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Tumour deposits that have travelled to the brain from a cancer elsewhere, ten times more common than cancers that start in the brain, mostly from lung, breast, melanoma and kidney cancer. Because the blood-brain barrier excludes most drugs, whether a medicine reaches and shrinks them now decides which drug is chosen, and trials report intracranial progression separately.
Lung cancer, breast cancer (especially HER2-positive and triple-negative), melanoma and kidney cancer account for most cases; 30-50% of driver-positive lung cancer patients develop them. Local treatment is stereotactic radiosurgery or surgery for limited disease and whole-brain radiotherapy for extensive disease. Because the blood-brain barrier excludes many drugs, CNS penetration and intracranial response rates (osimertinib, lorlatinib, tucatinib, T-DXd in DESTINY-Breast12) increasingly determine which drug is chosen, and trials now report intracranial progression-free survival separately.
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, NTRK fusion-positive non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid), Large cell neuroendocrine carcinoma of the lung, Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Showing the organ this term concerns: Non-small-cell lung cancer.
Adjuvant treatment for lung cancer is now chosen by genotype. A resected ALK-positive tumour is treated with two years of a tablet instead of four cycles of platinum, which is a different life as well as a different outcome.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
It is the practical guide to what to do after transformation: treat it as small-cell lung cancer with platinum and etoposide, expect central nervous system disease, and do not expect a checkpoint inhibitor to help.
First-line ALK treatment moved to a drug designed for the brain, and brain metastasis prevention became an explicit design goal rather than a hoped-for side effect. ALK-positive lung cancer is now among the longest-surviving metastatic solid tumours.
The trial that made ALK testing worth doing. It is also the clearest case in oncology of a drug finding its disease after the fact: crizotinib entered the clinic as a MET inhibitor and became an ALK drug because somebody checked.
The 13.3-month median is the pre-immunotherapy, pre-antibody-drug conjugate benchmark against which first-line trials now reporting medians near two years are measured; the brain metastasis rate is why trials that exclude active brain disease leave the question unanswered.
The first time a targeted biological agent extended survival in lung cancer, and the first time median survival in the advanced setting crossed twelve months. It also set the pattern that a drug's exclusion criteria can matter as much as its mechanism.
Treating the brain before the cancer gets there works in small-cell lung cancer, and it is the proof of principle behind every later attempt to prevent rather than treat brain metastases.
Shares JROSG 99-1 (Aoyama): stereotactic radiosurgery with or without whole-brain radiotherapy, CheckMate 204, Patient positioning and surface guidance systems (AlignRT, Catalyst, ExacTrac Dynamic), Whole-brain radiotherapy (WBRT).
Shares CNS penetration (brain-penetrant drugs), ALESIA, J-ALEX, eXalt3.
Shares eXalt3, ARCHER 1050, ALEX, Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer.
Shares ALTA, ALTA-1L, ALEX, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer.
Shares ALESIA, J-ALEX, Alectinib in resected ALK-positive non-small-cell lung cancer, ALEX.
Shares Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases, Trials that include, and report, brain metastases in triple-negative breast cancer, Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission, Measure brain metastasis prevention as a primary endpoint, not as a secondary one.