Factors associated with tumor volume and primary metastases in Ewing tumors: Results from the (EI)CESS studies

Background: Tumor volumes of more than 100 ml and the presence of primary m etastases have been identified as determinants of poor prognosis in patient s with Ewing tumors. We sought to assess the prevalence of critical tumor s ize and primary metastases in a large national sample of patients at the ti me of first diagnosis and to identify factors that are associated with thei r occurrence. Patients: The present report is based on data of 945 German patients who we re enrolled into the (EI)CESS therapy studies between 1980 and 1997. It is assumed that registration of German patients with Ewing tumors under the ag e of 15 years was almost complete since around 1985. Diagnoses of primary t umors were ascertained exclusively by biopsies. Analyses were restricted to patients with Ewing tumors of bone due to the few occurrences in soft tiss ues. Methods: Tumor volume data as assessed by radiography, computed tomography or nuclear magnetic imaging were available for 821 patients. The diagnosis of primary metastases was based on thoracic computed tomography or on whole body bone scans in 936 patients. Suspicious lesions had to be confirmed by bone marrow biopsies. We explored how year of first diagnosis, age at firs t diagnosis, sex, histological subtype and site of the primary tumor relate d to tumor size and presence of metastases by univariate and multivariate s tatistical techniques. Results: Sixty-eight percent of the patients (n = 559) had a volume above 1 00 ml with smaller tumors being more common in childhood than in late adole scence and early adulthood. Extensive volumes were observed in almost 90% o f the tumors located in femur and pelvis while they were less common in oth er sites (P < 0.001). On average, 26% of all patients presented with clinic ally apparent primary metastases. The detection rate of metastases was mark edly higher in patients diagnosed after 1991 (P < 0.001). Primary metastase s were also significantly more common for tumors originating in the pelvis and for peripheral neuroectodermal tumors (PNET; P < 0.01). Tumors greater than 100 ml were positively associated with metastatic disease (P < 0.001). Multivariate analyses, which included simultaneously all univariate predic tors in a logistic regression model, indicated that most of the observed as sociations were essentially unconfounded. The adjusted odds ratios (OR) for the presence of tumor volumes greater than or equal to 100 ml were OR = 1. 5 per age rise of 10 years, and OR = 5.8 for pelvis and OR = 7.1 for femur as primary tumor site (all P < 0.001). The presence of metastases was signi ficantly associated with the year of diagnosis (OR = 1.9, after 1991 vs. be fore 1986), pelvis as site of the primary tumor (OR = 1.8), a PNET (OR = 1. 5), and tumor size greater than or equal to 100 ml (OR = 1.6). Conclusions: In conclusion, we find that the prevalence of established fact ors for an unfavorable prognosis is disturbingly high among patients diagno sed with Ewing tumors. Recent progress in imaging techniques seems to accou nt for much of the rise in the detection rate of metastases after 1991. We identify age and, in particular, pelvic and femoral site as the major deter minants of local tumor extension. Occurrence of primary metastases is indep endently related to tumor size, pelvic site, and PNET.