Faculty Bibliography

STUDY DESIGN/METHODS:Systematic literature review. OBJECTIVE:To assess the toxicity, common radiation doses, and local control (LC) rates of radiation therapy for chordoma of the spine and sacrum and identify the difference in LC and toxicity between adjuvant, salvage, and primary therapy using radiation. SUMMARY OF BACKGROUND DATA/BACKGROUND:Chordoma of the spine is typically a low-grade malignant tumor thought to be relatively radioresistant with a high rate of local recurrence and the potential for metastases. Improved results of modern radiation therapy in the treatment of chordoma support exploration of its role in the management of primary/de novo chordoma or recurrent chordoma. METHODS:We conducted a systematic literature review using PubMed and Embase databases to assess information available regarding the toxicity, LC rates, and overall survival (OS) rates for adjuvant, salvage, and primary radiation therapy for spinal and sacral chordoma. RESULTS:A total of 40 articles were reviewed. Evidence quality was low or very low. The highest rates of LC and OS were with early adjuvant RT for primary/de novo disease. Salvage RT for recurrent disease has very small cohorts and thus strong conclusions were not able be made. CONCLUSION/CONCLUSIONS:The use of pre- and/or post-operative photon image-guided radiotherapy (IGRT), proton or carbon ion therapy should be considered for patients undergoing surgery for the treatment of primary and recurrent chordomas in the mobile spine and sacrum, since these RT modalities may improve local control. Preoperative evaluation by the surgeon and radiation oncologist should be used to formulate a cohesive treatment plan.The use of photon IGRT or carbon ion therapy as the primary treatment of chordoma, when currently in its developmental stage, shows promise and requires clear delineation of toxicity profile and long-term local control. LEVEL OF EVIDENCE/METHODS:2.

Metastatic lung cancer to the spine occurs at high rates with patients usually given poor prognoses. Recent studies have observed that patients with certain genetic and molecular aberrations have better responses to adjuvant therapy. As such, current metastatic spine disease treatment algorithms grading all lung primaries' prognosis as poor may lead to inadequate treatment of spinal metastases. The aims of this study are to determine current survival patterns in 
metastatic spine disease secondary to lung cancer and identify relevant parameters that influence the prognostication of these patients. A systematic review in accordance with PRISMA guidelines was conducted for literature published between January 1, 1996 and September 31, 2015. The 27 studies identified were Level IV retrospective studies with an overall 'low' level of evidence. The overall median survival of patients with spine involved metastatic lung cancer was poor, ranging from 3.6 to 9months. Median survival of patients with non-small cell lung cancer being treated with epidermal growth factor receptor (EGFR) inhibitors were observed to be better, with survival of up to 18months. This review reports a subset of lung cancer patients with oncogenic molecular mutations that appear to confer a better overall survival. In these patients, individualized assessment rather than strict adherence to current metastatic scoring algorithms when determining management may be preferred.

STUDY DESIGN/METHODS:Systematic review. OBJECTIVE:The aim of this study was to review the techniques, indications, and outcomes of minimally invasive surgery (MIS) and separation surgery with subsequent radiosurgery in the treatment of patients with metastatic spine disease. SUMMARY OF BACKGROUND DATA/BACKGROUND:The utilization of MIS techniques in patients with spine metastases is a growing area within spinal oncology. Separation surgery represents a novel paradigm where radiosurgery provides long-term control after tumor is surgically separated from the neural elements. METHODS:PubMed, Embase, and CINAHL databases were systematically queried for literature reporting MIS techniques or separation surgery in patients with metastatic spine disease. PRISMA guidelines were followed. RESULTS:Of the initial 983 articles found, 29 met inclusion criteria. Twenty-five articles discussed MIS techniques and were grouped according to the primary objective: percutaneous stabilization (8), tubular retractors (4), mini-open approach (8), and thoracoscopy/endoscopy (5). The remaining 4 studies reported separation surgery. Indications were similar across all studies and included patients with instability, refractory pain, or neurologic compromise. Intraoperative variables, outcomes, and complications were similar in MIS studies compared to traditional approaches, and some MIS studies showed a statistically significant improvement in outcomes. Studies of mini-open techniques had the strongest evidence for superiority. CONCLUSIONS:Low-quality evidence currently exists for MIS techniques and separation surgery in the treatment of metastatic spine disease. Given the early promising results, the next iteration of research should include higher-quality studies with sufficient power, and will be able to provide higher-level evidence on the outcomes of MIS approaches and separation surgery. LEVEL OF EVIDENCE/METHODS:N/A.

