Secondary Brain and Spinal Cord Tumors

Rimas V. Lukas¹, Patrik Gabikian², and Steven J. Chmura¹

¹The University of Chicago, Chicago, IL, USA

²Kaiser Foundation Hospital, Los Angeles, CA, USA

Case study 71.1

A 70-year-old man with metastatic castration-resistant prostate cancer diagnosed 4 years ago presents to clinic with complaints of unsteady gait. His systemic disease burden had been stable for quite some time. He has received numerous prior lines of chemotherapy that have included neurotoxic agents. His medical history is also notable for hypertension and atrial fibrillation for which he is on anticoagulation with warfarin. He notes progressive difficulty walking over the past week. Examination reveals no reflexes in the upper or lower extremities. Babinski sign is present bilaterally. Imaging reveals an enhancing epidural lesion with frank compression of the spinal cord (Figure 71.1).

Figure 71.1 T1 postcontrast axial image of the thoracic spine. The red arrow indicates the spinal cord, which is being compressed by the extra-axial mass posteriorly (white arrow).

1. What would the optimal management of this patient involve?

High-dose steroids (dexamethasone 10–100 mg dose) alone
Surgical decompression alone
Stereotactic radiosurgery
Initiation of steroids followed by surgical decompression and radiation

High-dose steroids decrease edema within the spinal cord providing symptomatic improvement that may be associated with an improved long-term outcome. High-dose dexamethasone (96 mg followed by 24 mg QID for 3 days and then a taper) with radiation (28 Gy) has been compared in a randomized trial to radiation alone in patients with symptomatic acute cord compression. The steroid-treated group had a better ambulatory status at both the completion of therapy and 6 months later. This supports the rapid initiation of steroids when there is significant concern for metastatic disease causing spinal cord compression. Additional studies comparing doses of steroids have not revealed any obvious superiority of the very-high-dose (96 mg) dexamethasone as opposed to more moderate doses (10–16 mg).

Surgical decompression without additional radiation has not been studied in a randomized fashion. For symptomatic extra-axial metastatic lesions from solid tumors compressing the spinal cord, a single nonblinded randomized trial comparing surgery followed by focal fractionated radiation (30 Gy) versus radiation alone has demonstrated a higher ambulatory rate after completion of treatment (84% vs. 57%; P = 0.001), overall survival (OS) (126 days vs. 100 days; P = 0.033), maintenance of continence (156 days vs. 17 days; P = 0.016), and duration of retained ability to walk (122 days vs. 13 days; P = 0.003) in the combined treatment arm. The benefit of surgical intervention decreases with increasing age. Radiation therapy (RT) alone without surgery has been evaluated in a large, prospective nonrandomized study using a number of different dosing schedules. Long course (10–30 fractions, 30–40 Gy) compared to short course (1–5 fractions, 8–20 Gy) demonstrated superior local control (81% vs. 61% at 1 year; P = 0.005), but similar functional outcome and survival. In patients with expected favorable survival, surgical decompression followed by long-course radiation should be considered. In those with poor expected survival, short course is a reasonable option. In either scenario, realistic expectations regarding goals of care should be presented to the patient during the decision-making process. While there is some evidence supporting the benefit for stereotactic radiosurgery (SRS) for mechanically stable non-cord-compressing vertebral body lesions, evidence of benefit in acute cord compression is lacking, and ongoing randomized trials to assess tumor control and quality of life are being conducted by cooperative groups.

Case study 71.2

A 57-year-old male with no past medical history presents with new-onset complex partial seizures. Three enhancing lesions, each approximately 1 cm in size, are noted on magnetic resonance imaging (MRI) in the left anterior temporal, left posterior temporal, and right parietal lobes. The patient’s neurological examination is unremarkable. A single lung lesion is noted as well. Biopsy of this lesion reveals adenocarcinoma consistent with non-small-cell lung cancer (NSCLC).

1. Which of the following statements regarding the prognostic category this patient falls into is correct?

Median overall survival (OS) is ∼2 months.
Median OS is ∼7–10 months.
Median OS is ∼12 months.
Median OS is ∼24 months.

