title: Bone and brain metastasis in lung cancer: recent advances in therapeutic strategies.
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 followed by a response rate of 70-80%, and a longer progression-free and overall survival than those obtained with standard chemotherapeutic regimens. This review is focused on the evidence for therapeutic strategies in bone and brain metastases due to lung cancer.
authors.affiliation: 1st Oncological Pulmonary Unit/Department of Medical and Surgical Sciences and Translational Medicine, 'Sapienza' University of Rome, Sant'Andrea Hospital San Camillo, High Specialization Hospital/University of Rome, Sant'Andrea Hospital, Cir. ne Gianicolense 87, 00151, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Antonio
authors.affiliation: Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Passaro
authors.affiliation: 1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gori
authors.affiliation: Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Del Signore
authors.affiliation: 1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Migliorino
authors.affiliation: 1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ricciardi
authors.affiliation: 1st Oncological Pulmonary Unit, San Camillo, High Specialization Hospital, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fulvi
authors.affiliation: Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
keywords: afatinib; bone; brain; epidermal growth factor; erlotinib; gefitinib; lung cancer; metastases