Salvage Therapy Efficacy is Modified by Risk Group at Diagnosis in Patients With Relapsed Rhabdomyosarcoma

Patients with relapsed rhabdomyosarcoma (RMS) are treated with varying approaches and have a poor overall survival (OS). We performed an observational comparison of salvage regimens exploring whether high-dose alkylator combinations were associated with longer OS.

We categorized 110 patients with relapsed RMS from five institutions into two groups, those treated with regimens including a high-dose alkylator (Group A) and those treated without a high-dose alkylator (Group B). We compared OS between the two, adjusting for risk group at diagnosis and institution using Kaplan-Meier and Cox proportional hazards analyses.

Median follow-up in the 32 survivors was 4 years (range: 1.0-16.7 years) with a 28% (95% CI: 19%-37%) 4-year OS. Group A patients had a longer OS compared to Group B (4-year OS 41%, 95% CI: 27%-58%, vs. 14%, 95% CI: 4%-24%, respectively, p = 0.002). Adjustment for risk group at diagnosis abrogated the association (HR 1.4, 95% CI: 0.8-2.3, p = 0.16), while controlling for institution had no effect. In stratified analyses, patients with low risk at diagnosis had the highest effect size, suggesting a benefit after high-dose alkylator regimens (stratified HR 4.4, 95% CI: 0.96-20.3, p = 0.06, reference Group A) compared to intermediate- (stratified HR 1.6, 95% CI: 0.9-3.2, p = 0.13) or high- (stratified HR 0.9, 95% CI: 0.4-1.8, p = 0.7) risk patients.

Patients with relapsed RMS and low-risk group at diagnosis may benefit from high-dose alkylator chemotherapy, while the high-risk group has a dismal outcome regardless of treatment selection. It is inconclusive whether intermediate-risk patients may benefit from such therapy.