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Annals of Surgical Oncology

, Volume 19, Issue 6, pp 1800–1807 | Cite as

Long-Term Outcome of Isolated Limb Perfusion in Advanced Soft Tissue Sarcoma of the Extremity

  • R. Olofsson
  • P. Bergh
  • Ö. Berlin
  • K. Engström
  • B. Gunterberg
  • M. Hansson
  • P. Lindnér
  • J. Mattsson
Bone and Soft Tissue Sarcomas

Abstract

Background

Isolated limb perfusion with tumor necrosis factor alpha and melphalan (TM-ILP) has proven to be a successful option in treating advanced soft tissue sarcomas (STS), where amputation otherwise is needed to achieve safe surgical margins.

Methods

From 2000 to 2009, 54 patients with locally advanced STS, who all were candidates for amputation, were treated with totally 57 TM-ILP procedures and then followed prospectively. The median follow-up time was 30 months. Median tumor size was 10 cm, and 94% of the patients had high-grade tumors.

Results

The clinical overall response after TM-ILP was 71% (including 21% CR), and 60% of the patients underwent resection of the tumor remnant after a median of 2 months. The histopathologic response rate in the resected specimens was 76%. Local recurrence/progress occurred in 37% of the patients after a median of 7 months. Thirteen patients finally underwent amputation after a median of 11 months, giving a long-term limb salvage of 76%.

Conclusions

TM-ILP of advanced soft tissue sarcoma of the extremities makes limb-sparing surgery possible in a high proportion of patients.

