Faculty Bibliography

STUDY DESIGN/METHODS:Systematic review. OBJECTIVE:Surgical decompression and reconstruction of symptomatic spinal metastases has improved the quality of life in cancer patients. However, most data has been collected on cohorts of patients with mixed tumor histopathology. We systematically reviewed the literature for prognostic factors specific to the surgical treatment of prostate metastases to the spine. METHODS:A systemic review of the literature was conducted to answer the following questions: Question 1. Describe the survival and functional outcomes of surgery or vertebral augmentation for prostate metastases to the spine. Question 2. Determine whether overall tumor burden, Gleason score, preoperative functional markers, and hormonal naivety favor operative intervention. Question 3. Establish whether clinical outcomes vary with the evolution of operative techniques. RESULTS:A total of 16 studies met the preset inclusion criteria. All included studies were retrospective series with a level of evidence of IV. Included studies consistently showed a large effect of hormone-naivety on overall survival. Additionally, studies consistently demonstrated an improvement in motor function and the ability to maintain/regain ambulation following surgery resulting in moderate strength of recommendation. All other parameters were of insufficient or low strength. CONCLUSIONS:There is a dearth of literature regarding the surgical treatment of prostate metastases to the spine, which represents an opportunity for future research. Based on existing evidence, it appears that the surgical treatment of prostate metastases to the spine has consistently favorable results. While no consistent preoperative indicators favor nonoperative treatment, hormone-naivety and high Karnofsky performance scores have positive effects on survival and clinical outcomes.

BACKGROUND:Hepatocellular carcinoma (HCC) frequently metastasizes to the spine. The impact of medical and/or surgical intervention on overall survival has been examined in a limited number of clinical studies, and herein we systematically review these data. METHODS:We performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles that reported survival, clinical outcomes, and/or prognostic factors associated with patients diagnosed with spinal metastases. The methodologic quality of each review was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses tool. RESULTS:There were 26 articles (152 patients) that met the inclusion criteria and were treated with either surgery, radiotherapy, chemotherapy, and/or observation. There were 3 retrospective cohort studies, 17 case reports, 5 case series, and 1 longitudinal observational study. Of the patients with known overall survival after diagnosis of spinal metastasis, survival at 3 months, 6 months, 1 year, 2 years, and 5 years was 95.2%, 83.0%, 28.6%, 2.0%, and 1.4%, respectively. The median survival after diagnosis of the metastasis was 0.7 months in the patients who received no treatment, 7 months in the patients treated with surgical intervention alone, 6 months for patients who received chemotherapy and/or radiation, and 13.5 months in the patients treated with a combination of surgery and medical management. All other clinical or prognostic parameters were of low or insufficient strength. CONCLUSIONS:Patients diagnosed with HCC spinal metastasis have a 10.6-month overall survival. Further analysis of patients in prospective controlled trials will be essential to the development of treatment algorithms for these patients in the future.

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 Literature review. Objective Functional secretory tumors metastatic to the spine can secrete hormones, growth factors, peptides, and/or molecules into the systemic circulation that cause distinct syndromes, clinically symptomatic effects, and/or additional morbidity and mortality. En bloc resection has a limited role in metastatic spine disease due to the current paradigm that systemic burden usually determines morbidity and mortality. Our objective is to review the literature for studies focused on en bloc resection of functionally active spinal metastasis as the primary indication. Methods A review of the PubMed literature was performed to identify studies focused on functional secreting metastatic tumors to the spinal column. We identified five cases of patients undergoing en bloc resection of spinal metastases from functional secreting tumors. Results The primary histologies of these spinal metastases were pheochromocytoma, carcinoid tumor, choriocarcinoma, and a fibroblast growth factor 23-secreting phosphaturic mesenchymal tumor. Although studies of en bloc resection for these rare tumor subtypes are confined to case reports, this surgical treatment option resulted in metabolic cures and decreased clinical symptoms postoperatively for patients diagnosed with solitary functional secretory spinal metastasis. Conclusion Although the ability to formulate comprehensive conclusions is limited, case reports demonstrate that en bloc resection may be considered as a potential surgical option for the treatment of patients diagnosed with solitary functional secretory spinal metastatic tumors. Future prospective investigations into clinical outcomes should be conducted comparing intralesional resection and en bloc resection for patients diagnosed with solitary functional secretory spinal metastasis.

