Tumour volume reduction (i.e. response), assessed following induction chemotherapy, has been identified as a prognostic factor for localized embryonal rhabdomyosarcoma (RME) in the CWS studies. In combination with other risk factors, it has been used to stratify secondary local and systemic treatment. It is however unclear whether the poor outcome of non-responders is due to insufficient local and/or systemic post-induction treatment.

We analyzed post-induction therapy of RME-patients < 21 years with unresected localized tumours (IRS-III) and poor response (NR, i.e. < 33% tumour volume reduction) treated 1980–2005 in five consecutive CWS-trials. The NR were reviewed and subclassified (Objective Response (OR; i.e.< 33%–0%) vs. Stable Disease/Progression (PD; i.e. no reduction)).

From 758 IRS-III RME-patients, 59 were NR (n=34 OR, n=25 PD). Induction for NR included dactinomycin, vincristine, alkylators ± anthracyclines in all patients. There were no significant differences in comparison of the control group and NR with regard to age, size, TN-classification, apart from site (p=0.04), and no differences regarding these parameters between OR and PD. Twenty-four NR received continued induction chemotherapy, n=32 other combinations, and n=3 no further chemotherapy following response assessment. Four patients were treated with additional high-dose chemotherapy. Fourty-two NR were irradiated with a median dose of 48Gy (control group: 45Gy). In 20 NR, the tumours were completely resected. As of 9/2008, with a median follow-up of 4.5 years (range: 0.9–12.1) for NR survivors, 34 NR are alive in CR. Reasons for the 25 deaths were: local/combined failure (n=21), systemic failure (n=1), and other reasons (n= 3). 5-yrs-OS was 71±4% for the control group, 78±15% for OR, but only 43±15% for PD (p< 0.01).

Response is an important surrogate marker of outcome, but per se associated with a poor prognosis only in tumours without any volume regression to induction chemotherapy. Ineffective local control drives mortality in these patients.