Daniel Orbach1, Bernadette Brennan2, Angela De Paoli3, Soledad Gallego4, Peter Mudry5, Nadine Francotte6, Max van Noesel7, Anna Kelsey8, Rita Alaggio9, Dominique Ranchère10, Gian Luca De Salvo3, Michela Casanova11, Christophe Bergeron12, Johannes H M Merks13, Meriel Jenney14, Michael C G Stevens15, Gianni Bisogno16, Andrea Ferrari11. 1. Department of Pediatric, Adolescent and Young Adult Oncology, Institut Curie, Paris, France. Electronic address: daniel.orbach@curie.fr. 2. Department of Pediatric Oncology, Royal Manchester Children's Hospital, Manchester, United Kingdom. 3. Clinical Trials and Biostatistics Unit, IRCCS Istituto Oncologico Veneto, Padova, Italy. 4. Paediatric Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 5. Department of Pediatric Oncology, University Children's Hospital, Brno, Czech Republic. 6. Department of Pediatrics, CHC-Clinique Esperance, Montegnée, Belgium. 7. Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands. 8. Department of Diagnostic Paediatric Histopathology, Royal Manchester Children's Hospital, Manchester, United Kingdom. 9. Pathology Department, Padova University, Padova, Italy. 10. Pathology Department, Institut d'Hematologie et d'Oncologie Pediatrique, Centre Léon Bérard, Lyon, France. 11. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. 12. Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique, Centre Léon Bérard, Lyon, France. 13. Department of Pediatric Oncology, Emma Children's Hospital-Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 14. Department of Pediatric Oncology, Children's Hospital for Wales, Heath Park, Cardiff, United Kingdom. 15. Department of Pediatric Oncology, Royal Hospital for Children, University of Bristol, United Kingdom. 16. Pediatric Hematology and Oncology Division, Padova University, Padova, Italy.
Abstract
BACKGROUND: Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. MATERIAL AND METHODS: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. RESULTS: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). CONCLUSIONS: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.
BACKGROUND:Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. MATERIAL AND METHODS: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. RESULTS: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). CONCLUSIONS: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.
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