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.

OBJECTIVE:The existing literature regarding preoperative cervical spinal tumor embolization is sparse, with few discussions on the indications, risks, and best techniques. We present our experience with the preoperative endovascular management of hypervascular cervical spinal tumors. METHODS:We performed a retrospective review of all patients who underwent preoperative spinal angiography (regardless of whether tumor embolization was performed) at our institution (from 2002 to 2012) for primary and metastatic cervical spinal tumors. Tumor vascularity was graded from 0 (tumor blush equal to the normal adjacent vertebral body) to 3 (intense tumor blush with arteriovenous shunting). Tumors were considered "hypervascular" if they had a tumor vascular grade from 1 to 3. Embolic materials included particles, liquid embolics, and detachable coils. The main embolization technique was superselective catheterization of an arterial tumor feeder followed by injection of embolic material. This technique could be used alone or supplemented with occlusion of dangerous anastomoses of the vertebral artery as needed to prevent inadvertent embolization of the vertebrobasilar system. In cases when superselective catheterization of the tumoral feeder was not feasible, embolization was performed from a proximal catheter position after occlusion of branches supplying areas other than the tumor ("flow diversion"). RESULTS:A total of 47 patients with 49 cervical spinal tumors were included in this study. Of the 49 total tumors, 41 demonstrated increased vascularity (vascularity score > 0). The most common tumor pathology in our series was renal cell carcinoma (RCC) (N = 16; 32.7% of all tumors) followed by thyroid carcinoma (N = 7; 14.3% of all tumors).Tumor embolization was undertaken in 25 hypervascular tumors resulting in complete, near-complete, and partial embolization in 36.0% (N = 9), 44.0% (N = 11), and 20.0% (N = 5) of embolized tumors, respectively. We embolized 42 tumor feeders in 25 tumors. The most commonly embolized tumor feeders were branches of the vertebral artery (19.0%; N = 8), the deep cervical artery (19.0%; N = 8), and the ascending cervical artery (19.0%; N = 8). Sixteen hypervascular tumors were not embolized because of minimal hypervascularity (8/16), unacceptably high risk of spinal cord or vertebrobasilar ischemia (4/16), failed superselective catheterization of tumor feeder (3/16), and cancellation of surgery (1/16). Vertebral artery occlusion was performed in 20% of embolizations. There were no new post-procedure neurological deficits or any serious adverse events. Estimated blood loss data from this cohort show a significant decrease in operative blood loss for embolized tumors of moderate and significant hypervascularity. CONCLUSIONS:Preoperative embolization of cervical spinal tumors can be performed safely and effectively in centers with significant experience and a standardized approach.

