Written by Dr Daniel Cagney, Clinical Director, Radiation Oncology, Mater Private Hospital Dublin
Brain metastases have a significant impact on quality of life and clinical outcomes of patients with cancer. Although the incidence of brain metastases in patients with breast cancer is low, brain metastases are relatively common in patients with metastatic breast cancer, particularly in patients with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer (TNBC) subtype. Despite the extracranial efficacy of many systemic therapies for patients with breast cancer, the bloodbrain barrier limits penetration of many systemic agents into the brain, and patients often experience intracranial progression. Therefore, radiation, in the form of whole brain radiotherapy (WBRT) or now more commonly stereotactic radiation, is the mainstay of the therapy for many patients with breast cancer and brain metastases. The management choice in patients with newly diagnosed brain metastases depends on number of brain metastasis, histological subtype, performance status, estimated prognosis, and extent of extracranial disease.
Thankfully brain radiation treatment has evolved over the past decade to lead to better outcomes for patients from a cancer perspective but also side effects and toxicities have been reduced. This article highlights two such developments.
Hippocampal avoidance Whole brain radiotherapy (HA-WBRT)
Whole-brain radiotherapy (WBRT) remains an important treatment modality in many patients with brain metastases because it reduces symptoms, improves intracranial control, and diminishes the chance of death. However, numerous patients experience cognitive deterioration after WBRT, which highlights concerns about the toxicity of WBRT. Preclinical and clinical studies have suggested that relatively low doses of radiation to neural stem cells within the subgranular zone of the hippocampus may contribute to radiotherapy (RT)–induced cognitive toxicity. A recent prospective multi-institutional randomized phase III trial investigated the role of WBRT with or without HA in patients with brain metastases. The use of HA during WBRT (Figure 1) was shown to effectively spare the neurocognitive damage from radiation to better preserve cognitive function and patientreported symptoms. This is fantastic news for patients with breast cancer and brain metastases. However even with the use of HA-WBRT, patients can still experience side effects. Thus, in patients with limited number of brain metastases stereotactic radiation is the preferred treatment course.
Stereotactic Radiation (SRS)
SRS is a novel radiation technique developed by a Swedish neurosurgeon, Lars Leksell, for lesions not amenable to surgical resection. SRS is a distinct discipline that utilises x-rays to inactivate defined target(s) in the head and spine without the need to make an incision. The target is identified by high-resolution imaging. SRS is mainly performed in a single session, using a mask and a stereotactic image guidance system, but can be conducted up to a maximum of five days. Brain metastases tend to be spherical with sharp demarcation from brain tissue. They are thus ideal for SRS because precision targeting can be easily generated using radiosurgical systems. Compared with resection, SRS is advantageous as it can treat surgically inaccessible lesions and multiple lesions. In general, asymptomatic patients with up to four lesions smaller than 4 cm are regarded as suitable for SRS. Local tumour control rates with SRS are consistently greater than 80%. Patients with newly diagnosed brain metastases may be treated with wholebrain radiotherapy alone versus whole-brain radiotherapy and SRS boost. In practice we tend to omit whole brain radiotherapy from this treatment paradigm due to enhanced toxicity, impact on quality of life and no improvement in overall survival. Whole brain radiotherapy is then reserved for future salvage use if required. SRS, unlike whole brain radiotherapy, has the additional advantage of being able to integrate with systemic treatment. Patients with brain metastasis treated with SRS can be treated without chemotherapy treatment breaks thus optimizing extracranial disease control in addition to their intracranial disease.
Despite the efficacy and improvements radiation delivery, many patients ultimately progress intracranially, both locally and in distant or uninvolved regions of the brain. The challenge and unanswered question for doctors and patients is how to sequence all the treatments, both local and systemic, to optimize the patient’s quality of life and survival. This is an area of intense clinical research. The treatment of patients with breast cancer brain metastases should be discussed by a multidisciplinary team of breast cancer experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include number of brain metastasis, resectability, breast cancer subtype, performance status, and the presence of extracranial disease.
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