Alveolar rhabdomyosarcoma with regional nodal involvement: results of a
combined analysis from two cooperative groups
Abstract
Background: Treatment of children and adolescents with alveolar
rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been
approached differently by North American and European cooperative
groups. In order to define the better therapeutic strategy, we analyzed
two studies conducted between 2005 and 2016 by the European paediatric
Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group
(COG). Methods: We retrospectively identified patients with ARMS N1
enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in
RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin,
doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in
ARST0531 it consisted on either VAC (vincristine, dactinomycin,
cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan).
Local treatment was similar in both protocols. Results: The analysis of
the clinical characteristics of 239 patients showed some differences
between study groups: in RMS2005, advanced IRS Group and large tumors
predominated. There were no differences in outcomes between the two
groups: 5-year event-free survival (EFS), 49% (95%CI=39-59) and 44%
(95%CI=30-58), and overall survival (OS), 51% (95%CI=41-61) and
53.6% (95%CI=40-68), in RMS2005 and ARST0531, respectively. In
RMS2005, EFS of patients with FOXO1-positive tumors was significantly
inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast,
in ARST0531, EFS of patients with FOXO1-positive tumors was 45%
compared with 43.8% for those FOXO1-negative. Conclusions: The outcome
of patients with ARMS N1 was similar using different schemas of
chemotherapy. However, patients with FOXO1 fusion-negative tumors
enrolled in RMS2005 showed a significantly better outcome, suggesting
that this subgroup may benefit from the EpSSG strategy which included
maintenance chemotherapy.