Advertisement

Lymph node metastases in paediatric and young adult patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): Findings from Children's Oncology Group (COG) study ARST0332

Published:December 23, 2022DOI:https://doi.org/10.1016/j.ejca.2022.11.014

      Highlights

      • Large prospective study of NRSTS with lymph node (LN) involvement in young patients.
      • Occult lymph node involvement is exceedingly rare.
      • Isolated LN metastases have a favourable prognosis so should be treated aggressively.
      • Complete enlarged LN excision and nodal bed radiation correlate with better outcome.

      Abstract

      Purpose

      The aim of this paper is to better define the clinical features and outcomes of young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) with regional and distant lymph node (LN) metastases treated in a standardised fashion, we analysed LN involvement in COG study ARST0332, which evaluated a risk-based treatment strategy for young patients with all stages of NRSTS.

      Patients and methods

      Patients <30 years old with newly diagnosed NRSTS and LN metastases enrolled on ARST0332 were studied. Regional LN sampling was required for those with epithelioid sarcoma, clear cell sarcoma or clinically/radiographically enlarged LNs. Tumour features and extent of pre-enrolment resection determined treatment, including chemotherapy, radiotherapy, and delayed surgery. Recommendations for LN metastases included LN dissection at the time of primary tumour resection and dose-adapted radiotherapy based on extent of LN resection.

      Results

      Twenty of 529 eligible and evaluable ARST0332 patients with NRSTS had LN metastases; epithelioid sarcoma had the highest incidence (18%, 5 of 28). Pre-treatment imaging identified LN enlargement in 19 of 20 patients; 1 had no pre-treatment LN imaging. At 6.9 years median follow-up for surviving patients, 5-year overall survival was 85.7% (95% CI: 33.4%, 97.9%) for seven patients with isolated LN metastases and 15.4% (95% CI: 2.5%, 38.8%) for 13 patients with additional extranodal metastases. LN recurrence occurred in only one patient without LNs sampled at initial diagnosis.

      Conclusion

      LN metastases occur in about 4% of paediatric/young adult NRSTS, are limited to a few histologic subtypes, and are rare in patients who did not have clinical or imaging evidence of lymphadenopathy, suggesting that biopsies of non-enlarged LNs are not necessary to identify occult involvement. Patients with isolated LN metastases have high 5-year overall survival (∼85%) and should be treated with curative intent.

      Clinicaltrials.gov Registry No.

      NCT00346164.

      Keywords

      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:

      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

      References

        • Ries L.A.G. S.M.
        • Gurney J.G.
        • Linet M.
        • Tamra T.
        • Young J.L.
        • Bunin G.R.
        Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995.
        National Cancer Institute, SEER Program, 1999
        • Spunt S.L.
        • Poquette C.A.
        • Hurt Y.S.
        • et al.
        Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.
        J Clin Oncol. 1999; 17: 3697-3705
        • Ferrari A.
        • Casanova M.
        New concepts for the treatment of pediatric nonrhabdomyosarcoma soft tissue sarcomas.
        Expert Rev Anticancer Ther. 2005; 5: 307-318
        • Pappo A.S.
        • Rao B.N.
        • Jenkins J.J.
        • et al.
        Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience.
        Med Pediatr Oncol. 1999; 33: 76-82
        • Ferrari A.
        • van Noesel M.M.
        • Brennan B.
        • et al.
        Paediatric 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; 5: 546-558
        • 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
        • Basile G.
        • Mattei J.C.
        • Alshaygy I.
        • et al.
        Curability of patients with lymph node metastases from extremity soft-tissue sarcoma.
        Cancer. 2020; 126: 5098-5108
        • Keung E.Z.
        • Chiang Y.J.
        • Voss R.K.
        • et al.
        Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma.
        Eur J Surg Oncol. 2018; 44: 170-177
        • Cancer AJCo
        AJCC Cancer Staging Manual.
        8th ed. Springer, 2018
        • Fisher S.B.
        • Roland C.L.
        ASO Author Reflections: location-specific staging in sarcoma-a step in the right direction.
        Ann Surg Oncol. 2018; 25: 930-931
        • Cates J.M.M.
        The AJCC 8th edition staging system for soft tissue sarcoma of the extremities or trunk: a cohort study of the SEER database.
        J Natl Compr Canc Netw. 2018; 16: 144-152
        • Spunt S.L.
        • Hill D.A.
        • Motosue A.M.
        • et al.
        Clinical features and outcome of initially unresected nonmetastatic pediatric nonrhabdomyosarcoma soft tissue sarcoma.
        J Clin Oncol. 2002; 20: 3225-3235
        • Brennan B.
        • Zanetti I.
        • De Salvo G.L.
        • et al.
        Dermatofibrosarcoma protuberans in children and adolescents: the European Paediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005).
        Pediatr Blood Cancer. 2020; 67e28351
        • van Noesel M.M.
        • Orbach D.
        • Brennan B.
        • et al.
        Outcome and prognostic factors in pediatric malignant peripheral nerve sheath tumors: an analysis of the European Pediatric Soft Tissue Sarcoma Group (EpSSG) NRSTS-2005 prospective study.
        Pediatr Blood Cancer. 2019; 66e27833
        • 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.
        • Spunt S.L.
        • Sparber-Sauer M.
        • et al.
        Controversies and challenges in the management of paediatric non-rhabdomyosarcoma soft tissue sarcomas.
        Lancet Child Adolesc Health. 2022; 6: 221-223
        • Spunt S.L.
        • Francotte N.
        • De Salvo G.L.
        • et al.
        Clinical features and outcomes of young patients with epithelioid sarcoma: an analysis from the Children's Oncology Group and the European paediatric soft tissue Sarcoma Study Group prospective clinical trials.
        Eur J Cancer. 2019; 112: 98-106
        • 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; 21: 145-161
        • Fletcher CDMB J.A.
        • Hogendron P.
        • Mertens F.
        WHO classification of tumours of soft tissue and bone. Fourth Addition.
        2013
        • Parham D.M.
        • Webber B.L.
        • Jenkins 3rd, J.J.
        • et al.
        Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading.
        Mod Pathol. 1995; 8: 705-710
        • Coindre J.M.
        • Trojani M.
        • Contesso G.
        • et al.
        Reproducibility of a histopathologic grading system for adult soft tissue sarcoma.
        Cancer. 1986; 58: 306-309
        • Riad S.
        • Griffin A.M.
        • Liberman B.
        • et al.
        Lymph node metastasis in soft tissue sarcoma in an extremity.
        Clin Orthop Relat Res. 2004; : 129-134
        • Behranwala K.A.
        • A'Hern R.
        • Omar A.M.
        • et al.
        Prognosis of lymph node metastasis in soft tissue sarcoma.
        Ann Surg Oncol. 2004; 11: 714-719
        • Massarweh N.N.
        • Dickson P.V.
        • Anaya D.A.
        Soft tissue sarcomas: staging principles and prognostic nomograms.
        J Surg Oncol. 2015; 111: 532-539
        • Fong Y.
        • Coit D.G.
        • Woodruff J.M.
        • et al.
        Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.
        Ann Surg. 1993; 217: 72-77
        • Andreou D.
        • Boldt H.
        • Werner M.
        • et al.
        Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread--results of a large prospective trial.
        Ann Oncol. 2013; 24: 1400-1405
        • Roberge D.
        • Vakilian S.
        • Alabed Y.Z.
        • et al.
        FDG PET/CT in initial staging of adult soft-tissue sarcoma.
        Sarcoma. 2012; 2012960194