Birth characteristics and risk of Ewing sarcoma.

PURPOSE: The incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown. METHODS: We compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978-2015 and diagnosed in 1988-2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models. We also assessed whether Ewing sarcoma clustered within families. RESULTS: Compared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03-0.18), Asian (OR = 0.57, 95% CI 0.41-0.80), and Hispanic (OR = 0.73, 95% CI 0.62-0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00-1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles. CONCLUSIONS: This population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.

Sociodemographic Disparities in Presentation and Survival of Pediatric Bone Cancers.

Osteosarcoma (OST) and Ewing sarcoma (ES) are the most common pediatric bone cancers. Patients with metastatic disease at diagnosis have poorer outcomes compared with localized disease. Using the Surveillance, Epidemiology, and End Results registries, we identified children and adolescents diagnosed with OST or ES between 2004 and 2015. We examined whether demographic and socioeconomic disparities were associated with a higher likelihood of metastatic disease at diagnosis and poor survival outcomes. In OST, Hispanic patients and those living in areas of high language isolation were more likely to have metastatic disease at diagnosis. Regardless of metastatic status, OST patients with public insurance had increased odds of death compared to those with private insurance. Living in counties with lower education levels increased odds of death for adolescents with metastatic disease. In ES, non-White adolescents had higher odds of death compared with white patients. Adolescents with metastatic ES living in higher poverty areas had increased odds of death compared with those living in less impoverished areas. Disparities in both diagnostic and survival outcomes based on race, ethnicity, and socioeconomic factors exist in pediatric bone cancers, potentially due to barriers to care and treatment inequities.

Comparative international incidence of Ewing sarcoma 1988 to 2012.

Ewing sarcoma (ES) is the second most common primary bone tumor in children and adolescents. There are few known epidemiological or genetic risk factors for ES. Numerous reports describe incidence rates and trends within the United States, but international comparisons are sparse. We used the Cancer Incidence in Five Continents (CI5) data to estimate age standardized incidence rates (ASRs; cases per million) and 95% confidence intervals (95% CIs), male-to-female incidence rate ratios (IRRs; 95% CI), and the average annual percent change in incidence (AAPC; 95% CI) for ES by geographic region for children and adults aged 0 to 49 years. We also estimated the ASR for each country or country subpopulation among the 10- to 19-year-old age range; capturing the peak incidence of ES. In total, 15 874 ES cases ages 0 to 49 were reported in the CI5 series between 1988 and 2012. AAPC estimates varied by age group and geographic region. Most of the statistically significant AAPCs showed an increased incidence over time; the only statistically significant decreases in incidence were observed among 20- to 29-year-olds and 30- to 39-year-olds in Southern Asia at -1.93% and -1.67%. When categorized by predominant ancestry, we observed countries and subpopulations with predominately African, East Asian, and Southeast Asian ancestry had the lowest incidence rates, whereas Pacific Islanders and populations with predominantly European and North African/Middle Eastern ancestry had the highest. An excess incidence in males was observed in most regions. Our results highlight substantial variation in ES incidence across geographic populations, reflecting potential ancestral influence on disease risk.

Evaluating Age-related Disparity of Outcomes in Ewing Sarcoma Patients Treated at a Pediatric Academic Medical Center.

Adolescent and young adult (AYA) patients with Ewing sarcoma have inferior survival compared with pediatric patients even when treated with similar regimens. Investigation into specific explanations is lacking. A retrospective chart review of Ewing sarcoma patients at a single institution was performed, and 104 patients were identified, 45 were 15 to 39 years of age (AYA cohort) and 59 younger than 15 years (pediatric cohort). AYA patients demonstrated more metastatic disease (50% vs. 24%, P=0.009), peripheral tumor location (64% vs. 41%, P=0.025), percentage of male patients (76% vs. 51%; P=0.010), and tumor size ≥5 cm (93% vs. 70%, P=0.016) than pediatric patients. Five-year overall survival was 77.7% and 53.0% and event-free survival was 68.7% and 40.6% for pediatric versus AYA, respectively. Similar rates of toxicity and chemotherapeutic dose adjustments were demonstrated. In this cohort, increased AYA patient mortality appears to be related to disease characteristics rather than treatment-related differences.

