Outcome of Ewing sarcoma in children and adolescents with Ewing sarcoma: a five-year survival from a single institution

Ewing sarcoma, together with neuroblastoma and central nervous system tumors, has got the lowest percentage of complete cure among all malignant diseases in children. From 1993 to 2003, 26 patients with Ewing sarcoma were treated in Pediatric Hematology and Oncology Department, Medical University in Lublin, Poland. In this study the character and time of the clinical symptoms to making the diagnosis, the abnormalities of laboratory tests, and the primary site of tumor were analyzed. The prognosis and results of treatment in children and adolescents were evaluated.     

Risk of recurrence and survival after relapse in patients with Ewing sarcoma

Background

The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.

Procedure

We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow‐up or death.

Results

Median follow‐up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2–24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five‐year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5‐year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five‐year OSr was 0.07 (SE = 0.01) in patients who relapsed 0–2 years after the diagnosis of primary disease, as compared to a 5‐year OSr of 0.29 (SE = 0.03) when relapse occurred later.

Conclusions

5‐year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse. Pediatr Blood Cancer 2011; 57: 549–553. © 2011 Wiley‐Liss, Inc.     

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents

Background

Reported overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented.

Procedure

Thirty‐one newly diagnosed ESFT patients were enrolled onto this phase II, single‐arm, non‐randomized protocol. Courses 1, 2 and 4 consisted of cyclophosphamide 4.2 g/m², doxorubicin 75 mg/m², and vincristine 2 mg/m² (CDV). Cycles 3 and 5 consisted of ifosfamide 9 g/m² and etoposide 500 mg/m² (IE). Course 5 ifosfamide was 14 g/m² if necrosis was <90%.

Results

Twenty‐four patients had loco‐regional disease and seven had metastases. The 4‐year event‐free survival (EFS) rate for patients with localized tumors is 83% and overall survival (OS) is 92%. The 3‐year EFS rate for patients with distant metastases is 28% and OS rate is 42%. EWS‐FLI1 fusion genes were detected in 17 cases (74%) and EWS‐ERG in six cases (26%). Type 1 EWS‐FLI1 variant was present in 6/7 metastatic patients and 3/16 loco‐regional cases (P = 0.001). None of the patients experienced tumor progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n = 3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow‐up of 4.3 years for surviving patients.

Conclusions

In this pilot study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non‐metastatic ESFT reducing the risk of secondary malignancies. Pediatr Blood Cancer 2011;57:69–75. © 2011 Wiley‐Liss, Inc.     

Extraskeletal Ewing sarcoma in children and adolescents: impact of narrow but negative surgical margin

Purpose

The aim of the study was to determine the impact of negative but close resection margins on local recurrence in children with extraskeletal Ewing sarcoma (EES).

Method

We reviewed records of 32 patients with EES treated between March 2005 and March 2013. All patients except one underwent surgical excision either upfront or after induction chemotherapy. Patients with viable tumor and negative surgical margins, which were categorized as less than or greater than 1 cm, were selected. Local control and survival analysis were performed for patients in both the groups.

Results

The 5-year event-free and overall survival rates of entire cohort is 68 and 77 %, respectively. Surgical margins were negative in 23/26 (90.3 %) patients. There were no local recurrences in any of the patients with margins of less than 1 cm. Only one patient with a margin greater than 1 cm had a local recurrence along with distant metastases. A tumor-free margin of more than 1 cm did not affect overall or event-free survival (p = NS).

Conclusion

Optimal local control is feasible in children with EES regardless of the quantitative extent of negative margins. Achieving a three-dimensional tumor-free margin should be the goal of surgical resection.     

Fine needle aspiration cytology in the diagnosis and management of children and adolescents with Ewing sarcoma and peripheral primitive neuroectodermal tumor

PURPOSE: The utility of fine needle aspiration cytology (FNAC) in conjunction with immunocytochemistry in the diagnosis of Ewing sarcoma and peripheral primitive neuroectodermal tumor, the Ewing family of tumors (EFT), is retrospectively described. PATIENTS AND METHODS: During a 10-year period 24 children and adolescents were diagnosed at Karolinska Hospital to have EFT of bone or soft tissue using FNAC. Criteria for diagnosis was based on cytomorphology combined with immunocytochemistry. The median age was 14.1 years (range 0.7-20.2). FNAC was performed within a median time of 1 day after referral. RESULTS: Forty aspiration procedures were performed, 24 at primary work up in 23 patients and 16 at suspected relapses in 10 patients. A primary cytologic diagnosis of EFT was obtained in 22 of 23 cases. In nine cases with primary disease there was no histologic confirmation. Two tumors were on FNAC diagnosed as neuroblastoma versus EFT, and EFT, respectively. Histopathology on resected tumor tissue from these patients showed EFT and small cell osteosarcoma, respectively. Suspected relapse was found to be positive at five and negative at 11 occasions. Immunocytochemistry was positive for CD45 (LCA) in 0/12, for desmin in 2/21, for MIC2 in 15/15, for NB84 in 1/3, for NFP in 7/7, for NSE in 12/18, for S-100 in 4/11 and for vimentin in 18/19. CONCLUSIONS: The results show that FNAC together with immunocytochemistry is a rapid, physically atraumatic and accurate method in diagnosing both primary EFT of bone and soft tissue as well as relapses.     

