Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2006

01-04-2006

Isolated Limb Perfusion With Tumor Necrosis Factor α and Melphalan for Locally Advanced Soft Tissue Sarcoma: The Value of Adjuvant Radiotherapy

Authors: Katja M. J. Thijssens, MD, Robert J. van Ginkel, MD, PhD, Elisabeth Pras, MD, PhD, Albert J. H. Suurmeijer, MD, PhD, Harald J. Hoekstra, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2006

Login to get access

Abstract

Background

The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor α and melphalan followed by limb-saving surgery.

Methods

From 1991 to 2003, 73 patients (median age, 54 years; range, 14–80 years) underwent 77 ILPs, followed by resection in 68 patients (93%). Radiotherapy was administered in case of marginally or microscopically positive resection margins. Local recurrences were scored and calculated according to the Kaplan-Meier method and log-rank test.

Results

After residual tumor mass resection, 58% received radiotherapy (external beam radiotherapy [EBRT]+ group), and 42% did not (EBRT group). The median follow-up was 28 months (range, 2–159 months). A significantly better local control rate was observed in the EBRT+ compared with the EBRT group (P < .0001). When only R0 resections in patients without metastasis were considered, the significance remained between groups (P = .0003). In the EBRT group, an R1 or R2 resection resulted in earlier relapse of local disease compared with R0 resections (P = .0475).

