Alveolar Rhabdomyosarcoma (RMA) are characterised by chromosomal translocations fusing the PAX3 or PAX7 gene with FKHR in ~85%. Previous studies have suggested that PAX3/7-FKHR fusion types are related to prognosis. In order to prove these findings we performed a retrospective analysis of the PAX-FKHR fusion status and its relation to outcome in patients treated in the CWS trials.

Between 1986 and 2004, out of 446 RMA patients treated in four consecutive CWS trials (CWS-86, -91, -96 or -2002-P), tumor samples from 121 patients with adequate quality for analysis of PAX-FKHR fusion status by RT-nested PCR were available. Survival analysis depending on clinical risk factors and fusion status was performed using the Kaplan-Meier Method, the log rank test and the Cox regression model.

There were no major differences in distribution of known risk factors in the analysed cohort of 121 patients compared to all patients enrolled in the CWS trials. PAX-FKHR fusions were detected in 83%: 72 PAX3-, 29 PAX7-FKHR fusions. Patients with PAX3-FKHR positive tumors more often showed a pattern of adverse clinical risk factors (age > 10 years, primary metastases, lymph node involvement) than the PAX7-FKHR positive group. The 5-year event free survival rate of patients with initially metastatic tumors positive for either of the two fusion transcripts was significantly lower compared with the fusion transcript negative cohort and the non-analysed RMA patients. There was no significant outcome difference between patients with PAX3-FKHR and PAX7-FKHR positive tumors in uni- and multivariate analysis.

In the present analysis, which is to our knowledge the largest reported so far, PAX-FKHR fusion type was no significant predictor for prognosis, thus not supporting results of previous studies.

Liposarcoma (LPS) is among the most common soft tissue sarcoma (STS) in adults, accounting for > 10% of all STS. In children and adolescents, however, LPS are a rarity. Limited data about best treatment of pediatric LPS are derived from the scarce single-centre reports encompassing no more than a dozen patients.

Between 10/1980-6/2008, 18 of > 3,500 patients < 19 years with sufficient clinical data registered with CWS in Germany and Poland had a first diagnosis of LPS confirmed by reference pathologic review.

Median age was 14 years, median follow-up for survivors as of 2/2009 seven years. Sixteen patients had localized, two metastatic LPS at diagnosis. Lymphnodes were affected in a single case. The most frequent primary site were the limbs (n=11), the remaining seven were trunk tumours (abdomen n=4, thorax n=3). 10/18 primary tumours were > 5cm. Thirteen LPS were completely resected at best surgery, and microscopically residual disease remained in two more tumours. Six individuals received radiation with a median dose of 45Gy, including one of the two R1-resected patients. Nine patients received multiagent chemotherapy (only two of them since 1996 onwards). Response to induction treatment could be assessed in three of these nine individuals, but tumour volume regression occured in a single case only. Four patients died of disease, among them two of the three patients who did not achieve a CR with primary treatment. Two relapses (one combined, one metastatic), both involving the lungs, occurred one years after diagnosis and these patients were not salvaged. Actuarial 5-year EFS and OS survival rates were 69±23 and 81±20%, respectively.

LPS account for < 0.1% of childhood STS. The golden standard of treatment and key to cure is complete surgical excision. The role of radiation and/or chemotherapy remains unclear, but both modalities do not appear to be indicated in completely resected, localized tumours.

Tumour volume reduction (i.e. response), assessed following induction chemotherapy, has been identified as a prognostic factor for localized embryonal rhabdomyosarcoma (RME) in the CWS studies. In combination with other risk factors, it has been used to stratify secondary local and systemic treatment. It is however unclear whether the poor outcome of non-responders is due to insufficient local and/or systemic post-induction treatment.

We analyzed post-induction therapy of RME-patients < 21 years with unresected localized tumours (IRS-III) and poor response (NR, i.e. < 33% tumour volume reduction) treated 1980–2005 in five consecutive CWS-trials. The NR were reviewed and subclassified (Objective Response (OR; i.e.< 33%–0%) vs. Stable Disease/Progression (PD; i.e. no reduction)).

From 758 IRS-III RME-patients, 59 were NR (n=34 OR, n=25 PD). Induction for NR included dactinomycin, vincristine, alkylators ± anthracyclines in all patients. There were no significant differences in comparison of the control group and NR with regard to age, size, TN-classification, apart from site (p=0.04), and no differences regarding these parameters between OR and PD. Twenty-four NR received continued induction chemotherapy, n=32 other combinations, and n=3 no further chemotherapy following response assessment. Four patients were treated with additional high-dose chemotherapy. Fourty-two NR were irradiated with a median dose of 48Gy (control group: 45Gy). In 20 NR, the tumours were completely resected. As of 9/2008, with a median follow-up of 4.5 years (range: 0.9–12.1) for NR survivors, 34 NR are alive in CR. Reasons for the 25 deaths were: local/combined failure (n=21), systemic failure (n=1), and other reasons (n= 3). 5-yrs-OS was 71±4% for the control group, 78±15% for OR, but only 43±15% for PD (p< 0.01).

Response is an important surrogate marker of outcome, but per se associated with a poor prognosis only in tumours without any volume regression to induction chemotherapy. Ineffective local control drives mortality in these patients.

Objective: providing the rarity of malignant and intermediate vascular tumours (MVTs, IVTs) in children little is known about their clinical course, optimal treatment and variables predicting survival.

Material and methods: 32 children with MIVTs (14 angiosarcomas-AS, 5 epithelioid haemangioendotheliomas-EHE and 13 IVTs), registered in Polish and German Paediatric Soft Tissue Sarcomas (STS) Study Groups, treated with CWS-81, −86, −91 and −96 protocols.

Results: AS presented with advanced disease (84%), deep-seated T2 invasive tumours (71%), > 5cm in diameter (64%). Primary excision (PE) was incomplete in all and response to CHT/RTX disappointing. Nine/14 children entered CR; however all relapsed and, except one, died of disease. EHE and IVTs presented mainly in local stages (66,7%) and tumours > 5cm (72%). Complete PE was feasible in 30% and response to CHT/IFN poor in half. 16 patients entered CR, but six relapsed and, except one, died of disease.

In multivariate analysis male gender, AS histology, tumour size > 5cm, T2 invasiveness and lack of CR after Ist line therapy were independent predictors of poorer 5-year-OS, while AS histology and T2 invasiveness – of inferior 5-year-EFS. Radicality of PE was an independent prognostic factor for survival in univariate but not multivariate analysis.

Conclusions:

Current WHO classification has placed EHE in MVTs, however it may behave similarly rather to IVTs than AS.