Faculty Bibliography

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 TYPE/METHODS:A review of the literature. OBJECTIVE:The aim of this study was to discuss the evolution of molecular signatures and the history and development of targeted therapeutics in metastatic tumor types affecting the spinal column. SUMMARY OF BACKGROUND DATA/BACKGROUND:Molecular characterization of metastatic spine tumors is expected to usher in a revolution in diagnostic and treatment paradigms. Molecular characterization will provide critical information that can be used for initial diagnosis, prognosticating the ideal treatment strategy, assessment of treatment efficacy, surveillance and monitoring recurrence, and predicting complications, clinical outcome, and overall survival in patients diagnosed with metastatic cancers to the spinal column. METHODS:A review of the literature was performed focusing on illustrative examples of the role that molecular-based therapeutics have played in clinical outcomes for patients diagnosed with metastatic tumor types affecting the spinal column. RESULTS:The impact of molecular therapeutics including receptor tyrosine kinases and immune checkpoint inhibitors and the ability of molecular signatures to provide prognostic information are discussed in metastatic breast cancer, lung cancer, prostate cancer, melanoma, and renal cell cancer affecting the spinal column. CONCLUSION/CONCLUSIONS:For the providers who will ultimately counsel patients diagnosed with metastases to the spinal column, molecular advancements will radically alter the management/surgical paradigms utilized. Ultimately, the translation of these molecular advancements into routine clinical care will greatly improve the quality and quantity of life for patients diagnosed with spinal malignancies and provide better overall outcomes and counseling for treating physicians. LEVEL OF EVIDENCE/METHODS:N/A.

STUDY DESIGN/METHODS:Systematic review and consensus expert opinion. OBJECTIVE:To provide surgeons and other health care professionals with guidelines for surgical reconstruction of metastatic spine disease based on evidence and expert opinion. SUMMARY OF BACKGROUND DATA/BACKGROUND:The surgical treatment of spinal metastases is controversial. Specifically two aspects of surgical reconstruction are addressed in this study: (i) choice of bone graft used during surgery for metastatic spine tumors and (ii) the design of reconstruction or construct to stabilize. METHODS:A systematic review of the available medical literature from 1980 to 2015 was conducted, and combined with consensus expert opinion from a recent survey of spine surgeons who treat metastatic spine tumors. RESULTS:There is very little evidence in the literature to provide guidance on the use of bone graft in metastatic tumor reconstruction. There is little evidence in the literature to support the preferential use of one graft type over the other. Approximately, 41% of respondents said they used bone graft or bone graft substitutes to accomplish fusion. There were 17 studies that described the use of a prefabricated prosthetic, 10 studies describing the use of polymethyl methacrylate (PMMA) bone cement, and only three studies describing the use of bone graft for anterior column reconstruction. The use of structural allograft was most popular among the experts for anterior reconstruction, followed by cage reconstruction, and PMMA bone cement. CONCLUSION/CONCLUSIONS:Achieving bony union may be of importance for the maintenance of spinal stability in the long term after reconstruction. Whether bony union is required for patients with shorter life expectancies is debatable. The literature supports the use of anterior reconstruction with either a prefabricated prosthetic or PMMA bone cement. It also supports the use of an anterior construct reinforced with bilateral posterior instrumentation when performing a three-column reconstruction. LEVEL OF EVIDENCE/METHODS:N/A.

