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Background The role of tumor genomic profiling is rapidly growing as it results in targeted, personalized, cancer therapy. Though routinely used in clinical practice, there are no data exploring the reliability of genomic data obtained from spine metastases samples often leading to multiple biopsies in clinical practice. This study compares the genomic tumor landscape between spinal metastases and the corresponding primary tumors as well as between spinal metastases and visceral metastases. Methods Spine tumor samples, obtained for routine clinical care from 2013 to 2019, were analyzed using MSK-IMPACT, a next-generation sequencing assay. These samples were matched to primary or metastatic tumors from the corresponding patients. A concordance rate for genomic alterations was calculated for matching sample pairs within patients for the primary and spinal metastatic tumor samples as well as for the matching sample pairs within patients for the spinal and visceral metastases. For a more robust and clinically relevant estimate of concordance, subgroup analyses of previously established driver mutations specific to the main primary tumor histologies were performed. Results Eighty-four patients contributed next-generation sequencing data from a spinal metastasis and at least one other site of disease: 54 from the primary tumor, 39 had genomic tumor data from another, nonspinal metastasis, 12 patients participated in both subsets. For the cohort of matched primary tumors and spinal metastases (n = 54) comprised of mixed histologies, we found an average concordance rate of 96.97% for all genetic events, 97.17% for mutations, 100% for fusions, 89.81% for deletions, and 97.01% for amplifications across all matched samples. Notably, >25% of patients harbored at least one genetic variant between samples tested, though not specifically for known driver mutations. The average concordance rate of driver mutations was 96.99% for prostate cancer, 95.69% (P = .0004513) for lung cancer, and 96.43% for breast cancer. An average concordance of 99.02% was calculated for all genetic events between spine metastases and non-spinal metastases (n = 41) and, more specifically, a concordance rate of 98.91% was calculated between spine metastases and liver metastases (n = 12) which was the largest represented group of nonspine metastases. Conclusion Sequencing data performed on spine tumor samples demonstrate a high concordance rate for genetic alterations between the primary tumor and spinal metastasis as well as between spinal metastases and other, visceral metastases, particularly for driver mutations. Spine tumor samples may be reliably used for genomic-based decision making in cancer care, particularly for prostate, NSCLC, and breast cancer.

Spine metastases are very common in cancer patients often requiring urgent assessment and the initiation of therapy. Treatment paradigms have changed exponentially over the past decade with the evolution and integration of stereotactic body radiotherapy, minimally invasive spine techniques, and systemic options including biologics and checkpoint inhibitors. These advances necessitate multidisciplinary assessments and interventions to optimize outcomes. The NOMS framework provides a mechanism for all practitioners to evaluate the 4 sentinel assessments required to make decisions in patients with spine metastases: Neurologic, Oncologic, Mechanical Stability, and Systemic disease. The NOMS framework is continuously updated with the integration of newer technologies and evidence-based medicine as they become available. This paper presents the current iteration of NOMS with a focus on the role of medical and neuro-oncologists in the assessment and treatment of metastatic spine tumors.

Background Patient-reported outcomes (PRO) represent an important measure of cancer therapy effect. For patients with metastatic epidural spinal cord compression (MESCC), hybrid therapy using separation surgery and stereotactic radiosurgery preserves neurologic function and provides tumor control. There is currently a paucity of data reporting PRO after such combined modality therapy for MESCC. Delineation of hybrid surgery–radiosurgery therapy effect on PRO validates the hybrid approach as an effective therapy resulting in meaningful symptom relief. Patients and Methods Brief Pain Inventory (BPI) and MD Anderson Symptom Inventory—Spine Tumor (MDASI-SP), PROs validated in the cancer population, were prospectively collected. Patients with MESCC who underwent separation surgery followed by stereotactic radiosurgery were included. Separation surgery included a posterolateral approach without extensive cytoreductive tumor excision. A median postoperative radiosurgery dose of 2700 cGy was delivered. The change in PRO 3 months after the hybrid therapy represented the primary study outcome. Preoperative and postoperative evaluations were analyzed using the Wilcoxon signed-rank test for matched pairs. Results One hundred eleven patients were included. Hybrid therapy resulted in a significant reduction in the BPI items “worst” and “right now” pain (P < .0001), and in all BPI constructs (severity, interference with daily activities, and pain experience, P < .001). The MDASI-SP demonstrated reduction in spine-specific pain severity and interference with general activity (P < .001), along with decreased symptom interference (P < .001). Conclusions Validated PRO instruments showed that in patients with MESCC, hybrid therapy with separation surgery and radiosurgery results in a significant decrease in pain severity and symptom interference. These prospective data confirm the benefit of hybrid therapy for treatment of MESCC and should facilitate referral of patients with MESCC for surgical evaluation.

