TY - JOUR
T1 - Integrative clinical and biopathology analyses to understand the clinical heterogeneity of infantile rhabdomyosarcoma
T2 - A report from the French MMT committee
AU - Butel, Thibault
AU - Karanian, Marie
AU - Pierron, Gaelle
AU - Orbach, Daniel
AU - Ranchere, Dominique
AU - Cozic, Nathalie
AU - Galmiche, Louise
AU - Coulomb, Aurore
AU - Corradini, Nadège
AU - Lacour, Brigitte
AU - Proust, Stéphanie
AU - Guerin, Florent
AU - Boutroux, Hélène
AU - Rome, Angélique
AU - Mansuy, Ludovic
AU - Vérité, Cécile
AU - Defachelles, Anne Sophie
AU - Tirode, Franck
AU - Minard-Colin, Veronique
N1 - Publisher Copyright:
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Background: Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed. Methods: From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed. Results: Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2-, one NTRK-, and two (B)RAF-fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1- or PAX3-fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five-year event-free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47-82) and 52% (95%CI, 37-72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion-positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and “VGLL2-fusion” cluster, consisting of SRMS and ERMS. Conclusions: Biopathology findings from this study support the different prognosis of infantile RMS. New fusion-positive SRMS has a very good outcome which may allow more conservative treatment in the future.
AB - Background: Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative clinical, histological, and molecular analysis was performed. Methods: From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed. Results: Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2-, one NTRK-, and two (B)RAF-fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1- or PAX3-fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five-year event-free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47-82) and 52% (95%CI, 37-72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion-positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and “VGLL2-fusion” cluster, consisting of SRMS and ERMS. Conclusions: Biopathology findings from this study support the different prognosis of infantile RMS. New fusion-positive SRMS has a very good outcome which may allow more conservative treatment in the future.
KW - VGLL2
KW - infants
KW - newborns
KW - rhabdoid tumor
KW - rhabdomyosarcoma
KW - spindle cell rhabdomyosarcoma
UR - http://www.scopus.com/inward/record.url?scp=85083623128&partnerID=8YFLogxK
U2 - 10.1002/cam4.2713
DO - 10.1002/cam4.2713
M3 - Article
C2 - 32087612
AN - SCOPUS:85083623128
SN - 2045-7634
VL - 9
SP - 2698
EP - 2709
JO - Cancer Medicine
JF - Cancer Medicine
IS - 8
ER -