Various prognostic classification systems exist for patients with solid tumor brain metastases. The Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) classification system is derived from data from three RTOG studies evaluating different whole-brain radiation therapy (WBRT) treatment regimens in patients with solid tumor brain metastases from varying histologies. A significant percentage (61%) of patients had lung cancer. Three prognostic classes were established with performance status having the greatest correlation with survival. Patients with Karnovsky performance score (KPS) <70% have a median OS of 2.3 months. For the younger patients with KPS ≥70 and controlled primary disease, median OS was 7.1 months. As our patient has a good performance status, is young, and does not have an uncontrolled primary, he would be categorized in prognostic group 1 (median OS: 7.1 months). A more nuanced brain metastases prognostic classification system, the Disease Specific Graded Prognostic Assessment (DS-GPA), has been described more recently. It is based on a multi-institutional retrospective database analysis and provides survival estimates for various histologies based on a number of potential factors that may include age, performance status, presence of extracranial metastases, and the number of brain metastases. Using this system, estimated median OS in patients with similar characteristics such as ours would be 9.43 months.

2. The optimal management for this patient’s brain metastases involves which of the following?

Surgical resection of all three lesions followed by WBRT
Surgical resection of the anterior temporal lesion, which was the most likely focus of the seizure followed by WBRT
SRS to all three lesions either with or without WBRT
WBRT

We present the case of a patient with excellent performance status and three new brain metastases. There are no randomized studies evaluating the role of surgical resection in patients with three brain metastases. While it is possible that the anterior temporal lesion is the focus of seizure activity, it is likely that this could be well controlled with anti-epileptic medications. Surgical resection for seizure control is typically employed in the setting of medically refractory seizures. While WBRT would treat the radiographically evident metastases as well as any micrometastatic disease, it is not without consequences. SRS has been studied in a number of trials, the majority of which involved patients with more than one central nervous system (CNS) metastasis. One study comparing SRS versus SRS plus WBRT in patients with one to four brain metastases revealed no significant difference in OS, but there was a significantly increased risk of recurrence outside of the SRS field in the SRS-alone group. Another similar study compared patients with one to three brain metastases treated initially with either surgery or SRS and subsequently randomized to observation versus WBRT. No improvement in OS was noted, although risk of CNS relapse and neurologic death was significantly decreased in the WBRT arm. Comparison of WBRT versus WBRT plus SRS in patients with one to four brain metastases demonstrated superior local control with the addition of SRS but no significant improvement in OS. Additionally, WBRT was associated with a decrease in health-related quality-of-life (QOL) measures. However, more recent randomized trials examining memory with WBRT in the prophylactic cranial irradiation (PCI) setting (RTOG 02-14) demonstrated no significant declines in global cognitive function, evaluated via Mini-Mental Status Examination (MMSE), or QOL after PCI in the absence of tumor progression. In our case, although one could reasonably argue for the use of WBRT or SRS alone, in this patient with an excellent performance status, brain metastases within the size parameters for SRS, reasonable likelihood for controlling his limited systemic disease burden, and a desire on the patient’s part to follow an aggressive treatment path, it was decided to treat him with SRS and WBRT in order to maximize CNS tumor control. In multivariate analysis by histology and treatment in the retrospective DS-GPA study, NSCLC patients treated with SRS and WBRT had an improved OS and decreased risk of death compared to those treated with WBRT alone.

Case study 71.3

A 58-year-old male with only a history of hypertension presents with only mild headache. As part of the work-up, an MRI of the brain with and without contrast reveals five enhancing lesions without any significant mass effect. Work-up for an underlying malignancy reveals moderately differentiated adenocarcinoma of the gastroesophageal junction.

1. In this patient with synchronous minimally symptomatic brain metastases, what would the optimal management involve?

WBRT
WBRT plus SRS boost
Surgical resection of all five lesions followed by WBRT
Close observation

This is a case of multiple brain metastases. There are no strong data supporting surgical resection in patients with multiple asymptomatic brain metastases. The randomized studies evaluating SRS, discussed in Question 2 in Case study 71.2, included patients with up to four brain metastases. Although in certain settings SRS to more than four lesions is performed, the data to support this approach are limited when compared to the data evaluating the role of SRS in four or fewer lesions. It is presumed that in patients with multiple radiographically evident brain metastases, there are additional micrometastases as is noted in other organ systems. In turn, WBRT is the modality most often employed in this clinical setting. As the incidence of metastases to the hippocampi is quite low, hippocampal-sparing techniques of WBRT in an effort to decrease potential neurologic toxicities were being investigated in an attempt to limit some of the neurocognitive effects of radiation (NCT01227954 and NCT01414738).

2. The optimal radiation dosing schedule in the patient described in Question 1 would involve:

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71: Secondary Brain and Spinal Cord Tumors

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