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.     

Primary chemotherapy and tumor resection in Ewing's sarcoma of the ribs. Report of the French society of paediatric oncology

Fifteen patients with primary Ewing's sarcoma of the ribs were entered into the same protocol: thirteen of them had localized disease while two had metastatic disease. The protocol consisted of (1) initial chemotherapy according to size of tumor: patients with a small tumor were given rwo courses of VAC (vincristine, actinomycine D. cyclophosphamide); patients with a large tumor, pleuraj effusion or metastatic disease were given alternating courses of VAC and VAd (vincristine. adriamycine) until maximum regression of the tumor: (2) local radiotherapy: (3) maintenance chemotherapy with VAC/VAd: (4) complete surgical excision at diagnosis in 4 patients, after primary chemotherapy in 6 patients, after chemotherapy and radiotherapy in 2 patients. Six of the 9 evaluable patients had tumor regression higher than 50% after primary chemotherapy. Fourteen patients achieved complete remission. Six patients with localized disease remained disease-free for a median duration of 50 months. These 6 patients were treated by chemotherapy, complete surgical excision and radiotherapy. The results suggest that aggressive treatment with chemotherapy and surgery improve disease-free survival in patients with Ewing's sarcoma of the ribs. Chemotherapy, Ewing's Sarcoma, Rib, Surgery     

Value of routine bone scans in patients with bone sarcomas before local treatment

During modern treatment of children with bone sarcomas, the children undergo multiple diagnostic imaging procedures, including bone scan (BS) with Tc99m. The aim of the BS is to establish the metastatic status of the skeletal system at the time of initial diagnosis and thereafter. We retrospectively reviewed 85 medical charts of patients with osteosarcoma (n = 40) and Ewing sarcoma (n = 45) who had been treated in our department between 01.01.1995 and 01.11.2009. Every patient underwent routine imaging studies including BS at the time of initial diagnosis and before local treatment. Median age of all patients was 15.5 years (range, 8 to 29). Fifteen patients had metastases at diagnosis. All patients were treated with neoadjuvant chemotherapy. No patient with localized disease developed metastatic disease to the skeletal system before local treatment; those with localized disease who developed metastases did so some time after completion of the treatment plan. As the probability of developing bone metastatic disease while receiving therapy is very low, routine BS in asymptomatic patients before local treatment may safely be omitted.     

Cutaneous Ewing sarcoma: report of 2 cases and literature review of presentation, treatment, and outcome of 76 other reported cases

Cutaneous Ewing sarcoma is a rare variant that has been poorly characterized and has no standard therapy. We report 2 patients with cutaneous Ewing sarcoma and review 76 other cases reported in the literature for demographics, presentation, treatment, and outcome. Only 2 patients presented with metastatic disease, and only 8 patients developed metastatic disease. Ninety-one percent of all patients are alive despite wide variations in treatment regimens. On the basis of this summary, treatment consisting of local control with surgery and/or radiation and abbreviated chemotherapy is proposed as a treatment option for this less aggressive Ewing sarcoma.     

Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience

Clear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.     

Treatment results and prognostic factors in Ewing sarcoma

Files of 133 children with Ewing sarcoma (median age 10 years) were reviewed. Frequent primary sites were extremities, trunk, pelvis, and cranium. Half of 43 patients with metastases had disease in the lungs. Ten-year overall and event-free survival rates were 31% and 19%, respectively. Five-year overall survival rates were 42% in localized and 15% in metastatic disease (p < .0001); 66% in cases with primary tumors < 8 cm and 29% in larger tumors (p = .013). VAC (vincristine, actinomycin D, and cyclophosphamide) regimens with anthracyclines resulted in better survival. Presence of distant metastases, large primary tumors, and pelvic localization were related to poor prognosis. Novel therapeutic approaches are needed to produce better results, especially in high-risk patients.     

