No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease.

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3-49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

Gallium Phosphide photoanode coated with TiO2 and CoOx for stable photoelectrochemical water oxidation.

Gallium Phosphide (GaP) has a band gap of 2.26 eV and a valance band edge that is more negative than the water oxidation level. Hence, it may be a promising material for photoelectrochemical water splitting. However, one thing GaP has in common with other III-V semiconductors is that it corrodes in photoelectrochemical reactions. Cobalt oxide (CoOx) is a chemically stable and highly active oxygen evolution reaction co-catalyst. In this study, we protected a GaP photoanode by using a 20 nm TiO2 as a protection layer and a 2 nm cobalt oxide co-catalyst layer, which were both deposited via atomic layer deposition (ALD). A GaP photoanode that was modified by CoOx exhibited much higher photocurrent, potential, and photon-to-current efficiency than a bare GaP photoanode under AM1.5G illumination. A photoanode that was coated with both TiO2 and CoOx layers was stable for over 24 h during constant reaction in 1 M NaOH (pH 13.7) solution under one sun illumination.

Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity.

Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.

Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing Sarcoma Study.

BACKGROUND: The Cooperative Ewing Sarcoma Study (CESS 86), conducted by the German Society of Pediatric Oncology and Hematology (GPOH), was planned on the basis of the results of the preceding CESS 81 study. The prognostic significance of tumor volume in localized Ewing sarcoma of bone was well documented in the CESS 81 trial. As a consequence, the treatment intensity was adapted to volume in the follow-up CESS 86 trial: the four-drug combination used in CESS 81 was amended for patients with large tumor volume (> or = 100 ml), where ifosfamide was substituted for cyclophosphamide. PROCEDURE: From January 1986 to June 1991, 177 protocol patients with localized Ewing sarcoma of bone were registered in CESS 86. The prognostic implication of tumor volume and several covariates was evaluated using Kaplan-Meier life table analysis and Cox's proportional hazard model. RESULTS: The estimated 5- and 8-year event-free survival (EFS) rates were both 59%. Age, gender, tumor site, and a tumor volume of 100 ml did not distinguish groups of patients with different prognosis. However, the prognosis of patients with tumors >200 ml (8-year EFS rate: 42%) was significantly inferior compared to patients with tumors both of 100 to 200 ml (70%) and of <100 ml (63%). In contrast to CESS 81, the histological response to chemotherapy was no longer a significant prognostic factor (EFS: 64% for good and 50% for poor responders, respectively). CONCLUSIONS: Despite risk-adapted treatment intensity, tumor volume retained its prognostic significance; the cut point, however, was shifted toward larger volumes.

Ewing's tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing's Sarcoma Studies patients.

PURPOSE: To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewing's tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS: Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewing's Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS: On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION: Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.

[Prognosis in Ewing sarcoma patients with initial pathological fractures of the primary tumor site]. / Prognose bei Ewingsarkompatienten mit initialen pathologischen Frakturen im Primärtumorbereich.

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)

[Local therapy of Ewing sarcoma: radiotherapy aspects]. / Lokaltherapie beim Ewing-Sarkom: Radiotherapeutische Aspekte.

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.