Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

Arrieta, Óscar; Villarreal‐Garza, Cynthia; Zamora, J.; Blake-Cerda, M.; Mata, María D de la; Zavala, Diego G; Muñiz-Hernández, Saé; Garza, Jaime de la

doi:10.1186/1748-717x-6-166

Cited by 100 publications

(79 citation statements)

References 35 publications

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“…WBRT continues to be an important palliative treatment option for patients with brain metastases from NSCLC. In previous studies, WBRT combined with EGFR-TKI treatment was demonstrated to be a safe and effective treatment for EGFR mutation-positive NSCLC patients with brain metastases, with a median survival time of 7.7-13.0 months (9,17,18). The median survival time in the present analysis was 10.9 months, which confirms these expectations.…”

Section: Discussionsupporting

confidence: 80%

Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

Wei

Lin

et al. 2016

Oncology Letters

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Abstract. The survival time of non-small cell lung cancer (NSCLC) patients with brain metastases has been previously reported to be 6.5-10.0 months, even with systematic treatment. Patients that possess a certain epidermal growth factor receptor (EGFR) mutation alongside NSCLC with brain metastases also have a short survival rate, and a reliable prognostic model for these patients demonstrates a strong correlation between the outcome and treatment recommendations. The Cox proportional hazards regression and classification tree models were used to explore the prognostic factors in EGFR mutation-positive NSCLC patients with brain metastases following whole-brain radiation therapy (WBRT) and EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. A total of 66 EGFR mutation-positive NSCLC patients with brain metastases were retrospectively reviewed. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. The classification tree model was applied in order to identify prognostic groups of the patients. In the survival analysis, age, carcinoembryonic antigen (CEA) and status of the primary tumor were prognostic factors for progression free survival (P=0.006, 0.014 and 0.005, respectively) and overall survival (P= 0.009, 0.013 and 0.009, respectively). The classification tree model was subsequently applied, which revealed 3 patient groups with significantly different survival times: Group I, age <65 years and CEA ≤10 µg/ml; Group II, age <65 years and CEA >10 µg/ml or age ≥65 years and CEA ≤10 µg/ml; and Group III, age ≥65 years and CEA >10 µg/ml. The major prognostic predictors for EGFR mutation-positive NSCLC patients with brain metastases following WBRT and EGFR-TKI were age and CEA. In addition, primary tumor control may be important for predicting survival. IntroductionPatients with non-small cell lung cancer (NSCLC) possess a high risk of developing brain metastases. The incidence rate of brain metastases for patients with lung cancer is 23-65% (1). Once intracerebral metastases develop, the prognosis is poor. The median survival time for patients with untreated brain metastases is only ~1 month (2,3). The principle therapeutic modality for brain metastases is whole-brain radiation therapy (WBRT), and the median survival time following this treatment may increase to 4-6 months. Although therapies, including surgery, WBRT, stereotactic radiotherapy and systematic chemotherapy, are rapidly improving, the prognosis of patients with brain metastases from lung cancer remains poor, and the median survival time for patients remains at ~6.5-10 months (4-7).In 2004, the genes encoding the read code box of epidermal growth factor receptor (EGFR) were sequenced (8). In addition, the gene mutation status has been elucidated and is now widely used in clinical practice. As a result, the identification of the EGFR mutation and the introduction of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI) has improved clinical outcomes (9). EGFR-TKI regimens have a good efficacy against brain...

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Section: Discussionsupporting

confidence: 80%

Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

Wei

Lin

et al. 2016

Oncology Letters

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“…Factors affecting survival of synchronous oligometastatic NSCLC patients, such as performance status, N-stage, and thoracic stage, have been revealed in some reports (35)(36)(37). However, no study investigated factors predictive of survival specially for patients with ATT.…”

Section: Subgroup Analysesmentioning

confidence: 99%

Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis

Li¹,

Zhu²,

Wang³

et al. 2017

J. Thorac. Dis.

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Background: We performed a meta-analysis to compare overall survival (OS) outcomes in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) who underwent aggressive thoracic therapy (ATT) with those who did not. Methods: A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted. Hazard ratio (HR) for the main endpoint OS was pooled using a fixed-effects model. Subgroup analysis was performed in patients with single organ metastases, or with different numbers of brain metastases, or with different stages of thoracic disease. Pooled survival curves of OS were constructed. Results: Seven eligible retrospective observational cohort studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. For patients with synchronous oligometastatic NSCLC, ATT was associated with a significant improvement of OS (HR, 0.48; 95% CI, 0.39-0.60; P<0.00001). In subgroup analysis, the association with OS was similar or even strengthened, with a HR of 0.42 (95% CI, 0.31-0.56) in single organ metastases group, 0.49 (95% CI, 0.31-0.75) in solitary brain metastasis group, and 0.38 (95% CI, 0.20-0.73) in thoracic stage I-II group, respectively. The pooled cumulative survival rates for patients received ATT were 74.9% at 1 year, 52.1% at 2 years, 23.0% at 3 years, and 12.6% at 4 years. The corresponding pooled survival for patients who did not receive ATT were 32.3%, 13.7%, 3.7%, and 2.0%, respectively. Conclusions: Survival benefit from ATT is common in synchronous oligometastatic patients. Selected patients with synchronous oligometastatic NSCLC could also achieve long-term survival with ATT. Targeted therapy have shown efficacy in the treatment of advanced NSCLC, however, most patients progress after a median survival of 12 months because of resistance (4-6).Hellman and Weichselbaum proposed the existence of a clinically recognisable state termed 'oligometastases', which is an intermediate state of metastases characterized by a limited number and site of metastatic tumors. In these selected patients, eradication of oligometastases could be curative (7,8). However, whether the aggressive thoracic therapy (ATT) could potentially improve overall survival (OS) in oligometastatic NSCLC remains unclear. Removal of the primary tumor was shown to improve OS in patients with metastatic renal cancer (9), by contrast, locoregional treatment of the primary tumor did not affect OS in patients with metastatic breast cancer (10). More and more studies reported favorable long-term survivals in oligometastatic NSCLC treated with aggressive local therapy (11-13). However, these studies are retrospective and the validity of the survival benefit are challenging due to patient selection.Recently, Ashworth et al. did a systematic review of literature considering NSCLC patients with 1-5 metastases treated with local therapy and found that definitive treatment of the primary tumor was a good prognostic factor for survival (14). Moreo...

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“…Once these primary tumors become metastatic, risks of BM will increase rapidly. About 30%‐50% of lung cancer, particularly nonsmall cell lung cancer (NSCLC), will develop BM during the course of their diseases 8. Among metastatic breast cancer patients, approximately 10%‐16% patients develop symptomatic BM and another 10% patients are found to have asymptomatic brain involvement in postmortem 9.…”

Section: Introductionmentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

Cited by 100 publications

References 35 publications

Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis

Emerging findings into molecular mechanism of brain metastasis

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