HIGH-DOSE BUSULFAN AND MELPHALAN AS CONDITIONING REGIMEN FOR AUTOLOGOUS PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION IN HIGH-RISK EWING SARCOMA PATIENTS: A Long-Term Follow-Up Single-Center Study

The aim of this retrospective study was to analyze the outcome and identify risk factors associated to progression-free survival (PFS) in 47 children with high-risk Ewing sarcoma who underwent autologous peripheral blood stem cell (PBSC) transplantation in the authors’ institution between 1995 and 2009. The conditioning regimen used in all patients consisted of high dose of busulfan and melphalan. Median age was 13 years (range: 4–21 years). Forty-three percent of patients had metastases at diagnosis. The probability of transplant-related mortality (TRM) was 6% ± 3%. Recurrence/progressive disease was observed in 17 patients. The probability of recurrence/progression was 39% ± 7%. With a median follow-up of 92 months (range: 6–168 months), the PFS was 56% ± 4% for the whole group. In multivariate analysis, localized disease at diagnosis and obtaining complete remission (CR) by 3 months after transplantation were variables associated to better outcomes. The probability of PFS was 78% ± 8% and 27% ± 10% for patients with localized and metastatic disease at diagnosis, respectively (P = .0001). This retrospective study shows a high long-term survival using high dose of busulfan and melphalan as conditioning regimen in children with high-risk Ewing tumors. Patients with localized disease at diagnosis and those with good response to treatment before or after transplant would benefit most.     

Soft-tissue sarcomas of the diaphragm: a report from the Intergroup Rhabdomyosarcoma Study Group from 1972 to 1997

PURPOSE: To describe clinical details and outcome of children and adolescents with primary sarcomas of the diaphragm treated on Intergroup Rhabdomyosarcoma Studies (IRS) I through IV. PATIENTS AND METHODS: We reviewed the records of 15 patients with sarcoma of the diaphragm who were entered on IRS Group protocols between 1972 and 1997. Patient ages at diagnosis ranged from 0.5 to 20 years (median, 13 yrs), and 10 were girls. Patients had chest pain, dyspnea, and/or coughing, decreased breath sounds, and occasionally hepatomegaly. RESULTS: Localized, gross residual disease after initial surgery was present in 10 patients, and five had metastases at diagnosis (pleura, 3; pericardium, 1; lungs and bones, 1). Tumor subtypes were alveolar rhabdomyosarcoma (RMS) in five cases, embryonal RMS in three, undifferentiated sarcoma in three, extraosseous Ewing sarcoma in three, and unclassified sarcoma in one. Treatment consisted of radiation therapy to the primary tumor and metastases when feasible, and combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide with or without doxorubicin, ifosfamide, cisplatin, and etoposide. Ten patients achieved complete remission (67%), four obtained a partial remission, and one was improved. Five patients (33%) are continuously failure-free and alive at a median of 8.8 years from diagnosis (range, 1.1-15 yrs). However, the other 10 patients experienced relapse at 0.3 to 2 years from start of therapy (median, 1 yr). Sites of relapse were local in five, distant in three, and combined in two. Death after relapse occurred at 0.39 to 2.6 years (median, 1.6 yrs) from diagnosis. CONCLUSIONS: Sarcomas of the diaphragm are generally deemed unresectable at diagnosis and/or are metastatic. Most of them are not embryonal rhabdomyosarcomas. Treatment with more effective primary chemotherapy to shrink the tumor, followed-up by surgical resection and radiation therapy, should improve the prognosis for patients with sarcomas arising in the diaphragm, especially for the majority who have localized tumors.     

Superior vena cava syndrome associated with childhood malignancy: analysis of 24 cases

Twenty-four children with superior vena cava obstruction at initial presentation or associated with disease recurrence were treated at St. Jude Children's Research Hospital from 1973 to 1988. Of the 16 patients with superior vena cava syndrome at presentation, eight had non-Hodgkin's lymphoma, four had acute lymphoblastic leukemia, two had Hodgkin's disease, one had neuroblastoma, and one had a yolk sac tumor. Their clinical condition at presentation was often critical and required rapid treatment. In all cases, histopathologic diagnosis was obtained without complication by either bone marrow aspiration, lymph node biopsy, thoracentesis, or thoracotomy prior to the initiation of definitive therapy. Eight children had superior vena cava syndrome as a late complication during the course of their therapy. None had an antecedent history of superior vena cava obstruction. In contrast to the patients with superior vena cava obstruction at presentation, this group was composed predominantly of patients with recurrent solid tumors. Other causes included disseminated candidiasis and superior vena cava thrombosis, thus underscoring the importance of recognizing the etiology of superior vena cava syndrome to facilitate proper treatment.     

Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience.

BACKGROUND: Because the natural history of pediatric patients with metastatic nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) had not been well described, we retrospectively reviewed our single-institution experience with these tumors. PROCEDURE: We identified 26 patients with metastatic NRSTS who were treated at St. Jude Children's Research Hospital from December 1971 through July 1995. We evaluated the characteristics of each patient, including age, sex, primary site, stage, type of therapy received, and outcome. Sites of metastatic disease at diagnosis and relapse were noted. RESULTS: The median age of the 26 study patients at diagnosis was 14. 8 years; 54% of patients were male and 69% were white. The most common histologies were synovial sarcoma, alveolar soft-part sarcoma, and malignant fibrous histiocytoma. Most primary tumors (73% of cases) occurred in the trunk or extremities. Most patients presented with large (>5 cm), high-grade lesions. All 26 patients received chemotherapy, and 8 responded to an ifosfamide- or cyclophosphamide-doxorubicin-based regimen. Radiotherapy was administered to 15 patients, and 13 had a partial or complete resection of the primary tumor. Six patients underwent thoracotomy. The estimated 2-year survival for the cohort was 34.6% +/- 8.9%; the 2-year progression-free survival was 15.4% +/- 6.3%. The lung was the most common site of failure. CONCLUSIONS: Children with metastatic NRSTS have a poor outcome, which is similar to that in adults. More effective systemic chemotherapy is needed to facilitate complete surgical resection of primary and metastatic sites. Aggressive pulmonary metastatectomy can increase disease control.     

Imaging of pediatric bone tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%–5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.     

Local control of metastatic sites with radiation therapy in metastatic Ewing sarcoma and rhabdomyosarcoma

Approximately 20% of children with Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS) present with metastatic disease at initial diagnosis. Overall, the outcome is poor, with an event-free survival of < 20%. Local control at metastatic sites has not been previously reported. We reviewed control of metastatic sites in children with EWS and RMS that received curative intent radiation therapy to each metastatic site. In 13 children, at a median follow-up of 18 months, a single local failure was seen. Toxicity was minimal. Our data suggest that radiation therapy is effective and tolerable in children with metastatic EWS and RMS.     

Synovial sarcoma in young people: background, prognostic factors, and therapeutic questions

Synovial sarcoma represents 5% to 10% of all soft tissue sarcomas, with an estimated total of 800 new cases annually in the United States. The median age is 30 years; males and females are almost equally affected. About 70% of cases occur in patients more than 20 years old. Young people less than 20 years of age are mainly affected in the second decade of life. The majority of the tumors occur in para-articular structures in the extremities, and most of them are localized at diagnosis. A recent meta-analysis of 219 patients younger than 21 years old treated by the University of Texas M. D. Anderson Cancer Center's Division of Pediatrics, St. Jude Children's Research Hospital, the German Cooperative Group, and Istituto Nazionale dei Tumori, Milan, found that, as in older people, tumor size larger than 5 cm, residual local tumor or metastases at diagnosis, and progressive or recurrent disease all portended a poor outcome. There are currently no randomized studies of therapy for patients with synovial sarcoma, but such are needed to provide answers to the following questions: Is adjuvant chemotherapy useful in preventing recurrence in patients without visible residual disease after apparently complete surgical removal of localized tumor? Should local radiation therapy be given to all patients who have had complete removal of the primary tumor with clear margins at the time of diagnosis?     

Reactivation of TWIST1 contributes to Ewing sarcoma metastasis

1 Background

Ewing sarcoma is a cancer of bone and soft tissue. Despite aggressive treatment, survival remains poor, particularly in patients with metastatic disease. Failure to treat Ewing sarcoma is due to the lack of understanding of the molecular pathways that regulate metastasis. In addition, no molecular prognostic markers have been identified for Ewing sarcoma to risk stratify patients.

