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Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma

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Abstract

Background

Cutaneous Stewart-Treves lymphangiosarcomas represent a rare group of tumors characterized by a high grade of vascularization and by localization in an extremity with lymphedema. The multifocality and the localization makes these tumors eligible for treatment with isolated limb perfusion (ILP). ILP with tumor necrosis factor (TNF) and melphalan is a safe and highly effective procedure that can achieve limb salvage in ≥80% of all patients with nonresectable extremity soft tissue sarcoma or melanoma.

Methods

In 10 patients with multifocal Stewart-Treves lymphangiosarcoma of the extremities, 16 ILPs with TNF plus melphalan were performed. All patients would have been candidates for exarticulation of the extremity.

Results

We observed an 87% overall response rate (complete and partial responses); one patient had a mixed response, and one patient did not respond to the therapy. In nine perfusions (56%), a complete response was achieved, and five perfusions (31%) resulted in a partial response. Limb salvage was achieved in eight patients (80%), with a mean follow-up duration of 34.8 months (range, 3 to ≥115 months). Regional toxicity was limited and systemic toxicity minimal to moderate, with no toxic deaths.

Conclusions

Multifocal Stewart-Treves lymphangiosarcomas in extremities with chronic lymphedema can be successfully treated by ILP with TNF and melphalan.

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References

  1. Stewart F, Treves N. Lymphangiosarcoma in postmastectomy lymphedema.Cancer 1948;1:64–81.

    Article  PubMed  CAS  Google Scholar 

  2. Ironside P, Allen PW. Test and teach number eleven. Diagnosis: post-mastectomy lymphangiosarcoma of Stewart and Treves.Pathology 1977;9:110:178–9.

    Google Scholar 

  3. Dubin HV, Creehan EP, Headington JT. Lymphangiosarcoma and congenital lymphedema of the extremity.Arch Dermatol 1974;10:608–14.

    Article  Google Scholar 

  4. Laskas JJ, Shelley WB, Wood MG. Lymphangiosarcoma arising in congenital lymphedema.Arch Dermatol 1975;111:86–9.

    Article  PubMed  CAS  Google Scholar 

  5. Prudden JF, Wolarsky ER. Lymphangiosarcoma of the thigh. Case report.Arch Surg 1967;94:376–9.

    PubMed  CAS  Google Scholar 

  6. Baes H. Angiosarcoma in a chronic lymphedematous leg.Dermatologica 1967;134:331–6.

    Article  PubMed  CAS  Google Scholar 

  7. Chen KT, Gilbert EF. Angiosarcoma complicating generalized lymphangiectasia.Arch Pathol Lab Med 1979;103:86–8.

    PubMed  CAS  Google Scholar 

  8. Muller R, Hajdu SI, Brennan MF. Lymphangiosarcoma associated with chronic filarial lymphedema.Cancer 1987;59:179–83.

    Article  PubMed  CAS  Google Scholar 

  9. Sordillo EM, Sordillo PP, Hajdu SI, Good RA. Lymphangiosarcoma after filarial infection.J Dermatol Surg Oncol 1981;7:235–9.

    PubMed  CAS  Google Scholar 

  10. Cozen W, Bernstein L, Wang F, Press MF, Mack TM. The risk of angiosarcoma following primary breast cancer.Br J Cancer 1999; 81:532–6.

    Article  PubMed  CAS  Google Scholar 

  11. Sordillo PP, Chapman R, Hajdu SI, Magill GB, Golbey RB. Lymphangiosarcoma.Cancer 1981;48:1674–9.

    Article  PubMed  CAS  Google Scholar 

  12. Grobmyer SR, Daly JM, Glotzbach RE, Grobmyer AJ. Role of surgery in the management of postmastectomy extremity angiosarcoma (Stewart-Treves syndrome).J. Surg Oncol 2000;73:182–8.

    Article  PubMed  CAS  Google Scholar 

  13. Creech O Jr, Krementz E, Ryan J, Winblad J. Chemotherapy of cancer: regional perfusion utilising an extracorporeal circuit.Ann Surg 1958;148:616–32.

    Article  PubMed  Google Scholar 

  14. Lienard D, Ewalenko P, Delmotte JJ, 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.

    PubMed  CAS  Google Scholar 

  15. Klaase JM, Kroon BB, Benckhuijsen C, Van Geel AN, Albus-Lutter CE, Wieberdink J. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.Cancer 1989;64:616–21.

