Biomedical subjects

J Dunst

Publications and source records attributed to J Dunst.

154 records · Page 9Linked to original sources

PubMedDate not supplied

[Results of treatment of primary exclusively pulmonary metastatic Ewing sarcoma. A retrospective analysis of 41 patients].

41 patients presenting with primary metastatic Ewing's sarcoma or malignant peripheral neuroectodermal tumor (PNET) with initial metastases restricted to the lungs and/or pleural space were analysed with respect to clinical manifestation and treatment results retrospectively. All patients were treated according to the protocols CESS 81 and CESS 86 of the German Society of Pediatric Oncology and Hematology (GPOH). The time since diagnosis ranges from 19 to 137 months, with a median of 72 months. Median relapse-free survival time was 21.8 months. 18 patients were female, 23 were male. The majority of primary tumors exceeded 100 ml of volume. Preferred sites were the pelvis with 16 cases, the limbs with 14 cases and the chest wall with 6 cases. The histological specification of the tumor was Ewing's sarcoma in 22 and PNET in 11 patients, in 8 cases no specific distinction was given. As to local therapy of the primary tumor, 12 patients underwent radiotherapy, 11 surgery, and 18 a combination of both. Patients were allocated to one of these three options on an individual basis. Cytostatic drug treatment was given according to the GPOH-CESS 81 and CESS 86 protocols. As calculated by means of the Kaplan-Meier analysis, relapse-free survival was 30% ten years after diagnosis. Surgery or pulmonary irradiation of 12-20 Gy was applied to lung metastases. 12 of 27 patients are in continuous complete remission following this therapeutic approach.

Adolescent↗

PubMedDate not supplied

[Ependymoma with cervical lymph node metastases].

The authors report a case of an ependymoma in which metastases in cervical lymph nodes appeared four and a half years after diagnosis and operation. The primary tumor, an ependymoma grade I (WHO) in the left occipital region, had been completely resected and irradiated. Beside metastases in the cervical lymph nodes, several recurrences in the primary region and multiple metastases to the spinal canal had occurred.

Brain Neoplasms↗

PubMedDate not supplied

[The German Society of Pediatric Oncology Cooperative Ewing Sarcoma Studies CESS 81/86: report after 6 1/2 years].

The GPO Cooperative Ewing's Sarcoma Study (CESS 81 with 10 months four-drug combination chemotherapy (vincristine, actinomycin D, cyclophosphamide, and adriamycin = VACA) and local control with surgery and/or radiation, following week 18, resulted in a Kaplan-Meier estimated disease-free survival of 51% after 6 1/2 years (51/93 patients disease-free). Tumor volume and histological response to primary chemotherapy were identified as most significant prognostic factors. As a consequence, the CESS 86 regimen was stratified according to risk of relapse. Standard risk patients (extremity tumors less than 100 ml tumor volume) were continued on VACA chemotherapy. In high risk patients (extremity tumors greater than 100 ml tumor volume, central tumors), cyclophosphamide in conventional dose (1200 mg/m2/course) was replaced by high doses of ifosfamide (6 g/m2/course) with mesna uroprotection (VAIA). Local control was obtained following week 9. Patients with radiation were randomised for conventional fractionation or accelerated split-course hyperfractionation. The study was piloted from February to December 1985: 27/37 patients were disease-free on October 1, 1987. The ongoing trial was started on January 1, 1986. On October 1, 1987. 63/66 patients were disease-free. In patients with large primaries, according to Kaplan-Meier life-table analysis, the disease-free survival was significantly better in patients receiving VAIA chemotherapy, compared to the previous VACA regimen. The toxicity of both combination chemotherapy regimens was comparable.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[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.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

[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.

Adult↗

PubMedDate not supplied

[Prognosis in Ewing sarcoma patients with initial pathological fractures of the primary tumor site].

In this retrospective analysis, data of 52 patients with Ewing's sarcoma or PNET with a pathological fracture in the area of the primary tumor were evaluated. All patients were treated according to the trials CESS 81, CESS 86 P, CESS 86, CESS 91 P and EICESS 92 of the German Society of Pediatric Oncology and Haematology (GPOH). At the date of evaluation (15. September 1994) all patients had completed treatment and had been under observation for at least one year following diagnosis. The median follow-up time was 28 months. 22 patients were female, 30 male. The median age was 12 years. 75% of primary tumors had a volume of > or = 100 ml. 30 patients presented with fractures in proximal, 12 in central and 10 in distal parts of the skeleton. 10 patients had primary metastases. The histological definition was Ewing's sarcoma (including atypical Ewing's sarcoma) in 43 patients, PNET in 8 and small-cell osteosarcoma in 1 patient. For local therapy the patients underwent surgery, definitive radiotherapy or a combination of both. The percentage of primary metastases in the group of the patients with pathological fractures is comparable to the whole reference group. The present analysis focuses on those patients with pathological fractures who had no metastases at diagnosis. The relapse-free survival of patients with a pathological fracture and no primary metastases is 58%, the overall survival 65%. These rates are similar to those of the reference group of protocol patients without pathological fractures at diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

[Local therapy of Ewing sarcoma: radiotherapy aspects].

