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.

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