Faculty Bibliography

PURPOSE/OBJECTIVE:Conventional radiation treatment (20-40 Gy in 5-20 fractions, 2-5 Gy per fraction) for sarcoma metastatic to the spine provides subtherapeutic doses, resulting in poor durable local control (LC) (50%-77% at 1 year). Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic radiosurgery (IG-SRS) may provide a more effective means of managing these lesions. METHODS AND MATERIALS/METHODS:Patients with pathologically proven high-grade sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. LC and overall survival (OS) were analyzed by the use of Kaplan-Meier statistics. Univariate and multivariate analyses were performed by the use of Cox regression with competing-risks analysis; all confidence intervals are 95%. Toxicities were assessed according to Common Terminology Criteria for Adverse Events, version 4.0. RESULTS:From May 2005 to November 11, 2012, 88 patients with 120 discrete metastases received HF (3-6 fractions; median dose, 28.5 Gy; n=52, 43.3%) or SF IG-SRS (median dose, 24 Gy; n=68, 56.7%). The median follow-up time was 12.3 months. At 12 months, LC was 87.9% (confidence interval [CI], 81.3%-94.5%), OS was 60.6% (CI, 49.6%-71.6%), and median survival was 16.9 months. SF IG-SRS demonstrated superior LC to HF IG-SRS (12-month LC of 90.8% [CI, 83%-98.6%] vs 84.1% [CI, 72.9%-95.3%] P=.007) and retained significance on multivariate analysis (P=.030, hazard ratio 0.345; CI, 0.132-0.901]. Treatment was well tolerated, with 1% acute grade 3 toxicity, 4.5% chronic grade 3 toxicity, and no grade >3 toxicities. CONCLUSIONS:In the largest series of metastatic sarcoma to the spine to date, IG-SRS provides excellent LC in the setting of an aggressive disease with low radiation sensitivity and poor prognosis. Single-fraction IG-SRS is associated with the highest rates of LC with minimal toxicity.

OBJECT/OBJECTIVE:Radiation therapy is known to impair wound healing. Higher dose per fraction is believed to increase this risk. This study sought to quantify rates of wound complication in patients receiving preoperative conventionally fractionated radiotherapy (XRT) or high-dose hypofractionated image-guided radiation therapy (IGRT) for spinal metastasis, and to identify predictors of wound complication. METHODS:The records of 165 consecutive patients who underwent spine surgery for metastasis at Memorial Sloan-Kettering Cancer Center between 1999 and 2010, with a history of prior radiation therapy, were reviewed. Patients with primary spine tumors, 2 courses of prior radiation therapy to the surgical site, total dose < 9 Gy, or radiation therapy adjacent to or partially overlapping the surgical site, were excluded. One hundred thirty patients received XRT (≤ 3 Gy/fraction) and 35 received IGRT (> 3 Gy/fraction). The total dose prescribed to the 100% isodose line to treat the planning target volume was 18-30 Gy in 1-5 fractions. Clinical factors evaluated included age, Karnofsky Performance Scale score, body mass index, presence of diabetes, smoking, ambulatory status, prior surgery at same spinal site, preoperative laboratory results (hemoglobin, lymphocyte count, and albumin), perioperative chemotherapy or steroids, estimated blood loss, extent of stabilization hardware, time between radiation therapy and surgery, number of vertebral bodies irradiated, total radiation dose, and dose per fraction of radiation therapy. Wound complication was defined as poor healing, dehiscence, or infection. Potential predictors of wound complication were assessed by univariate analyses using competing-risk methods to adjust for risk of death. results: For XRT patients, median dose was 30 Gy (range 11.5-70 Gy) with 72% of them receiving 3 Gy × 10 fractions. For IGRT patients, 66% received 18-24 Gy × 1 fraction and 23% received 6 Gy × 5 fractions. Groups differed only by the mean number of vertebral bodies treated (4.6 XRT and 1.8 IGRT, p < 0.0001). Wound complications occurred at a median of 0.95 months (range 0.4-3.9 months). A total of 22 wound events occurred in the XRT group and 2 in the IGRT group. The 6-month cumulative incidence of wound complications for XRT was 17% and for IGRT was 6%. There was no significant difference in wound complications between groups (IGRT vs XRT: hazard ratio 0.31, 95% CI 0.08-1.3; p = 0.11). Higher dose per fraction appeared to be associated with a lower risk of wound complication (hazard ratio 0.27, 95% CI 0.06-1.15; p = 0.08), which trended toward significance. Univariate analyses did not reveal any significant predictors of wound complications. CONCLUSIONS:Patients who underwent XRT or IGRT did not have significantly different rates of postoperative wound complications. This finding may be explained by the treatment of fewer vertebral bodies in IGRT patients, or by the low overall number of total events. With a wound complication rate of 6%, preoperative IGRT, a highly conformal treatment, resulted in a very low rate of surgical wound complication.