In CESS 86, radiotherapy and surgery as local treatment modalities yielded the same survival rates. Irradiated patients developed more local recurrences as compared to surgically treated patients (14% versus 4%), but less systemic metastases (16% versus 28%). The local recurrence rate after definitive radiotherapy dropped from 50% in CESS 81 to 14% in CESS 86. This was probably caused by an earlier start of radiotherapy (in week 10 in CESS 86 as compared to week 19 in CESS 81) and the high quality of radiation therapy in CESS 86 due to central treatment planning (only 2% protocol violations). Patients with local recurrences showed no differences in the distribution of major prognostic parameters (tumor volume, response to chemotherapy) as compared to patients with local control of disease. As a consequence of these results the concept of early irradiation with subsequent "consolidant" surgery for high-risk patients has been established.

Adolescent↗

PubMedDate not supplied

Radiosensitization in sarcoma cell lines with a p53 missense mutation correlates with prevention of irradiation G2/M arrest but not with induction of apoptosis.

We analysed the effects of caffeine and taxol on the radiobiological behaviour of two human sarcoma cell lines (RD, SK-LMS-1) each with a p53 missense mutation. Treatment with 2 mM caffeine resulted in an inhibition of the irradiation induced G2/M arrest in both cell lines. This effect was coupled with a radiosensitization in cell line SK-LMS-1 after an irradiation with 6 Gy (enhancement factor of 5.0). However, the effect of radiosensitization was not correlated with an induction of apoptosis. Incubation with 20 nM taxol increased the irradiation induced apoptosis almost 3-fold in cell line SK-LMS-1, but not in cell line RD. However, taxol had no effect on the irradiation induced G2/M arrest or radiosensitivity in either cell line. The results support the hypothesis that the prevention of irradiation induced G2/M arrest but not the induction of apoptosis plays a critical role in determining radiosensitivity in sarcoma cell lines with p53 mutations.

Apoptosis↗

PubMedDate not supplied

G2/M checkpoint is p53-dependent and independent after irradiation in five human sarcoma cell lines.

To determine the role of p53 in G2/M arrest, G2/M transition and apoptosis, we investigated five human sarcoma cell lines with different p53 gene status in their response to X-rays. The p53 status of the cell lines was mutant (US 8-93, LMS 6-93 and RD), null (SAOS-2) and wildtype (A-204). Clonogenic survival of the cell lines varied as the survival fraction at 2 Gy (SF2) ranged from 0.28 to 0.79. Compared with the mutated p53 cell lines (SF2 with a range from 0.46 to 0.79) the clonogenic survival of the wildtype p53 (wt-p53) cell line A-204 (SF2 = 0.34) was lower. The p53 null cell line (SAOS-2) was also sensitive to X-rays (SF2 = 0.28). We detected, in all cell lines a similar behavior in their response to irradiation with G2/M arrest and apoptosis. However, the maximal rate of apoptosis with a range from 7.0 to 18.0% was rather small. The decrease of G2/M cells was coupled with an increased percentage of apoptotic cells. However, a different delay in G2/M did not result in a change of radiation sensitivity. Western analyses showed an increased P53 level only for the cell line A-204 (wt-p53) after irradiation. Our results point out that there is not always a simple relationship between p53 gene status and radiation sensitivity. We suggest, that wt-p53 plays an active role in G2/M arrest and in decreasing the number of G2/M cells as a response to apoptosis. Therefore, p53-dependent regulation in G2/M may be as important as p53-independent mechanisms.

Apoptosis↗

PubMedDate not supplied

Transfection with mdm2-antisense or wtp53 results in radiosensitization and an increased apoptosis of a soft tissue sarcoma cell line.

Soft tissue sarcomas (STS) are mostly resistant after radiation treatment and are characterized by a rather low rate of apoptosis. The aim of this study was to test, in the p53 mutant STS cell line US8-93, the effect of a combined treatment with DNA transfection--either with mdm2 antisense oligodesoxynucleotides (mdm2-AS) or with a wild-type p53-plasmid (wtp53)--and the effects of irradiation on radiosensitivity. Mdm2-sense oligodesoxynucleotides (mdm2-SE) and a GFP-plasmid (GFP) were applied as controls. In order to evaluate the treatment radiation sensitization (clonogenic survival), apoptotic cell death and P53/MDM2-protein expression were determined. A moderately increased radiation sensitization was observed when comparing clonogenic survival after 2 Gy irradiation between cells transfected either with the control mdm2-SE (48%) or with mdm-2 AS (30%). At the same irradiation dose, clonogenic survival of wtp53-plasmid transfected cells (32%) was about 2-fold less than in the cells transfected with the control GFP-plasmid (61%). This enhancement factor of radiation sensitization was increased by about 3-fold at 4 Gy irradiation. Furthermore, an increase in apoptotic cells was already detectable by up to 7.7% (mdm2-AS) in comparison to 3.1% (mdm2-SE control) 72 hours after transfection. In parallel, the percentage of apoptotic cells could be further elevated after subsequent irradiation with 12 Gy by up to 15% (mdm2-AS) compared to 5.7% (mdm2-SE control). A striking result was obtained with the combined treatment of a wtp53 and 12 Gy irradiation which produced in 25% and 38.9% of apoptotic cells 48 hours and 72 hours after transfection, respectively. We can therefore conclude that the sensitivity of radiation therapy is enhanced by DNA transfection with wtp53 or mdm-2 AS ODNs for the correction of the p53-mdm2 balance in STS in vitro.

Apoptosis↗