2 Procedure

Ewing sarcoma patients were divided into high or low Twist1 gene expression and survival curves were generated using the R2 microarray‐based Genomic Analysis platform ( http://r2.amc.nl ). Tumors from Ewing sarcoma patients were also evaluated for TWIST1 expression by immunohistochemistry. Ewing sarcoma xenografts were established to evaluate the role of TWIST1 in metastasis. The effects of Twist1 on migration and invasion were evaluated using migration and invasion assays in A673 and RDES cells.

3 Results

Twist1 expression was a negative prognostic marker for overall survival in a public Ewing sarcoma patient data set based on Twist1 mRNA levels and in patient tumor samples based on Twist1 immunohistochemistry. TWIST1 is detected in significantly higher percentage of patients with metastatic diseases than localized disease. Using Ewing sarcoma tumor xenografts in mice, we found that suppressing TWIST1 levels suppressed metastasis without affecting primary tumor development. Knockdown of Twist1 inhibited the migration and invasion capability, while overexpression of Twist1 promoted migration and invasion in Ewing sarcoma cells.

4 Conclusion

These results suggest that TWIST1 promotes metastasis in Ewing sarcoma and could be used as a prognostic marker for treatment stratification; however, further validation is required in a larger cohort of patients.     

Brain metastases in pediatric Ewing sarcoma and rhabdomyosarcoma: the St. Jude Children's Research Hospital experience.

PURPOSE: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS. PATIENTS AND METHODS: The clinical characteristics, therapy, and outcome of all patients treated at St. Jude Children's Research Hospital over a 36-year period who had ES or RMS with brain metastases were reviewed. RESULTS: Of 419 patients with RMS, 10 (2.4%) had brain metastases. Of 335 patients with ES, 11 (3.3%) had brain metastases. The median age of the 21 patients was 10.4 years (range, 0.4-18.0 years) at the time of primary diagnosis. All had clinical signs of central nervous system (CNS) involvement. Outcome was dismal: The median duration of survival after diagnosis of brain metastasis was 2.7 months. The estimated survival 1 year after detection of brain involvement was 23.8%+/-8.5% (mean +/- standard error). One patient, who underwent chemotherapy, surgical resection, and radiotherapy, at the time of this writing is a long-term survivor. CONCLUSIONS: Brain metastases are rare in children with ES and RMS, but carry a grave prognosis. Because most brain metastases are accompanied by signs of neurologic involvement, routine imaging studies of asymptomatic children are not necessary. Combined-modality treatment offers the best chance of long-term survival.     

Thromboembolism in children with sarcoma

BACKGROUND: Thromboembolism (TE) is a common complication and cause of death in adults with cancer. Cancer has been identified as a major risk factor in children with TE. However, the information regarding the epidemiology of TE in children with cancer, especially in association with childhood solid tumors, is scant. OBJECTIVE: To define the prevalence and epidemiology of TE in children with sarcoma. PROCEDURE: Hospital records of children 相似文献   

Papillary thyroid carcinoma: Demographics,treatment, and outcome in eleven pediatric patients treated at a single institution

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7–25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 11), parathyroid reimplantation (n = 1), ¹³¹I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0–22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.8 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients, although complications may require close follow-up in a multidisciplinary setting. Med. Pediatr. Oncol. 28:433–440, 1997. © 1997 Wiley-Liss, Inc.     

Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: a Southwest Oncology Group study.

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 15 to 20 mg/m2, given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.     

Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: A southwest oncology group study

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 1 5 to 20 mg/m², given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.     

Cardiac metastases of Ewing sarcoma detected by 18F-FDG PET/CT

Positron emission tomography (PET) is widely used in the diagnostic evaluation and staging of different malignant tumors. The role of PET/computed tomographic scan in detecting distant metastases in the workup of Ewing sarcoma in children or young adults is less well defined. We report a case of a boy affected by a metastatic Ewing sarcoma with cardiac asymptomatic metastasis detected by F-FDG PET/computed tomography.