Ewing's sarcoma of the ribs. A report from the Cooperative Ewing's Sarcoma Study

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.     

An Unusual Location of Extraosseous Ewing's Sarcoma

Ewing''s sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.Key words: Extraosseous Ewing''s sarcoma, Surgery, Chemotherapy, Multimodality care     

Ten-Year Follow-Up of a Patient with Metastatic Ewing's Sarcoma of the Pelvis

Patient: We report a 32-year-old women with a pelvic Ewing's sarcoma, who developed skeletal metastases within 20 months of diagnosis but following treatment remains disease-free at 10 years.Discussion: Ewing's sarcoma is a highly malignant tumour of bone. Presentation of a pelvic tumour over the age of 30 years is extremely rare and associated with a poor prognosis. Early recurrence is also associated with an extremely grave prognosis. In our patient there was little or no response to salvage chemotherapy, but, against the odds, remission was induced with pamidronate and palliative radiotherapy to some but not all sites of disease.This remission has been maintained without additional therapy for a further 5 years.     

Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86

The Cooperative Ewing's Sarcoma Studies, CESS 81 and CESS 86, are multiinstitutional trials with more than 80 participating institutions from Germany, the Netherlands, Austria, and Switzerland. Treatment consists of four courses of multiagent chemotherapy and local therapy. Local therapy was not randomized and was either radical surgery or resection plus postoperative irradiation or definitive radiation therapy. Here results according to local therapy have been analyzed for 93 protocol patients with localized Ewing's sarcoma (ES) who have been recruited in CESS 81 from January 1981 to February 1985 and 122 protocol patients recruited in CESS 86 from January 1986 to November 1989. The 3-year relapse-free survival (RFS) was 55% in CESS 81 and 62% in CESS 86. In CESS 81, the RFS was better for surgically treated than for irradiated patients. In this study there was an extremely high incidence of local failures (50%) after definitive irradiation. In CESS 86, however, the results after radiation therapy have been improved markedly (3-year RFS 67% after radiation therapy, 65% after surgery, and 62% after resection plus irradiation). Possible explanations for the improvement of radiotherapeutic results are as follows: selections for patients for radiation therapy, start of local therapy, and quality of radiation therapy. In CESS 86, irradiated patients were randomized to receive either conventionally fractionated irradiation with less intense chemotherapy or hyperfractionated irradiation with simultaneous chemotherapy. There was no difference in treatment results at the time of analysis. The authors conclude that selection of patients for local treatment modalities and quality of treatment performance has an impact on local and overall treatment results in ES.     

Prognostic factors in the treatment of Ewing's sarcoma. The Ewing's Sarcoma Study Group of the German Society of Paediatric Oncology CESS 81

From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (greater than 100 ml) and histopathologic response to initial chemotherapy were identified as major prognostic factors. Tumour site and type of local therapy were not significant if patients were categorised by tumour volume. In small lesions, surgery and radiotherapy were equally effective. In large lesions greater than 100 ml volume, a trend towards a better prognosis in surgically treated patients was observed. The results of CESS 81 emphasize the importance of permanent local control in Ewing's sarcoma even in the presence of systemic control by an effective multi-drug chemotherapy.     

Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group.

PURPOSE: To further elaborate on prognostic factors for Ewing's sarcoma of bone and to document improvements in relapse-free survival (RFS) and trends in local therapy over the study period (1977 to 1993). PATIENTS AND METHODS: A retrospective analysis was performed on a combined Gesellschaft Für P?diatrische Onkologie und H?matologie/Cooperative Ewing Sarcoma Study and United Kingdom Children's Cancer Study Group/Medical Research Council data set of 975 patients registered with the respective trial offices before the current collaborative European Intergroup Cooperative Ewing's Sarcoma Study trial. Both groups independently undertook studies with similar chemotherapy during the period. RESULTS: The key adverse prognostic factor is metastases at diagnosis (5-year RFS, 22% of patients with metastases at diagnosis v 55% of patients without metastases at diagnosis; P: <.0001). For the group with metastases, there was a trend for better survival for those with lung involvement compared with those with bone metastases or a combination of lung and bone metastases (P: <.0001). In the group of patients with no metastases at diagnosis, multivariate analysis demonstrated that site (axial v other), age-group (< 15 v > or = 15 years), and period of diagnosis had significant influence on RFS (all P: <.005). RFS was superior in the period after 1985 compared with the period before 1985 for nonmetastatic patients (45% v 60%, respectively; P: <.0001) and for metastatic patients (16% v 30%, respectively; P: =.016). Patients who relapsed within 2 years of diagnosis had a less favorable prognosis than patients who relapsed later (5-year survival after relapse, 4% v 23%, respectively; P: <. 0001). There were other changes over the period; in particular, radiotherapy or amputation were more common in the period before 1986, whereas endoprosthetic surgery was widely used in the later period. CONCLUSION: Survival and RFS improved over the period. Prognostic factors are metastases at diagnosis, primary site, and age.     

