title: Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma.
abstract: BACKGROUND
  Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes.
  
  
  METHODS
  Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥ 33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD).
  
  
  RESULTS
  Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001).
  
  
  CONCLUSIONS
  Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.
authors.affiliation: Paediatrics 5 (oncology, hematology, immunology), Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Dantonello
authors.forename: Monika
authors.initials: M
authors.lastname: Stark
authors.forename: Beate
authors.initials: B
authors.lastname: Timmermann
authors.forename: Jörg
authors.initials: J
authors.lastname: Fuchs
authors.forename: Barbara
authors.initials: B
authors.lastname: Selle
authors.forename: Christin
authors.initials: C
authors.lastname: Linderkamp
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.forename: Simone
authors.initials: S
authors.lastname: Feuchtgruber
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kube
authors.forename: Daniel
authors.initials: D
authors.lastname: Kosztyla
authors.forename: Bernarda
authors.initials: B
authors.lastname: Kazanowska
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladenstein
authors.forename: Felix
authors.initials: F
authors.lastname: Niggli
authors.forename: Gustaf
authors.initials: G
authors.lastname: Ljungman
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Bielack
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Ewa
authors.initials: E
authors.lastname: Koscielniak
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008207:Lymphatic Metastasis; D008297:Male; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
keywords: chemotherapy; embryonal rhabdomyosarcoma; response