OBJECTIVE The aim of this study was to report the first detailed analysis of patterns of failure within the spinal axis of patients treated with stereotactic body radiotherapy (SBRT) for sarcoma spine metastases. METHODS Between 2005 and 2012, 88 consecutive patients with metastatic sarcoma were treated with SBRT for 120 spinal lesions. Seventy-one percent of patients were enrolled on prospective institutional protocols. For patients who underwent routine posttreatment total-spine MRI (64 patients, 88 lesions), each site of progression within the entire spinal axis was mapped in relation to the treated lesion. Actuarial rates of local-, adjacent-, and distant-segment failure-free survival (FFS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up for the cohort was 14.4 months, with 81.7% of patients followed up until death. The 12-month actuarial rate of local FFS was 85.9%; however, 83.3% of local failures occurred in conjunction with distant-segment failures. The 12-month actuarial rates of isolated local-, adjacent-, and distant-segment FFS were 98.0%, 97.8%, and 74.7%, respectively. Of patients with any spinal progression (n = 55), only 25.5% (n = 14) had progression at a single vertebral level, with 60.0% (n = 33) having progression at ≥ 3 sites within the spine simultaneously. Linear regression analysis revealed a relationship of decreasing risk of failure with increasing distance from the treated index lesion (R(2) = 0.87), and 54.1% of failures occurred ≥ 5 vertebral levels away. Treatment of the index lesion with a lower biological effective dose (OR 3.2, 95% CI 1.1-9.2) and presence of local failure (OR 18.0, 95% CI 2.1-152.9) independently predicted for distant spine failure. CONCLUSIONS Isolated local- and adjacent-segment failures are exceptionally rare for patients with metastatic sarcoma to the spine treated with SBRT, thereby affirming the treatment of the involved level only. The majority of progression within the spinal axis occurs ≥ 5 vertebral levels away. Thus, total-spine imaging is necessary for surveillance posttreatment.

OBJECT Despite advances in therapies using radiation oncology and spinal oncological surgery, there is a subgroup of patients with spinal metastases who suffer from progressive or recurrent epidural disease and remain at risk for neurological compromise. In this paper the authors describe their initial experience with a novel therapeutic approach that consists of intraarterial (IA) infusion of chemotherapy to treat progressive spinal metastatic disease. METHODS The main inclusion criterion was the presence of progressive, metastatic epidural disease to the spine causing spinal canal compromise in patients who were not candidates for the standard treatments of radiation therapy and/or surgery. All tumor histological types were eligible for this trial. Using the transfemoral arterial approach and standard neurointerventional techniques, all patients were treated with IA infusion of melphalan in the arteries supplying the epidural tumor. The protocol allowed for up to 3 procedures repeated at 3- to 6-week intervals. Outcome measures included physiological measures: 1) periprocedural complications according to the National Cancer Institute's Common Terminology Criteria for Adverse Events; and 2) MRI to assess for tumor response. RESULTS Nine patients with progressive spinal metastatic disease and cord compression were enrolled in a Phase I clinical trial of selective IA chemotherapy. All patients had metastatic disease from solid organs and were not candidates for further radiation therapy or surgery. A total of 19 spinal intraarterial chemotherapy (SIAC) procedures were performed, and the follow-up period ranged from 1 to 7 months (median 3 months). There was 1 serious adverse event (febrile neutropenia). Local tumor control was seen in 8 of 9 patients, whereas tumor progression at the treated level was seen in 1 patient. CONCLUSIONS These preliminary results support the hypothesis that SIAC is feasible and safe.

Many cancer patients will develop spinal metastases. Local control is important for preventing neurologic compromise and to relieve pain. Stereotactic body radiotherapy or spinal radiosurgery is a new radiation therapy technique for spinal metastasis that can deliver a high dose of radiation to a tumor while minimizing the radiation delivered to healthy, neighboring tissues. This treatment is based on intensity-modulated radiotherapy, image guidance and rigid immobilization. Spinal radiosurgery is an increasingly utilized treatment method that improves local control and pain relief after delivering ablative doses of radiation. Here, we present a review highlighting the use of spinal radiosurgery for the treatment of metastatic tumors of the spine. The data used in the review were collected from both published studies and ongoing trials. We found that spinal radiosurgery is safe and provides excellent tumor control (up to 94% local control) and pain relief (up to 96%), independent of histology. Extensive data regarding clinical outcomes are available; however, this information has primarily been generated from retrospective and nonrandomized prospective series. Currently, two randomized trials are enrolling patients to study clinical applications of fractionation schedules spinal Radiosurgery. Additionally, a phase I clinical trial is being conducted to assess the safety of concurrent stereotactic body radiotherapy and ipilimumab for spinal metastases. Clinical trials to refine clinical indications and dose fractionation are ongoing. The concomitant use of targeted agents may produce better outcomes in the future.