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Isolated limb perfusion with high-dose tumor necrosis factor-α for locally advanced extremity soft tissue sarcomas

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Soft Tissue Sarcomas: Present Achievements and Future Prospects

Part of the book series: Cancer Treatment and Research ((CTAR,volume 91))

Abstract

Sixty percent of the 6000 new cases of soft tissue sarcomas diagnosed in the United States each year occur in the extremities and are often large at the time of initial diagnosis [1]. Surgery for locally advanced extremity soft tissue sarcomas may consist of an amputation or exarticulation. Limb-sparing surgical procedures in these advanced cases, if at all possible, usually consist of extensive but still marginal resections requiring adjuvant radiation therapy to a large area. In those cases where location of the tumor dictate the sacrifice of functionally crucial muscles and or joint-spanning radiation therapy treatment may mutilate and compromise limb function considerably, some form of induction therapy prior to surgery should be considered. Preservation of the limb and limb function has become all the more important in light of evidence that amputations do not improve survival rates because the prognosis in patients with large (>5 cm) deep-seated, high-grade soft tissue sarcomas is not, or is only marginally, influenced by the extent of the procedure dealing with the primary tumor [2]. Although local recurrence rates vary according to the initial surgical procedure and improved local control has been reported to correlate with better survival [3], several recent studies have not been able to show that ‘inadequate treatment,’ that is, marginal excisions with a high risk for local recurrence, influences survival significantly [2,4-7].

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References

  1. Boring CC, Squires TS, Tong T, Montgomery S. Cancer Statistics, 1994. CA Cancer J Clin 44:7–26, 1994.

    Article  PubMed  CAS  Google Scholar 

  2. Gaynor JJ, Tan CC, Casper ES, et al. Refinement of clincopathologic staging for localized soft tissue sarcoma of the extremity: A study of 423 adults. J Clin Oncol 10:1317–1327, 1992.

    PubMed  CAS  Google Scholar 

  3. Suit HD, Tepper JE. Impact of improved local control on survival in patients with soft tissue sarcoma. Int J Radiat Oncol Biol Phys 12:699–700, 1986.

    Article  PubMed  CAS  Google Scholar 

  4. Brennan MF, Shiu MH, Collin C, et al. Extremity soft tissue sarcomas. Cancer Treat Symp 3:71–81, 1985.

    Google Scholar 

  5. Potter DA, Kinsella D, Gladstein E, et al. High grade soft tissue sarcomas of the extremities. Cancer 59:190–205, 1986.

    Article  Google Scholar 

  6. Stotter AT, A’Hearn RP, Fisher C, Mott AF, Fallowfield ME, Westbury G. The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival. Cancer 65:1119–1129, 1990.

    Article  PubMed  CAS  Google Scholar 

  7. Gustafson P, Rööser B, Rydholm A. Is local recurrence of minor importance for metastases in soft tissue sarcoma? Cancer 67:2083–2086, 1991.

    Article  PubMed  CAS  Google Scholar 

  8. Suit HD, Proppe KH, Mankin HJ, Wood WC. Preoperative radiation therapy for sarcoma of soft tissue. Cancer 47:2269–2274, 1981.

    Article  PubMed  CAS  Google Scholar 

  9. Rouësse JG, Friedman S, Sevin DM, et al. Preoperative induction chemotherapy in the treatment of locally advanced soft tissue sarcomas. Cancer 60:296–300, 1987.

    Article  PubMed  Google Scholar 

  10. Eilber FR, Mirra JJ, Grant T, Weisenburger T, Morton DL. Is amputation necessary for sarcoma: A 7-year experiment with limb salvage. Ann Surg 192:431–437, 1980.

    Article  PubMed  CAS  Google Scholar 

  11. Eilber FR, Morton DL, Eckhardt J, Grant T, Weisenburger T. Limb salvage for skeletal and soft-tissue sarcomas: Multidisciplinary preoperative therapy. Cancer 53:2579–2584, 1984.

    Article  PubMed  CAS  Google Scholar 

  12. Wanebo HJ, Temple WJ, Popp MB, Constable W, Aron B, Cunningham SL. Preoperative regional therapy for extremity sarcoma: A tricenter update. Cancer 75:2299–2306, 1995.

    Article  PubMed  CAS  Google Scholar 

  13. Shiu MH, Hilaris BS, Harrison LB, Brennan MF. Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb. Int J Radiat Oncol Biol Phys 21:1485–1492, 1991.

