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Isolated Limb Perfusions With Tumor Necrosis Factor and Melphalan for Locally Recurrent Soft Tissue Sarcoma in Previously Irradiated Limbs

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Abstract

Background

Recurrent extremity soft tissue sarcoma (STS) in a previously operated and irradiated area can usually be managed only by amputation. Tumor necrosis factor (TNF)-α–based isolated limb perfusion (ILP) is an established alternative to achieve limb salvage but is assumed to require sufficient vasculature. Because radiotherapy is known to destroy vasculature, we wanted to evaluate retrospectively whether the outcome of ILP in patients with radiotherapy for their primary tumor nonetheless showed a benefit from TNF treatment.

Methods

We consulted a prospective database of TNF-based ILPs at the Erasmus MC–Daniel den Hoed Cancer Center in Rotterdam. Out of 342 TNF-based ILPs between 1991 and 2003, 30 ILPs were performed in 26 patients with recurrent STS in the irradiated field after prior surgery and radiotherapy. Eleven patients (42%) had multiple tumors (n = 2–20). All patients were candidates for amputation.

Results

We observed 6 complete responses (20%), 15 partial responses (50%), no change in 8 patients (27%), and progressive disease in 1 patient (3%). The median duration of response was 16 months (range, 3–56 months) at a median follow-up of 22 months (range, 3–67 months). The local recurrence rate was 45% in patients with multiple tumors and 27% in patients with single tumors. Ten patients (35%) died of systemic metastases. Limb salvage was achieved in 17 patients (65%). Regional toxicity was limited and systemic toxicity minimal.

Conclusions

TNF-based ILP can avoid amputations in most patients with recurrent extremity STS in a prior operated and irradiated field.

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References

  1. D Lienard P Ewalenko JJ Delmotte N Renard FJ Lejeune (1992) ArticleTitleHigh-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 10 52–60 Occurrence Handle1:STN:280:By2D1M3gslQ%3D Occurrence Handle1727926

    CAS  PubMed  Google Scholar 

  2. AMM Eggermont H Schraffordt Koops D Lienard et al. (1996) ArticleTitleIsolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial J Clin Oncol 14 2653–65 Occurrence Handle1:CAS:528:DyaK28XmsFCgtr0%3D Occurrence Handle8874324

    CAS  PubMed  Google Scholar 

  3. AMM Eggermont KH Schraffordt JM Klausner et al. (1996) ArticleTitleIsolated 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 224 756–65 Occurrence Handle10.1097/00000658-199612000-00011 Occurrence Handle1:STN:280:ByiC383pvVU%3D Occurrence Handle8968230

    Article  CAS  PubMed  Google Scholar 

  4. AMM Eggermont H Schraffordt Koops JM Klausner et al. (1999) ArticleTitleLimb salvage by isolation limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced extremity soft tissue sarcomas: results of 270 perfusions in 246 patients (abstract) Proc Am Soc Clin Oncol 11 497

    Google Scholar 

  5. RJ Ginkel Particlevan HJ Hoekstra AMM Eggermont E Pras H Schraffordt-Koops (1996) ArticleTitleIsolated limb perfusion of an irradiated foot with tumor necrosis factor, interferon, and melphalan Arch Surg 131 672–4 Occurrence Handle8645079

    PubMed  Google Scholar 

  6. J Wieberdink C Benckhuysen RP Braat EA Slooten Particlevan GA Olthuis (1982) ArticleTitleDosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions Eur J Cancer Clin Oncol 18 905–10 Occurrence Handle10.1016/0277-5379(82)90235-8 Occurrence Handle1:STN:280:BiyC3s7nslc%3D Occurrence Handle6891640

    Article  CAS  PubMed  Google Scholar 

  7. MF Brennan MH Shiu C Collin et al. (1985) ArticleTitleExtremity soft tissue sarcomas Cancer Treat Symp 3 71–81

    Google Scholar 

  8. DA Potter D Kinsella E Gladstein et al. (1986) ArticleTitleHigh grade soft tissue sarcomas of the extremities Cancer 59 190–205

    Google Scholar 

  9. AT Stotter RP A’Hearn C Fisher AF Mott ME Fallowfield G Westbury (1990) ArticleTitleThe influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival Cancer 65 1119–29 Occurrence Handle1:STN:280:By%2BC2M%2Fgt1A%3D Occurrence Handle2302663

    CAS  PubMed  Google Scholar 

  10. P Gustafson B Rööser A Rydholm (1991) ArticleTitleIs local recurrence of minor importance for metastases in soft tissue sarcoma? Cancer 67 2083–6 Occurrence Handle1:STN:280:By6C28fhtVU%3D Occurrence Handle2004326

    CAS  PubMed  Google Scholar 

  11. A Stojadinovic DP Jaques DH Leung et al. (2001) ArticleTitleAmputation for recurrent soft tissue sarcoma of the extremity: indications and outcome Ann Surg Oncol 8 509–18 Occurrence Handle1:STN:280:DC%2BD38%2Fit1ersQ%3D%3D Occurrence Handle11456050

    CAS  PubMed  Google Scholar 

  12. R Essner M Selch FR Eilber (1991) ArticleTitleReirradiation for extremity soft tissue sarcomas. Local control and complications Cancer 67 2813–7 Occurrence Handle1:STN:280:By6B38zks1c%3D Occurrence Handle2025846