A nomogram for predicting overall survival in patients with Ewing sarcoma: a SEER-based study.

BACKGROUND: Ewing sarcoma, the second most frequent bone tumor in children and adolescents, is often presented with localized disease or metastatic-related symptoms. In this study, we aim to construct and validate a nomogram for patients with Ewing sarcoma to predict the 3- and 5-year overall survival (OS) based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Demographic and clinic pathological characteristics of patients with Ewing sarcoma diagnosed between 2010 and 2015 were extracted from SEER database. Univariate and multivariate Cox analyses were carried out to identify the independent characteristics. The independent factors were further included into the construction of a nomogram. Finally, c-index and calibration curves were used to validate the nomogram. RESULTS: A total of 578 patients were enrolled into our analysis. The results of univariate Cox analysis showed that age, 7th AJCC stage, 7th AJCC T stage, 7th AJCC N stage, 7th AJCC M stage, metastatic status to lung, liver and bone were significant factors. Multivariate Cox analysis was performed and it confirmed age, N stage and bone metastasis as independent variables. Next, a nomogram was constructed using these independent variables in prediction to the 3- and 5-year OS. Furthermore, favorable results with c-indexes (0.757 in training set and 0.697 in validation set) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. CONCLUSIONS: The individualized nomogram demonstrated a good ability in prognostic prediction for patients with Ewing sarcoma.

Clinicopathologic features of undifferentiated round cell sarcomas of bone & soft tissues: An attempt to unravel the BCOR-CCNB3- & CIC-DUX4-positive sarcomas.

Background & objectives: Certain genetically defined undifferentiated round cell sarcomas, namely BCOR-CCNB3 and CIC-DUX4 positive, have been described. Here we present detailed clinicopathologic features and molecular results in such cases. Methods: Fifty one cases of undifferentiated round cell sarcomas, including 32 cases, tested for BCOR-CCNB3 and CIC-DUX4 fusions, by reverse transcription polymerase chain reaction technique and 44 tumours, for CCNB3 immunostaining, were analyzed. Results: Twenty seven (52.9%) tumours occurred in males and 24 (47%) in females; in soft tissues (38; 74.5%), commonly, trunk and extremities and bones (13; 25.4%), frequently, femur and tibia. Five of 32 (15.6%) tested cases were positive for BCOR-CCNB3 fusion and seven (21.8%) for CIC-DUX4 fusions. Histopathologically, CIC-DUX4-positive sarcomas comprised nodular aggregates of round to polygonal cells, containing hyperchromatic nuclei, prominent nucleoli and moderate cytoplasm, with focal myxoid stroma and variable necrosis, in certain cases. BCOR-CCNB3- positive sarcomas mostly comprised diffusely arranged, round to oval to short spindly cells with angulated nuclei, vesicular chromatin, inconspicuous nucleoli and interspersed vessels. Immunohistochemically, tumour cells were positive for MIC2 in 24 of 49 (48.9%) and CCNB3 in 12 of 44 (27.2%) cases. Four of five BCOR-CCNB3-positive sarcomas showed CCNB3 immunostaining and 6 of 7 CIC-DUX4-positive sarcomas displayed WT1 immunostaining. Most patients (27/37) (72.9%) underwent surgical resection and chemotherapy. Median overall survival was 12 months, and disease-free survival was seven months. Interpretation & conclusions: Undifferentiated round cell sarcomas are rare; mostly occur in soft tissues of extremities, with CIC-DUX4 positive, as these are relatively more frequent than BCOR-CCNB3 positive sarcomas. CCNB3 and WT1 are useful immunostains for triaging such cases for BCOR-CCNB3 and CIC-DUX4 fusion testing, respectively. Overall, these are relatively aggressive tumours, especially CIC-DUX4-positive sarcomas.

