Brain Metastases

Each type of cancer has unique characteristics and responds differently when treated. Our highly trained staff and physicians combine their skills with the latest equipment and techniques to treat all forms of cancer. The webpages below contain detailed information about specific types of cancer, related issues and the treatment options available.

Brain Metastases

TrEATMENT OPTIONS

Observation

Data from the early 1970s showed that with observation alone the median survival for patients with multiple metastases was four weeks, with the cause of death being uncontrollable edema. If patients were treated symptomatically with steroids alone, the median survival was doubled to eight weeks.

Chemotherapy

in general, it can be said that chemotherapy treatment does not work. Only few agents cross the BBB (VP16, VM26, Vinblastine). The biodistribution CSF-tumor is highly variable, as well as the intra-metastatic drug concentration. In 81% of the cases, brain metastasis are metachronous, often after chemotherapy, which probably represents a widespread drug-resistant systemic relapse

Whole Brain Radiation Therapy

Over the past several decades, whole brain external beam radiotherapy (WBXRT) has become the treatment of choice for patients with metastatic brain disease. From 1971 to 1976, the Radiation Therapy Oncology Group (RTOG) conducted two Phase III prospective randomized trials, in an attempt to evaluate several treatment schedules. The results were published together, showing an equivalent response to the treatment in all areas, with no differences in duration of improvement or time to progression within the various treatment schedules. The median survival in these studies was 15-18 weeks, with the degree of palliation being the same in the two studies. From those studies, 30 Gy in 10 fractions emerged as the standard treatment for patients with brain metastasis. In a subsequent RTOG study carried out between 1979 and 1983, 30 Gy in 10 fractions was compared in a randomized fashion with the same treatment schedule plus Misonidazole, a hypoxic cell sensitizer. Both were equally effective, with an overall median survival of 3.9 months. In these studies, a group of patients with favorable prognostic factors was identified. More precisely, those with a Karnofsky Performance Status (KPS)>70, primary tumor systemically controlled, and age less than 60 years, with the brain as the only metastatic site, had the best outcome.

Accelerated fractionation and dose escalation have also been evaluated by RTOG in a phase I/II trial for patients with controlled systemic disease. The whole brain received 32 Gy given as 1.6 Gy bid (two fractions a day), with boosts to the area of gross disease from 16 Gy to 22.4 Gy, 32 Gy and 42.2 Gy, at 1.6 Gy per fraction, bid. The median survival was increasingly higher, with no changes in toxicity. The best results were in the 70.4 Gy group (Whole brain 32 Gy, plus 42.4 Gy boost), with a median survival of 6.4 months. Survival was significantly increased in the subgroup of patients with solitary brain metastases treated with a higher dose (6).

The Radiation Therapy Oncology Group (RTOG) has reported the results of a prospective randomized trial testing the potential role of bromodeoxyuridine as a radiosensitizer. Bromodeoxyuridine did not enhance the efficacy of the radiotherapeutic schedule tested (37.5 Gy in 15 fractions of 2.5 Gy), despite the fact that brain metastases have shown high labeling indices.

Morbidity of Whole Brain Irradiation

Acute

Erythema in scalp, dry desquamation, hair loss, otitis media, HA, nausea and visual disturbances, due to increased ICP.

Early Delayed

Somnolence syndrome (1-4 mo after XRT), due to interference in the metabolic turnover of the myelin.

Long-term Effects

The literature of the early and mid-80s is flooded with papers reporting long-term side effects, such as dementia, memory loss, radiation-induced necrosis, leukoencephalopathy, in up to 50% of two year survivors. It is now known that WBXRT below 60 Gy@2 Gy/fx very seldom produces radionecrosis, although there is a strong dependency on the fraction size.

Very few patients survive longer than a year, so in general, long-term effects are not a concern, with the exception of patients with solitary brain metastasis. Because of the relationship between large fraction size and long-term side effects, the so called standard of 30 Gy/10 fractions is being challenged; in modern research protocols that include whole brain irradiation, the recommended treatment is 37.50 Gy in 15 fractions.

Surgery

Potential indications for surgery (mostly true for solitary brain metastasis):

· Diagnosis (When we do not have tissue evidence of cancer);

· Solitary metastasis;

· Life threatening situations, or metastasis critically located within the brain;.

· Recurrent or persistent symptoms after non-surgical treatment;

· Treatment of complications (infection, bleeding);

· Placement of chemotherapy or isotope delivery devices (Ommaya).

COMBINATION OF SURGERY PLUS WBXRT

The potential role of more aggressive approaches such as surgery and WBXRT have been the subject of several prospective randomized trials. The first one, carried out at the University of Kentucky and reported by Patchell, showed that patients who underwent WBXRT and surgical resection of a solitary brain metastasis did better than those who received WBXRT only. In patients treated with both modalities, the median survival was 40 weeks with an actuarial local control at 70 weeks of 57%, compared to 15 weeks and 13%, respectively, for the WBXRT alone area. More recently, in a Dutch trial reported by Noordjik, 66 patients were randomized to 40 Gy at 2 Gy bid of whole brain irradiation plus or minus surgical debulking . The results from these trials showed that several prognostic factors for increased survival were again identified, such as aggressive treatment, controlled systemic disease and young age. Little over a year ago, in a second trial the University of Kentucky evaluated in a prospective randomized fashion, the role of whole brain radiotherapy in patients with solitary brain metastasis that had been completely resected was studied. The question was to evaluate if whole brain radiotherapy was really necessary. The results of the trial were very interesting because it was seen that even though radiation therapy did not increased survival, it did increase local control. When the data on local control were evaluated closely it was found that the local control offered by radiation was mostly in the tumor bed and its vicinity. This has raised the question of local radiation after surgical resection with three dimensional conformal radiotherapy.