Soledad Gallego1, Yueh-Yun Chi2, Gian Luca De Salvo3, Minjie Li4, Johannes H M Merks5, David A Rodeberg6, Sheila Terwisscha van Scheltinga5, Leo Mascarenhas2, Daniel Orbach7, Meriel Jenney8, Lynn Million9, Veronique Minard-Colin10, Suzanne Wolden11, Ilaria Zanetti12, David M Parham2, Henry Mandeville13, Rajkumar Venkatramani14, Gianni Bisogno12, Douglas S Hawkins15. 1. University Hospital Vall d'Hebron, Barcelona, Spain. 2. Children's Hospital Los Angeles, University of Southern California, Los Angeles, California. 3. Clinical Trials and Biostatistics Unit, Veneto Oncologic Institute IOV-IRCCS, Padua, Italy. 4. University of Florida, Gainesville, Florida. 5. Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands. 6. East Carolina University, Greenville, North Carolina. 7. SIREDO Oncology Center, Institut Curie, PSL University, Paris, France. 8. Children Hospital for Wales Cardiff and Vale University Health Board, Cardiff, UK. 9. Stanford University School of Medicine, Stanford, California. 10. Gustave Roussy, University Paris-Saclay, Villejuif, France. 11. Memorial Sloan Kettering Cancer Center, New York, New York. 12. Padova University Hospital, Padua, Italy. 13. The Royal Marsden NHS Foundation Trust, Sutton, UK. 14. Texas Children's Hospital, Baylor College of Medicine, Houston, Texas. 15. Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
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 a 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 ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). 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 Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [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 with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative. CONCLUSIONS: The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
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 a 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 ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). 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 Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [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 with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative. CONCLUSIONS: The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
Authors: Odile Oberlin; Annie Rey; José Sanchez de Toledo; Hélène Martelli; Meriel E M Jenney; Marcelo Scopinaro; Christophe Bergeron; Johannes H M Merks; Nathalie Bouvet; Caroline Ellershaw; Anna Kelsey; David Spooner; Michael C G Stevens Journal: J Clin Oncol Date: 2012-06-04 Impact factor: 44.544
Authors: Michael A Arnold; James R Anderson; Julie M Gastier-Foster; Frederic G Barr; Stephen X Skapek; Douglas S Hawkins; R Beverly Raney; David M Parham; Lisa A Teot; Erin R Rudzinski; David O Walterhouse Journal: Pediatr Blood Cancer Date: 2016-01-12 Impact factor: 3.167
Authors: Poul H B Sorensen; James C Lynch; Stephen J Qualman; Roberto Tirabosco; Jerian F Lim; Harold M Maurer; Julia A Bridge; William M Crist; Timothy J Triche; Frederic G Barr Journal: J Clin Oncol Date: 2002-06-01 Impact factor: 44.544
Authors: David A Rodeberg; Norbert Garcia-Henriquez; Elizabeth R Lyden; Elai Davicioni; David M Parham; Stephen X Skapek; Andrea A Hayes-Jordan; Sarah S Donaldson; Kenneth L Brown; Timothy J Triche; William H Meyer; Douglas S Hawkins Journal: J Clin Oncol Date: 2011-02-28 Impact factor: 44.544
Authors: Julia C Chisholm; Julien Marandet; Annie Rey; Marcelo Scopinaro; Jose Sánchez de Toledo; Johannes H M Merks; Anne O'Meara; Michael C G Stevens; Odile Oberlin Journal: J Clin Oncol Date: 2011-02-28 Impact factor: 44.544
Authors: F Flamant; C Rodary; A Rey; M T Praquin; D Sommelet; E Quintana; S Theobald; M Brunat-Mentigny; J Otten; P A Voûte; J L Habrand; H Martelli; A Barrett; M J Terrier-Lacombe; O Oberlin Journal: Eur J Cancer Date: 1998-06 Impact factor: 9.162
Authors: Daniel M Green; Vikki G Nolan; Pamela J Goodman; John A Whitton; DeoKumar Srivastava; Wendy M Leisenring; Joseph P Neglia; Charles A Sklar; Sue C Kaste; Melissa M Hudson; Lisa R Diller; Marilyn Stovall; Sarah S Donaldson; Leslie L Robison Journal: Pediatr Blood Cancer Date: 2013-08-12 Impact factor: 3.167
Authors: Aaron R Weiss; Elizabeth R Lyden; James R Anderson; Douglas S Hawkins; Sheri L Spunt; David O Walterhouse; Suzanne L Wolden; David M Parham; David A Rodeberg; Simon C Kao; Richard B Womer Journal: J Clin Oncol Date: 2013-08-12 Impact factor: 44.544