    Article  PubMed  CAS  Google Scholar 

  14. Creech OJ, Krementz ET, Ryan RF, Winblad JN. Chemotherapy of cancer: Regional perfusion utilizing an extracorporeal circuit. Ann Surg 148:616–632, 1958.

    Article  PubMed  Google Scholar 

  15. Benckhuijsen C, Kroon BBR, Van Geel AN, Wieberdink J. Regional perfusion treatment with melphalan for melanoma in a limb: Evaluation of drug kinetics. Eur J Surg Oncol 14:157–163, 1988.

    PubMed  CAS  Google Scholar 

  16. Thompson JF, Gianoutsos MP. Isolated limb perfusion for melanoma: Effectiveness and toxicity of cisplatin compared with that of melphalan and other drugs. World J Surg 61:227–233, 1992.

    Article  Google Scholar 

  17. Krementz ET, Carter RD, Sutherland CM, Hutton I. Chemotherapy of sarcomas of the limbs by regional perfusion. Ann Surg 185:555–564, 1977.

    Article  PubMed  CAS  Google Scholar 

  18. Klaase JM, Kroon BBR, Benckhuysen C, Van Geel AN, Albus-Lutter ChE, Wieberdink J. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities. Cancer 64:616–621, 1989.

    Article  PubMed  CAS  Google Scholar 

  19. Rossi CR, Vecchiato A, Foletto M, et al. Phase II study on neoadjuvant hyperthermicantiblastic perfusion with doxorubicin in patients with intermediate of high grade limb sarcomas. Cancer 73:2140–2146, 1994.

    Article  PubMed  CAS  Google Scholar 

  20. Filippo FD, Calabro AM, Cavallari A, et al. The role of hyperthermic perfusion as a first step in the treatment of soft tissue sarcomas of the extremities. World J Surg 12:332–339, 1988.

    Article  PubMed  Google Scholar 

  21. McBride CM. Sarcomas of the limbs: Result of adjuvant chemotherapy using isolation perfusion. Arch Surg 109:304–308, 1974.

    Article  PubMed  CAS  Google Scholar 

  22. Stehlin JS, de Ipolyi PD, Giovanella BC, Gutierrez AE, Anderson RF. Soft tissue sarcomas of the extremity: Multidisciplinary therapy employing hyperthermic perfusion. Am J Surg 130:643–646, 1975.

    Article  PubMed  Google Scholar 

  23. Lethi PM, Stephens MH, Janoff K, Stevens K, Fletcher WS. Improved survival for soft tissue sarcoma of the extremities by regional hyperthermic perfusion, local excision and radiation therapy. Surg Gynecol Obstet 162:149–152, 1986.

    Google Scholar 

  24. Hoekstra HJ, Schraffordt Koops H, Molenaar WM, Oldhoff J, Results of isolated regional perfusion in the treatment of malignant soft tissue tumors of the extremities. Cancer 60:1703–1707, 1987.

    Article  PubMed  CAS  Google Scholar 

  25. Braat RP, Wieberdink J, van Slooten EA, Olthuis G. Regional perfusion with Adriamycin in soft tissue sarcomas. In K Schwemmle, K Aigner, eds. Vascular Perfusion in Cancer Therapy. Recent Results in Cancer Research, Vol. 86. Berlin: Springer-Verlag, 1983:260–263.

    Chapter  Google Scholar 

  26. Liénard D, Delmotte JJ, Renard N, Ewalenko P, Lejeune FJ. High doses of rTNF-α in combination with IFN-gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol 10:52–60, 1992.

    PubMed  Google Scholar 

  27. Eggermont AMM, Liénard D, Schraffordt Koops H, Van Geel AN, Hoekstra HJ, Lejeune FJ. Limb salvage by high dose tumor necrosis factor-alpha (TNF), gamma-interferon (IFN) and melphalan isolated limb perfusion (ILP) in patients with irresectable soft tissue sarcomas (abstr). Proc Am Soc Cin Oncol 11:412, 1992.

    Google Scholar 

  28. Eggermont AMM, Schraffordt Koops H, Liénard D, Kroon BBR, Van Geel AN, Hoekstra HJ, Lejeune FJ. Isolated limb perfuson with high-dose tumot necrosis factor-α in combination with inteferon-γ and melphalan for irresectable extremity soft tissue sarcomas: A multicenter trial. J Clin Oncol 14:2556–2565, 1996.

    Google Scholar 

  29. Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults; study of pathologic prognostic variables and definition of a histopathological grading system. Int J Cancer 33:37–42, 1984.