Ewing's Sarcoma Treatment in Scandinavia 1984-1990: Ten-year Results of the Scandinavian Sarcoma Group Protocol SSGIV

A report on the long-term follow up of the first cooperative Scandinavian Sarcoma Group study in Ewing's sarcoma of bone is presented. Fifty-two previously untreated patients entered the study between 1984 and 1990. Half of the tumors were located in the extremities and one quarter in the pelvis. The combined modality treatment consisted of 5 cycles of chemotherapy-including vincristine, methotrexate, doxorubicin, cyclophosphamide, bleomycin and dactinomycin. The first two cycles were followed by local resection or amputation in 35 patients and by radiotherapy alone in 17 patients. When surgery was not performed, was incomplete or yielded poor margins radiotherapy was given at a dose of 40-60 Gy. Local tumor relapses developed in 10 patients and in all but one patient were accompanied by metastatic disease. Five patients had metastasis at diagnosis and distant metastases developed after primary treatment in 27 patients after a median of 14 months. The median follow-up time for the 20 surviving patients is 10 years. At 5 years the tumor-related survival was 46% and the metastasis-free survival 43%. Late tumor relapses occurred in 4 patients, which reduced the 10-year tumor related survival to 41% and the metastasis-free survival to 38%. Histopathological tumour response correlated with survival with 5-year metastasis-free survival rates of 73% for the good responders and 35% for the poor responders.     

Presenting Symptoms and Treatment Delay in Osteosarcoma and Ewing's Sarcoma

Presenting symptoms and treatment delay were investigated in a series of 84 osteosarcomas and 40 Ewing's sarcomas. The treatment delay averaged 6.4 months for osteosarcomas and 9.6 months for Ewing's sarcomas. In both types the delay was relatively short in patients with constant pain and swelling. The prognosis was about the same whether the delay was short or long. This may be explained by the more severe nature of the presenting symptoms, in particular the constant pain and swelling, in aggressive tumours, a factor that also tends to mask other relevant prognostic parameters. It is concluded that the presenting symptoms and the treatment delay constitute important pathophysiologic factors which should be given more attention when analysing material from bone sarcomas.     

Differentiation of a Ewing's Sarcoma Cell Line towards Neural and Mesenchymal Cell Lineages

Two different pathways of differentiation were investigated in Ewing's sarcoma (ES) cell line, designated CADO-ES1, which has been established in our laboratory. This cell line was induced to differentiate and display a neural phenotype when treated with dibutyryl cyclic adenosine mono-phosphate or when cultured in serum-free medium (HB101). In these in vitro differentiation studies, two different phenotypes were demonstrated by light and electron microscopy. One phenotype, present in a major portion of the cell population, had long neurites in which microtubules were ultrastructurally demonstrated. The other one, present in a minor portion of the cell population, consisted of flat cells with many short processes. After differentiation in serum-free medium, tumorigenicity in nude mice or colony-forming efficiency in soft agar was strongly depressed. In the cells, N- myc , c- fos and c- src genes were not amplified, and although c- myc was amplified by up to 2-fold, depending on the culture conditions, this appeared to be unrelated to the changes of phenotype. When tumor cells were transplanted into nude mice, cartilage was formed. The cartilage was immunoreactive with the antibody for HLA-ABC, indicating that it was derived from the tumor cells, not from mouse tissue.     

