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A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

ABSTRACT: In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases. This retrospective study evaluated 1510 NSCLC patients diagnosed between November 2010 and March 2014. Among these patients, 234 patients had de novo bone metastases. We found that 121 of these 234 patients (51.7%) had positive EGFR mutation tests, and a positive EGFR mutation test significantly affected overall survival (OS) (EGFR mutant: 15.2 months, EGFR wild type: 6.5 months; p < 0.001). Other prognostic factors significant in the multivariable analysis for NSCLC with de novo bone metastases included Eastern Cooperative Oncology Group performance status (PS) (OS; PS 0-2: 11.2 months, PS 3-4: 4.9 months; p = 0.002), presence of extraosseous metastases (OS; with extraosseous metastases: 8.8 months, without extraosseous metastases: 14.0 months; p = 0.008), blood lymphocyte-to-monocyte ratio (LMR) (OS; LMR > 3.1: 17.1months, LMR ? 3.1: 6.9months; p < 0.001). A positive EGFR mutation status reversed the poor outcomes of NSCLC patients with de novo bone metastases. A simple and useful survival scoring system including the above clinical parameters was thus created for NSCLC patients with de novo bone metastases.

SUBMITTER: Chen YM

PROVIDER: S-EPMC5145216 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

Chen Yu-Mu YM Fang Ying-Tang YT Lai Chien-Hao CH Rau Kun-Ming KM Huang Cheng-Hua CH Chang Huang-Chih HC Chao Tung-Ying TY Tseng Chia-Cheng CC Fang Wen-Feng WF Wang Chin-Chou CC Chen Yung-Che YC Chung Yu-Hsiu YH Wang Yi-Hsi YH Su Mao-Chang MC Liu Shih-Feng SF Huang Kuo-Tung KT Chen Hung-Chen HC Chang Ya-Chun YC Chang Yu-Ping YP Lin Meng-Chih MC

PloS one 20161208 12

In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC pat ...[more]

PMID: 27930702

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Project description:Background and objectiveBone metastases are common in patients with non-small cell lung cancer (NSCLC) and remain a significant source of morbidity, mortality, and diminished quality of life, despite the considerable progress made in the overall management of patients with metastatic NSCLC over the last decade. Understanding the molecular pathogenesis of bone metastases is critical to improving survival, preserving function, and managing symptoms in this patient population. The objective of our review is to provide a comprehensive review of the pathophysiology, clinical presentation, management, and factors predicting the development and prognosis of patients with NSCLC with bone metastases.MethodsAn online electronic search was performed on PubMed and Google Scholar of all English-language literature using combinations of the following keywords: bone metastases, non-small cell lung cancer, pathophysiology, skeletal related events, response to therapy, predictive factors, and immunotherapy. Bibliographies of identified papers were reviewed for additional articles of interest. Observational cohort, retrospective studies, randomized controlled trials (RCTs), meta-analyses, and review articles were examined for this review.Key content and findingsBone metastases in lung cancer patients remain a common occurrence, impacting morbidity, mortality, and quality of life. Patients with skeletal related events (SREs) have worse prognosis. There is data supporting use of bisphosphonates and/or denosumab, and these should be considered in all patients with bone metastases. Novel studies comparing the genomic alterations of skeletal metastases and primary tumors are needed. As therapy for patients with advanced disease evolves, more studies are needed to evaluate the interplay between immunotherapy and bone metastases, and in determining the response to treatment in bone.ConclusionsPredicting development and progression of bone metastases could allow earlier and targeted therapy in patients with bone metastases. Predicting and evaluating response to conventional chemotherapy and immune checkpoint inhibitors in NSCLC patients with bone metastases remains an unmet need and merits further study.

Project description:BackgroundThe selection of radiation therapy dose fractionation schedules for bone metastases is often based on the estimation of life expectancy. Therefore, accurate prognosis prediction is an important issue. It is reported that the Katagiri scoring system can be used to predict the survival of patients with bone metastases. We aimed to assess prognostic factors and validate the Katagiri scoring system in patients who were treated with radiation therapy for bone metastases.Materials/methodsWe retrospectively reviewed data of all patients who were treated with radiation therapy for bone metastases between 2004 and 2013. Age, sex, Karnofsky performance status (KPS), Eastern Cooperative Oncology Group performance status (ECOG PS), primary site (lesions and characteristics), visceral metastases, laboratory data, previous chemotherapy, and multiple bone metastases were analyzed for associations with overall survival (OS). Katagiri scores were calculated for each patient and were used to compare OS.ResultsOut of the 616 patients included in this analysis, 574 had died and 42 remained alive. The median follow-up time for survivors was 42 months. Univariate analysis revealed that age (P = 0.604) and multiple bone metastases (P = 0.691) were not significantly associated with OS. Multivariate analysis revealed that sex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significantly associated with OS. The survival rates at 3, 6, 12, and 24 months, categorized by Katagiri score, were as follows: score 0-3, 94.4, 77.8, and 61.1%, respectively; score 4-6, 67.7, 48.7, and 31.2%, respectively; and score 7-10, 39.1, 22.1, and 9.0%, respectively (P < 0.001).ConclusionSex, ECOG PS, KPS, primary characteristics, visceral metastases, laboratory data, and previous chemotherapy were significant predictors of survival in patients with bone metastases. The Katagiri scoring system was significantly correlated with OS and can help us select the optimal dose-fractionation.

Project description:BackgroundMetastatic epidermal growth factor receptor-mutated (EGFR+) non-small-cell lung cancer (NSCLC) can present de novo or following previous nonmetastatic disease (secondary). Potential differences between these two patient subsets are unclear at present.MethodsWe retrospectively analyzed characteristics of tyrosine kinase inhibitor (TKI)-treated patients with de novo vs. secondary metastatic EGFR+ NSCLC until December 2019 (n = 401).ResultsDe novo metastatic disease was 4× more frequent than secondary (n = 83/401), but no significant differences were noted regarding age (median 66 vs. 70 years), sex (65% vs. 65% females), smoking history (67% vs. 62% never/light-smokers), and histology (both >95% adenocarcinoma). Patients with secondary metastatic disease showed a better ECOG performance status (PS 0-1 67%-32% vs. 46%-52%, p = 0.003), fewer metastatic sites (mean 1.3 vs. 2.0, p < 0.001), and less frequent brain involvement (16% vs. 28%, p = 0.022) at the time of stage IV diagnosis. Progression-free survival (PFS) under TKI (median 17 for secondary vs. 12 months for de novo, p = 0.26) and overall survival (OS, 29 vs. 25 months, respectively, p = 0.47) were comparable. EGFR alterations (55% vs. 60% exon 19 deletions), TP53 mutation rate at baseline (47% vs. 43%, n = 262), and T790M positivity at the time of TKI failure (51% vs. 56%, n = 193) were also similar. OS according to differing characteristics, e.g., presence or absence of brain metastases (19-20 or 30-31 months, respectively, p = 0.001), and ECOG PS 0 or 1 or 2 (32-34 or 20-23 or 5-7 months, respectively, p < 0.001), were almost identical for de novo and secondary metastatic disease.ConclusionsDespite the survival advantage reported in the pre-TKI era for relapsed NSCLC, molecular features and outcome of TKI-treated metastatic EGFR+ tumors are currently independent of preceding nonmetastatic disease. This simplifies design of outcome studies and can assist prognostic considerations in everyday management of patients with secondary metastatic EGFR+ tumors.

Dataset Information

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

Publications

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases.

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