BACKGROUND CONTEXT: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. PURPOSE: To identify early MRI biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. STUDY DESIGN/SETTING: Retrospective case series at a large tertiary cancer center. PATIENT SAMPLE: From 2011 to 2014, nine consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with DCE-MRI both pre- and post-SBRT. OUTCOME MEASURE: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multi-parametric MRI (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. METHODS: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t-tests were used to compare groups. P<0.05 was deemed statistically significant. RESULTS: The median time from SBRT until post-treatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared to pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <0.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2 = 0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared to the mpMRI score change post-SBRT (R2 = 0.026). CONCLUSIONS: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at two months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

The best clinical treatment for spinal metastases requires an integrated approach with input from an interdisciplinary cancer team. The principle goals of treatment are maintenance or improvement in neurologic function and ambulation, spinal stability, durable tumor control, and pain relief. The past decade has witnessed an explosion of new technologies that have impacted our ability to reach these goals, such as separation surgery and minimally invasive spinal procedures. The biggest advance, however, has been the evolution of stereotactic radiosurgery that has demonstrated durable tumor control both when delivered as definitive therapy and as a postoperative adjuvant even for tumors considered markedly resistant to conventional external beam radiation. In this paper, we perform an update on the management of spinal metastases demonstrating the integration of these new technologies into a decision framework NOMS that assesses four basic aspects of a patient's spine disease: Neurologic, Oncologic, Mechanical Instability and Systemic disease.

PURPOSE/OBJECTIVE:To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. METHODS AND MATERIALS/METHODS:The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. RESULTS:Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥ 3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen treated levels (36.1%) in 12 patients demonstrated progressive vertebral body collapse or endplate fractures at a median of 25.7 months (range 11.6-76.0), of which 5 (14%) became symptomatic and subsequently required percutaneous cement augmentation or surgery. CONCLUSIONS:In the longest-term series to date, high-dose single-fraction spinal SRS retained an excellent safety profile among long-term survivors (>5 years).

BACKGROUND CONTEXT/BACKGROUND:Pathologic vertebral compression fractures (VCFs) represent a major source of morbidity and diminished quality of life in the spinal oncology population. Procedures with low morbidity that effectively treat patients with pathologic fractures are especially important in the cancer population where life expectancy is limited. Vertebroplasty and kyphoplasty are often not effective for mechanically unstable pathologic fractures extending into the pedicle and facet joints. Combination of cement augmentation and percutaneous instrumented stabilization represents a minimally invasive treatment option that does not delay radiation and systemic therapy. PURPOSE/OBJECTIVE:The objective of the study was to evaluate the safety and efficacy of cement-augmented short-segment percutaneous posterolateral instrumentation for tumor-associated VCF with pedicle and joint involvement. METHODS:Forty-four consecutive patients underwent cement-augmented percutaneous spinal fixation for unstable tumors between 2011 and 2014. Retrospective analysis of prospectively collected data, including visual analog pain scale (VAS) response score and procedural complications, was performed. RESULTS:Patients with a median composite Spinal Instability Neoplastic Scale score of 10 (range=8-15) were treated with constructs spanning one to four disk spaces (median of two spaces, constituting 84% of all cases). The proportion of patients with severe pain decreased from 86% preoperatively to 0%; 65% of patients reported no referable instability pain postoperatively. There was one adjacent-level fracture responsive to kyphoplasty, and one case of asymptomatic screw pullout. Two patients subsequently required decompression in the setting of disease progression despite radiation; there was no perioperative morbidity. CONCLUSIONS:Percutaneous cement-augmented posterolateral spinal fixation is a safe and effective option for palliation of appropriately selected mechanically unstable VCF that extends into pedicle and/or joint.

PURPOSE/OBJECTIVE:Sterilization of surgical margins for lesions involving the dura is complicated by the tolerance of the spinal cord and/or cauda equina, especially in the setting of prior radiation therapy (RT); use of intraoperative brachytherapy may allow local delivery of therapeutic dose without damaging sensitive structures. METHODS AND MATERIALS/METHODS:Patients with malignant lesions involving the dura received intraoperative brachytherapy with a (32)P plaque after maximal resection of the tumor. Local recurrence (LR) was analyzed using competing risks analysis; overall survival was analyzed using Kaplan-Meier statistics. RESULTS:Between September 2009 and April 2013, 68 patients with 69 lesions in the spine were treated with the (32)P plaque. Median followup was 10 months. Most patients (n=59, 85.5%) had previously been treated with at least one course of prior RT to the treated site. About 38 (55%) lesions received postoperative RT (median dose, 30 Gy; range, 18-30 Gy). The LR and overall survival at 12 months were 25.5% (95% confidence interval [CI]=15.5-37%) and 59.5% (95% CI=46-73%), respectively. For patients who received postoperative RT, LR at 12 months was 18.5% (95% CI=7.5-33%) compared with 34% (95% CI=18-51%) for those who were treated with the plaque alone (p=0.08 and 0.04 on univariate and multivariable analysis, respectively). There were no acute or long-term complications from treatment observed in this cohort. CONCLUSIONS:The (32)P intraoperative brachytherapy plaque is a useful adjunct to surgical intervention for primary recurrent and metastatic lesions of the spine involving the dura, and is not associated with additional toxicity.