Treatment and survival of osteosarcoma and Ewing sarcoma of the skull: a SEER database analysis.

BACKGROUND: Common primary bone tumors include osteosarcomas (OSC) and Ewing sarcomas (EWS). The skull is a rare site, and literature about their treatment and survival is scarce. Using the Surveillance, Epidemiology, and End Results (SEER) database, this study aims to assess the treatment and survival of skull OSC and skull EWS, as well as predictors for survival. METHODS: Skull OSC and EWS cases were obtained from the SEER database. Patient and tumor characteristics, treatment modalities, and survival were extracted. Overall survival (OS) was assessed using multivariable Cox proportional hazard regression stratified by tumor histology. Kaplan-Meier curves were constructed for OS comparing OSC and EWS, as well as histological subtypes in OSC. RESULTS: A total of 321 skull OSC and 80 skull EWS patients were registered from 1973 to 2013. EWS was more common in younger patients (p < 0.001). Resection was the predominant treatment strategy (80.1%), frequently in combination with adjuvant radiotherapy (30.4%). The 5-year survival rate varied significantly between OSC and EWS (51.0% versus 68.5%, p = 0.02). Kaplan-Meier curves show that EWS had a significantly better survival compared to OSC. Comparing histological subtypes of skull OSC, chondroblastic OSC had the best OS, Paget OSC the worst. Older age, tumor advancement, no surgical treatment, and the use of radiotherapy were identified as independent predictors of decreased OS in skull OSC. CONCLUSION: Overall prognosis is better for EWS compared to OSC. Chondroblastic OSC have the best overall survival, while OSC associated with Paget's disease of the bone has the poorest overall survival.

Childhood cancer incidence and survival in Japan and England: A population-based study (1993-2010).

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5192 children with cancer (age 0-14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993-2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).

Management of uterine sarcomas and prognostic indicators: real world data from a single-institution.

BACKGROUND: Uterine sarcomas consist a heterogeneous group of mesenchymal gynecological malignancies with unclear therapeutic recommendations and unspecific but poor prognosis, since they usually metastasize and tend to recur very often, even in early stages. METHODS: We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression. RESULTS: Data were retrieved from 61 women with a median age of 53 (range: 27-78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS (P < 0.001) and worse DFS (P = 0.028). CONCLUSIONS: Mitotic count appears to be independent prognostic factor while further insights are needed to improve adjuvant and palliative treatment of uterine sarcomas.

Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

BACKGROUND: The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. OBJECTIVE: The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. DESIGN/METHOD: EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. RESULTS: The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. CONCLUSIONS: Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations.

Descriptive epidemiology and outcomes of bone sarcomas in adolescent and young adult patients in Japan.

BACKGROUND: There have been fewer improvements in the clinical outcomes of adolescent and young adult (AYA) patients with cancer than for children and older adults, possibly because fewer studies focus on patients in this age group. The aims of this study were (1) to determine survival rates of bone sarcoma among AYAs in Japan (for comparison with other age groups), and (2) to establish whether belonging to the AYA age group at diagnosis was correlated with poor cancer survival in Japan. METHODS: A total of 3457 patients diagnosed with bone sarcoma (1930 male and 1527 female) were identified from 63,931 records in the Bone and Soft Tissue Tumor (BSTT) registry, a nationwide Japanese database, from 2006 to 2013. The histologic subtypes of bone sarcoma were osteosarcoma, chondrosarcoma, and Ewing sarcoma. The primary endpoints for prognosis were the occurrence of tumor-related death. We compared the epidemiological features of AYAs with other age groups. The cancer survival rates were calculated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze the prognostic factors for cancer survival. RESULTS: The majority of AYA had osteosarcoma 631 (56.2%), while 198 (17.6%) had chondrosarcoma. The frequency of bone sarcoma occurrence was highest among AYA patients, who accounted for a marked proportion of patients with each type of sarcoma. With the exception of sarcoma type, AYA patients did not significantly differ from patients in other age groups for any of the investigated clinicopathological parameters. Cancer survival of AYA patients was significantly higher than in the elderly. Univariate and multivariate analyses revealed that AYA status was not a predictor of poor cancer survival. However, older age (≥65 years) was a predictor of poor cancer survival in patients with overall bone sarcoma, osteosarcoma, chondrosarcoma. CONCLUSION: This epidemiological study is the first to investigate AYA patients with bone sarcoma using the nationwide BSTT Registry. We found that cancer survival of AYA patients was significantly higher than that of the elderly. AYA status was not a predictor of poor cancer survival in Japan.

