Original Research| Volume 169, P179-187, July 2022

Download started.


Adult-type non-rhabdomyosarcoma soft tissue sarcomas in pediatric age: Salvage rates and prognostic factors after relapse


      • Pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are heterogeneous.
      • The chances of being cured for NRSTS patients who relapsed are limited.
      • In the series, median post-relapse survival was 20 months, 10-year survival was 19.1%.
      • Survivals were better after local and late relapses and after secondary remission.
      • Prognostic factors were combined in a risk-adapted model.



      Though the prognosis for patients with pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is generally good, the chances of being cured after relapse are limited. This report describes a series of relapsing NRSTS patients treated at a referral center for pediatric sarcoma, investigating the pattern of relapse, salvage rates, and factors correlating with the final outcome.


      The analysis concerned 103 patients <21 years old with relapsing adult-type NRSTS treated from 1985 to 2020. For risk-adapted stratification purposes, the patient outcome was examined using univariable and multivariable analyses based on patients’ clinical features at first diagnosis, first-line treatments, clinical findings at first relapse, and second-line treatments.


      The first relapse occurred within 2–102 months (median 14 months) after patients' first diagnosis and was local in 47%, metastatic in 34%, and both in 19%. Treatment at relapse included chemotherapy in 72 patients, radiotherapy in 38, and surgery in 55. The median overall survival (OS) was 20 months. Post-relapse OS was 56.1%, 25.8%, and 19.1% at 1, 5, and 10 years, respectively. Cox's multivariable regression analysis showed that OS was significantly better for patients with local and late relapses (occurring more than 12 months after their first diagnosis) and for those achieving secondary remission.


      The outcome of patients with recurrent NRSTS is poor. The above-mentioned variables (type and time of relapse and achievement of secondary remission) were combined in a risk-adapted model to develop a tool for estimating the chance of salvage and deciding the best second-line treatment approach.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ferrari A.
        • Sultan I.
        • Huang T.T.
        • et al.
        Soft tissue sarcoma across the age spectrum: a population-based study from the Surveillance Epidemiology and End Results database.
        Pediatr Blood Cancer. 2011; 57: 943-949
        • Pfister S.M.
        • Reyes-Múgica M.
        • Chan J.K.C.
        • et al.
        A summary of the inaugural WHO Classification of Pediatric Tumors: transitioning from the optical into the molecular era.
        Cancer Discov, 2021 Dec 17 ([Online ahead of print])
        • Spunt S.L.
        • Million L.
        • Chi Y.-Y.
        • et al.
        A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study.
        Lancet Oncol. 2020 Jan; 21: 145-161
        • Ferrari A.
        • van Noesel M.M.
        • Brennan B.
        • et al.
        Pediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European pediatric Soft tissue sarcoma Study Group (EpSSG).
        Lancet Child Adolesc Health. 2021 Aug; 5: 546-558
        • Ferrari A.
        • Casanova M.
        • Collini P.
        • et al.
        Adult-type soft tissue sarcomas in pediatric-age patients: experience at the Istituto Nazionale Tumori in Milan.
        J Clin Oncol. 2005; 23: 4021-4030
        • Trojani M.
        • Contesso G.
        • Coindre J.M.
        • et al.
        Soft tissue sarcomas of adults: study of pathological prognostic variables and definitions of a histopathological grading system.
        Int J Cancer. 1984; 33: 37-42
        • Ferrari A.
        • De Salvo G.L.
        • Dall'Igna P.
        • et al.
        Salvage rates and prognostic factors after relapse in children and adolescents with initially localized synovial sarcoma.
        Eur J Cancer. 2012; 48: 3448-3455
        • Bergamaschi L.
        • Bisogno G.
        • Manzitti C.
        • et al.
        Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors.
        Pediatr Blood Cancer. 2018; 65e26816
        • Maurer H.M.
        • Beltangady M.
        • Gehan E.A.
        • et al.
        The Intergroup rhabdomyosarcoma study I: a final report.
        Cancer. 1998; 61: 209-220
        • Therasse P.
        • Arbuck S.G.
        • Eisenhauer E.A.
        • et al.
        New guidelines to evaluate the response to treatment in solid tumors. European Organization for research and treatment of cancer, National cancer Institute of the United States, National cancer Institute of Canada.
        J Natl Cancer Inst. 2000 Feb 2; 92: 205e16
        • Kaplan E.L.
        • Meier P.
        Non-parametric estimation from incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Conover W.J.
        Practical nonparametric statistics.
        Wiley, New York,NY1980: 153-169
        • Cox D.R.
        Regression models and life tables.
        J Roy Stat Soc. 1972; 34: 187-220
        • Ferrari A.
        • De Salvo G.L.
        • Brennan B.
        • et al.
        Synovial sarcoma in children and adolescents: the European pediatric soft tissue sarcoma study group prospective trial (EpSSG NRSTS 2005).
        Ann Oncol. 2015; 26: 567-572
        • Ferrari A.
        • Miceli R.
        • Rey A.
        • et al.
        Non-metastatic unresected pediatric nonrhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups.
        Eur J Cancer. 2011; 47: 724e31
        • Gronchi A.
        • Miah A.B.
        • Dei Tos A.P.
        • et al.
        Soft tissue and visceral sarcomas: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2021 Jul 22; (7534(21)02184-0): S0923
        • Le Cesne A.
        • Antoine E.
        • Spielmann M.
        • et al.
        High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.
        J Clin Oncol. 1995; 13: 1600-1608
        • Meazza C.
        • Casanova M.
        • Luksch R.
        • et al.
        Prolonged 14-day continuous infusion of high-dose ifosfamide with an external portable pump: feasibility and efficacy in refractory pediatric sarcoma.
        Pediatr Blood Cancer. 2010; 55: 617-620
        • Maki R.G.
        • Wathen J.K.
        • Patel S.R.
        • et al.
        Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of Sarcoma Alliance for Research through Collaboration Study 002 [corrected].
        J Clin Oncol. 2007; 25: 2755-2763
        • Demetri G.D.
        • von Mehren M.
        • Jones R.L.
        • et al.
        Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial.
        J Clin Oncol. 2016; 34: 786-793
        • van der Graaf W.T.
        • Blay J.Y.
        • Chawla S.P.
        • et al.
        Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.
        Lancet. 2012; 379: 1879-1886
        • Schoffski P.
        • Chawla S.
        • Maki R.G.
        • et al.
        Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.
        Lancet. 2016; 387: 1629-1637
        • van der Graaf W.T.A.
        • Orbach D.
        • et al.
        Soft tissue sarcomas in adolescents and young adults: a comparison with their paediatric and adult counterparts.
        Lancet Oncol. 2017; 18: e166-e175
        • Ferrari A.
        • Bleyer A.
        • Patel S.
        • et al.
        The challenge of the management of adolescents and young adults with soft tissue sarcomas.
        Pediatr Blood Cancer. 2018; 65e27013
        • Ferrari A.
        • Spunt S.L.
        • Sparber-Sauer M.
        • et al.
        Controversies and challenges in the management of pediatric non-rhabdomyosarcoma soft tissue sarcomas.
        Lancet Child Adolesc Health. 2022 published online Feb 14;
        • Ferrari A.
        • Orbach D.
        • Sparber-Sauer M.
        • et al.
        The treatment approach to pediatric non-rhabdomyosarcoma soft tissue sarcomas: a critical review from the International Soft Tissue SaRcoma ConsorTium.
        Eur J Cancer. 2022; 169: 10-19