Supportive care for patients receiving CESS 81 chemotherapy for Ewing's sarcoma (author's transl)

To apply safely an aggressive chemotherapy regimen like CESS 81 requires intensive supportive care. Bleomycin is evaluated as part of the protocol for treatment of primary Ewing's sarcoma. Bleomycin might cause pulmonary fibrosis at higher cumulative doses as toxic effect directly to the lungs or most likely in addition by the formation of vascular microthrombi. A randomized study is designed to evaluate if pulmonary changes due to Bleomycin can be prevented using heparin. As severe bone marrow depression is anticipated the effect of lithium on the leucocyte nadir is also subject of a randomized study.     

Ewing's sarcoma: therapeutic experience (author's transl)

Since 1978, four patients with Ewing's sarcoma have been on a treatment-regimen based on the T-6 and T-2 Protocols according to Rosen. Preoperative chemotherapy produced tumor regression and thus enabled surgical resection in three cases. In the first case, radiation therapy was felt necessary because the surgical resection was performed after the first course of the T-6 Protocol and cells suspected to be malignant were found on histological examination of the resected tumor. The experience prompted us to refrain from using radiation therapy in the next two cases but to conduct the surgical resection after two cycles of T-6 Protocol. Here, histological examinations of the resected tumors showed no evidence of malignant cells. The fourth patient had a pathologic fracture in addition to the tumor. In this case, it was possible, by means of chemotherapy to heal the fracture and also to produce a regression of the tumor. Because of the radiation morbidity, we believe that it is a notable progress in the treatment of Ewing's sarcoma if radiation therapy can be avoided.     

Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases]

The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin).     

Radiotherapy in Ewing sarcoma: current results of the German Society of Pediatric Oncology studies CESS 81 and CESS 86

In CESS 81 the rate of local recurrences was high particularly in patients with radiation for local control. To improve the safety of local control, in the follow-up study CESS 86 chemotherapy for high risk patients was intensified. The combination of surgery with postoperative radiation was favoured when possible, local control was brought forward from week 18 to week 9, the doses of postoperative radiotherapy was increased from 36 to 46 Gy, and a radiation planning center was established for centralized planning of radiotherapy on the basis of tumor extension at diagnosis. In addition patients with radiation were randomized for conventional fractionation or a scheme of accelerated split course hyperfractionation with simultaneous chemotherapy. Preliminary results of 76 CESS 86 patients (incl. pilot phase), show a lowered rate of local recurrences compared to CESS 81: 6% local recurrences and 15% local recurrences in patients with radiation. With selection of patients with small and chemoresponsive tumors for radiotherapy no longer a disadvantage was seen for patients with radiotherapy concerning the safety of local control.     

Ewing's sarcoma in the occipital bone. Case report.

The head is a very rare primary site for Ewing's sarcoma which occurs most often in the long bones of the extremities and in the pelvis. This report describes an unusual case of Ewing's sarcoma arising from the occipital bone in a seven year old girl. The tumour compressed the venous sinuses, thus lowering the intracranial pressure resulted in temporary recovery which made the diagnosis difficult.     

Ewing's sarcoma in a child with human immunodeficiency virus (type 1) infection

A male child with vertically transmitted human immunodeficiency virus type 1 (HIV) infection developed a Ewing's sarcoma of the left fibula at 6.1 years of age. We report the antitumour chemotherapy given and the response of the tumour. Six months after tumour diagnosis the child died of probable HIV encephalopathy. This is the first reported case of Ewing's sarcoma in an HIV-infected child. © 1993 Wiley-Liss, Inc.     