NCCN Guidelines Insights: Bone Cancer, Version 2.2017.

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.

Pediatric solid tumors in Africa: different biology?

PURPOSE OF REVIEW: To review the recent literature regarding biologic characteristics of pediatric solid tumors in African children. RECENT FINDINGS: Data regarding pediatric solid tumors in Africa, while increasing, remain sparse when considering the ethnic and geographic diversity of the continent. Recent work, especially regarding nephroblastoma in Kenya, has identified some biologic variability among local tribes but also when compared with North American tumors. In general, reports from across the continent reveal markedly poorer survival for pediatric patients with solid tumors when compared with high-resourced regions. SUMMARY: Multiple resource-related and infrastructure-related challenges contribute to poorer outcomes, and these require systematic, multidisciplinary, and structured solutions. Socioeconomic factors and limited access to care currently seem to drive the survival outcomes in children with solid cancers in Africa.

Bacteremia in nonneutropenic pediatric oncology patients with central venous catheters in the ED.

OBJECTIVE: To examine clinical characteristics associated with bacteremia in febrile nonneutropenic pediatric oncology patients with central venous catheters (CVCs) in the emergency department (ED). BACKGROUND: Fever is the primary reason pediatric oncology patients present to the ED. The literature states that 0.9% to 39% of febrile nonneutropenic oncology patients are bacteremic, yet few studies have investigated infectious risk factors in this population. METHODS: This was a retrospective cohort study in a pediatric ED, reviewing medical records from 2002 to 2014. Inclusion criteria were patients with cancer, temperature at least 38°C, presence of a CVC, absolute neutrophil count greater than 500 cells/µL, and age less than 22 years. Exclusion criteria were repeat ED visits within 72 hours, bloodwork results not reported by the laboratory, and patients without oncologic history documented at the study hospital. The primary outcome measure is a positive blood culture (+BC). Other variables include age, sex, CVC type, cancer diagnosis, absolute neutrophil count, vital signs, upper respiratory infection (URI) symptoms, and amount of intravenous (IV) normal saline (NS) administered in the ED. Data were analyzed using descriptive statistics and a multiple logistic regression model. RESULTS: A total of 1322 ED visits were sampled, with 534 enrolled, and 39 visits had +BC (7.3%). Variables associated with an increased risk of +BC included the following: absence of URI symptoms (odds ratio [OR], 2.30; 95% CI, 1.13-4.69), neuroblastoma (OR, 3.65; 95% CI, 1.47-9.09), "other" cancer diagnosis (OR, 4.56; 95% CI, 1.93-10.76), tunneled externalized CVC (OR, 5.04; 95% CI, 2.25-11.28), and receiving at least 20 mL/kg IV NS (OR, 2.34; 95% CI, 1.2-4.55). The results of a multiple logistic regression model also showed these variables to be associated with +BC. CONCLUSION: The absence of URI symptoms, presence of an externalized CVC, neuroblastoma or other cancer diagnosis, and receiving at least 20 mL/kg IV NS in the ED are associated with increased risk of bacteremia in nonneutropenic pediatric oncology patients with a CVC.

Pediatric bone tumors in Germany from 1987 to 2011: incidence rates, time trends and survival.

