Anti-Tumour TreatmentSystemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: An overview of the literature
Introduction
Metastatic brain tumors are the most common intracranial neoplasms in adults and are a significant cause of deleterious effects on many critical neurological functions. Moreover, morbidity and mortality rates are higher for patients who develop brain metastasis (BM); over the last few years, the frequency of BM has increased due to longer survival of patients through more effective systemic treatment and earlier BM detection by improved neuro-imaging.
Estimates of BM incidence vary from 20% to 50% [1]; analyses of patient data from the Metropolitan Detroit Cancer Surveillance System showed a total incidence proportion of BM of 9.6% [1]; the incidence proportion of BM was highest for lung cancer (19.9%), followed by 6.9% for melanoma, 6.5% for renal cancer, 5.1% for breast cancer. However, as described in various studies, the incidence of BM may be higher than observed, due to asymptomatic BM [2].
Radiation therapy and surgery remain the cornerstone of treatment in selected patients, while cytotoxic drugs have a limited impact. On the other hand, in recent years, advances in the understanding of the biology of BM have led to the development of new targeted therapies and interesting results have been obtained so far.
In this review, we analyzed systemic treatments, both cytotoxic and, in particular, new molecular drugs for BM from solid tumors in adults, such as breast cancer, lung cancer, renal cancer and melanoma.
Section snippets
Breast cancer
Recent improvements in systemic therapy have increased the overall survival of breast cancer (BC) patients, including metastatic patients. In the context of controlled systemic disease, the prevalence of BM from BC is increasing. BC is the second leading cause of BM after lung cancer and accounts for 17–20% of all cases. BM treatment options currently include whole-brain radiotherapy (WBRT), surgery, stereotactic radiosurgery (SRS), chemotherapy and a combination of these methods (see Table 1).
Non-small cell lung cancer
In patients with non-small cell lung cancer (NSCLC), brain metastases develop in approximately 30% of cases [18]. In the literature, BM from NSCLC was treated with various cytotoxic drugs or new molecular drugs with or without RT.
Melanoma
Melanoma BM are common since at least one patient out of three with advanced melanoma will ultimately develop BM. Survival remains dismal with an expected median OS of 16–22 weeks, probably because of the poor efficacy of conventional treatments due to radioresistency of melanoma cells and the low blood–brain barrier penetrance of systemic cytotoxic agents commonly used in metastatic melanoma. More recently, new therapeutic agents have proven their efficacy in progressing metastatic melanoma and
Renal cell carcinoma
Brain metastasis from renal cell carcinoma (RCC) occurs in approximately 5–10% of cases; data from Maastricht Cancer Registry showed that the 5-year cumulative incidence of brain metastases from RCC was 9.8% [1], [62].
The median survival of patients with untreated RCC BM averages from 3 to 4 months [63]; the outcome for these patients is poor, with median OS of only 4–11 months after diagnosis even after surgical resection, WBRT, or stereotactic radiosurgery [64]. Moreover, metastatic RCC is
Conclusions
In recent years, the frequency of metastatic brain tumors has been increasing and primitive lung cancer is the most common cause. Radiation therapy and surgery can be used in selected patients but can be responsible for acute or delayed neurological deficits. Recently, new targeted drugs have been developed and employed either on established brain metastases or in a preventive setting. Interestingly, these new molecular drugs reported interesting activity and safety in selected cases and in
Conflict of interest
None.
Acknowledgment
We thank Ms. Christina Drace for English support.
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All authors contributed equally to the writing of the paper.