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Initial Patient Characteristics Can Predict Pattern and Risk of Relapse in Localized Rhabdomyosarcoma

Tobias M. Dantonello, Christoph Int-Veen, Peter Winkler, Ivo Leuschner, Andreas Schuck, Bernhard F. Schmidt, Helmut Lochbuehler, Sylvia Kirsch, Erika Hallmen, Iris Veit-Friedrich, Stefan S. Bielack, Felix Niggli, Bernarda Kazanowska, Ruth Ladenstein, Thomas Wiebe, Thomas Klingebiel, Joern Treuner, Ewa Koscielniak

From the Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Department of Pediatric Oncology, and Department of Pediatric Surgery; Katharinenhospital, Department of Radiotherapy, Klinikum Stuttgart, Stuttgart; Institute of Pediatric Pathology, University of Kiel, Kiel; Department of Radiotherapy, University of Muenster; Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster; Department of Pediatric Oncology, University of Frankfurt (Main), Frankfurt; Department of Pediatric Oncology, University of Tuebingen, Tuebingen, Germany; Department of Pediatric Oncology, University of Zurich, Zurich, Switzerland; Department of Pediatric Oncology, University of Wroclaw, Wroclaw, Poland; Department of Pediatric Oncology, St. Anna Kinderspital, Vienna, Austria; and the Department of Pediatric Oncology, University of Lund, Lund, Sweden

Corresponding author: Tobias M. Dantonello, MD, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Klinikum Stuttgart, Bismarckstrasse 8, D-70176 Stuttgart, Germany; e-mail: tobias.dantonello{at}olgahospital-stuttgart.de or t.dantonello{at}olgahospital.de

Purpose Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor-directed surveillance program for patients with localized rhabdomyosarcoma (RMS).

Patients and Methods One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 (median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed.

Results Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis (range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size.

Conclusion Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor-directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor-directed guidance for detection of recurrent disease in localized RMS.

Supported by Grant No. 50-2721 from the Deutsche Krebshilfe, Bonn, Germany, and by the Foerderkreis Krebskranke Kinder e.V., Stuttgart, Germany.

Presented in part at the 1st International Sarcoma Meeting Stuttgart, June 15-17, 2005, Stuttgart, Germany.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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