Current therapeutic approaches in patients with brain metastases

Abstract

The development of brain metastases is often viewed as the end stage of a disease course and engenders skepticism about the efficacy of treatment. Aggressive management of brain metastases is effective in both symptom palliation and the prolongation of life. The majority of patients with controlled intracranial metastases will expire from systemic disease rather than from recurrence of these metastases. Single brain metastases should be treated with surgical resection or stereotactic radiosurgery, though it is unclear at this time if one modality is more effective than the other. Surgical resection is preferred when a pathologic diagnosis is needed, for tumors larger than 3.5 cm, or when immediate tumor mass decompression is required. Stereotactic radiosurgery (SRS) should be applied for single tumors less than 3.5 cm in surgically inaccessible areas and for patients who are not surgical candidates. Small tumors (ie, < 3.5 cm) that cause minimal edema and are surgically accessible may be treated with either surgery or SRS. There is controversy over whether whole brain radiation therapy (WBRT) can be omitted following surgical resection or SRS. Omission of WBRT increases intracranial tumor recurrence; however, this has not been correlated with decreased survival. Clinicians who choose to omit upfront WBRT are obligated to monitor the patient closely for intracranial recurrence, at which time further salvage therapy in the form of surgery, SRS, or WBRT may be considered. Histology is of particular importance when considering WBRT for patients with radioresistant tumors such as melanoma, renal cell carcinoma, or sarcoma. WBRT may be of less clinical benefit in this setting. Chemotherapy has been demonstrated to improve response rates when used as an adjunct to radiation therapy. These improvements in response rates have not been correlated with an improvement in median survival. Noncytotoxic radiosensitizing agents such as motexafin and efaproxiral show promise. Phase III trials to assess the benefit of motexafin in patients with metastatic lung cancer and efaproxiral in patients with metastatic breast cancer are ongoing. Targeted therapies offer promise in achieving therapeutic efficacy while minimizing side effects. Surgical adjuncts such as BCNU (carmustine) wafers and the GliaSite Radiation System (Cytyc Corporation, Marlborough, MA) may be useful in the future in achieving optimal local tumor control.

The proceedings of brain metastases from lung cancer

“…Recent studies [28] showed that the blood-brain Barrier (blood brain barrier, BBB) has been destroyed in the process of brain metastases, and with whole brain radiotherapy, mannitol and other dehydration drugs can make the BBB open in a variety degrees, which allows chemotherapy drugs across the blood -brain barrier into the central nervous system to kill tumor cells. Nitrosourea, cisplatin, teniposide, paclitaxel, vermeer, temozolomide are chemotherapy drugs that have been commonly used [29].…”

Diagnosis and Treatment Options for Brain Metastasis of Melanoma

“…This effect is most likely due to elimination of micrometastases that were present at the time [61,62]. External WBRT is thus advantageous and typically considered the mainstay of treatment for most patients with multiple metastatic deposits from melanoma in the brain [38,63,64]. More localized treatment modalities would be less beneficial in such situations because it would require targeting of each lesion individually.…”

“…More localized treatment modalities would be less beneficial in such situations because it would require targeting of each lesion individually. However, solitary metastases that are too large for either surgical resection or stereotactic surgery or those that impinge on sensitive areas of the brain are often treated with WBRT [63,65]. The broad application of radiation to the brain can also be an important disadvantage.…”

“…Side effects are typically dependent on the total dosage, dosing interval, and fraction size. Acute side effects of external WBRT include memory loss, fatigue, headaches, temporary hair loss, scalp rash or desquamation, hyperpigmentation, otitis media, and cerebral edema [63,66]. Somnolence syndrome is a set of symptoms, often seen in children, involving lethargy, anorexia, and irritability that www.intechopen.com present 1 to 4 months after treatment.…”

“…In these studies, the median survival time after surgery varies between 5 and 22 months with the more recent ones showing a median survival time between 8 and 16 months [87][88][89]. In contrast to solitary metastasis, the role of surgical intervention in cases of multiple brain metastases remains controversial due to lack of randomized control trials [63]. Previously, this was typically a contraindication, but one retrospective study challenged this notion.…”