Skip to main content
SpringerLink
Log in

Neoadjuvant isolated limb perfusion in newly diagnosed untreated patients with locally advanced soft tissue sarcomas of the extremities: the Gustave Roussy experience

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

Limb-sparing surgery in locally advanced soft tissue sarcomas (LA STS) is challenging. The aim of this study is to evaluate upfront isolated limb perfusion (ILP) in untreated patients with LA STS.

Methods

All consecutive patients with LA STS of the limbs deemed borderline or unresectable and treated with upfront ILP as induction treatment between 2003 and 2016 were included. Demographic, clinical and long-term characteristics were obtained and retrospectively analyzed.

Results

41 patients (pts), with a median age of 51 years [range 21–76], were identified (lower limb 68%, upper limb 32%). Liposarcoma and undifferentiated pleomorphic sarcoma were the most common subtypes (27% and 22%, respectively). Acute toxicities, using Wieberdink classification, were grade II (35 pts, 85%), grade III (2 pts, 5%) and no grade IV–V. Local control rate was 98%. 32 pts had limb-sparing surgery (78%). 1 pt had an early amputation due to progressive disease after ILP. 8 pts were not operated (four had RT alone, one had distant metastases, two had a complete response and one died 3 months after ILP of a pulmonary embolism). 36 pts (84%) received postoperative RT. After a median follow-up of 43 months, 18 pts (47%) relapsed. Median disease-free survival (DFS) was 6.7 years. The median overall survival (OS) was not reached. The 1-year, 5-year and 10-year DFS and OS rates were, respectively, 75%, 50% and 45%, and 90%, 63% and 55%.

Conclusion

Upfront ILP is an efficient and well-tolerated limb-sparing procedure in borderline or unresectable LA STS without hampering OS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Honore C, Méeus P, Stoeckle E, Bonvalot S. Soft tissue sarcoma in France in 2015: epidemiology, classification and organization of clinical care. J Visc Surg. 2015;152:223–30.

    Article  CAS  PubMed  Google Scholar 

  2. Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, et al. Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer. 2013;49:684–95.

    Article  CAS  PubMed  Google Scholar 

  3. Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017;18:812–22.

    Article  CAS  PubMed  Google Scholar 

  4. Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, et al. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012;30:850–6.

    Article  CAS  PubMed  Google Scholar 

  5. Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay J-Y, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15:415–23.

    Article  CAS  PubMed  Google Scholar 

  6. Lienard D, Ewalenko P, Delmotte J-J, Renard N, Lejeune FJ. High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol. 1992;10:52–60.

    Article  CAS  PubMed  Google Scholar 

  7. Lejeune FJ, Pujol N, Lienard D, Mosimann F, Raffoul W, Genton A, et al. Limb salvage by neoadjuvant isolated perfusion with TNFα and melphalan for non-resectable soft tissue sarcoma of the extremities. Eur J Surg Oncol EJSO. 2000;26:669–78.

    Article  CAS  PubMed  Google Scholar 

  8. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. World Health Organization Classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013.

    Google Scholar 

  9. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, De Mascarel A, et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;33:37–42.

    Article  CAS  PubMed  Google Scholar 

  10. Wieberdink J, Benckhuysen C, Braat RP, Van Slooten EA, Olthuis GAA. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur J Cancer Clin Oncol. 1982;18:905–10.

    Article  CAS  PubMed  Google Scholar 

  11. Eggermont AM, Koops HS, Klausner JM, Kroon BB, Schlag PM, Liénard D, et al. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg. 1996;224:756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Health UD of, Services H. Common terminology criteria for adverse events (CTCAE) version 4.0. Natl Inst Health Natl Cancer Inst. 2009;4.

  14. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359:2235–41.

    Article  PubMed  Google Scholar 

  15. Cheng EY, Dusenbery KE, Winters MR, Thompson RC. Soft tissue sarcomas: preoperative versus postoperative radiotherapy. J Surg Oncol. 1996;61:90–9.

    Article  CAS  PubMed  Google Scholar 

  16. Bickels J, Manusama ER, Gutman M, Eggermont AMM, Kollender Y, Abu-Abid S, et al. Isolated limb perfusion with tumour necrosis factor-α and melphalan for unresectable bone sarcomas of the lower extremity. Eur J Surg Oncol EJSO. 1999;25:509–14.

    Article  CAS  PubMed  Google Scholar 

  17. Grabellus F, Kraft C, Sheu S-Y, Ebeling P, Bauer S, Lendemans S, et al. Evaluation of 47 soft tissue sarcoma resection specimens after isolated limb perfusion with TNF-α and melphalan: histologically characterized improved margins correlate with absence of recurrences. Ann Surg Oncol. 2009;16:676–86.

    Article  PubMed  Google Scholar 

  18. Hoven-Gondrie ML, Bastiaannet E, van Ginkel RJ, Suurmeijer AJ, Hoekstra HJ. TNF dose reduction and shortening of duration of isolated limb perfusion for locally advanced soft tissue sarcoma of the extremities is safe and effective in terms of long-term patient outcome. J Surg Oncol. 2011;103:648–55.