    CAS  PubMed  Google Scholar 

  13. NA Janjan C Crane M Delclos M Ballo (2002) ArticleTitleBrachytherapy for locally recurrent soft-tissue sarcoma Am J Clin Oncol 25 9–15 Occurrence Handle10.1097/00000421-200202000-00002 Occurrence Handle11823688

    Article  PubMed  Google Scholar 

  14. DB Pearlstone NA Janjan BW Feig et al. (1999) ArticleTitleRe-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field Cancer J Sci Am 5 26–33 Occurrence Handle1:STN:280:DyaK1M3gtlyksQ%3D%3D Occurrence Handle10188058

    CAS  PubMed  Google Scholar 

  15. D Nori K Shupack MH Shiu MF Brennan (1991) ArticleTitleRole of brachytherapy in recurrent extremity sarcoma in patients treated with prior surgery and irradiation Int J Radiat Oncol Biol Phys 20 1229–33 Occurrence Handle1:STN:280:By6B2Mfhs1c%3D Occurrence Handle2045297

    CAS  PubMed  Google Scholar 

  16. C Catton A Davis R Bell et al. (1996) ArticleTitleSoft tissue sarcoma of the extremity. Limb salvage after failure of combined conservative therapy Radiother Oncol 41 209–14 Occurrence Handle10.1016/S0167-8140(96)01856-7 Occurrence Handle1:STN:280:ByiC2sbmvF0%3D Occurrence Handle9027935

    Article  CAS  PubMed  Google Scholar 

  17. RD Issels S Abdel-Rahman C Wendtner et al. (2001) ArticleTitleNeoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults: long-term results of a phase II study Eur J Cancer 37 1599–608 Occurrence Handle10.1016/S0959-8049(01)00183-6 Occurrence Handle1:CAS:528:DC%2BD3MXmt1Oqtbo%3D Occurrence Handle11527684

    Article  CAS  PubMed  Google Scholar 

  18. BC Vrouenraets AMM Eggermont AA Hart et al. (2001) ArticleTitleRegional toxicity after isolated limb perfusion with melphalan and tumour necrosis factor-alpha versus toxicity after melphalan alone Eur J Surg Oncol 27 390–19 Occurrence Handle10.1053/ejso.2001.1124 Occurrence Handle1:STN:280:DC%2BD3MzlslGrsQ%3D%3D Occurrence Handle11417986

    Article  CAS  PubMed  Google Scholar 

  19. BC Vrouwenraets BBR Kroon AC Ogilvie et al. (1999) ArticleTitleAbsence of severe systemic toxicity after leakage controlled isolated limb perfusion with tumor necrosis factor alpha and melphalan Ann Surg Oncol 6 405–12 Occurrence Handle10.1007/s10434-999-0405-9 Occurrence Handle1:STN:280:DyaK1Mzgs1GgsA%3D%3D Occurrence Handle10379864

    Article  CAS  PubMed  Google Scholar 

  20. TC Stam AJ Swaak MR Vries Particlede TLM ten Hagen AMM Eggermont (2000) ArticleTitleSystemic toxicity and cytokine/acute phase protein levels in patients after isolated limb perfusion with tumor necrosis factor-alpha complicated by high leakage Ann Surg Oncol 4 268–75 Occurrence Handle10.1007/s10434-000-0268-6

    Article  Google Scholar 

  21. B Etten Particlevan AN Geel Particlevan JHW Wilt Particlede AMM Eggermont (2003) ArticleTitleFifty tumor necrosis factor-based isolated limb perfusions for limb salvage in patients older than 75 years with limb-threatening soft tissue sarcomas and other extremity tumors Ann Surg Oncol 27 32–7 Occurrence Handle10.1245/ASO.2003.03.076

    Article  Google Scholar 

  22. TE Lans JHW Wilt Particlede AN Geel Particlevan AMM Eggermont (2002) ArticleTitleIsolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma Ann Surg Oncol 9 1004–9 Occurrence Handle10.1245/ASO.2002.03.048 Occurrence Handle1:STN:280:DC%2BD38jgt1Grsg%3D%3D Occurrence Handle12464594

    Article  CAS  PubMed  Google Scholar 

  23. AMM Eggermont JHW deWilt TLM ten Hagen (2003) ArticleTitleCurrent uses of isolated limb perfusion in the clinic and a model system for new strategies Lancet Oncol 4 429–37 Occurrence Handle10.1016/S1470-2045(03)01141-0 Occurrence Handle12850194

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical Oncology, Erasmus MC–Daniel den Hoed Cancer Center, PO Box 5201, 3008 AE Rotterdam, The Netherlands

    T. E. Lans MD, PhD, D. J. Grünhagen MD, J. H. W. de Wilt MD, PhD, A. N. van Geel MD, PhD & A. M. M. Eggermont MD, PhD

Authors
  1. T. E. Lans MD, PhD
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  2. D. J. Grünhagen MD
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  3. J. H. W. de Wilt MD, PhD
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  4. A. N. van Geel MD, PhD
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  5. A. M. M. Eggermont MD, PhD
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Corresponding author

Correspondence to A. M. M. Eggermont MD, PhD.

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Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.

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Lans, T.E., Grünhagen, D.J., de Wilt, J.H.W. et al. Isolated Limb Perfusions With Tumor Necrosis Factor and Melphalan for Locally Recurrent Soft Tissue Sarcoma in Previously Irradiated Limbs. Ann Surg Oncol 12, 406–411 (2005). https://doi.org/10.1245/ASO.2005.03.093

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  • DOI: https://doi.org/10.1245/ASO.2005.03.093

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