Treating patients with spinal metastatic disease is a challenging and humbling proposition when one considers that these are patients who are often quite medically ill with life expectancies measured in months. Therefore, any treatment in these patients is primarily palliative in intent and, as such, should be aimed at ameliorating the most distressing symptoms without causing signicant morbidity.

A variety of scoring systems and algorithms have been devised over time to help the spinal surgeon decide if and when surgical management is indicated. Unfortunately, however, all these systems have signicant aws that can lead the practitioner to decide on surgical intervention when non-operative treatment is really the better course of action. We currently lack more up-todate methods of determining, rst, whether surgery is called for and, second, which method of either operative or non-operative management is best for the particular patient. This is especially concerning in light of the anticipated increasing proportion of patients who will be faced with metastatic spinal disease who now can only be

R. A. W. Marco, MD Department of Orthopaedic Surgery, Houston Methodist Hospital, Houston, TX, USA

J. Brindise, DO · D. Dong, BS (*) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, USA e-mail: jpbrindise@houstonmethodist.org

assessed by outdated frameworks that do not take into account newer nonsurgical treatments with a proven efcacy that makes surgery the least desirable option in most cases. For all of these urgent reasons, we have developed a framework that we believe is more up to the task of assessing patients with metastatic disease to the spine. Our framework considers several variables, the most important one, in our estimation, being the medical status of the patient. It also takes into consideration all available surgical and nonsurgical treatment options and their relative merits in a given patient. This integrated analysis has proven, in our experience, to identify the least invasive, and at the same time the most optimal, approach to the management of patients with spinal metastasis.

Historical Approaches

The treatment of patients with MSCC has changed signicantly over time. Before the advent of radiotherapy, laminectomy was the only effective treatment for this problem [1]. With the advent of radiotherapy, however, there was a paradigm shift in the management of these patients, but not without a rigorous debate over the relative effectiveness of radiotherapy alone compared with the combination of laminectomy and radiotherapy. This led to the conduct of several small retrospective studies, which did indeed fail to show that the combination of laminectomy

R. A. W. Marco et al.

and radiotherapy had any signicant advantage over radiotherapy alone in relieving epidural metastatic compression [2, 3].

In 1980, Young etal. were the rst to publish their ndings from a prospective randomized study examining the relative merits of the two treatments. These authors also found that neither pain relief, ambulation, nor sphincter function was better after laminectomy plus radiotherapy than after radiotherapy alone [4]. It was still believed, however, that laminectomy alone could provide decompression and pain control. However, a further problem with this surgery not recognized at the time was that by the time of intermediate follow-up, the spinal column had collapsed in many patients because of the removal of supportive structures during the laminectomy. This therefore once again raised questions about the advisability of laminectomy. With the development of improved spinal instrumentation, some practitioners began to believe that decompression with a laminectomy or vertebrectomy, in conjunction with the implantation of the new instrumentation, could produce better functional outcomes, especially in relatively healthy patients with longer survival expectancies [5].

Then, in 2005, surgery got a boost when Patchell et al. published ndings from a landmark randomized trial showing that patients with metastatic spinal cord compression who underwent surgery could expect a more favorable outcome than those treated only with radiotherapy [6]. Interestingly these investigators found that with circumferential decompression, stabilization, radiotherapy, and steroids as opposed to radiotherapy and steroids alone, signicantly more patients were able to walk and maintained the ability to walk for longer duration after treatment. Additionally, those who were nonambulatory for less than 48h when they entered the study regained their ability to walk, and the need for corticosteroids and opioid pain medications was considerably less for the surgical treatment group. These authors therefore concluded that the best treatment for metastatic spinal cord compression is surgery followed by radiotherapy. This therefore led to a dramatic swing of the pendulum toward the use of aggressive surgical man-

agement in patients with metastatic epidural spinal cord compression.