Background. Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan-Kettering Cancer Center to determine the optimal therapy for patients with spine metastases. Methods. We provide a literature review of the integral publications that serve as the basis for the NOMS framework and report the results of systematic implementation of the NOMS-guided treatment. Results. The NOMS decision framework consists of the neurologic, oncologic, mechanical, and systemic considerations and incorporates the use of conventional external beam radiation, spinal stereotactic radiosurgery, and minimally invasive and open surgical interventions. Review of radiation oncology and surgical literature that examine the outcomes of treatment of spinal metastatic tumors provides support for the NOMS decision framework. Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population. Conclusion. NOMS paradigm provides a decision framework that incorporates sentinel decision points in the treatment of spinal metastases. Consideration of the tumor sensitivity to radiation in conjunction with the extent of epidural extension allows determination of the optimal radiation treatment and the need for surgical decompression. Mechanical stability of the spine and the systemic disease considerations further help determine the need and the feasibility of surgical intervention.

BACKGROUND: Oligometastatic disease (5 metastases) is considered an intermediate cancer state of limited metastatic capacity and improved prognosis. Hence, in recent years, treatment of oligometastatic spinal disease has trended towards more definitive, ablative therapies. Little is known about the actual prognosis of patients presenting with oligometastatic spinal disease. The focus of this study was to compare oligometastatic spine patients to those with polymetastatic disease (>5 metastases). METHODS: This is an international, multicenter analysis of prospectively collected data. Data collected included demographics, survival, local control, histology, number and location of spine metastases, epidural spine cord compression (ESCC), the Spinal Instability Neoplastic Score (SINS), systemic disease burden, and treatment details. Health-related quality of life (HrQOL) measures included; numeric rating scale (NRS) for pain, EuroQol-5D (EQ-5D-3L), short form 36 version 2 (SF-36v2) and the spine oncology study group outcomes questionnaire (SOSGOQ). RESULTS: A total of 393 patients were included, of which 215 presented with oligometastatic disease and 178 with polymetastatic disease. A significant survival advantage was found for patients presenting with oligometastatic disease compared to those with polymetastatic disease at time of initial treatment of spinal metastases. This survival advantage was noticeable in both operative and non-operative patients. Local control rates were higher in the oligometastatic group for the spinal level treated. Furthermore, both groups experienced significant improvement in multiple HrQOL measures at 6 months post-treatment with no differences in these outcome measures between the two groups. CONCLUSION: At time of treatment of spinal metastatic disease, oligometastatic disease offers a significant survival advantage compared to polymetastatic disease, regardless of treatment choice. Local control can be achieved in both groups. HrQOL measures improve in both groups post-treatment, thus demonstrating a palliative treatment benefit for all treated patients. Our results support the oligometastatic theory and the current trend of ablative treatment for oligometastatic spine disease.

Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.

Metastases to the spine represent a challenging problem in an oncology practice. Treatment decisions require multidisciplinary review. Radiation therapy remains the primary treatment for metastatic spinal tumor, but advances in radiation therapy, chemotherapy, and surgery have changed the roles of each and lead to improved patient outcomes. Regardless of the treatment, diagnosis and treatment before the development of significant neurologic and functional deficits improve outcomes. Physician awareness and appropriate imaging greatly assist in the early detection of tumor.

Background Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.