BACKGROUND: Malignant bone tumors are a rare group of childhood cancer. MATERIALS AND METHODS: This study describes incidence rates, survival probabilities, and time trends for 1831 children below 15 years of age with a bone tumor registered at the population-based German Childhood Cancer Registry between 1987 and 2011. RESULTS: Overall age-standardized annual incidence rate (ASR) was 5.5 per million. Osteosarcomas (ASR 2.8) and Ewing tumors (ASR 2.6) were the most frequent diagnostic groups. The incidence of bone tumors overall tended to increase slightly over time by 0.7% each year on average. Thirty-nine of the bone tumor cases reported were subsequent primaries and not included into the survival analysis. Survival probabilities remained largely constant. DISCUSSION: Possibly survival was largely constant because chemotherapy has not changed much over time. Overall, the results are similar to other results reported from Europe.

Marriage and fertility in long-term survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma.

PURPOSE: We investigated the marital status and the presence or absence of children in survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma and examined the influence of these factors on the quality of life (QOL) of these survivors. METHODS: Thirty-eight survivors of childhood and AYA high-grade sarcoma (18 males, 20 females) participated in a questionnaire survey on marital status and presence or absence of children, as well as on the health-related QOL (HR-QOL), using the Short Form 36 Health Survey. Diagnoses among these survivors were osteosarcoma (28 participants), Ewing's sarcoma (4 participants), synovial sarcoma (4 participants) and others (2 participants). RESULTS: Of the 18 males who participated in the survey, eight (44.4 %) were married, of whom five (62.5 %) had children. Fifteen (75.0 %) of the 20 females were married, of whom 14 (93.3 %) had children. The proportions of surviving male patients who were married and who had children, respectively, were lower than those of surviving female patients. The proportion of ifosfamide-treated men with children was significantly lower than that of non-ifosfamide-treated men (p = 0.018). With respect to the relationship between marital status and HR-QOL, the scores for the vitality and mental health domains of the SF-36 of survivors who were married were significantly higher than those of unmarried survivors. CONCLUSIONS: The results of our questionnaire survey reveal that among the male survivors of high-grade sarcoma, the proportions of those who were married and of those with children were lower than those of female survivors, suggesting that strategies providing support for marriage and child-rearing may be necessary for the male survivor group. In the married group, mental QOL was high.

Radiation for bone metastases in Ewing sarcoma and rhabdomyosarcoma.

BACKGROUND: The role, optimal dose, and efficacy of radiotherapy (RT) for the treatment of bone metastases in rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are unclear. PROCEDURE: All patients with ES or RMS who received RT for bone metastases with curative intent during frontline therapy at Memorial Sloan Kettering Cancer Center (MSKCC) between 1995 and 2013 were reviewed. Among the 30 patients (8 RMS and 22 ES), 49 bone metastases were irradiated. RESULTS: Median biologically effective dose (BED) was 42.4 Gy (range, 34.9-59.7) for RMS and 50.7 Gy (range, 31.3-65.8) for ES. Tumor recurrence occurred in six of 49 irradiated bone metastases. Cumulative incidence of local failure at a treated metastatic site was 6.6% at 1 year and 9.0% at 3 years. Dose, fractionation, and RT technique did not impact local control at an irradiated site. The presence of >5 bone metastases was associated with worse local control at an irradiated site (P = 0.07). The 3-year EFS was 33% in RMS and 16% in ES. CONCLUSIONS: RT appears to be an effective modality of local control for bone metastases in ES and RMS. Local control at sites of metastatic bone irradiation is similar to local control at the primary site after definitive RT. Doses in the biologic range prescribed for the definitive treatment of primary disease should be used for metastatic sites of disease.

Primary cutaneous and subcutaneous Ewing sarcoma.