    Article  PubMed  CAS  Google Scholar 

  30. Hoekstra HJ, Naujocks T, Schraffordt Koops H, et al. Continuous leakage monitoring during hyperthermic isolated regional perfusion of the lower limb: Techniques and results. Reg Cancer Treat 4:301–304, 1992.

    Google Scholar 

  31. Klaase JM, Kroon BBR, Van Geel AN, Eggermont AMM, Franklin HR. Systemic leakage during isolated limb perfusion for melanoma. Br J Surg 80:1124–1126, 1993.

    Article  PubMed  CAS  Google Scholar 

  32. WHO Handbook for Reporting Results of Cancer Treatment. WHO Offset Publication No. 48. Geneva: WHO, 1979.

    Google Scholar 

  33. Wieberdink J, Benckhuijsen 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 18:905–910, 1982.

    Article  PubMed  CAS  Google Scholar 

  34. Sijens PE, Eggermont AMM, Van Dijk P, Oudkerk M. 31P magnetic resonance spectroscopy as predictor for clinical response in human extremity sarcomas treated by single dose TNFα + melphalan isolated limb perfusion. NMR Biomed 8:215–224, 1995.

    Article  PubMed  CAS  Google Scholar 

  35. Nieweg OE, Pruim J, Hoekstra HJ, et al. Positron emission tomography with fluorine-18-fluorodeoxyglucose for the evaluation of therapeutic isolated regional limb perfusion in a patient with soft-tissue sarcoma. J Nucl Med 35:90–92, 1994.

    PubMed  CAS  Google Scholar 

  36. Hill S, Fawcett WJ, Sheldon J, Soni N, Williams T, Thomas JM, Low-dose tumour necrosis factor a and melphalan in hyperthermic isolated limb perfusion. Br J Surg 80:995–997, 1993.

    Article  PubMed  CAS  Google Scholar 

  37. Vaglini M, Belli F, Ammatuna M, et al. Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon and melphalan. Cancer 73:483–492, 1994.

    Article  PubMed  CAS  Google Scholar 

  38. Thorn AK, Alexander HR, Andrich MP, Barker WC, Rosenberg SA, Fraker DL. Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor, interferon gamma, and melphalan. J Clin Oncol 13:264–273, 1995.

    Google Scholar 

  39. Swaak AJG, Liénard D, Schraffordt Koops H, Lejeune FJ, Eggermont AMM. Effects of recombinant tumour necrosis factor (rTNF-α) in cancer. Observations on the acute phase protein reaction and Immunoglobulin synthesis after high dose recombinant TNF-α administration in isolated limb perfusions in cancer patients. Eur J Clin Invest 23:812–818, 1993.

    Article  PubMed  CAS  Google Scholar 

  40. Lejeune FJ, Liénard D, Eggermont AMM, et al. Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma. Circ Shock 43:191–197, 1994.

    PubMed  CAS  Google Scholar 

  41. Posner M, Liénard D, Lejeune FJ, Rosenfelder D, Kirkwood JM. Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor (TNF) alone for metastatic intransit melanoma (abstr). Proc Am Soc Clin Oncol 13:1351, 1994.

    Google Scholar 

  42. Manusama ER, Nooijen PTGA, Stavast J, Durante NMC, Marquet RL, Eggermont AMM. Synergistic antitumour effect of recombinant human tumour necrosis factor α with melphalan in isolated limb perfusion in the rat. Br J Surg 83:551–555, 1996.

    Article  PubMed  CAS  Google Scholar 

  43. Spriggs DR, Sherman ML, Michie H, et al. Recombinant human tumor necrosis factor administered as a 24 h intravenous infusion. A phase I and pharmacologic study. J Natl Cancer Inst 80:1039–1044, 1988.

    Article  PubMed  CAS  Google Scholar 

  44. Blick MB, Sherwin SA, Rosenblum M, et al. A phase I trial of recombinant human tumor necrosis factor in cancer patients. Cancer Res 47:2986–2989, 1987.

    PubMed  CAS  Google Scholar 

  45. Chapman PB, Lester TJ, Casper ES, et al. Clinical pharmacology of recombinant human tumor necrosis factor in patients with advanced cancer. J Clin Oncol 5:1942–1951, 1987.

    PubMed  CAS  Google Scholar 

  46. Feinberg B, Kurzrock R, Talpaz M, et al. A phase I trial of intravenously administered recombinant tumor necrosis factor alpha in cancer patients. J Clin Oncol 6:1328–1334, 1988.

