# Children and Young People With First Relapse or Progression of Upfront Metastatic Rhabdomyosarcoma: An Analysis of Clinical Features and Outcomes From the INternational Soft Tissue saRcoma ConsorTium (INSTRuCT)

## TL;DR

This study analyzed survival outcomes for children and young adults with metastatic rhabdomyosarcoma after their first relapse or disease progression.

## Contribution

The study provides new insights into prognostic factors for survival following first relapse in metastatic rhabdomyosarcoma patients.

## Key findings

- Three-year overall survival after first event was only 8% in patients with metastatic rhabdomyosarcoma.
- Survivors had fewer adverse prognostic features at diagnosis and longer time to first event.
- Locoregional lymph node involvement and higher Oberlin scores were associated with worse outcomes.

## Abstract

We evaluated the survival rate/survivor characteristics following first progression/relapse of metastatic rhabdomyosarcoma (M1 RMS), using pooled European and US collaborative group data from the INternational Soft Tissue saRcoma ConsorTium (INSTRuCT).

Patients with first diagnosis of M1 RMS aged 0–40 years were identified within the INSTRuCT database (Upfront Cohort; UC). The First Event Cohort (FEC) included UC patients with first event of disease progression/relapse. Clinical features and survival of FEC patients were described.

UC included 1095 eligible M1 RMS patients. 5‐year Overall and Event Free Survival were 32.0% (95% Confidence Interval (CI) 29.2–34.9) and 27.5% (95% CI 24.8–30.2) respectively. Median time to event was 13.9 months (range 1 day‐172.6 months). Among UC patients, 727 with first event of progression/relapse were included in FEC. 3‐year Overall Survival for FEC from first event was 8.0% (95% CI 6.1–10.2). Thirty‐four (4.7%) FEC patients were alive with > 3 years follow up (“disease free”) and 16 (2.2%) with < 3 years follow up. FEC patients alive > 3 years were significantly more likely than deceased FEC patients to have: younger age (p = 0.0031); no locoregional lymph node involvement (p = 0.0013); fewer metastatic sites (p = 0.006); no bone and/or bone marrow disease (p < 0.001 for each); lower Oberlin scores (p < 0.0001); time to first event > 18 months (p < 0.0001). Univariate and multivariable analyses conducted in FEC to investigate factors impacting OS showed that Oberlin score ≥ 2 (Hazard Ratio (HR) 1.295, 95% Confidence Limits (CL) 1.07–1.57, p = 0.0074) and involvement of loco‐regional lymph nodes at diagnosis (HR 1.28, 95% CL 1.08–1.52, p = 0.0053) were associated with worse outcome.

Outcomes following first progression/relapse of M1 RMS are dismal. Survivors had fewer adverse prognostic features at first presentation and later first events. Further work is required to predict survivors of first relapse more reliably.

In this pooled analysis of 1095 patients with metastatic rhabdomyosarcoma, 3‐year overall survival was only 8% among the 727 patients with first event of relapse or progression. Patients “disease‐free” 3 years after first event had less locoregional lymph node involvement, fewer known adverse risk factors and lower Oberlin scores at first presentation than those who died and were more likely to have their first event > 18 months from diagnosis. In a multivariable Cox regression model stratified for time to relapse/progression, locoregional lymph node involvement and > 2 Oberlin risk factors at diagnosis were associated with worse outcome.