BACKGROUND The role of doxorubicin (Doxo) as part of multidrug regimens used to treat children with soft tissue sarcoma (STS) is controversial. To evaluate the feasibility of combining Doxo with the well established ifosfamide, vincristine, and actinomycin D (IVA) regimen, the Italian STS Committee performed a pilot study on a series of children with metastatic STS. METHODS Between July 2002 and February 2004, 29 evaluable patients were enrolled in this study; 19 patients had rhabdomyosarcoma, 5 patients had peripheral neuroectodermal tumor, and 5 patients had other types of STS. The IVA‐Doxo (IVADo) regimen included ifosfamide 3 g/m2 on Days 1 and 2, vincristine 1.5 mg/m2 on Day 1, actinomycin D 1.5 mg/m2 on Day 1, and Doxo 30 mg/m2 on Days 1 and 2. Three courses of IVADo were to be administered in the initial part of treatment and analyzed for toxicity and tumor response. RESULTS Overall, 92 cycles were delivered. Major regimen‐related toxicity was myelosuppression, with Grade 4 neutropenia in 67% of cycles and fever and neutropenia in 37% of cycles. Nonhematologic toxicity included Grade 3–4 mucositis (6.5% of cycles), constipation (9.7%), and peripheral neuropathy (6.5%). Other manifestations of major toxicity were venoocclusive disease and seizures, which occurred in one patient each. All but 1 patient with a malignant schwannoma showed some degree of tumor volume reduction; however, considering only complete and partial remissions, the response rate was 76% (± 7.9%). CONCLUSIONS The intensive IVADo regimen was effective against pediatric STS with acceptable toxicity. This combination will be investigated in high‐risk patients with rhabdomyosarcoma in a randomized trial launched by the European pediatric Soft tissue sarcoma Study Group. Cancer 2005. © 2005 American Cancer Society.

BACKGROUND.The purpose of the current study was to analyze the influence of the initial surgical approach (biopsy vs resection with macroscopic residual tumors) on the outcome of patients with localized Intergroup Rhabdomyosarcoma Study (IRS) Group III rhabdomyosarcoma (RMS) enrolled in the Italian studies between 1979 and 2003. METHODS.Among the 394 patients evaluated, 323 underwent biopsy, as recommended by the protocols, and 71 patients underwent surgical resection with macroscopic residual tumors (debulking operation [DO]), although this procedure was discouraged. All these patients were classified at the same risk group and received the same treatment. The different characteristics (patient age, tumor site, T classification and size, histology) and outcome in the 2 groups were considered.Supported in part by a grant from Fondazione ''Citt a della Speranza''.We thank Miss Gloria Tridello for statistical analysis, and the pediatric surgeons, pediatricians, and radiotherapists involved in the Soft Tissue Sarcoma cooperative studies, who collaborated by providing information regarding their patients:

Our study confirmed the unsatisfactory prognosis for pediatric patients with relapsing MPNST and pointed to a risk-adapted stratification model for the purposes of deciding second-line treatments. For the time being, an aggressive surgical approach seems to be the only effective salvage treatment and should be recommended. New therapeutic approaches are under evaluation with a view to improving current outcomes.

Better outcomes in this series were associated with the feasibility of conservative surgery due to the favorable location of the tumor, in particular in the common bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive surgery or liver transplant, which were linked to worse outcomes in our series.

The experience of the Italian STSC confirms that NPM-HN RMS has a favorable prognosis, which has improved over the years due to a better, multimodal treatment approach. RT has an important role, but different modalities such as proton therapy and brachytherapy should be explored in systematic ways in very young children.