However, this study had signicant shortcomings, which raised questions about the general applicability of its ndings. For example, the patients in the non-operative arm had signicantly worse outcomes than those historically observed in patients treated with radiotherapy alone [7–15]. In addition, despite the participation of many high-volume centers, the enrollment of patients in the study was particularly slow, with sometimes only a single patient enrolled over the course of a decade. Understanding why so few patients being treated at these busy centers were considered eligible for inclusion in the study is key to accurately interpreting the applicability of this study’s ndings to one’s own practice. One reason for this slow recruitment was that the inclusion criteria allowed only patients with a single area of spinal involvement and those who had not been totally paraplegic for longer than 48 h to be entered into the study. Another questionable aspect of the study was that 18/51 (35%) patients randomized to non- operative treatment presented with an unstable spine. Perhaps these patients should have undergone stabilization and not even considered as candidates for radiotherapy alone. Another criticism of the Patchell study is that tumor histology was not considered in the randomization of patients in the study. That and the relatively short median survival of 3–4months in both the operative and non-operative groups further raise questions about the degree to which one should be inuenced by the study conclusions. A nal concern about the study was raised by Chi et al. [16], who conducted a sub-analysis to determine the effect of age on the outcomes. They made the troubling discovery that as patient age increased, the benets of the combination of surgery and radiotherapy decreased. In fact, by age 65, there was no observable difference in outcomes between the two groups. Considering that over 60% of patients with cancer are over the age of 65, this may give surgery a more limited role in the care of older patients with metastatic epidural compression.

1 MOSS: A Patient-Centered Approach

In 2008, George etal. discussed the results of a Cochrane review [17], which also questioned the generalizability of the ndings in the Patchell study. This study was designed with the overall purpose of determining denitively the effectiveness of radiotherapy, surgery, and corticosteroids in the treatment of patients with metastatic epidural spinal cord compression. Specically, the authors assessed the quality of six randomized controlled trials of radiotherapy, surgery, and corticosteroids and calculated the relative risk ratios and numbers of patients needed to enable treatment with 95% condence intervals. Among their conclusions, they found that high-dose steroids are associated with more serious side effects than moderate-dose steroids. They also concluded that patients with stable spines can be treated with radiation therapy only and still retain their ability to walk. Surgery was deemed benecial for ambulatory patients with a relatively radioresistant tumor, as well as for nonambulatory patients with a single area of involvement who had been paraplegic for less than 48h, had a relatively radioresistant tumor, and had a more than 3-month life expectancy.

Now, with improvements in technology and renements in treatment options, an effort has been made to develop comprehensive, multidisciplinary decision frameworks for determining the most optimal treatment in patients with metastatic epidural spinal compression. The most popular of these has been the neurologic, oncological, mechanical, and systemic (NOMS) framework, developed at Memorial Sloan- Kettering Cancer Center over 15years ago [18, 19].

The goal of NOMS is to provide a dynamic framework that will identify the optimal treatment for these patients. It does so by integrating the four sentinel decision points (i.e., neurological, oncological, mechanical, and systemic), which guides the type and extent of radiation therapy, surgery, and/or systemic therapy. Although this framework has been useful in accomplishing these goals, it is not without signicant drawbacks.

For example, the neurological component of the NOMS framework focuses on the degree of spinal cord compression shown by MRI [19],

which is then classied as high or low grade. The treatment algorithm then directs the clinician to the oncologic diagnosis, which involves classifying the tumors as radioresistant or radiosensitive. The algorithm is most suitable, however, for directing non-operative treatment in patients with low-grade spinal cord compression and radiosensitive or radioresistant tumors. However, the way the algorithm is designed, it favors surgery for the treatment of high-grade spinal cord compression caused by radioresistant tumors even though the clinical signicance of this compression is not yet entirely clear.

In addition, the framework generally regards renal cell carcinoma (RCC), lung carcinoma, and sarcoma as radioresistant tumors. Thus, according to the NOMS framework, a patient with RCC and high-grade epidural compression should undergo surgical intervention. We believe, however, that such patients could benet more from antiangiogenic chemotherapeutic agents (e.g., sunitinib, sorafenib, and pazopanib) that can provide sufcient local control, increase time to tumor progression, and potentially sensitize the tumor to radiation therapy; at the same time, these patients would be spared the risks and morbidity associated with surgery [20, 21]. Similarly, despite the presence of high-grade spinal cord compression, some patients with non- small cell lung carcinoma and small cell lung carcinoma are amenable to treatment with chemotherapy, such as erlotinib, combined with decompressive stereotactic radiotherapy. A nal criticism of the NOMS framework is that sarcoma is generally considered a radioresistant tumor in this treatment algorithm, when in fact sarcomas such as Ewing’s sarcoma, leiomyosarcoma, alveolar softparts sarcoma, myxoid liposarcoma, and synovial sarcoma are relatively radiosensitive tumors compared to many other sarcomas and carcinomas.