Agreement of specific IgE and skin prick test in an unselected cohort of two-year-old children

The objective of this study was to evaluate the agreement between specific IgE (sIgE) and skin prick test (SPT), and the possible association between total IgE concentration and allergy-related disorders, when performed in an unselected cohort of 353 two-year olds. Median total IgE was within the reference value for two-year-old children regardless of the presence or absence of allergy-related disorders. 18.7% of the children had one or more positive reactions to SPT and/or sIgE in a panel of 12 allergens. Agreement between SPT and sIgE was variable, being best for peanut and poorest for milk. Conclusion: In young children total IgE is of limited value when evaluating allergy-related disorder. The lack of agreement among the positive tests of the sIgE and SPT for some allergens imply that these tests should not be used interchangeably, and both tests should probably be used complementarily when diagnosing atopic sensitization in small children.     

Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors

PURPOSE: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies. PATIENTS AND METHODS: The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment. RESULTS: Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group. CONCLUSION: Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.     

Mobilization of tumour cells during biopsy in an infant with Ewing sarcoma

Conclusion

The application of RTPCR to monito shedding of tumour cells during surgical intervention will nelp to evaluate if open biopsy potentially contributes to metastatic tumour cell spread.     

Outcome in 43 children presenting with metastatic Ewing sarcoma: The St. Jude Children's Research Hospital experience, 1962 to 1992

The purpose of this work was to review the St. Jude Children's Research Hospital experience of patients presenting with metastatic Ewing sarcoma over a 30-year period. Forty-three of 212 cases of Ewing sarcoma presented with metastases at diagnosis. These patients were analyzed to determine whether primary tumor site or size, metastatic site(s), or advances in therapy have had a positive impact on survival. The overall survival for our 43 patients was 35% (95% confidence intervals, 20% to 50%). Comparing patients treated prior to 1979 with those treated after 1979, the overall survival was significantly different (P = 0.0002). Comparing overall survival between pelvic and nonpelvic primaries (P = 0.24), among metastatic sites (P = 0.83), and between tumors measuring >8 cm in diameter to tumors measuring <8 cm in diameter (P = 0.12), no significant differences were observed. Approximately one-third of patients presenting with metastatic Ewing sarcoma may achieve long-term survival. Children with metastatic Ewing sarcoma may benefit from clinical trials which intensify the doses of doxorubicin, and the highly effective combination of ifosfamide/etoposide. © 1996 Wiley-Liss, Inc.     

Congenital Ewing sarcoma in retroperitoneum with multiple metastases

A 7-day-old Japanese female showed the absence of spontaneous movement in her both legs. MRI revealed tumors in the retroperitoneum invading into the spinal canal, the left cerebral hemisphere and the right eyeball. Histological examination of retroperitoneal tumor revealed the sheets of undifferentiated small round cells with hyperchromatic nuclei and scanty cytoplasm. EWS-FLI1 fusion gene was detected by RT-PCR, indicating Ewing sarcoma. She received chemo-radiotherapy and survived for 2 years and 10 months despite the multiple metastases at initial presentation.     

Hematometrocolpos in an adolescent female treated for pelvic Ewing sarcoma

Radiation therapy is often used to achieve local control of pelvic Ewing sarcoma in children. The effects of radiation on the female reproductive tract have been well documented in adults with gynecological malignancies, but the long-term consequences of pelvic radiation in pre-pubertal or adolescent girls are not as well described. We report a case of hematometrocolpos developing in an adolescent previously treated with chemotherapy and radiation therapy for pelvic Ewing sarcoma. We describe the clinical presentation, radiographic features, gross pathology, treatment strategies, outcome, as well as putative predisposing factors and preventative interventions.     

Outcome of hypospadias repair in toilet-trained children and adolescents

Purpose  

To review a leading causes and surgical outcome of hypospadias repair in toilet-trained children and adolescents in our department.     

尤文肉瘤的诊断和治疗进展

尤文肉瘤是儿童常见的恶性骨肿瘤,发病时临床表现无特异性,早期易出现漏诊.目前的治疗方案包括放疗、手术治疗、化疗以及靶向治疗,其中化疗的出现使局部肿瘤的生存率达到70％,但难治及复发患者的预后不良.靶向治疗可针对肿瘤细胞的特异性位点杀死肿瘤细胞,有望提高复发及难治性肿瘤患者的生存率.该文就尤文肉瘤的诊断及治疗作一综述.