Arkansas Cancer Research Center Neuro Oncology Program Strategy

What follows is a description of our current treatment philosophy and priority ranking in the Neuro-Oncology Program at the Arkansas Cancer Research Center. A breakdown of our case distribution for each treatment modality over the past 3.5 years according to tumor number and the tumor location relative to eloquent brain is given in Figure 55-6. All patients with breast cancer and solid brain tumor metastases receive WBRT at our institution. A single brain metastasis as the only evidence of residual disease (isolated metastasis) is extremely rare with breast cancer, as compared with the situation with non-small cell lung cancer, melanoma, or renal cell carcinoma. We reserve additional measures to maximize local control, such as surgical resection or SRS, in an effort to increase life expectancy for patients with a KPS score of 70 or greater who have controlled or "controllable" disease (defined as a reasonable chance of at least a 6-month life expectancy if the CNS disease were not present). If patients are candidates for surgical resection or SRS for this goal, care is taken to ensure that WBRT fraction size is no greater than 2 Gy, with a total dose of 40 Gy, to limit long-term cognitive side effects as well as the cumulative risk of radiation necrosis (if SRS is to be used) in these patients with longer projected life spans.

In our program, we consider open surgical resection as the clearly superior treatment choice for (1) the rare breast cancer patient with an isolated solid metastatic brain tumor (the only evidence of disease) who has the potential for cure, (2) patients

Metastatic Brain Tumours

FIGURE 55-5 A 55-year-old man with a head and neck neuroendocrine (carcinoid) tumor developed multiple new brain metastases despite successful whole-brain radiation therapy (WBRT) and three separate Gamma Knife stereotactic radiosurgery (SRS) procedures over 3 years for previous metastatic lesions. He was placed on oral temozolomide chemotherapy and within 3 months demonstrated a significant response as seen by neuroimaging. A, Before chemotherapy, Tl-weighted, contrast-enhanced magnetic resonance (MR) axial image of one of the new (not previously treated) tumors. B, Before chemotherapy, T2-weighted MR axial image demonstrating surrounding vasogenic edema. C, Tl-weighted, contrast-enhanced MR axial image obtained 3 months after starting chemotherapy, demonstrating a complete tumor response. D, T2-weighted MR axial image obtained 3 months after starting chemotherapy, demonstrating resolution of vasogenic edema.

FIGURE 55-5 A 55-year-old man with a head and neck neuroendocrine (carcinoid) tumor developed multiple new brain metastases despite successful whole-brain radiation therapy (WBRT) and three separate Gamma Knife stereotactic radiosurgery (SRS) procedures over 3 years for previous metastatic lesions. He was placed on oral temozolomide chemotherapy and within 3 months demonstrated a significant response as seen by neuroimaging. A, Before chemotherapy, Tl-weighted, contrast-enhanced magnetic resonance (MR) axial image of one of the new (not previously treated) tumors. B, Before chemotherapy, T2-weighted MR axial image demonstrating surrounding vasogenic edema. C, Tl-weighted, contrast-enhanced MR axial image obtained 3 months after starting chemotherapy, demonstrating a complete tumor response. D, T2-weighted MR axial image obtained 3 months after starting chemotherapy, demonstrating resolution of vasogenic edema.

Table 55-4 Advantages and Disadvantages of Surgical Resection versus Stereotactic Radiosurgery plus WBRT for Patients with Breast Cancer Solid Brain Tumor Metastases

Advantage Surgical Resection/Disadvantage Stereotactic Radiosurgery

Tissue diagnosis without additional procedure Can treat lesions >3.5 cm in maximal diameter Can immediately relieve symptomatic mass effect Potential for cure with an "isolated" brain metastasis More complete and faster relief of vasogenic edema Faster time to improvement in baseline neurological deficit

No risk of radiation necrosis

Relative Equivalence For Both

Local control of disease Extension of life span Maximization of quality of life Reduction in incidence of "cerebral death"

Advantage Stereotactic Radiosurgery/ Disadvantage Surgical Resection

Can treat lesions in any location

Can easily treat multiple lesions

One-day return to preoperative functional level

No general anesthesia

Minimally invasive

Lower cost and less hospitalization time No craniotomy morbidity/mortality

"Cerebral death," Death from growth of cerebral (metastatic) tumor; WBRT, Whole-brain radiation therapy.

100%

Craniotomy Stereotactic Biopsy GKRS

Multiple Single Single Single

FIGURE 55-6 Case analysis for metastatic central nervous system disease referred to the multidisciplinary Neuro-Oncology Program at Arkansas Cancer Research Center from December 1993 through June 2001 (3.5 years). A, Pie graph demonstrating the distribution of carcinomatous meningitis relative to solid tumor disease. B, Pie chart demonstrating the relative distributions of patients with single solid tumors arising in eloquent brain, patients with single solid tumors arising in noneloquent brain, and patients with multiple tumors, among patients with solid tumor disease. C, Bar graph depicting the relative frequency of surgical intervention with diagnostic stereotactic biopsy, microsurgical resection, or Gamma Knife stereotactic radiosurgery depending on whether the patient had a single lesion located in noneloquent brain, a single lesion located in eloquent brain, or multiple lesions.

with symptomatic mass effect from tumors larger than 3.5 cm in greatest diameter, and (3) patients with obstructive hydro-cephalus from their tumor or at high risk for obstructive hydro-cephalus from a large posterior fossa tumor abutting the fourth ventricle. We consider open surgical resection to be the preferred option for breast cancer patients with a single solid brain tumor metastasis in a surgically resectable location who (1) have no evidence of systemic disease outside of the CNS and (2) are younger than 65. We consider SRS to be the preferred option for breast cancer patients (1) with a single solid brain tumor metastasis located in an eloquent brain location, (2) with a single solid brain tumor metastasis who have systemic disease outside of the CNS, (3) with a single solid brain tumor metastasis who pose an unacceptable medical risk for general anesthesia or open surgery, (4) who refuse recommended open surgical resection, and (5) with two to four solid metastatic tumors of appropriate size.

Patients with more than four solid metastatic brain tumors or with one to four lesions who have rapidly progressing systemic disease are candidates for systemic chemotherapy after their WBRT. The choice of agents must be determined by the extent of extracranial disease and the prior chemotherapy history. Occasionally, breast cancer patients with more than four solid metastatic brain tumors and with actively progressing systemic disease will benefit from additional intervention with either surgical resection or SRS for purely palliative QOL reasons. Targeting the correct lesion for this approach requires that the symptom or sign adversely affecting QOL be one that can accurately localize the specific offending lesion neu-roanatomically. Ideally, the candidate offending lesion should be one that has been shown to have grown or increased in the amount of surrounding vasogenic edema during the clinical period in question. In this setting it is reasonable to selectively target the offending lesion while leaving the other lesions alone. If the lesion is 3.5 cm in maximal diameter or larger or is causing symptoms from obstructive hydrocephalus and is surgically accessible, we advocate an open surgical approach. If it is smaller than 3.5 cm and is not causing obstructive hydro-cephalus, we advocate selective SRS as the preferred approach.

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