缩短疗程化疗治疗儿童青少年局限期尤文氏肉瘤家族肿瘤的研究

目的局限型尤文氏肉瘤家族肿瘤(ESFT)合适的化疗疗程数尚未确定。本研究探讨8个疗程化疗联合局部治疗对儿童青少年局限期ESFT的疗效,并分析局部治疗方式对预后的影响。方法 2002年3月至2010年3月在中山大学肿瘤防治中心收治的46例儿童、青少年局限期ESFT入组。所有患者均接受CDV/IE交替方案8个疗程的化疗,每3周重复。CDV化疗包括环磷酰胺(1000 mg/m~2,d1)、长春新碱(1.5 mg/m~2,d1)、阿霉素(50 mg/m~2,d1);IE化疗包括异环磷酰胺(1.5 g/m~2,d1-5)、足叶乙甙(100 mg/m~2,d1-5)。局部治疗采用手术和(或)放疗。结果 46例患者中位年龄11岁(8个月~19岁)。男34例,女12例。肿瘤位于躯干17例,头颈15例,四肢12例,腹膜后2例。骨尤文氏肉瘤24例,骨外尤文氏肉瘤22例。35例局部晚期患者接受术前化疗,化疗客观有效率为88.6%。11例先行手术完整切除后化疗。局部治疗方式为手术加放疗19例,单纯手术13例和单纯放疗14例。中位随访64个月,全组5年无事件生存率(EFS)和总生存率(OS)分别为67.0%±7.0%和73.6%±6.5%。局部治疗采用手术加放疗、单纯手术和单纯放疗的患者的5年EFS分别为73.7%±10.1%、61.5%±13.5%和62.5%±13.5%(P>0.05)。局部早期和局部晚期患者5年EFS分别为79.5%±13.1%和62.9%±8.2%(P>0.05)。随访结束时,无心脏毒性或第二肿瘤发生。结论 8个疗程化疗联合有效的局部治疗对于局限期儿童青少年ESFT患者可获得较好的生存率。     

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     

Resection of a primarily inoperable Ewing's sarcoma of the pelvis (author's transl)

A primarily inoperable Ewing's sarcoma in a 10 yrs. old boy arising from the pelvis was totally resected following preoperative T-6 chemotherapy and radiotherapy. A new approach to the treatment of Ewing's sarcoma is discussed.     

Late effects of therapy in adult survivors of osteosarcoma and Ewing's sarcoma.

To study the late consequences of primary bone cancer, we interviewed 82 osteosarcoma and 29 Ewing's sarcoma survivors regarding their health, fertility and offspring, employment, annual income, and activities of daily living. All subjects had been diagnosed before age 20 (mean age, 14.6 years), had survived at least 5 years from diagnosis, and were at least 21 years of age. On average, they were 32.5 years of age at interview. As controls, 151 siblings were interviewed. During the follow-up period, eight survivors had died, and eight survivors had been diagnosed with a second malignancy (7.2%; P = .002). No other health condition distinguished survivors from controls. Although the survivors were more likely than controls to have some difficulty climbing stairs and to have had employment disability, employment status and annual income at follow-up were similar. Deficits in marriage and fertility were not significant. Adult survivors of primary bone tumors diagnosed during childhood or adolescence are at high risk for second malignancies and premature death, making continued medical follow-up of utmost importance. Despite the physical impairment following limb amputation for many, the majority of outcomes we measured did not differ from controls, suggesting few adverse psychosocial outcomes in this group of cancer survivors.     

VM-26 and dimethyl triazeno imidazole carboxamide in Ewing's sarcoma

Twenty-seven patients with biopsy proven Ewing's sarcoma were randomised to receive one of two adjuvant chemotherapy regimens for two years. Group A were given monthly courses of vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (DIC); Group B received monthly courses of VM-26, adriamycin and DIC. Chemotherapy was commenced after biopsy confirmation of disease. The primary tumour was treated with irradiation to 3,000-5,000 rad and by resection in three patients. With a median follow-up of 26 months, 52% of patients are disease free. Ten patients died, seven from recurrent disease and three from complications of treatment. There was a significant difference in disease free survival rate of patients with long bone lesions (11/12) compared with patients with flat bone lesions (6/15). The disease free survival rate of Groups A and B was similar. Our results suggest that in combination chemotherapy for Ewing's sarcoma, vincristine and VM-26 have similar anti-tumour activity.     

Coincidental occurrence of actinomycosis and Ewing's sarcoma in a child

Pulmonary consolidation, rarefaction of adjacent ribs and pleural effusion, a triad frequently considered characteristic of actinomycosis, seemed in the present case to support this serologically entertained diagnosis. However, the subsequent course of disease disclosed the most uncommon association of actinomycosis and metastatic Ewing's sarcoma of the lung. The possibility of combined occurrence of an opportunistic infection by actinomyces and malignancy, calls for open biopsy in cases not responding to penicillin treatment or with an unexpected evolution of the clinical manifestations.     