Regardless, since the NOMS framework was rst adopted into clinical use, the picture in patients with metastasis to the spine has been changed dramatically by the increasing availability of very effective noninvasive treatments. Recent advances in the image-guided delivery of high-dose radiation therapy have further changed

R. A. W. Marco et al.

the nature of therapy in these patients. These advances have already translated into great improvements in the outcome of treatment.

One of these new radiotherapies is stereotactic radiosurgery (SRS), which can deliver high doses of radiation close to the spinal cord without exposing the cord and other adjacent vital structures to unsafe levels of radiation. In many cases now, SRS can achieve durable local tumor control regardless of tumor pathology, degree of spinal cord compression, and its past response to conventional radiotherapy. As proof of this, clinical response rates of greater than 85% and partial or complete pain response rates of 85–92% have been reported for patients treated with this technique [22–26].

Despite these signicant advances, Bilsky et al. [19] have relegated the use of SRS to patients with radioresistant tumors who do not have high-grade epidural compression. They advocate surgical intervention in those patients with radioresistant tumors who have high-grade compression. This decided overemphasis on the MRI ndings to determine whether the patient requires surgery unfortunately ignores other less invasive treatment options with proven efcacy that should be considered before surgery.

Of further concern, Bilsky et al. justied their recommendation for surgery in patients with high-grade epidural compression on the basis of the Patchell study, which showed a more favorable outcome in such patients compared with those who underwent radiotherapy alone. However, the surgery these authors advocate for such patients is separation surgery, not the decompression and debulking procedure Patchell etal. performed. In separation surgery, the intent is to do only minimal tumor resection to separate the tumor margin from the spinal cord, usually by as little as 2mm, thereby leaving the bulk of the tumor to be treated with radiation, not the more extensive surgical debulking procedure Patchell et al. described. Furthermore, only conventional radiotherapy was available at the time of the Patchell study, which differs considerably in scope and intent from the SRS used by Bilsky etal. Therefore, one must question the appropriateness of using

data from one study of somewhat outmoded treatments, or at least the only available treatments at the time, to support the adoption of new ones that, albeit, fall into the same categories as the earlier treatments but are far different in nature and effectiveness.

There are additional important drawbacks to the NOMS framework that in the light of current knowledge further make its reliability questionable. One of these has to do with the fact that it relies on the Spine Oncology Study Group (SOSG) proposed system for the mechanical assessment of the spine. The Spine Instability Neoplastic Score (SINS) yielded by the assessment evaluates spinal instability on the basis of clinical and radiographic information [27]. The SINS uses six variables: location, type of pain, radiographic spinal alignment, nature of the lesion (lytic, mixed, or blastic), vertebral body collapse, and involvement of the posterior elements. In this assessment, each variable is given a numerical score and these are totaled to arrive at an overall score. A low score (0–6) indicates a stable lesion that does not require surgical intervention. A high score (13–18) indicates spinal instability that does call for surgical intervention. Intermediate scores (7–12) are considered to indicate potential, but not denite, instability. Although SINS helps the clinician decide whether to consider surgical intervention for spinal instability in a patient with metastatic spinal disease, it does not offer much help in identifying the best surgical intervention in a particular patient. Furthermore, curiously, the SOSG also gave higher scores to metastases in the junctional regions of the spine such as the occipitocervical junction. This would suggest to practitioners that surgery is the preferable treatment option in these patients. In our experience, however, tumors at the occipito-cervical and lumbosacral junctions can frequently be treated non-operatively and rarely become unstable. For example, because odontoid tumors often spread in a cephalocaudal direction, they rarely cause spinal cord compression or instability. The SOSG also gave a high score for vertebral body collapse of more than 50%. Our experience has shown, however, that, even in cases where there is 100% vertebral body

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Contents

Contributors

MOSS: A Patient-Centered Approach

Background

Historical Approaches