    PubMed  CAS  Google Scholar 

  47. Asher AL, Mule JJ, Reichert CM, Shilone E, Rosenberg SA. Studies of the antitumor efficacy of systemically administered recombinant tumor necrosis factor against several murine tumors in vivo. J Immunol 138:963–974, 1987.

    PubMed  CAS  Google Scholar 

  48. Carswell EA, Old LJ, Kassel RL, et al. An endotoxin induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–4370, 1975.

    Article  PubMed  CAS  Google Scholar 

  49. Sugarman BJ, Aggarwal BB, Hass PE, et al. Recombinant tumor necrosis factor-alpha: Effects on proliferation of normal and transformed cells in vitro. Science 230:943–945, 1985.

    Article  PubMed  CAS  Google Scholar 

  50. Renard N, Liénard D, Lespagnard L, Eggermont AMM, Heimann R, Lejeune FJ. Early endothelium activation and polymorphonuclear cell invasion precede specific necrosis of human melanoma and sarcoma treated by intravascular high-dose tumour necrosis factor alpha (TNFα). Int J Cancer 57:656–663, 1994.

    Article  PubMed  CAS  Google Scholar 

  51. Renard N, Nooijen PTGA, Schalkwijk L, et al. VWF release and platelet aggregation in human melanoma after perfusion with TNFα. J Pathol 176:279–287, 1995.

    Article  PubMed  CAS  Google Scholar 

  52. Watanabe N, Niitsu Y, Umeno H, et al. Toxic effect of TNF on tumor vasculature in mice. Cancer Res 49:2179–2183, 1988.

    Google Scholar 

  53. Sato N, Goto T, Haranaka K, et al. Actions of TNF on cultured vascular endothelial cells: Morphological modulation, growth inhibition and cytotoxicity. J Natl Cancer Inst 76:1113–1121, 1986.

    PubMed  CAS  Google Scholar 

  54. Bloksma N, van de Wiel PA, Kuper CF, Hofhuis FMA. Multiple facets of induction of tumor necrosis. Ann Inst Pasteur/Immunol 139:294–299, 1988.

    Article  CAS  Google Scholar 

  55. Nawroth P, Handley D, Matsueda G, et al. TNF/cachectin-induced intravascular fibrin formation in Meth-A fibrosarcomas. J Exp Med 168:637–647, 1988.

    Article  PubMed  CAS  Google Scholar 

  56. Manusama ER, Stavast J, Marquet RL, Eggermont AMM. Total body irradiation (TBI) attenuates antitumor effects of TNFα in isolated limb perfusions (ILP) in the rat (abstr). Eur J Surg Res 27(Suppl l):110, 1995.

    Google Scholar 

  57. Prograbniak HW, Witt CJ, Terrill R, et al. Isolated lung perfusion with tumor necrosis factor: A swine model in preparation of human trials. Ann Thorac Surg 57:1477–1483, 1994.

    Article  Google Scholar 

  58. Fraker DL, Alexander HR, Thorn AK. Use of tumor necrosis factor in isolated hepatic perfusion. Circ Shock 44:45–50, 1994.

    PubMed  CAS  Google Scholar 

  59. Vries de MR, Borel Rinkes IHM, Wiggers T, Jonker AM, Weijers-Hille MJ, Eggermont AMM. Hyperthermie isolated hepatic perfusion with TNFα with and without melphalan in pigs (abstr). Eur J Surg Res 27(Suppl 1):81, 1995.

    Google Scholar 

  60. Veen van de AH, Manusama ER, Kampen van CA, Durante NMC, Marquet RL, Eggermont AMM. Eur J Surg Oncol 20:404–405, 1994.

    Google Scholar 

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Authors
  1. A. M. M. Eggermont
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  2. H. Schraffordt Koops
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  3. J. M. Klausner
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  4. P. M. Schlag
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  5. B. B. R. Kroon
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  6. G. Ben-Ari
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  7. F. J. Lejeune
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Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Rotterdam Cancer Institute, Rotterdam, The Netherlands

    J. Verweij

  2. Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands

    H. M. Pinedo

  3. Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    H. D. Suit

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Eggermont, A.M.M. et al. (1997). Isolated limb perfusion with high-dose tumor necrosis factor-α for locally advanced extremity soft tissue sarcomas. In: Verweij, J., Pinedo, H.M., Suit, H.D. (eds) Soft Tissue Sarcomas: Present Achievements and Future Prospects. Cancer Treatment and Research, vol 91. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6121-7_13

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  • DOI: https://doi.org/10.1007/978-1-4615-6121-7_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7805-1

  • Online ISBN: 978-1-4615-6121-7

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