Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies

Abstract

Bone metastasis in lung cancerLung cancer is the third most common form of cancer to spread to bone. About 30-40% of patients with lung cancer developed bone metastases during the course of their disease; the median survival time of patients with this secondary lesion is 7 months [Coleman, 2001]. These metastases are associated with significant morbidity, loss of functional independence and reduction in quality of life (QOL) [Berenson et al. 2006]. Bone metastasis accounts for 350,000 cancer patients deaths each year [Mundy, 2002] and in lung cancer is associated with increased social costs due to medical care, hospitalization days and cost of treatment [Botteman et al. 2007].In a retrospective study of 259 nonsmall cell lung cancer (NSCLC) patients, the most common site of skeletal metastases was the spine in 50% of patients, followed by the ribs (27.1%), ilium (10%), sacrum (7.1%), femur (5.7%) and humerus, scapula and sternum (2.9%) [Tsuya et al. 2007]. The prognosis was worse in patients with metastasis to the appendicular bone than in patients with metastases only on an axial bone [Sugiura et al. 2008].Pain is usually the first symptom of lung cancer with bone metastases in 80% of patients [Kosteva and Langer, 2008]. Patients with osseous metastases complain of pain at some point with wide variation in pattern and severity [Delaney et al. 2008]. Many factors are implicated in the pain of osseous metastases but a significant portion of the pain seems to be related to osteoclastic bone resorption. Bone and brain metastasis in lung cancer: recent advances in therapeutic strategiesChiara D'Antonio, Antonio Passaro, Bruno Gori, Ester Del Signore, Maria Rita Migliorino, Serena Ricciardi, Alberto Fulvi and Filippo de Marinis Abstract: Bone and brain metastases are a very common secondary localization of disease in patients with lung cancer. The prognosis of these patients is still poor with a median survival of less than 1 year. Current therapeutic approaches include palliative radiotherapy and systemic therapy with chemotherapy and targeted agents. For bone metastasis, zoledronic acid is the most commonly used bisphosphonate to prevent, reduce the incidence and delay the onset of skeletal-related events (SREs). Recently, denosumab, a fully human monoclonal antibody directed against the receptor activator of nuclear factor κB (RANK) ligand inhibiting the maturation of pre-osteoclasts into osteoclasts, showed increased time to SREs and overall survival compared with zoledronic acid. The treatment of brain metastasis is still controversial. Available standard therapeutic options, such as whole brain radiation therapy and systemic chemotherapy, provide a slight improvement in local control, overall survival and symptom relief. More recently, novel target agents such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and afatinib have shown activity in patients with brain metastasis. Inter alia, in patients harboring EGFR mutations, the administration of EGFR TKIs is ...

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

“…The number of metastatic organ sites was associated with a poorer PFS and OS time. Between 30 and 40% of patients with lung cancer develop bone metastases during the course of their disease (24). 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.…”

Bevacizumab, pemetrexed and carboplatin in first-line treatment of non-small cell lung cancer patients: Focus on patients with brain metastases

“…Patients with BM were therefore excluded from chemotherapy and were ineligible for clinical trials (22). Nowadays, it is known that the blood brain barrier is disrupted when brain metastases develop (27,28). Certain trials have been performed on the activity of first-line chemotherapy on brain metastases in NSCLC and have shown response rates ranging from 23-50% (27).…”

“…This was due to alleged concerns over an increased risk of intracranial hemorrhage after the mortality due to cerebral hemorrhage of a woman with hepatocellular carcinoma treated in a phase I study (28,34,35). Hepatocellular carcinoma, however, may itself lead to cerebral hemorrhage due to impaired liver function and subsequent coagulopathy (34,36).…”

Lung Cancer: Risk Factors, Management, And Prognosis

“…In advanced cases, appropriate chemotherapy improves average survival over supportive care alone, as well as improving quality of life [100].In targeted therapy, several drugs that target molecular pathways in lung cancer are available, especially for the treatment of advanced disease. Some of the drugs used in targeted therapy may be useful in the treatment of bone metastases [90].…”

“…The common treatments include palliative care, surgery, chemotherapy, and radiation therapy [89,10].Targeted therapy of lung cancer is growing in importance for advanced lung cancer [90].…”