BACKGROUND: Primary cutaneous/subcutaneous Ewing sarcoma (scEWS) is extremely rare. We describe clinical features, treatment, and outcome of this Ewing localization. PROCEDURE: Retrospective study (1996-2012) on 56 patients. RESULTS: Most primary scEWS occurred in late adolescent/young adult females (F/M = 1.9; median age 21.5 years), with primary tumor in the extremity/trunk (48.5%/39%). Only 35/56 samples had Real-Time-Polymerase-Chain-Reaction/Fluorescent-In-Situ-Hybridization analysis, 32/35 had EWS-translocation. Most of them exhibited known favorable prognostic factors: localized disease (54/56), initial tumor volume < 200 ml (51/53). Thirty and 25 patients received chemotherapy according to Euro-Ewing99 or a shorter/less intense chemotherapy regimen associated with milder toxicity. One patient had not received chemotherapy. Surgery was performed at diagnosis in 37 patients (18/37 marginal/intra-lesional resections) followed by secondary surgery in 8/37 (three remained marginal). Nineteen other patients had an initial biopsy followed by chemotherapy, 15/19 underwent late surgery (4/15 marginal/intra-lesional resections). Overall, 27/56 patients received radiotherapy. Median follow-up was six years (1-15). Two patients with metastatic disease progressed at metastatic sites. Four patients with localized disease experienced progression/relapse (local n = 3, metastatic n = 1). Survival was excellent: 5y-OS and 5y-EFS were 93.8% (95%CI = 83-98%) and 88.5% (95%CI-= 77-95), respectively. CONCLUSIONS: Unplanned primary surgery should be avoided to try to minimize potential long term sequels due to secondary surgery or radiotherapy. Biopsy with molecular analysis and staging should be performed at diagnosis to inform treatment recommendations. Patients with metastases should be treated aggressively as for other metastatic EWS. Further studies are necessary to clarify whether a less intensive chemotherapy regimen could be safely used in localized disease to minimize acute/late toxicities.

[Ewing/PNET sarcoma family of tumors: towards a new paradigm?]. / Tumeurs de la famille Ewing/PNET : vers un nouveau paradigme ?

Ewing sarcoma family of tumors are mainly aggressive sarcomas of bone and also arising in soft tissues, which share common features: morphological features of basophilic round cell tumors, immunohistochemical features by expression of membrane CD99 protein, and genetic features with a translocation involving EWS and FLI1 in approximately 90% of cases. The discovery of this translocation has made it possible to unify in a single entity several lesions such as PNET, neuropitheliomas, Askin tumors, Ewing sarcomas… Since then, the extensive use of molecular/genetic methods has helped to identify an increasing number of molecular anomalies in unclassified round cell sarcomas, these sarcomas often harboring an atypical morphology and a less frequent CD99 positivity. Besides the rearrangements between the FET family of genes (EWS or FUS) and the wide ETS family of genes (FLI1, ERG, FEV, ETV…), new partner genes are gradually identified: cases with EWS-non ETS partners are extremely rare, but there are more important groups which are CIC-DUX4 and BCOR-CCNB3 translocation-positive sarcomas. These findings raise the problem of the nosological borders of the Ewing/PNET entity and its links with new "Ewing-like" groups of tumors, and raise the therapeutic problems. The forward-looking identification of new round cell sarcomas should enable studies of wider series to try to answer these questions.

[Combined therapy for children and adolescents with Ewing tumors (a 25-year experience)].

A total of 115 children (median age 10.5 years, range 2-17) with Ewing sarcoma family tumors (ESFT) received therapy in N.N. Petrov Institute of Oncology pediatric department from April 1985 till August 2013. These patients were divided into two groups depending on treatment tactics used: patients treated according to modified T9 protocol (n = 64) and patients treated according to EICESS-92 or Euro-Ewing 99 regimens (n = 51). Twenty four patients from the second group with adverse prognostic factors received high-dose chemotherapy with autologous stem cell transplantation. All patients received surgical treatment and/or irradiation for primary tumor local control. Five-year overall and disease-free survival was 39% and 37,9% in the first group. In the second group these values were significantly higher; 55% and 39.5%, accordingly (p = 0.03 and 0.25). All patients from the first group with primary metastatic ESFT died of disease progression, while in the second group OS and DFS reached 45.8% and 28.9%, accordingly. There was a statistically significant correlation between local relapse rate and irradiation dose biological equivalent (in TDF units). The local relapse cumulative rate was minimal (12,6%) in patients receiving 80 TDF.