Predictive Factors of Histological Response to Primary Chemotherapy in Ewing's Sarcoma

Clinicopathologic variables associated with a good histological response to primary chemotherapy in Ewing's sarcoma are identified. The histological response to preoperative chemotherapy in 243 cases of Ewing's sarcoma treated with neoadjuvant chemotherapy was analyzed in relation to different clinicopathological features (sex and age of the patients, tumor size, serum lactate dehydrogenase (LDH) levels, tumor site) and to the type and schedule of anticancer drugs delivered preoperatively according to three consecutive chemotherapy regimens. A higher rate of good responses was achieved with the use of ifosfamide and dactinomycin in addition to a conventional three-drug VAC regimen, suggesting that these drugs should be included from the beginning in neoadjuvant regimens for the treatment of Ewing's sarcoma. The analysis of event-free survival in 158 patients with a 4-year minimum follow-up confirmed that histological response to preoperative chemotherapy is a reliable predictor of outcome in Ewing's sarcoma.     

Five-year results in Ewing's sarcoma. The Scandinavian Sarcoma Group experience with the SSG IX protocol

The first Scandinavian protocol for Ewing's sarcoma, SSG IV, resulted in a local control rate of 74% and 5-year metastasis-free survival (MFS) of 43%. The second protocol, SSG IX, was started in order to improve upon these results. It featured four chemotherapy cycles, each consisting of two courses of VAI (vincristine, doxorubicin, ifosfamide) alternating with one course of PAI (cisplatin, doxorubicin, ifosfamide) at 3-weekly intervals. Total treatment time was 35 weeks. Local therapy was given at week 9. Inoperable or non-radically operated patients received hyperfractionated accelerated radiotherapy 1.5 Gy twice daily between chemotherapy courses to a total dose of 42-60 Gy, depending on surgical radicality and tumour localisation. 88 patients were included (58 male, 30 female, mean age 20 years; range 5-65 years). The tumour (73 M0 and 15 M1) was located centrally in 31 patients (35%), in the extremities in 34 (39%) and other sites in 23 (26%) of cases. The median size of tumour was 10 cm (range 2-23), soft tissue was invaded in 87%. Surgery was the local therapy for 60 (68%) patients: amputation in 8 and local excision in 52. The surgical margins were wide in 35 patients, marginal in 14 and intralesional in 3. Radiotherapy was given to 17 non-radically operated patients postoperatively and to 28 patients with inoperable tumours primarily. Histological responses were evaluated in 52 patients. 9 local recurrences were observed (10%). Distant metastases developed in 24 M0 patients (33%). The estimated 5-year MFS was 58% and overall survival (OS) 70% for M0 and 27% and 28% for M1 patients, respectively. Survival was favourable in patients with non-metastatic extremity tumours (90%) and tumours operated with wide margins (90%). Patients with a total necrosis after chemotherapy had a better OS than those with a partial or poor response (P=0.003). The toxicity (World Health Organisation) was acceptable (gastrointestinal G1-2; haematological G3-4). The SSG IX protocol gave better local control and survival rates than the SSG IV. Whether this is due to a higher therapeutic efficacy of the present protocol cannot be ascertained in this comparison with a historical control.     

Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.

PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.     

Nerve Growth Factor Plays a Divergent Role in Mediating Growth of Rat C6 Glioma Cells via Binding to the P75 Neurotrophin Receptor

Dysregulation of proliferation, differentiation and cell death play a major role in glial tumors, and there is evidence for regulatory mechanisms involving nerve growth factor (NGF) and its receptors in various CNS-derived tumor cell lines. The aim of our study was to observe the effect of exogenous recombinant NGF on C6 rat glioma growth, to characterize the role of endogenous NGF and the p75 neurotrophin receptor (p75) and to rule out whether p75 is necessary to mediate the effect of exogenous NGF. Recombinant exogenous NGF (1–100ng/ml) was applied under different serum conditions (0%, 1%, 5%) and knockdown of endogenous NGF and p75 was achieved by lipid-mediated antisense oligonucleotide treatment. In presence of serum, NGF had a positive whereas in absence of serum NGF produced a negative effect on C6 cell number. A knockdown of NGF or p75 increased cell numbers and enhanced BrdU incorporation. In p75-knocked down cells NGF did not enhance C6 glioma growth in presence of serum. We conclude that (1) exogenous recombinant NGF enhances C6 glioma growth under serum conditions but decreases cell number in absence of serum, that (2) the effect of exogenous NGF is mediated by p75 alone or by heterodimers containing p75 and that (3) either basal levels of endogenous NGF or basal levels of p75 receptor moderate C6 glioma growth and represent an autoregulatory potential of C6 glioma cells.     

