Second Malignant Neoplasms (SMN) In Children Treated For Rhabdomyosarcoma: A Report From The Intergroup Rhabdomyosarcoma Studies (IRS) I-IV

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 15, 2001

Presenter: Sheri L. Spunt
Affiliation: Children's Oncology Group Soft Tissue Sarcoma Committee, Arcadia, CA


  1. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of the childhood (5%).
  2. Multimodality therapy can provide cure in > 70% of pts.
  3. Treatment related late squalae become important as long term survival increases.
  4. SMNs are a devastating complication of successful contemporary multimodal therapy for pediatric rhabdomyosarcoma.

Materials and Methods:

  1. Reviewing 4367 patients enrolled in five consecutive IRS studies (I, II, III, IV-Pilot, IV) from 1972-1997
  2. IRS chemotherapy regimens prescribed two or more drugs: vincristine ± dactinomycin ± alkylating agent ± doxorubicin ± cisplatin ± etoposide.
  3. Radiation delivered as per protocol.


  1. There were 67 pts developed a SMN at a median of 5.5 years (range, 11 weeks - 16.7 years) after the diagnosis of rhabdomyosarcoma; 2 developed a third malignancy.
  2. Thirty-five of the 67 patients (52%) were male and 54 (81%) were white; the median age at the time of diagnosis of rhabdomyosarcoma was 5 years (range, 16 weeks - 20 years). Only 7 patients had a recognized, defined genetic predisposition syndrome.
  3. Radiotherapy was delivered to the primary site in 57 patients (median dose 50 Gy, range 37.3 - 62 Gy) and to metastatic sites in 18 patients.
  4. At a median follow-up of 9.5 years, the estimated cumulative incidence of SMNs for all IRSG I-IV patients is 3.5% at 20 years. The estimated 5-year survival after the development of a SMN is 20% [95% CI (8%, 31%)].
  5. The 67 SMNs included 27 leukemias/lymphomas (MDS/AML=21), 27 soft tissue/bone sarcomas (osteosarcoma, n=19), and 13 other cancers (carcinoma=8, brain tumor=5). The estimated 20- year cumulative incidences of leukemia/lymphoma, soft tissue/bone sarcoma, and other cancers were 1.1%, 1.7%, and 0.7%, respectively.

Authors' Conclusions

  1. Cummulative incidenct of SMN is 3.4% at 20 yrs.
  2. Leukemia/lymphoma as a SMN developed early (median time of 3.7 yrs) as compared to solid tumor at 9 yr.
  3. 5yr. survival is poor with SMN (20%).

Clinical/Scientific Implications:

    Risk adapted therapy should be utilized, ie. minimized alkylating chemotherapeutic agent and use of novel agents, decrease radiothearpy exposure (dose and volume) by using radiation sensitizers.

OncoLink ASCO 2001 coverage is provided by an unrestricted educational grant from Amgen


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