Keywords

Soft Tissue Sarcoma Synovial Sarcoma Soft Tissue Sarcoma Isolate Limb Perfusion Histopathologic Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Cormier JN, Pollock RE. Soft tissue sarcomas. CA Cancer J Clin. 2004;54:94–109.PubMedCrossRefGoogle Scholar
  2. 2.
    Bauer HC, Trovik CS, Alvegard TA, et al. Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register. Acta Orthop Scand. 2001;72:150–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Lienard D, Ewalenko P, Delmotte JJ, et al. 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.PubMedGoogle Scholar
  4. 4.
    Eggermont AM, Schraffordt Koops H, 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Lejeune FJ, Pujol N, Lienard D, et al. Limb salvage by neoadjuvant isolated perfusion with TNFalpha and melphalan for non-resectable soft tissue sarcoma of the extremities. Eur J Surg Oncol. 2000;26:669–78.PubMedCrossRefGoogle Scholar
  6. 6.
    Rossi CR, Foletto M, Mocellin S, et al. Hyperthermic isolated perfusion with low-dose TNFalpha and doxorubicin in patients with locally advanced soft tissue limb sarcomas. J Chemother. 2004;16(Suppl. 5):58–61.PubMedGoogle Scholar
  7. 7.
    Bonvalot S, Laplanche A, Lejeune F, et al. Limb salvage with isolated perfusion for soft tissue sarcoma: could less TNF-alpha be better? Ann Oncol. 2005;16:1061–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Di Filippo F, Giacomini P, Rossi CR, et al. Hyperthermic isolated perfusion with tumor necrosis factor-alpha and doxorubicin for the treatment of limb-threatening soft tissue sarcoma: the experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO). In Vivo. 2009;23:363–7.PubMedGoogle Scholar
  9. 9.
    Lev-Chelouche D, Abu-Abeid S, Kollander Y, et al. Multifocal soft tissue sarcoma: limb salvage following hyperthermic isolated limb perfusion with high-dose tumor necrosis factor and melphalan. J Surg Oncol. 1999;70:185–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Broders A, Hargrave R, Meyerding H. Pathological features of soft tissue fibrosarcoma with special reference to the grading of its malignancy. Surg Gynecol Obstet. 1939;69:267.Google Scholar
  11. 11.
    Eggermont AM, Schraffordt Koops H, 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.PubMedGoogle Scholar
  12. 12.
    Schraffordt Koops H, Oldhoff J, Oosterhuis JW, Beekhuis H. Isolated regional perfusion in malignant melanoma of the extremities. World J Surg. 1987;11:527–33.PubMedCrossRefGoogle Scholar
  13. 13.
    World Health Organization. WHO handbook for reporting results of cancer treatment. Geneva: World Health Organization, 1979.Google Scholar
  14. 14.
    Wieberdink J, Benckhuysen C, Braat RP, et al. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Aksnes LH, Bauer HC, Jebsen NL, et al. Limb-sparing surgery preserves more function than amputation: a Scandinavian sarcoma group study of 118 patients. J Bone Joint Surg Br. 2008;90:786–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Pardasaney PK, Sullivan PE, Portney LG, Mankin HJ. Advantage of limb salvage over amputation for proximal lower extremity tumors. Clin Orthop Relat Res. 2006;444:201–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Gortzak E, Azzarelli A, Buesa J, et al. A randomised phase II study on neo-adjuvant chemotherapy for “high-risk” adult soft-tissue sarcoma. Eur J Cancer. 2001;37:1096–103.PubMedCrossRefGoogle Scholar
  18. 18.
    Al-Absi E, Farrokhyar F, Sharma R, et al. A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma. Ann Surg Oncol. 2010;17:1367–74.PubMedCrossRefGoogle Scholar
  19. 19.
    Issels RD, Lindner LH, Verweij J, et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010;11:561–70.PubMedCrossRefGoogle Scholar
  20. 20.
    Muramatsu K, Ihara K, Miyoshi T, et al. Clinical outcome of limb-salvage surgery after wide resection of sarcoma and femoral vessel reconstruction. Ann Vasc Surg. 2011;25:1070–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Noorda EM, Vrouenraets BC, Nieweg OE, et al. Isolated limb perfusion with tumor necrosis factor-alpha and melphalan for patients with unresectable soft tissue sarcoma of the extremities. Cancer. 2003;98:1483–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Grunhagen DJ, de Wilt JH, Graveland WJ, et al. Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alpha and melphalan for limb-threatening soft tissue sarcoma. Cancer. 2006;106:1776–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Thijssens KM, van Ginkel RJ, Pras E, et al. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: the value of adjuvant radiotherapy. Ann Surg Oncol. 2006;13:518–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Cherix S, Speiser M, Matter M, 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.PubMedCrossRefGoogle Scholar
  25. 25.
    Hayes AJ, Neuhaus SJ, Clark MA, Thomas JM. Isolated limb perfusion with melphalan and tumor necrosis factor alpha for advanced melanoma and soft-tissue sarcoma. Ann Surg Oncol. 2007;14:230–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Pennacchioli E, Deraco M, Mariani L, 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Bonvalot S, Rimareix F, Causeret S, 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Lasithiotakis K, Economou G, Gogas H, et al. Hyperthermic isolated limb perfusion for recurrent melanomas and soft tissue sarcomas: feasibility and reproducibility in a multi-institutional Hellenic collaborative study. Oncol Rep. 2010;23:1077–83.PubMedGoogle Scholar
  29. 29.
    Schuetze SM, Baker LH, Benjamin RS, Canetta R. Selection of response criteria for clinical trials of sarcoma treatment. Oncologist. 2008;13(Suppl. 2):32–40.PubMedCrossRefGoogle Scholar
  30. 30.
    Stacchiotti S, Collini P, Messina A, et al. High-grade soft-tissue sarcomas: tumor response assessment—pilot study to assess the correlation between radiologic and pathologic response by using RECIST and Choi criteria. Radiology. 2009;251:447–56.PubMedCrossRefGoogle Scholar
  31. 31.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl. 1):122S–50S.PubMedCrossRefGoogle Scholar
  32. 32.
    Been LB, Suurmeijer AJ, Elsinga PH, et al. 18F-fluorodeoxythymidine PET for evaluating the response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcomas. J Nucl Med. 2007;48:367–72.PubMedGoogle Scholar
  33. 33.
    Stener B. Musculoskeletal tumor surgery in Göteborg. Clin Orthop Relat Res. 1984(191):8–20.Google Scholar
  34. 34.
    Casali PG, Blay JY. Soft tissue sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl. 5):v198–203.PubMedCrossRefGoogle Scholar
  35. 35.
    Engstrom K, Bergh P, Cederlund CG, et al. Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology. Acta Oncol. 2007;46:838–45.PubMedCrossRefGoogle Scholar
  36. 36.
    Deroose JP, Burger JW, van Geel AN, 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.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • R. Olofsson
    • 1
  • P. Bergh
    • 2
  • Ö. Berlin
    • 2
  • K. Engström
    • 3
  • B. Gunterberg
    • 2
  • M. Hansson
    • 4
  • P. Lindnér
    • 5
  • J. Mattsson
    • 1
  1. 1.Department of SurgerySahlgrenska University HospitalGöteborgSweden
  2. 2.Department of OrthopaedicsSahlgrenska University HospitalGöteborgSweden
  3. 3.Department of OncologySahlgrenska University HospitalGöteborgSweden
  4. 4.Department of PathologySahlgrenska University HospitalGöteborgSweden
  5. 5.Transplant InstituteSahlgrenska University HospitalGöteborgSweden

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