BACKGROUND:The treatment of epidural spinal cord compression due to metastatic cancer represents an important clinical challenge. The NOMS (neurologic, oncologic, mechanical, and systemic) framework facilitates the determination of the optimal combination of systemic, radiation, and surgical therapies for individual patients. Spinal stereotactic radiosurgery (SRS) is an effective and safe modality for achieving durable control of local disease. Integrating SRS into the postoperative treatment plan allows surgical goals to be modified, thus decreasing the extent of tumor resection required. METHODS:Separation surgery is indicated for patients with spinal cord compression secondary to solid tumor metastases. During separation surgery, the spinal column is stabilized and the epidural tumor is resected without requiring significant vertebral body resection. RESULTS:Tumor separation from the spinal cord allows patients to undergo postoperative SRS. CONCLUSIONS:The combination of separation surgery and high-dose hypofractionated or single-fraction SRS results in high local tumor control at 1 year and is an effective palliative paradigm for this patient population.

Treatment options for metastatic and primary spinal tumors have expanded in recent years, in part due to the advances made in stereotactic radiosurgery. For metastatic spinal tumors, our institution utilizes the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which provides a treatment paradigm based on the neurologic, oncologic, mechanical and systemic status of the patient. Radiosurgery as a supplement to surgical decompression has allowed for less-invasive surgical procedures carrying minimal morbidity while still providing effective local tumor control. Although wide en bloc excision has traditionally been the goal for the treatment of high-grade primary spine tumors, recent studies have shown promise for radiosurgery in providing control in tumors such as chordomas and high-grade sarcomas. Despite advances in radiosurgery, there continues to be limitations in providing effective conformational doses with minimal toxicity to critical structures. One of the ways to circumvent this and supplement external beam radiation is through the use of brachytherapy delivered by radioactive plaque or seeds.

BACKGROUND:En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies. OBJECTIVE:To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum. METHODS:Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up. RESULTS:The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis. CONCLUSION/CONCLUSIONS:High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.

BACKGROUND:Notochord-related lesions of the spinal column include benign notochordal cell tumors (BNCTs), ecchordosis physaliphora, both generally considered benign lesions, and chordomas, which represent malignant tumors. The histological similarity of these lesions to the notochord and each other and their strong predilection to the axial skeleton have led to the hypothesis that these lesions represent a continuum of malignant transformation from notochordal remnants, BNCTs, and finally chordomas. OBJECTIVE:To present a cohort of biopsy-proven BNCTs with a description of radiographic features, histology, and follow-up to help elucidate the optimal management of these lesions. METHODS:A retrospective chart review identified 13 patients with notochordal rest lesions confirmed by histology. Histologic inclusion criteria included notochordal features without evidence of septation, myxoid matrix, nuclear atypia, or mitotic figures. Tumors exhibiting evidence of cortical expansion or destruction were excluded. The natural history and histological and radiographic features were examined. RESULTS:Sixteen spinal lesions from 8 patients met the diagnostic criteria for BNCTs, identified on imaging after the patient presented with back pain. Radiographically, all lesions were hypointense on T1-weighted magnetic resonance imaging sequences and hyperintense on T2-weighted and short T1 inversion recovery. The median radiographic follow-up was 21.6 months (range, 8.5-71.2 months). None of the lesions exhibited radiographic or symptomatic progression. CONCLUSION/CONCLUSIONS:Although limited by short follow-up, our series confirms that these lesions may be safely observed without evidence of malignant transformation, which emphasizes the importance of distinction of BNCT from chordoma at diagnosis and the possibility of close follow-up for these lesions instead of aggressive treatment indicated in patients with chordomas.

