Treatment of Primary Spine Tumors

Mark H. Bilsky and Yoshiya Yamada

Primary malignant bone tumors of the spine present significant treatment challenges with regard to achieving local tumor control while preserving neurologic function. The most common primary tumors involving the spinal column are chordoma, chondrosarcoma, and osteogenic sarcoma. Significant advances in both surgery and radiation are redefining their roles in the treatment of these lesions. Advanced surgical techniques for en bloc resection of primary spine tumors improves the ability to achieve marginal or wide curative resections;1–3 however, many tumors are not amenable to en bloc resection. Conventional external beam radiation is not an effective adjuvant for many primary spine tumors. Poor outcomes with conventional radiation therapy are likely related to the relatively low dose of radiation that can be given near the spinal cord. Concern for spinal cord tolerance has typically limited radiation doses to < 5400 cGy in standard fractions.^4,5 Low-dose areas within the irradiated field are the most likely to result in disease recurrence.⁶ Three radiation techniques are currently being used to increase the dose to the tumor while sparing normal tissue tolerance in an attempt to treat primary spine tumors: particle beam treatment, such as proton beam therapy; brachytherapy; and high-dose conformal photon therapy, such as image-guided intensity-modulated radiation therapy (IGRT) and CyberKnife. Although no class 1 evidence exists to demonstrate the contribution of high-dose radiation in achieving local tumor control for spine sarcomas, several studies have lent support to this hypothesis. The ability to deliver stereotactic radiosurgery using IGRT may also be useful in the neoadjuvant or postoperative setting.

Surgery

The role of en bloc resection to achieve a marginal or wide resection is well established for extremity sarcomas.^7–9 Over the past 10 years, spine surgeons have developed techniques for en bloc resection of primary spine tumors that improve cure rates compared with piecemeal, curettage techniques. These techniques are safe for patients with isolated vertebral body or posterior element disease. Boriani et al published a surgical series regarding en bloc spondylectomy for low-grade chondrosarcoma of the mobile spine in 22 patients.¹⁰ Of the 12 patients who underwent en bloc excision, 9 (75%) maintained local control at a median follow-up of 81 months (range 2–236 months). Of the three recurrences, two had contaminated margins at surgery from epidural disease. The remaining 10 patients underwent curettage resection and by definition had intralesional resections with positive histologic margins. At a median follow-up of 36 months, the recurrence rate was 100%, and 80% died of disease.¹⁰ Of note, in this group, three patients received conventional-dose external beam radiation, and no patients received high-dose conformal radiation with proton beams or IGRT.

Although curative resections are feasible in some patients, many present with factors that may preclude en bloc resection that achieves negative histologic margins. En bloc resection of the isolated vertebral body or posterior elements is technically feasible. However, according to the classification by Boriani et al,¹¹ patients who present with epidural tumor, multilevel large paraspinal masses, or circumferential bone disease are not candidates for marginal or wide excisions (i.e., en bloc with negative margins). The feasibility of achieving a wide or marginal excision is limited by the risk of neurologic or adjacent structure injury. For example, resecting the dura en bloc with a specimen will possibly provide a margin on epidural tumor. Unfortunately, the loss of spinal fluid buffering the spinal cord increases the probability of injury to the spinal cord and complications of cerebrospinal fluid (CSF) leak. If tumor is spilled during resection, there seems to be a higher probability of intradural seeding as well.¹² In a series of 59 spine sarcomas reviewed using the radiographic criteria established by Boriani et al’s classification, about 15% of patients were candidates for en bloc excisions that could achieve a wide or marginal margins. As noted in extremity sarcomas, once the tumor is violated, the risk of recurrence significantly increases.¹³ However, the treatment of sarcomas at other sites has demonstrated the utility of adjuvant high-dose radiation in the setting of microscopic or gross residual disease postresection.14

Radiation Therapy

Radiation therapy is an extremely important modality in the treatment of primary spine tumors. However, the relative radioresistance of these tumors requires doses well above spinal cord tolerance for potential local tumor control. From the paradigm of extremity sarcomas, radiation doses > 60 Gy in 2 Gy per fraction are required for the control of positive microscopic margins and > 70 Gy for gross residual disease.¹⁵ Traditional concepts of spinal cord tolerance using conventional radiation techniques establishes the TD 5/5 (the dose at which there is a 5% probability of myelitis necrosis at 5 years from treatment) at 50 Gy in 1.2 to 2.0 Gy per fraction, above which there appears to be a significantly increased risk of developing radiation myelitis.¹⁶ Toxicity to the spinal cord may also be associated with the length of cord irradiated. In addition to the spinal cord, additional toxicities to paraspinal structures, such as bowel, kidneys, and the esophagus, need to be considered. Three radiation techniques are currently being used to increase the dose to the spinal cord while sparing normal tissue tolerance: proton beam therapy, brachytherapy, and high-dose conformal photon therapy, such as image-guided IGRT.

Proton Beam

The rationale for using proton beams is the excellent dose distribution at the tumor target and virtually no exit dose beyond the target volume. The Bragg peak phenomenon characteristic of proton beam radiation results in an extremely steep dose fall-off that can be measured over a course of millimeters. A relatively large experience exists in the treatment of neuraxis tumors using proton beams to deliver fractionated therapy. Proton beam radiotherapy’s main limitation is the extreme expense of building and maintaining such facilities. The cost–benefit ratio of proton beam treatment is controversial. Excellent results for uveal melanoma have been reported using proton beam therapy in a hypofractionated manner (median dose 70 cobalt gray equivalent [CGE] in five fractions),¹⁷ but there are no data reporting the use of single-fraction radiation with proton beam therapy for the management of tumors of the neuraxis.

Hug reported radiation results from 47 patients treated for primary or recurrent osteogenic and chondrogenic tumors treated with combined proton/photon therapy.¹⁸

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