Tumour Volume Reduction After Neoadjuvant Chemotherapy Impacts Outcome in Localised Embryonal Rhabdomyosarcoma

BackgroundResponse (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. ProcedurePatients 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). ResultsFifty-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 >5cm 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 764% for PAR, 79 +/- 14% for OR, but only 40 +/- 19% for SPD (P<0.001). ConclusionResponse to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control. Pediatr Blood Cancer 2015;62:16-23. (c) 2014 Wiley Periodicals, Inc.