    Article  PubMed  CAS  Google Scholar 

  16. Eggermont AM, Schraffordt KH, Klausner JM, 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;224:756–64.

    Article  PubMed  CAS  Google Scholar 

  17. Eggermont AM, Schraffordt KH, Lienard D, et al. Isolated 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 1996;14:2653–65.

    PubMed  CAS  Google Scholar 

  18. Manusama ER, Stavast J, Durante NM, Marquet RL, Eggermont AM. Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumour approach.Eur J Surg Oncol 1996;22:152–7.

    Article  PubMed  CAS  Google Scholar 

  19. Blick M, Sherwin SA, Rosenblum M, Gutterman J. Phase I study of recombinant tumor necrosis factor in cancer patients.Cancer Res 1987;147:2986–9.

    Google Scholar 

  20. Feinberg B, Kurzrock R, Talpaz M, Blick M, Saks S, Gutterman JU. A phase I trial of intravenously-administered recombinant tumor necrosis factor-alpha in cancer patients.J Clin Oncol 1988; 6:1328–34.

    PubMed  CAS  Google Scholar 

  21. Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GA. 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  PubMed  CAS  Google Scholar 

  22. Janse AJ, van Coevorden F, Peterse H, Keus RB, van Dongen JA. Lymphedema-induced lymphangiosarcoma.Eur J Surg Oncol 1995;21:155–8.

    Article  PubMed  CAS  Google Scholar 

  23. Yap BS, Yap HY, McBride CM, Bodey GP. Chemotherapy for postmastectomy lymphangiosarcoma.Cancer 1981;47:853–6.

    Article  PubMed  CAS  Google Scholar 

  24. Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic lymphedematous extremities.Cancer 1972;30:562–72.

    Article  PubMed  CAS  Google Scholar 

  25. Kaufmann T, Chu F, Kaufman R. Post-mastectomy lymphangiosarcoma (Stewart-Treves syndrome): report of two long-term survivals.Br J Radiol 1991;64:857–60.

    Article  PubMed  CAS  Google Scholar 

  26. Folli S, Pelegrin A, Chalandon Y, et al. Tumor-necrosis factor can enhance ratio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability.Int J Cancer 1993;53: 829–36.

    Article  PubMed  CAS  Google Scholar 

  27. Umeno H, Watanabe N, Yamauchi N, Tsuji N, Okamoto T, Niitsu Y. Enhancement of blood stasis and vascular permeability in Meth-A tumors by administration of hyperthermia in combination with tumor necrosis factor.Jpn J Cancer Res 1994;85:325–30.

    PubMed  CAS  Google Scholar 

  28. Manusama ER, Nooijen PT, Stavast J, Durante NM, Marquet RL, Eggermont AM. Synergistic antitumour effect of recombinant human tumour necrosis factor alpha with melphalan in isolated limb perfusion in the rat.Br J Surg 1996;83:551–5.

    Article  PubMed  CAS  Google Scholar 

  29. de Wilt JH, ten Hagen TL, de Boeck G, van Tiel ST, de Bruijn EA, Eggermont AM. Tumour necrosis factor alpha increases melphalan concentration in tumour tissue after isolated limb perfusion.Br J Cancer 2000;82:1000–3.

    Article  PubMed  Google Scholar 

  30. Ferrero E, Zocchi MR, Magni E, et al. Roles of tumor necrosis factor p55 and p75 receptors in TNF-alpha-induced vascular permeability.Am J Physiol Cell Physiol 2001;281:C1173–9.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgical Oncology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam, P.O. Box 5201, 3008 AE, Rotterdam, The Netherlands

    T. E. Lans 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
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  2. J. H. W. de Wilt MD, PhD
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  3. A. N. van Geel MD, PhD
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  4. A. M. M. Eggermont MD, PhD
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Correspondence to A. M. M. Eggermont MD, PhD.

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Lans, T.E., de Wilt, J.H.W., van Geel, A.N. et al. Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma. Annals of Surgical Oncology 9, 1004–1009 (2002). https://doi.org/10.1007/BF02574520

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  • DOI: https://doi.org/10.1007/BF02574520

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