The Tumour has Spread to the Brain…
What is the most common brain tumour in adults? It is actually metastatic brain tumour; estimated to be about 200,000 cases in the United States annually. The term for cancer spreading to the brain tissue is brain metastasis or brain secondaries. It is a serious condition presenting as a major hurdle for patients with cancer. It can occur when there is good control of the cancer in other parts of the body. This presents a frustrating problem for the patient and doctor looking after them. There is a general observation of an increase in brain metastases in recent years. Several possible reasons include improved systemic therapy (better chemotherapy and medication control of disease outside of the brain), better survival of patients and improved imaging and detection.
Progress in studying these groups of patients has been slow; most clinical trials would exclude patients with brain metastasis. However, our understanding of the unique brain microenvironment is improving, although the blood-brain barrier function in metastatic cancers is still not well understood. It is widely believed that tumour cells are protected from many therapeutic treatment including chemotherapy drugs by the blood-brain barrier. This creates a sanctuary site for the cancer.
In the course of their cancer, about 8 to 10% of adults develop symptomatic brain metastases. However, lung cancer, breast cancer and melanoma patients seem to have a higher probability of this happening. In breast cancers, this can range from 15 to 25% of women. In addition, Her2 positive (c-erbB2 positive) breast cancer and triple negative breast cancers seems to have a higher incidence of brain metastases compared to hormone positive breast cancer.
Some of the possible reasons this is happening are:
Improved imaging with modern scans allows earlier detection of brain involvement whereby it would not have been possible in the past.
Earlier detection of brain involvement from improved awareness by doctors.
Improved survival related to better treatment of the primary cancer and systemic control.
The brain remains a sanctuary site for some cancer treatment medications
Sites of involvement
The cerebral cortex forms the bulk of the brain tissue and blood flow, and is the most common site for brain metastases. Multiple brain metastases can occur at the time of brain secondaries diagnosis. The symptoms that patients present with is variable depending on which part of the brain the tumour has involved. This can be range from having no symptoms, to headache, weakness or other neurological deficits, seizures or fits. Some of these symptoms can be devastating on the patient especially when there is good control over the primary cancer at the time. Not being able to eat properly, having double vision, persistent weakness or numbness, facial muscle paralysis are often very difficult to manage.
Treatment of brain metastasis
This may involve the following procedure or a combination. However, not all patients are suitable for active treatment and need to be assessed individually. When possible, surgery allows tumour tissue to be collected to confirm the cancer metastasis. There have been occasions when the supposed spread to the brain is from a different cancer or other non-cancer conditions. (A recent HIV positive patient had seen us with a brain infection that simulated brain metastases)
Surgical techniques, expertise, anaesthesia and post-operative care have all improved to make surgery possible. Nonetheless, there are limitations depending on where the tumour is in the brain, the fitness of the patient and other factors. Radiotherapy – either as whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) have been employed. Studies in the past have shown improvement in survival for patients treated with whole-brain radiotherapy compared to no radiotherapy. In patients with a single metastatic brain lesion, surgery with WBRT or stereotactic radiosurgery combined with WBRT improved survival compared to WBRT alone. Of course, many factors decide how well patients will do. These include fitness or performance status of the patient, the type of cancer, the age of the patient, the control of metastases outside of the central nervous system (CNS) and the duration from diagnosis of cancer to the spread in the brain.
There are also patients where systemic treatment such as targeted therapies or chemotherapies (such as for small cell lung cancer) have been used for the treatment of brain metastases. In unselected patients with non-small cell lung cancer (NSCLC) and brain metastasis, the response rate reported with an oral tyrosine kinase (TKI) medication such as gefitinib or erlotinib is about 10 to 38%. Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to an oral ATP-competitive selective inhibitor of ALK such as crizotinib or alectinib. There have been several reports of responses to such drugs in brain metastasis from ALK-rearranged NSCLC.
In Her2 positive breast cancer, there is a higher incidence of brain metastases. Part of the reason could be that trastuzumab (Herceptin), a commonly used antibody targeted at Her2 breast cancers, has little penetration into the central nervous system. Penetration into CNS by small molecule tyrosine kinase inhibitors such as lapatinib (Tykerb) is suggested to be better. Lapatinib is a drug that we are using and had been involved in investigation before (Journal of Clinical Oncology, 2008 vol. 26 no. 18, 2999-300). Although there is limited activity as a single agent with refractory brain metastases, there is slightly higher activity when this is combined with an oral chemotherapy drug capecitabine (Xeloda).
The future in brain metastasis management might well be preventing the formation of such events in higher risk cancer.
Dr Peter Ang
MMed (Int Med)
FAMS (Medical Oncology)
Dr Benjamin Chuah
MRCP (United Kingdom) FRCP (Edinburgh)
FRCP (Medical Oncology)