Conclusions

Adjuvant EBRT reduces the risk for local recurrence after delayed resection in soft tissue sarcoma patients treated with ILP and tumor necrosis factor and is indicated when resection margins are close or microscopically positive. It also seems beneficial after an R0 resection.
Literature
1.
go back to reference Singer S, Demetri GD, Baldini EH, Fletcher CDM. Management of soft-tissue sarcomas: an overview and update. Lancet Oncol 2000;1:75–85CrossRefPubMed Singer S, Demetri GD, Baldini EH, Fletcher CDM. Management of soft-tissue sarcomas: an overview and update. Lancet Oncol 2000;1:75–85CrossRefPubMed
2.
go back to reference 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; discussion 764–5CrossRefPubMed 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; discussion 764–5CrossRefPubMed
3.
go back to reference Van Ginkel RJ, Thijssens K, Pras E, van der Graaf WTA, Suurmeijer AJH, Hoekstra HJ. Isolated limb perfusion with TNF and melphalan for locally advanced soft tissue sarcoma; three time periods at risk for amputation (abstract). Ann Surg Oncol 2004;11:S54 Van Ginkel RJ, Thijssens K, Pras E, van der Graaf WTA, Suurmeijer AJH, Hoekstra HJ. Isolated limb perfusion with TNF and melphalan for locally advanced soft tissue sarcoma; three time periods at risk for amputation (abstract). Ann Surg Oncol 2004;11:S54
4.
go back to reference Fletcher CDM, Unni KK, Mertens F, (eds). World Health Organisation: Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002 Fletcher CDM, Unni KK, Mertens F, (eds). World Health Organisation: Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press, 2002
5.
go back to reference Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997;15:350–62PubMed Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997;15:350–62PubMed
6.
go back to reference Hogeboom WR, Hoekstra HJ, Mooyaart EL, Freling NJ, Schraffordt Koops H. MRI or CT in the preoperative evaluation of soft-tissue tumors. Arch Orthop Trauma Surg 1991;110:162–4PubMed Hogeboom WR, Hoekstra HJ, Mooyaart EL, Freling NJ, Schraffordt Koops H. MRI or CT in the preoperative evaluation of soft-tissue tumors. Arch Orthop Trauma Surg 1991;110:162–4PubMed
7.
go back to reference Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag, 2002 Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag, 2002
8.
go back to reference Fontijne WP, Mook PH, Schraffordt Koops H, Oldhoff J, Wildevuur CR. Improved tissue perfusion during pressure regulated hyperthermic regional isolated perfusion: a clinical study. Cancer 1985;55:1455–61PubMed Fontijne WP, Mook PH, Schraffordt Koops H, Oldhoff J, Wildevuur CR. Improved tissue perfusion during pressure regulated hyperthermic regional isolated perfusion: a clinical study. Cancer 1985;55:1455–61PubMed
9.
go back to reference Schraffordt Koops H, Oldhoff J, Oosterhuis JW, Beekhuis H. Isolated regional perfusion in malignant melanoma of the extremities. World J Surg 1987;11:527–33PubMed Schraffordt Koops H, Oldhoff J, Oosterhuis JW, Beekhuis H. Isolated regional perfusion in malignant melanoma of the extremities. World J Surg 1987;11:527–33PubMed
10.
go back to reference Daryanani D, Komdeur R, Ter Veen J, Nijhuis PH, Piers DA, Hoekstra HJ. Continuous leakage measurement during hyperthermic isolated limb perfusion. Ann Surg Oncol 2001;8:564–5 Daryanani D, Komdeur R, Ter Veen J, Nijhuis PH, Piers DA, Hoekstra HJ. Continuous leakage measurement during hyperthermic isolated limb perfusion. Ann Surg Oncol 2001;8:564–5
11.
go back to reference World Health Organisation: Handbook for Reporting Results of Cancer Treatment. Geneva: WHO Offset Publication, 1979 World Health Organisation: Handbook for Reporting Results of Cancer Treatment. Geneva: WHO Offset Publication, 1979
12.
go back to reference Kaplan EL, Meier P. Nonparametric estimates from incomplete observations. J Am Stat Assoc 1958;53:457–81 Kaplan EL, Meier P. Nonparametric estimates from incomplete observations. J Am Stat Assoc 1958;53:457–81
13.
go back to reference Williard WC, Hajdu SI, Casper ES, Brennan MF. Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity. Ann Surg 1992;215:269–75PubMed Williard WC, Hajdu SI, Casper ES, Brennan MF. Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity. Ann Surg 1992;215:269–75PubMed
14.
go back to reference Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859–68PubMed Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859–68PubMed
15.
go back to reference Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196:305–15PubMed Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196:305–15PubMed
16.
go back to reference Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197–203PubMed Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197–203PubMed
17.
go back to reference Fein DA, Lee WR, Lanciano RM, et al. Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control? Int J Radiat Oncol Biol Phys 1995;32:969–76PubMed Fein DA, Lee WR, Lanciano RM, et al. Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control? Int J Radiat Oncol Biol Phys 1995;32:969–76PubMed
18.
go back to reference Olieman AF, Pras E, van Ginkel RJ, Molenaar WM, Schraffordt Koops H, Hoekstra HJ. Feasibility and efficacy of external beam radiotherapy after hyperthermic isolated limb perfusion with TNF-alpha and melphalan for limb-saving treatment in locally advanced extremity soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 1998;40:807–14CrossRefPubMed Olieman AF, Pras E, van Ginkel RJ, Molenaar WM, Schraffordt Koops H, Hoekstra HJ. Feasibility and efficacy of external beam radiotherapy after hyperthermic isolated limb perfusion with TNF-alpha and melphalan for limb-saving treatment in locally advanced extremity soft-tissue sarcoma. Int J Radiat Oncol Biol Phys 1998;40:807–14CrossRefPubMed
19.
go back to reference Trovik CS, Bauer HC, Berlin O, et al. Local recurrence of deep-seated, high-grade, soft tissue sarcoma: 459 patients from the Scandinavian Sarcoma Group Register. Acta Orthop Scand 2001;72:160–6PubMed Trovik CS, Bauer HC, Berlin O, et al. Local recurrence of deep-seated, high-grade, soft tissue sarcoma: 459 patients from the Scandinavian Sarcoma Group Register. Acta Orthop Scand 2001;72:160–6PubMed
20.
go back to reference Lin PP, Boland PJ, Healy JH. Treatment of femoral fractures after irradiation. Clin Orthop Relat Res 1998;352:168–78PubMed Lin PP, Boland PJ, Healy JH. Treatment of femoral fractures after irradiation. Clin Orthop Relat Res 1998;352:168–78PubMed
21.
go back to reference O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 2002;359:2235–41PubMed O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 2002;359:2235–41PubMed
22.
go back to reference Lans TE, Grunhagen DJ, de Wilt JHW, van Geel AN, Eggermont AMM. Isolated limb perfusions with TNF and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs. Ann Surg Oncol 2005;12:406–11CrossRefPubMed Lans TE, Grunhagen DJ, de Wilt JHW, van Geel AN, Eggermont AMM. Isolated limb perfusions with TNF and melphalan for locally recurrent soft tissue sarcoma in previously irradiated limbs. Ann Surg Oncol 2005;12:406–11CrossRefPubMed
23.
go back to reference van Ginkel RJ, Hoekstra HJ, Pruim J, et al. FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. J Nucl Med 1996;37:984–90PubMed van Ginkel RJ, Hoekstra HJ, Pruim J, et al. FDG-PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma. J Nucl Med 1996;37:984–90PubMed
Metadata
Title
Isolated Limb Perfusion With Tumor Necrosis Factor α and Melphalan for Locally Advanced Soft Tissue Sarcoma: The Value of Adjuvant Radiotherapy
Authors
Katja M. J. Thijssens, MD
Robert J. van Ginkel, MD, PhD
Elisabeth Pras, MD, PhD
Albert J. H. Suurmeijer, MD, PhD
Harald J. Hoekstra, MD, PhD
Publication date
01-04-2006
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 4/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/ASO.2006.02.005

Other articles of this Issue 4/2006

Annals of Surgical Oncology 4/2006 Go to the issue