TY - JOUR
T1 - Fusion status in patients with lymph node-positive (N1) alveolar rhabdomyosarcoma is a powerful predictor of prognosis
T2 - Experience of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)
AU - on behalf of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)
AU - Gallego, Soledad
AU - Zanetti, Ilaria
AU - Orbach, Daniel
AU - Ranchère, Dominique
AU - Shipley, Janet
AU - Zin, Angelica
AU - Bergeron, Christophe
AU - de Salvo, Gian Luca
AU - Chisholm, Julia
AU - Ferrari, Andrea
AU - Jenney, Meriel
AU - Mandeville, Henry C.
AU - Rogers, Timothy N
AU - Merks, Johannes H.M.
AU - Mudry, Peter
AU - Glosli, Heidi
AU - Milano, Giuseppe Maria
AU - Ferman, Sima
AU - Bisogno, Gianni
PY - 2018/8/1
Y1 - 2018/8/1
N2 - BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) with lymph node involvement (N1 classification) accounts for up to 10% of all cases of RMS. The prognosis is poor, and is comparable to that of distant metastatic disease. In the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS2005 protocol, patients with a histologic diagnosis of aRMS/N1 received intensified chemotherapy with systematic locoregional treatment. METHODS: Patients with aRMS/N1 were enrolled prospectively after primary surgery/biopsy and fusion status was assessed in tumor samples. All patients received 9 cycles of induction chemotherapy and 6 months of maintenance therapy. Local treatment included radiotherapy to the primary site and lymph nodes with or without secondary surgical resection. RESULTS: A total of 103 patients were enrolled. The clinical characteristics of the patients were predominantly unfavorable: 90% had macroscopic residual disease after initial surgery/biopsy, 63% had locally invasive tumors, 77% had a tumor measuring >5 cm, and 81% had disease at unfavorable sites. Fusion genes involving forkhead box protein O1 (FOXO1) were detected in 56 of 84 patients. Events occurred in 52 patients: 43 developed disease recurrence, 7 had disease that was refractory to treatment, and 2 patients developed second neoplasms. On univariate analysis, unfavorable disease site, tumor invasiveness, Intergroup Rhabdomyosarcoma Study group III, and fusion-positive status correlated with worse prognosis. The 5-year event-free survival rate of patients with fusion-positive tumors was 43% compared with 74% in patients with fusion-negative tumors (P =.01). On multivariate analysis, fusion positivity and tumor invasiveness proved to be unfavorable prognostic markers. CONCLUSIONS: Fusion status and tumor invasiveness appear to have a strong impact on prognosis in patients with aRMS/N1. Fusion status will be used to stratify these patients in the next EpSSG RMS study, and treatment will be intensified in patients with fusion-positive tumors. Cancer 2018.
AB - BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) with lymph node involvement (N1 classification) accounts for up to 10% of all cases of RMS. The prognosis is poor, and is comparable to that of distant metastatic disease. In the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS2005 protocol, patients with a histologic diagnosis of aRMS/N1 received intensified chemotherapy with systematic locoregional treatment. METHODS: Patients with aRMS/N1 were enrolled prospectively after primary surgery/biopsy and fusion status was assessed in tumor samples. All patients received 9 cycles of induction chemotherapy and 6 months of maintenance therapy. Local treatment included radiotherapy to the primary site and lymph nodes with or without secondary surgical resection. RESULTS: A total of 103 patients were enrolled. The clinical characteristics of the patients were predominantly unfavorable: 90% had macroscopic residual disease after initial surgery/biopsy, 63% had locally invasive tumors, 77% had a tumor measuring >5 cm, and 81% had disease at unfavorable sites. Fusion genes involving forkhead box protein O1 (FOXO1) were detected in 56 of 84 patients. Events occurred in 52 patients: 43 developed disease recurrence, 7 had disease that was refractory to treatment, and 2 patients developed second neoplasms. On univariate analysis, unfavorable disease site, tumor invasiveness, Intergroup Rhabdomyosarcoma Study group III, and fusion-positive status correlated with worse prognosis. The 5-year event-free survival rate of patients with fusion-positive tumors was 43% compared with 74% in patients with fusion-negative tumors (P =.01). On multivariate analysis, fusion positivity and tumor invasiveness proved to be unfavorable prognostic markers. CONCLUSIONS: Fusion status and tumor invasiveness appear to have a strong impact on prognosis in patients with aRMS/N1. Fusion status will be used to stratify these patients in the next EpSSG RMS study, and treatment will be intensified in patients with fusion-positive tumors. Cancer 2018.
KW - alveolar rhabdomyosarcoma
KW - lymph node involvement
KW - paired box (PAX)-forkhead box protein O1 (FOXO1) fusion
KW - prognostic factors
KW - rhabdomyosarcoma
UR - http://www.scopus.com/inward/record.url?scp=85047619319&partnerID=8YFLogxK
U2 - 10.1002/cncr.31553
DO - 10.1002/cncr.31553
M3 - Article (Academic Journal)
C2 - 29797665
AN - SCOPUS:85047619319
VL - 124
SP - 3201
EP - 3209
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 15
ER -