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

ABSTRACT Background 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. Procedure 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. Results 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. Conclusions 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.