Primary Spinal Epidural CIC-DUX4 Undifferentiated Sarcoma in a Child

Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas. These tumors primarily occur in peripheral soft tissues, but examples have been described within viscera and the brain. As far as we are aware, CIC-DUX4 positive primary epidural spinal sarcoma has not been reported. Herein, we describe a T5–T6 epidural tumor in a 15-year-old girl in which many neoplastic cells had moderate and focally abundant cytoplasm, including plasmacytoid or rhabdoid cells, rather than the more common Ewing-like morphology described in the majority of such tumors. The diagnosis was confirmed by fluorescent in situ hybridization after the tumor was found to be WT-1 positive, and comprehensive genomic profiling demonstrated breakpoints in exon 20 and exon 1 of the CIC and DUX4 genes, respectively. After treatment with local radiation and systemic chemotherapy, resected recurrent tumor demonstrated more pleomorphic neoplastic cells as well as intracytoplasmic eosinophilic globules and nuclear pseudoinclusions which may reflect therapy-related changes. Unfortunately, there was further progression of tumor including the development of intracranial lesions, and the patient succumbed to her tumor 22 months after the original resection.

Clinical, surgical, and molecular prognostic factors for survival after spinal sarcoma resection

OBJECTIVE The goal of this study was to investigate the local recurrence rate and long-term survival after resection of spinal sarcomas. METHODS A retrospective review of patients who underwent resection of primary or metastatic spinal sarcomas between 1997 and 2015 was performed. Tumors were classified according to the Enneking classification, and resection was categorized as Enneking appropriate (EA) if the specimen margins matched the Enneking recommendation, and as Enneking inappropriate (EI) if they did not match the recommendation. The primary outcome measure for all tumors was overall survival; local recurrence was also an outcome measure for primary sarcomas. The association between clinical, surgical, and molecular (tumor biomarker) factors and outcomes was also investigated. RESULTS A total of 60 patients with spinal sarcoma were included in this study (28 men and 32 women; median age 38 years). There were 52 primary (86.7%) and 8 metastatic sarcomas (13.3%). Thirty-nine tumors (65.0%) were classified as high-grade, and resection was considered EA in 61.7% of all cases (n = 37). The local recurrence rate was 10 of 52 (19.2%) for primary sarcomas; 36.8% for EI resection and 9.1% for EA resection (p = 0.010). Twenty-eight patients (46.7%) died during the follow-up period, and median survival was 26 months. Overall median survival was longer for patients with EA resection (undefined) compared with EI resection (13 months, p < 0.001). After multivariate analysis, EA resection significantly decreased the hazard of local recurrence (HR 0.24, 95% CI 0.06–0.93; p = 0.039). Age 40 years or older (HR 4.23, 95% CI 1.73–10.31; p = 0.002), previous radiation (HR 3.44, 95% CI 1.37–8.63; p = 0.008), and high-grade sarcomas (HR 3.17, 95% CI 1.09–9.23; p = 0.034) were associated with a significantly increased hazard of death, whereas EA resection was associated with a significantly decreased hazard of death (HR 0.22, 95% CI 0.09–0.52; p = 0.001). CONCLUSIONS The findings in the present study suggest that EA resection may be the strongest independent prognostic factor for improved survival in patients with spinal sarcoma. Additionally, patients who underwent EA resection had lower local recurrence rates. Patients 40 years or older, those with a history of previous radiation, and those with high-grade tumors had an increased hazard of mortality in this study.

Stereotactic body radiotherapy for metastatic spinal sarcoma: a detailed patterns-of-failure study

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 (R2 = 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.