Dactinomycin (A) and vincristine (V) with or without cyclophosphamide (C) and radiation therapy (RT) for newly diagnosed patients with low-risk embryonal/botryoid rhabdomyosarcoma (RMS). An IRS-V report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group (STS COG)

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 4, 2006

Presenter: Walterhouse JL et al.
Presenter's Affiliation: Children's Hospital of Los Angeles, Los Angeles, CA
Type of Session: Scientific

Background

The IRS-III and –IV studies defined 3 risk groups of rhabdomyosarcoma patients: low-risk (35%), intermediate-risk (50%), and high-risk (15%)
Low-risk patients have favorable histology, and have localized tumor at a favorable site, or tumor at an unfavorable site that has been grossly resected prior to initiation of chemotherapy
Low-risk patients were found to have a 5-year failure-free survival (FFS) of 83% and an overall survival (OS) of 95% on IRS-III and –IV

Materials and Methods

2 subgroups of patients were identified for the IRS-V low-risk RMS study (D9602) (1997 – 2004) per the hypothesis that different treatment intensities were required to achieve similar outcomes
- Subgroup A patients had Stage 1/Group I/IIA, Stage 1/Group III/orbit, or Stage 2/Group I disease and received VA with or without local RT (for residual tumor after surgery and beginning at approximately week 3 of chemotherapy)
- Subgroup B patients had Stage 1/Group IIB/C, Stage 2/Group II, Stage 1/Group III/non-orbit, or Stage 3/Group I/II disease and received VAC with or without local RT (for residual tumor after surgery and beginning at approximately week 3 of chemotherapy)
Radiation doses were decreased versus IRS-IV for node-negative Group II patients (36 Gy versus 41.4 Gy) and Group III orbit patients (45 Gy versus 50.4/59.4 Gy)
Eligibility requirements included patients < 50 years, no history of previous treatment, and with central pathologic confirmation of disease
The primary end-point was FFS

Results

Median follow-up was 2.9 years
Estimated 3-year FFS was 89% for Subgroup A patients and 89% for Subgroup B patients
Estimated 3-year FFS was 80% for Stage 1/Group IIA patients and 88% for Group III orbit disease

Author's Conclusions

There is no evidence to suggest differences in outcome for patients treated on D9602 versus similar patients treated on IRS-III and –IV

Clinical/Scientific Implications

An estimated 3-year FFS of > 85% may be achieved in patients with characteristics such as those in Subgroup A who are treated with VA or in patients with characteristics such as those in Subgroup B who are treated with VAC
Additionally, a similar FFS may be achieved in Subgroup A patients with Group III disease involving the orbit and who are treated with VA and 45 Gy RT
Modifying treatment intensity according to pre-defined patient disease characteristics may be of value in maintaining excellent FFS and OS rates in low-risk RMS patients