R. Miao

Extraskeletal osteosarcoma: A large series treated at a single institution:

Purpose: This study is to present a large cohort of extraskeletal osteosarcoma (ESOS) and evaluate prognostic factors and treatment options. Methods: Medical records were reviewed retrospectively for 41 patients with extraskeletal osteosarcoma that was diagnosed by pathology, and treated at our institution between 1960 and 2016. Kaplan-Meier analysis and Cox proportional hazards regression were used to identify variables that affect survival outcomes. Results: 41 patients were identified from 952 osteosarcomas. 32 patients had non-metastatic disease. Prognostic factors were identified by univariate analysis and multi-variate analysis. Surgery (p<0.001), and surgery type (p<0.001) both were shown to significantly affect overall survival (OS). Chemotherapy and radiation therapy (RT) did not show any significant effect on OS, local recurrence, or progression free survival as a whole. However for patients who had incomplete resection with residual tumor RT improved OS (p=0.03). The survival curve for ESOS follows more closely that of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Conclusions: ESOS is a very rare tumor. Attempt to achieve wide resection is the treatment of choice. However for patients who are not able to achieve complete resection, RT may improve OS. The behavior of ESOS more closely follows that of NRSTS than osteosarcoma of the bone.

Clinicopathologic characteristics of poorly differentiated chordoma

Chordoma is a rare malignant tumor of bone with high morbidity and mortality. Recently, aggressive pediatric poorly differentiated chordoma with SMARCB1 loss has been described. This study summarizes the clinicopathologic features of poorly differentiated chordoma with SMARCB1 loss in the largest series to date. A search of records between 1990–2017 at MGH identified 19 patients with poorly differentiated chordoma. Immunohistochemical stains were evaluated. Kaplan–Meier survival statistics and log-rank (Mantel Cox) tests compared survival with other subtypes. The patients (nu2009=u200919) were diagnosed at a median age of 11 years (range: 1–29). Tumors arose in the skull base and clivus (nu2009=u200910/19; 53%); cervical spine (nu2009=u20096/19; 32%); and sacrum or coccyx (nu2009=u20093/19; 16%). The clinical stage of these patients (AJCC 7e) was stage 2A (nu2009=u20097/16; 44%); stage 2B (nu2009=u20096/16; 38%); stage 4A (nu2009=u20091/16; 6%); and stage 4B (nu2009=u20092/16; 13%). The tumors were composed of sheets of epithelioid cells with nuclear pleomorphism, abundant eosinophilic cytoplasm, and increased mitoses. Tumors were positive for cytokeratin (nu2009=u200918/18; 100%) and brachyury (nu2009=u200918/18; 100%). Patients were treated with a combination of excision, radiation therapy, and chemotherapy. No difference in overall survival, progression free survival, local control time, and metastasis free survival was identified between poorly differentiated chordoma of the skull base and of the spine. Compared to other chordoma subtypes, poorly differentiated chordoma has a significantly decreased mean overall survival after stratification by site (pu2009=u20090.037). Pediatric poorly differentiated chordoma has a distinct clinical and immunohistochemical profile, with characteristic SMARCB1 loss and decreased survival compared to conventional/chondroid chordoma. Recognition of this subtype is important because these malignancies should be treated aggressively with multimodality therapy.

Characteristics and predictors for secondary leukemia and myelodysplastic syndrome in Ewing and osteosarcoma survivors

PURPOSEnLong-term survivors of Ewing sarcoma (ES) and osteosarcoma may be at risk for therapy-related acute leukemia or myelodysplastic syndrome (t-AL/MDS).nnnMETHODS AND MATERIALSnWe retrospectively reviewed the clinicopathologic characteristics of 1071 patients with osteosarcoma (nxa0=xa0757) and ES (nxa0=xa0314) who were treated between 1985 and 2014. Multivariable competing risk analysis was used to analyze predictors of t-AL/MDS, including a radiation dose (≥55.8xa0Gy vs <55.8xa0Gy)xa0×xa0disease site (pelvis/spine vs other) interaction term. A supplemental nested case-control study was conducted to assess the association between cumulative chemotherapy dose and t-AL/MDS.nnnRESULTSnThe median follow-up for surviving patients was 97xa0months (range, 0.03-380). Twenty patients developed t-AL/MDS, all of whom received chemotherapy and 15 of whom were treated with radiation therapy. Radiation therapy to ≥55.8xa0Gy was associated with development of t-AL/MDS (adjusted hazard ratio, 2.89; 95% confidence interval [CI], 1.23-6.80; Pxa0=xa0.015), and there was a significant radiation dosexa0×xa0disease site interaction term (adjusted hazard ratio, 6.70; 95% CI, 2.71-16.53; Pinteractionxa0<xa0.001). The 5-year cumulative incidence of t-AL/MDS in patients receiving ≥55.8xa0Gy radiation therapy to the pelvis or spine was 5.0% (95% CI,xa00.9-14.9) for osteosarcoma and 10.7% for ES (95% CI, 3.3-23.2). In our nested case-control study, cumulative doses of ifosfamide and etoposide were associated with development of t-AL/MDS.nnnCONCLUSIONSnPatients with osteosarcoma and ES receiving ≥55.8xa0Gy of radiation therapy to the pelvis or spine appear to be at increased risk for t-AL/MDS. Treatment with high cumulative doses of chemotherapy may further augment this risk.