VM-26 and dimethyl triazeno imidazole carboxamide in Ewing's sarcoma

ABSTRACT. Twenty-seven patients with biopsy proven Ewing's sarcoma were randomised to receive one of two adjuvant chemotherapy regimens for two years. Group A were given monthly courses of vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (DIC); Group B received monthly courses of VM-26, adriamcyin and DIC. Chemotherapy was commenced after biopsy confirmation of disease. The primary tumour was treatedd with irradiation to 3,000–5,000 rad and by resection in three patients. With a median follow-up of 26 months, 52% of patients are disease free. Ten patients died, seven from recurrent disease and three from complications of treatment. There was a significant difference in disease free survival rate of patients with long bone lesions (11/12) compared with patients with flat bone lesions (6/15). The disease free survival rate of Groups A and B was similar. Our results suggest that in combination chemotherapy for Ewing's sarcoma, vincristine and VM-26 have similar anti-tumour activity.     

Bone scintigraphy in nonsurgically treated Ewing's sarcoma at diagnosis and follow-up: Prognostic information of the primary tumor site

In order to detect skeletal metastases in patients with Ewing's sarcoma, bone scanning is commonly used. However, little information is available about the scintigraphic aspects of the primary Ewing's sarcoma during non-surgical treatment and follow-up. We studied retrospectively the significance of bone scintigraphic findings at the primary tumor site of 58 patients with a Ewing's sarcoma. These patients had chemotherapy and radiotherapy. At presentation 53/58 patients showed an increased tracer uptake at the primary tumor site while 5 patients with a pelvic or sacral bone localization had a normal scan. Bone scans made during treatment and more than 2 years thereafter in the 32 eligible patients demonstrated three patterns. In 16 patients the hot spot disappeared and no local tumor recurrence was encountered. In the other 16 patients the high uptake at the primary tumor site either persisted or diminished first to a normal uptake after a median period of 18 months (range 12-36 months) and returned again to a high uptake within 6-12 months. In these patients local Ewing's sarcoma was still present in 13, while in the other 3 cases a benign disorder (fracture, ectopic bone formation) was the underlying cause. These findings suggest that in non-surgically treated Ewing's sarcoma persisting increased tracer uptake or its recurrence is highly suspicious for the presence of Ewing's sarcoma, while bone scans becoming negative and remaining so for more than 12 months suggest the absence of local tumor. © 1994 Wiley-Liss, Inc.     

EICESS 92 (European Intergroup Cooperative Ewing's Sarcoma Study)-- preliminary results]

BACKGROUND: Ewing tumor patients' outcome is 50% to 60% with current treatment strategies. Questions concerning toxicity and secondary malignancies are of increasing importance. PATIENTS AND METHODS: 631 patients were registered with the German EICESS study center of the European Intergroup Cooperative Ewing's Sarcoma Study, 369 patients were randomized. Treatment apart from local therapy consisted of 14 courses of Vincristine, Actinomycin D, Cyclophosphamide or Ifosfamide, Adriamycin (Doxorubicin), with or without Etoposide. First results concerning event-free survival (EFS), toxicity, and the rate of secondary malignancies three years after diagnosis are presented. RESULTS: Three year EFS was 0.66 for patients with localized tumors, 0.43 for patients with primary pulmonary/pleural metastases, and 0.29 for patients with other metastases, respectively. Large tumor volume or pelvic site, especially if inoperable, were adverse prognostic factors. Both histological and MRT-defined response were positively correlated to outcome. Up to 67% of patients experienced WHO grade IV toxicity, mostly related to bone marrow depression. The treatment related mortality was 1% (6/631). Until 15.02.1999, six of 687 patients have suffered secondary malignancies, two of six after (additional) myeloablative therapy. CONCLUSIONS: EICESS 92 treatment is toxic, but manageable and compares favorably to international results. New strategies must be sought for certain risk groups of patients.