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.