1. INTRODUCTION
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and comprises two major histologic subtypes: alveolar RMS (ARMS) and embryonal RMS (ERMS) [1-3].
The prognosis of RMS has improved considerably over time due to numerous clinical trials conducted by collaborative groups working in North America: Intergroup Rhabdomyosarcoma Study Group (IRS) and Children’s Oncology Group (COG), and in Europe: International Society of Paediatric Oncology-Malignant Mesenchymal Tumour Group (SIOP-MMT), Italian Soft Tissue Sarcoma Committee-STSC, Gesellschaft Cooperative Soft Tissue Sarcoma Study Group-CWS and more recently, EpSSG (European paediatric Soft tissue sarcoma Study Group). Despite this successful history, the improvement in the prognosis of patients with RMS has not been uniform. While the probability of cure in pediatric patients with localized disease is over 70%, the prognosis of those with distant metastatic disease remains poor [4-8], and the presence of disseminated disease at diagnosis continues to be the most powerful prognostic factor in this neoplasm.
For patients with localized RMS, clinical and tumor characteristics are used to classify RMS in different risk categories and to determine treatment intensity. These characteristics include histology, tumor invasiveness, tumor location, nodal involvement, tumor size and patient age [9-11] and they constitute the basis for the risk stratification system used in North America by COG and in Europe by EpSSG. Patients with ARMS and regional lymph node involvement represent approximately 5-10% of all cases of RMS in children and adolescents. Previous experience suggested that these patients represent a group with particularly poor prognosis [9].
In the EpSSG RMS2005 study, we stratified these patients into a very high risk (VHR) category and treated them with an intensified regimen of chemotherapy that included doxorubicin added to the standard schema of IVA (ifosfamide, vincristine, and dactinomycin) in the first 4 cycles, followed by 5 cycles of IVA and six cycles of intravenous vinorelbine and daily oral cyclophosphamide [12]. During the same period, COG conducted the ARST0531 study for intermediate risk RMS patients that included those with non-metastatic ARMS at any primary site without distant metastases; these patients were randomly assigned to receive the standard schema VAC (vincristine, dactinomycin, and cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan) for 42 weeks [13].
Herein we report the results of a combined analysis of patients with ARMS and regional nodal involvement enrolled in the aforementioned studies, and we compare these results to determine which therapy optimizes survival.