In terms of surgical management outcomes of spine metastases, Patchell et al. (5) presented a prospective randomized trial comparing surgery and conventional external beam radiation therapy (cEBRT) to cEBRT alone for high-grade spinal cord compression that demonstrated the overall lack of radiosensitivity for solid tumor malignancies. Hematologic malignancies were excluded due to their exquisite radiosensitivity, although other radiosensitive solid tumors malignancies, such as breast carcinoma, were included. Surgery showed significant advantages in terms of overall maintenance and recovery of ambulation, continence, narcotic requirements, and even survival. While helping to establish surgery as the optimal treatment for patients with solid tumors harboring high-grade Epidural Spinal Cord Compression (ESCC), the poor responses to cEBRT were compelling. Patients undergoing cEBRT alone had a 57% rate of overall ambulation, but the durability was only 13 days. Nonambulatory patients recovered ambulation in 19% (3 of 16) (5). However, the study design was an intention to treat analysis. All three patients who recovered ambulation crossed over to the surgical arm. Essentially, no patient recovered ambulation without surgery due to the radiation insensitivity of solid tumor malignancies. Hence, the current recommendation for optimal functional outcomes in patients with high-grade spinal cord compression
resulting from solid tumor malignancies or in situations where gross spinal instability exists is that surgery should be first-line treatment where possible (5,23,24).

Radiation also does not “treat” spinal instability. This requires an open operation or a percutaneous procedure to reconstruct the spinal column integrity with instrumentation and/or vertebral body cement augmentation. In terms of the cervical spine, since most metastatic lesions originate in the vertebral body, an anterior cervical corpectomy results in the most direct approach for tumor excision. However, factors such a specific spine location and extent, preoperative neurologic deficits, aggressiveness and dissemination of primary malignancy, medical comorbidities, nutritional status, and patient’s quality of life must be factored in the ultimate treatment decisions.

Unfortunately, many patients presenting with spinal metastases have significant associated medical comorbidities that may preclude aggressive surgical treatment. Radiation continues to be the mainstay of treatment for many of these patients. Further surgery is very effective for spinal cord decompression, neurologic salvage, and stabilizing the spine but is not effective for providing durable tumor control. While the Patchell (5) study demonstrated the superiority of surgery for high-grade ESCC, radiation is essential for achieving postoperative local tumor control. The durability of the surgical improvement in terms of ambulation was not demonstrated due in large part to the short 4-month median survival in this study. Klekamp and Samii reported on 101 patients undergoing surgery for high-grade spinal cord compression. The majority of patients received postoperative cEBRT. The surgical approach was dorsolateral in 79% of cases and complete or aggressive partial resection was achieved in 91%. Postoperative adjuvant radiation, chemotherapy, or hormones were offered in all patients. The local recurrence was 57.9% at 6 months, 69.3% at 1 year, and 96% at 4 years (25).

The benefits of radiation therapy for treating spinal metastases have been repeatedly confirmed in large-scale retrospective studies showing improved or retained neurologic function (14,16, 17, 18, 19 and 20). Gerszten et al. (26) systematically evaluated the spinal metastases and radiation therapy literature reviewing 49 papers (three randomized and four prospective). They found that the postradiation ambulatory rate in patients was 60% to 80%, pain control was achieved in 50% to 70%, and local tumor control was achieved in 61% to 89% (mean 77%) of patients.

The underlying malignant pathology, however, impacts the efficacy of conventional radiation. The variable radioresponsiveness of spine metastases was initially reported in a series by Greenberg et al. (27), comparing outcomes of surgery and cEBRT to cEBRT alone. The surgical approach was principally laminectomy without instrumentation, which makes the operative technique somewhat antiquated. The evolution of ventral transcavitary or dorsolateral approaches with instrumentation has markedly improved surgical outcomes. While the surgical data may no longer be relevant, Greenberg et al. (27) demonstrated marked differences in radiation response rates based on tumor histology. Patients with breast carcinoma and hematologic malignancies had improved outcomes compared to radioresistant tumors, such as renal and lung carcinoma.

Maranzano and Latini (20) also demonstrated the histology-dependent responses based on radiosensitivity. This prospective study evaluated two different fractionation schedules: 30 Gy in 10 fractions compared to 5 Gy × 3 + 3 Gy × 5 delivered in split course. Of 275 patients, 20 were excluded for gross spinal instability. No difference was demonstrated in fractionation schedules. Of the 209 evaluable patients, 98% maintained ambulation while only 60% recovered. Of those who regained ambulation, 70% were considered to have favorable or radiosensitive tumors to cEBRT, such as hematologic malignancies (e.g., lymphoma, multiple myeloma), seminoma, and breast and prostate carcinoma. Unfavorable responders or radioresistant tumors included hepatocellular, bladder, renal cell, non-small cell lung, and colon carcinoma. For example, breast carcinoma demonstrated an 80% response rate compared to hepatocellular carcinoma with a 20% response rate. Furthermore, the durability of the response was 10 to 16 months for radiosensitive tumors compared to 1 to 3 months in radioresistant tumors. A number of other studies have also demonstrated this variable response based on tumor histology (28, 29, 30 and 31). This radioresistance, as well as an attempt to achieve more durable control and offer meaningful retreatment options, has been the impetuous to evaluate novel radiation delivery strategies.

While conventional radiation has been shown to reduce pain, control local disease progression, and potentially prevent or reverse neurologic dysfunction, the outcomes and improvements are often not durable. One of the main limitations to achieving effective treatment of spine metastases is the high dose required to eradicate the spinal metastasis. If delivered with conventional radiation, such a tumor “ablative” dose would exceed the maximal dose tolerance of the adjacent spinal cord and cauda equina and lead to myelopathy or edema (3,29,32). Similar to the evolution in surgical techniques for managing spine tumors, radiation therapy has also evolved making the delivery of high-dose targeted radiation with a steep dose fall-off gradient achievable.