The existing literature on preoperative spine tumor embolization is limited in size of patient cohorts and diversity of tumor histologies. This report presents our experience with preoperative embolization of hypervascular thoracic, lumbar, and sacral spinal column tumors in the largest series to date. We conducted a retrospective review of 228 angiograms and 188 pre-operative embolizations for tumors involving thoracic, lumbar and sacral spinal column. Tumor vascularity was evaluated with conventional spinal angiography and was graded from 0 (same as normal adjacent vertebral body) to 3 (severe tumor blush with arteriovenous shunting). Embolic materials included poly vinyl alcohol (PVA) particles and detachable platinum coils and rarely, liquid embolics. The degree of embolization was graded as complete, near-complete, or partial. Anesthesia records were reviewed to document blood loss during surgery. Renal cell carcinoma (44.2%), thyroid carcinoma (9.2%), and leiomyosarcoma (6.6%) were the most common tumors out of a total of 40 tumor histologies. Hemangiopericytoma had the highest mean vascularity (2.6) of all tumor types with at least five representative cases followed by renal cell carcinoma (2.0) and thyroid carcinoma (2.0). PVA particles were used in 100% of cases. Detachable platinum coils were used in 51.6% of cases. Complete, near-complete, and partial embolizations were achieved in 86.1%, 12.7%, and 1.2% of all cases, respectively. There were no new post-procedure neurologic deficits or other complications with long-term morbidity. The mean intra-operative blood loss for the hypervascular tumors treated with pre-operative embolization was 1745 cc. Preoperative embolization of hypervascular thoracic, lumbar, and sacral spine tumors can be performed with high success rates and a high degree of safety at high volume centers.

OPINION STATEMENT/UNASSIGNED:The management of recurrent chordomas are clinically challenging because of its relentless nature. Local therapy, whether surgery or radiation, are important considerations since local progression of disease results in significant morbidity and locally aggressive treatment is often required. Stereotactic radiosurgery, shown to be very effective for radioresistant histologies, may be an important radiotherapeutic approach for recurrent tumors. Ultimately, the treatment of recurrent chordoma is palliative in intent, thus, enthusiasm for improving local control must be tempered against the possible impact of treatment on quality of life. Judicious use of radiotherapy and surgery can often provide meaningful palliation and local control of recurrences. Systemic treatment options, particularly with targeted molecules have great potential for chordomas in the recurrent setting, as the risk of disseminated disease is higher. The development of tools to help assess potential targets for drug therapy will be crucial. The incorporation of locally aggressive therapy and effective systemic therapy will be critical for the successful management of recurrent chordomas. At present, there is a paucity of published data regarding salvage therapy. Nonetheless, advances in surgical, medical, and radiation oncology are providing new avenues of research and potentially may have significant impact upon successful salvage treatment.

PURPOSE/OBJECTIVE:Advances in stereotactic radiosurgery have improved local control of spine metastases, but local failure is still a problem and repeat irradiation is limited by normal tissue tolerance. A novel high-dose-rate (HDR) brachytherapy technique has been developed to treat these previously irradiated lesions. METHODS AND MATERIALS/METHODS:Five patients with progressive disease at previously irradiated sites in the spine who were not amenable to further external beam radiation were treated. Catheters were placed intraoperatively in 2 patients and percutaneously implanted in 3 patients with image-guided techniques. Conformal plans were generated to deliver dose to target tissues and spare critical structures. Patients received single-fraction treatment using HDR iridium-192 brachytherapy. RESULTS:Median dose was 14 Gy (range, 12-18 Gy) with a median gross total volume D90 of 75% (range, 31-94%); spinal cord/cauda equina dose constraints were met. At a median followup of 9 months, no local progression of disease has been observed. Four patients had reduction in pain 1-4 weeks after treatment. No brachytherapy-related complications have been observed. CONCLUSIONS:Intraoperative and percutaneous iridium-192 HDR spine brachytherapy techniques were not associated with complications or acute toxicity. There has been no local progression at treated sites, and most patients experienced reduction in cancer-related pain.