Takehiro; Kawamura, Takahisa; Tamai, Ken; Shibata, Yumi; Matsumoto, Takeshi; Nagata, Kazuma; Otsuka, Kyoko; Nakagawa, Atsushi; Otsuka, Kojiro; Katakami, Nobuyuki; Tomii, Keisuke

doi:10.1007/s10585-014-9648-3

Cited by 49 publications

(49 citation statements)

References 39 publications

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“…To the best of our knowledge, this is the first study to assess the association between bone metastasis and a poorer PFS time in EGFR mutation-positive NSCLC patients. In a previous report, Fujimoto et al (15) revealed that bone metastasis was a significant independent negative predictive factor for OS time in EGFR mutation-positive patients. By contrast, in the present study, bone metastasis was not associated with OS time.…”

Section: Discussionmentioning

confidence: 93%

“…The toxicities of EGFR-TKIs are decreased compared with those of cytotoxic drugs and patients can achieve a good quality of life while using them (8,12). In patients treated with first generation EGFR-TKIs, brain, bone and liver metastasis and pleural effusion (PE) predicted a poorer prognosis compared with patients without these metastasis (13)(14)(15)(16)(17). However, few reports concern the association between the site of metastasis and prognosis (18,19).…”

Section: Introductionmentioning

confidence: 99%

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Impact of metastatic status on the prognosis of EGFR mutation‑positive non‑small cell lung cancer patients treated with first‑generation EGFR‑tyrosine kinase inhibitors

et al. 2017

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Abstract. The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated. The association between the number of metastatic organ sites and patient prognosis was also investigated. The median age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients had adenocarcinoma; 156 were treated with gefitinib. Patients with brain metastases, bone metastases, liver metastases and pleural effusion exhibited a significantly reduced PFS and OS time in the univariate analysis, compared with patients without each of these symptoms. In the multivariate analysis, bone metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No association was observed between metastatic status and treatment response rates. Higher numbers of different sites of organ metastases were associated with significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of metastatic organ sites are negative prognostic factors for EGFR mutation-positive NSCLC patients treated with first-generation EGFR-TKIs.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Impact of metastatic status on the prognosis of EGFR mutation‑positive non‑small cell lung cancer patients treated with first‑generation EGFR‑tyrosine kinase inhibitors

et al. 2017

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“…The NOS was used to perform quality assessment on all 22 studies and 14 (17,18,(25)(26)(27)(28)30,(32)(33)(34)(35)(36)38,42) high-quality and 8 (16,19,29,31,37,(39)(40)(41) as low-quality.…”

Section: Study Description and Quality Assessmentmentioning

confidence: 99%

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

Luo

Lin

et al. 2017

J. Thorac. Dis.

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Background: Lung cancer is the leading cause of cancer-related death worldwide. Numerous studies have been performed to investigate the correlation between epidermal growth factor receptor (EGFR) mutation status and the incidence of brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC), however, the outcomes were inconsistent. Thus, we performed this study to establish the role of EGFR mutation status in BMs. Methods: Electronic databases PubMed, Embase, Cochrane Library, CBM, WanFang, CNKI were searched to identify relevant trials. The primary endpoint was the incidence of BMs in EGFR mutations or wild type NSCLC and the secondary endpoint was overall survival calculated from the BMs emerging (BMOS). Results: Twenty-two studies incorporating 8,152 participants were eligible. EGFR mutations group possessed a significantly higher risk of BMs (OR =1.99; 95% CI, 1.59-2.48; P=0.000) than EGFR wild type group. In the stratified analysis, compared with EGFR wild type group, EGFR mutations group had a significant higher incidence (OR =2.01; 95% CI, 1.56-2.59; P=0.000) of subsequent BMs while only a trend of increasing the incidence of initial BMs (OR =1.38; 95% CI, 0.98-1.94; P=0.066). Moreover, exon 19 deletion had a trend of increasing the incidence of BMs than exon 21 mutation (OR =1.44; 95% CI, 0.77-2.68; P=0.252). Compared with EGFR wild type group, EGFR mutations group possessed a prolonged overall BMOS (HR =0.68; 95% CI, P=0.038) and a longer BMOS in initial BMs (HR =0.50; 95% CI, 0.31-0.80; P=0.004) but no significant difference in NSCLC with subsequent BMs (HR =0.95; 95% CI, 0.42-2.15; P=0.901). Conclusions: Patients with EGFR mutations were more susceptible to develop into BMs than those with EGFR wild type, especially during the course of disease.

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“…The presence of bone metastases is associated with poor prognosis in some cancers, such as lung adenocarcinoma, gastric adenocarcinoma, hepatocellular carcinoma and ovarian carcinoma [16,17,18,19,20]. In a large series of 360 patients with MESCC, 7% were found to have bone metastases, against 16 and 13% in both of our cohorts [21].…”

Section: Discussionmentioning

confidence: 89%

First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control

Kotecki

Hiret²,

Etienne³

et al. 2016

Oncology

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Objective: This study aimed to identify predictors of tumor control (TC) in metastatic esophageal squamous cell carcinoma patients receiving first-line chemotherapy. Methods: A development cohort of 68 patients from a prospective multicenter trial (NCT01248299) was used to identify predictors of TC at first radiological tumor assessment and to generate a predictive score for TC. That score was applied in an independent retrospective single-center validation cohort of 60 consecutive patients. Results: Multivariate analysis identified three predictors of TC: body mass index ≥18.5 (OR 4.5, 95% CI 0.91-22.5), absence of bone metastasis (OR 4.6, 95% CI 0.91-23.2) and albumin ≥35 g/l (OR 3.5, 95% CI 1.0-12.1). Based on the presence or absence of these three independent prognosticators, we built a predictive model using a score from 0 to 3. In the development cohort, the TC rates were 14.3 and 78.0% and in the validation cohort 12.5 and 44.2%, for scores of 0-1 and 2-3, respectively. With negative predictive values of 85 and 88% in the development and validation cohorts, respectively, we were able to identify patients with a very low probability of TC. Conclusion: We have developed and validated a score that can be easily determined at the bedside to predict TC in metastatic esophageal squamous cell carcinoma patients.

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Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis

Cited by 49 publications

References 39 publications

Impact of metastatic status on the prognosis of EGFR mutation‑positive non‑small cell lung cancer patients treated with first‑generation EGFR‑tyrosine kinase inhibitors

Impact of metastatic status on the prognosis of EGFR mutation‑positive non‑small cell lung cancer patients treated with first‑generation EGFR‑tyrosine kinase inhibitors

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

First-Line Chemotherapy for Metastatic Esophageal Squamous Cell Carcinoma: Clinico-Biological Predictors of Disease Control

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