STUDY DESIGN/METHODS:Systematic literature review and expert survey OBJECTIVE.: The aim of this study was to determine factors associated with neurologic improvement in patients with neurologic deficits secondary to metastatic epidural spinal cord compression (MESCC). Clear understanding of these factors will guide surgical decision-making by helping to elucidate which patients are more likely to benefit from surgery and how surgeons can increase the probability of neurologic and functional restoration. SUMMARY OF BACKGROUND DATA/BACKGROUND:Surgical spinal cord decompression has been shown to improve neurologic function in patients with symptomatic MESCC. However, prognostication of neurologic improvement after surgery remains challenging, owing to sparse data and complexity of these patients. METHODS:PubMed and Embase databases were searched for relevant publications. PRISMA Statement guided publication selection and data reporting. GRADE guidelines were used for evidence quality evaluation and recommendation formulation. RESULTS:Low-quality evidence supports the use of the duration and severity of neurologic deficit as predictors of neurological recovery in patients with MESCC. Low-quality evidence supports the use of thoracic level of compression and previous irradiation as adverse predictors of neurological recovery. Nearly all of the AOSpine Knowledge Forum Tumor members who responded to the survey agreed that ambulation with assistance represented a successful surgical result and that duration of ambulation loss and the severity of weakness should be considered when trying to predict whether surgery would result in restoration of ambulation. CONCLUSIONS:Review of literature and expert opinion support the importance of duration of ambulation loss and the severity of neurologic deficit (muscle strength, bladder function) in prediction of neurologic recovery among patients with symptomatic MESCC. Efforts to reduce the duration of ambulation loss and to prevent progression of neurologic deficits should be made to improve the probability of neurologic recovery. LEVEL OF EVIDENCE/METHODS:2.

STUDY DESIGN/METHODS:Literature review. OBJECTIVE:To describe advancements in molecular techniques, biomarkers, technology, and targeted therapeutics and the potential these modalities hold to predict treatment paradigms, clinical outcomes, and/or survival in patients diagnosed with primary spinal column tumors. SUMMARY OF BACKGROUND DATA/BACKGROUND:Advances in molecular technologies and techniques have influenced the prevention, diagnosis, and overall management of patients diagnosed with cancer. Assessment of genomic, proteomic alterations, epigenetic, and posttranslational modifications as well as developments in diagnostic modalities and targeted therapeutics, although the best studied in nonspinal metastatic disease, have led to increased understanding of spine oncology that is expected to improve patient outcomes. In this manuscript, the technological advancements that are expected to change the landscape of spinal oncology are discussed with a focus on how these technologies will aid in clinical decision-making for patients diagnosed with primary spinal tumors. METHODS:A review of the literature was performed focusing on studies that integrated next-generation sequencing, circulating tumor cells/circulating tumor DNA, advances in imaging modalities and/or radiotherapy in the diagnosis and treatment of cancer. RESULTS:We discuss genetic and epigenetic drivers, aberrations in receptor tyrosine kinase signaling, and emerging therapeutic strategies that include receptor tyrosine kinase inhibitors, immunotherapy strategies, and vaccine-based cancer prevention strategies. CONCLUSION/CONCLUSIONS:The wide range of approaches currently in use and the emerging technologies yet to be fully realized will allow for better development of rationale therapeutics to improve patient outcomes. LEVEL OF EVIDENCE/METHODS:N/A.

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.

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.

STUDY DESIGN/METHODS:Review of the literature. OBJECTIVE:Surgery and cement augmentation procedures are effective palliative treatment of symptomatic spinal metastases. Our objective is to systematically review the literature to describe the survival, prognostic factors, and clinical outcomes of surgery and cement augmentation procedures for breast cancer metastases to the spine. METHODS:We performed a literature review using PubMed to identify articles that reported outcomes and/or prognostic factors of the breast cancer patient population with spinal metastases treated with any surgical technique since 1990. RESULTS:The median postoperative survival for metastatic breast cancer was 21.7 months (8.2 to 36 months), the mean rate of any pain improvement was 92.9% (76 to 100%), the mean rate of neurologic improvement was 63.8% (53 to 100%), the mean rate of neurologic decline was 4.1% (0 to 8%), and the local tumor control rate was 92.6% (89 to 100%). Kyphoplasty studies reported a high rate of pain control in selected patients. Negative prognostic variables included hormonal (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2) receptor refractory tumor status, high degree of axillary lymph node involvement, and short disease-free interval (DFI). All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSION/CONCLUSIONS:With respect to clinical outcomes, surgery consistently yielded neurologic improvements in patients presenting with a deficit with a minimal risk of worsening; however, negative prognostic factors associated with shorter survival following surgery include estrogen receptor/progesterone receptor negativity, HER2 negativity, and a short DFI.