Extraskeletal Ewing's Sarcoma Family of Tumours in Adults: Analysis of 57 Patients from a Single Institution

AimsExtraskeletal Ewing's sarcoma (EES) is a rare form of soft tissue sarcoma. The aim of the present study was to assess the outcome and the prognosis of adult patients presenting with EES treated with multi-modality therapy.Materials and methodsAll EES patients older than 15 years referred to our institution between January 1995 and December 2004 were reviewed. In total, 57 patients were identified. Their median age at diagnosis was 20 years (range 15–57).ResultsThe median size of the primary tumour was 11 cm (range 4–30 cm). Eighteen patients (31%) had metastatic disease at initial presentation. Wide surgical resection with negative margins was achieved in 23 cases (40%). Chemotherapy consisting of vincristine, adriamycin, ifosfamide, actinomycin D was given in 50 patients (88%). Radiotherapy was delivered in 37 patients (65%). Forty-one patients (72%) achieved complete remission and 16 (28%) progressed on therapy. Twenty-one patients (51%) relapsed. Local recurrence was encountered in 15 patients (36%). At a median follow-up of 46 months (range 6–143 months), the 5-year event-free survival and overall survival rates were 35 and 47%, respectively. Metastases at presentation, tumour size and surgical resection margin associated significantly with overall survival and event-free survival.ConclusionEES is an aggressive type of tumour with a high incidence of local recurrence and distant metastasis. This series showed that the outcome of adult EES is not unlike that of skeletal Ewing's sarcoma in terms of response to multi-modality treatment and the prognostic factors influencing treatment outcome. Adequate surgical resection, aggressive chemotherapy and adjuvant local radiation therapy, when indicated, constitute the optimal treatment to achieve the best results in this rare type of disease.     

Ewing's Sarcoma of the Head and Neck: A Retrospective Analysis of 24 Cases

Introduction and purpose. Primary Ewing's sarcoma arising from the bones of the head and neck region is extremely rare representing only 1- 4% of all Ewing's sarcoma cases. Previous reports suggest a better prognosis for that particular anatomic site. The purpose of this study was to analyze the clinico-epidemiologic characteristics of that rare clinical presentation, as well as its patterns of failure and prognosis following treatment.Materials and methods. This study included a retrospective review of the medical records of patients with the diagnosis of Ewing's sarcoma of the head and neck region treated at King Faisal Specialist Hospital and Research Center between 1975 and 1996.Results. Out of a total number of 24 cases analyzed, there were 17 males and 7 females with a ratio of 2.4:1. The median age at diagnosis was 16.5 years. A painful swelling was the most common clinical presentation.The maxilla was the most common site of presentation (9/24 cases). There were 3/24 cases who presented with metastatic disease at diagnosis.The majority of patients (16/24 cases) had a tumor size >10 cm. Most patients were treated with systemic chemotherapy plus localized irradiation following an initial biopsy.With a mean follow up of 3.4 years, the 5-year actual overall survival (OS) for the whole group was 53%, while the 5-year actuarial disease-free survival (DFS) was 30%. These figures were higher than those repor ted from our institution for young patients (相似文献   

Periosteal Ewing's Sarcoma: Report of Two New Cases and Review of the Literature

Background. The origin of Ewing''s sarcoma in a periosteal location is rare and not clearly documented. Other malignant bone tumors appear to have a somewhat better prognosis when confined between periosteum and bone. Is it the same for periosteal Ewing''s sarcoma? Methods. We describe two new cases and comprehensively review the literature consisting of 18 documented cases since the condition was first described in 1986 (S.M. Bator.Cancer 58:1781– 4). Results. Periosteal Ewing''s sarcoma differs from the other forms of Ewing''s sarcoma in terms of sex predominance, location of tumor, surgical stage at presentation and typical imaging studies. Eighteen out of the 20 patients were reported to be alive with no evidence of disease. Conclusions. It seems that the prognosis of this rare variant of Ewing''s sarcoma family of tumors might be better but the small number of cases precludes such a firm conclusion.