    Article  CAS  PubMed  Google Scholar 

  19. Noorda EM, Vrouenraets BC, Nieweg OE, van Coevorden F, van Slooten GW, Kroon BB. Isolated limb perfusion with tumor necrosis factor-α and melphalan for patients with unresectable soft tissue sarcoma of the extremities. Cancer. 2003;98:1483–90.

    Article  CAS  PubMed  Google Scholar 

  20. Trabulsi NH, Patakfalvi L, Nassif MO, Turcotte RE, Nichols A, Meguerditchian AN. Hyperthermic isolated limb perfusion for extremity soft tissue sarcomas: systematic review of clinical efficacy and quality assessment of reported trials. J Surg Oncol. 2012;106:921–8.

    Article  CAS  PubMed  Google Scholar 

  21. Jakob J, Tunn P-U, Hayes AJ, Pilz LR, Nowak K, Hohenberger P. Oncological outcome of primary non-metastatic soft tissue sarcoma treated by neoadjuvant isolated limb perfusion and tumor resection. J Surg Oncol. 2014;109:786–90.

    Article  PubMed  Google Scholar 

  22. Deroose JP, Burger JW, van Geel AN, Den Bakker MA, de Jong JS, Eggermont AM, et al. Radiotherapy for soft tissue sarcomas after isolated limb perfusion and surgical resection: essential for local control in all patients? Ann Surg Oncol. 2011;18:321–7.

    Article  PubMed  Google Scholar 

  23. Deroose JP, Eggermont AM, van Geel AN, Burger JW, den Bakker MA, de Wilt JH, et al. Long-term results of tumor necrosis factor α–and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas. J Clin Oncol. 2011;29:4036–44.

    Article  CAS  PubMed  Google Scholar 

  24. Neuwirth MG, Song Y, Sinnamon AJ, Fraker DL, Zager JS, Karakousis GC. isolated limb perfusion and infusion for extremity soft tissue sarcoma: a contemporary systematic review and meta-analysis. Ann Surg Oncol. 2017;24:3803–10.

    Article  PubMed  Google Scholar 

  25. Bonvalot S, Rimareix F, Causeret S, Le Péchoux C, Boulet B, Terrier P, et al. Hyperthermic isolated limb perfusion in locally advanced soft tissue sarcoma and progressive desmoid-type fibromatosis with TNF 1 mg and melphalan (T1-M HILP) is safe and efficient. Ann Surg Oncol. 2009;16:3350–7.

    Article  PubMed  Google Scholar 

  26. Pennacchioli E, Deraco M, Mariani L, Fiore M, Mussi C, Collini P, et al. Advanced extremity soft tissue sarcoma: prognostic effect of isolated limb perfusion in a series of 88 patients treated at a single institution. Ann Surg Oncol. 2007;14:553–9.

    Article  PubMed  Google Scholar 

  27. Gutman M, Inbar M, Lev-Shlush D, Abu-Abid S, Mozes M, Chaitchik S, et al. High dose tumor necrosis factor-α and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a > 90% response rate and limb preservation. Cancer. 1997;79:1129–37.

    Article  CAS  PubMed  Google Scholar 

  28. Cherix S, Speiser M, Matter M, Raffoul W, Liénard D, Theumann N, et al. Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas: long-term results on efficacy and limb salvage in a selected group of patients. J Surg Oncol. 2008;98:148–55.

    Article  PubMed  Google Scholar 

  29. Grunhagen DJ, de Wilt JH, Graveland WJ, van Geel AN, Eggermont AM. The palliative value of tumor necrosis factor α-based isolated limb perfusion in patients with metastatic sarcoma and melanoma. Cancer. 2006;106:156–62.

    Article  PubMed  Google Scholar 

  30. Kattan MW, Leung DH, Brennan MF. Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol. 2002;20:791–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Gustave Roussy Cancer Campus, 114, rue Edouard Vaillant, 94805, Villejuif Cedex, France

    T. Assi, A. Le Cesne, O. Camuzard, T. Ibrahim, O. Mir & S. Dumont

  2. Department of Surgical Oncology, Roussy Cancer Campus Gustave, Villejuif, France

    A. Cavalcanti, M. Faron, J. F. Honart, A. Hadiji & C. Honoré

  3. Department of Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France

    C. LePéchoux

  4. Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, France

    P. Terrier & J. Adam

Authors
  1. T. Assi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Cavalcanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Le Cesne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Faron
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. F. Honart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Hadiji
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. O. Camuzard
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. LePéchoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. O. Mir
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S. Dumont
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P. Terrier
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. Adam
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. C. Honoré
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Assi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

An approval of the institutional ethics board at Gustave Roussy was obtained.

Research involving human participants and/or animals

Not applicable.

Informed consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Assi, T., Cavalcanti, A., Le Cesne, A. et al. Neoadjuvant isolated limb perfusion in newly diagnosed untreated patients with locally advanced soft tissue sarcomas of the extremities: the Gustave Roussy experience. Clin Transl Oncol 21, 1135–1141 (2019). https://doi.org/10.1007/s12094-019-02034-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-019-02034-w

Keywords

Search

Navigation