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Erschienen in: Annals of Surgical Oncology 2/2007

01.02.2007

Preoperative Isolated Limb Infusion of Doxorubicin and External Irradiation for Limb-Threatening Soft Tissue Sarcomas

verfasst von: Mohamed A. F. Hegazy, Sherif Z. Kotb, Hanem Sakr, Ebrahim El Dosoky, Talal Amer, Refaat A. F. Hegazi, Omar Farouk

Erschienen in: Annals of Surgical Oncology | Ausgabe 2/2007

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Abstract

Background

At present, limb-sparing surgery is the most appropriate and acceptable treatment option for soft tissue sarcomas of the extremities. To increase the number of limb-sparing resections in the treatment of locally advanced soft tissue sarcomas of the extremities, preoperative radiotherapy and/or chemotherapy are often used. Isolated limb perfusion of cytostatic agents is an effective alternative option but technically complex. Isolated limb infusion, essentially a low-flow isolated limb perfusion without oxygenation via a percutaneous catheter, had been developed as a simple alternative.

Objective

The objective of this study was to achieve limb-sparing surgery in patients with locally advanced soft tissue sarcomas of the extremities that would otherwise have required an amputation or a functionally mutilating surgery by performing preoperative isolated limb infusion with doxorubicin and external beam irradiation to obtain local control and make limb-sparing surgery feasible.

Methods

A total of 40 patients with locally advanced soft tissue sarcomas of the extremities were evaluated between 2002 and 2005. Tumors were located in the lower limb in 28 patients (70%) and in the upper limb in 12 patients (30%). All of these patients were felt to be unresectable and were referred because amputation was considered the only available treatment option. They underwent preoperative isolated limb infusion with doxorubicin (0.7 and 1.4 mg/kg for the upper and lower limbs, respectively). Preoperative external beam radiotherapy started within 3–7 days after isolated limb infusion was administered. The total dose was 35 Gy in ten fractions. After 3–7 weeks, surgery was performed aiming at limb preservation.

Results

Tumor response was seen in 85% of patients, rendering these large sarcomas resectable in most cases. The mean values of pretreatment tumor volume and post-treatment volume were 2797 cm3 and 1781 cm3, respectively, with a significant p value of 0.0001. Histologic response was seen in 80% of patients. At a median followup of 15 months (range = 5–35), limb salvage was achieved in 82.5%. Procedure-related complications were limited and easily managed.

Conclusion

Isolated limb infusion with doxorubicin is a simple and safe method of regional chemotherapy. The addition of preoperative external beam irradiation helped to increase the rate of limb salvage in patients with large and/or high-grade soft tissue sarcomas of the extremities.
Literatur
1.
Zurück zum Zitat Pollock RE, Karnell LH, Menck HR, et al. The National Cancer Database Report on soft tissue sarcoma. Cancer 1996; 78:2247–2257PubMedCrossRef Pollock RE, Karnell LH, Menck HR, et al. The National Cancer Database Report on soft tissue sarcoma. Cancer 1996; 78:2247–2257PubMedCrossRef
2.
Zurück zum Zitat Pitcher ME, Ramanathan RC, Fish S, et al. Outcome of treatment of limb and limb girdle sarcoma at the Royal Marsden Hospital. Eur J Surg Oncol 2000; 26:548–551PubMedCrossRef Pitcher ME, Ramanathan RC, Fish S, et al. Outcome of treatment of limb and limb girdle sarcoma at the Royal Marsden Hospital. Eur J Surg Oncol 2000; 26:548–551PubMedCrossRef
3.
Zurück zum Zitat Billingsley KG, Lewis JJ, Leung DH, et al. Multifactorial analysis of the survival of patients with distant metastasis arising from extremity sarcoma. Cancer 1999; 85:389–395PubMedCrossRef Billingsley KG, Lewis JJ, Leung DH, et al. Multifactorial analysis of the survival of patients with distant metastasis arising from extremity sarcoma. Cancer 1999; 85:389–395PubMedCrossRef
4.
Zurück zum Zitat Suit HD, Tepper JE. Impact of improved local control on survival in patients with soft tissue sarcoma. Int J Radiat Oncol Biol Phys 1986; 12:699–700PubMed Suit HD, Tepper JE. Impact of improved local control on survival in patients with soft tissue sarcoma. Int J Radiat Oncol Biol Phys 1986; 12:699–700PubMed
5.
Zurück zum Zitat Morton DL, Eilber FR, Weisenberger TH, et al. Limb salvage using preoperative intra-arterial Adriamycin and radiation therapy for extremity soft tissue sarcomas. Aust NZ J Surg 1987; 48:56–59CrossRef Morton DL, Eilber FR, Weisenberger TH, et al. Limb salvage using preoperative intra-arterial Adriamycin and radiation therapy for extremity soft tissue sarcomas. Aust NZ J Surg 1987; 48:56–59CrossRef
6.
Zurück zum Zitat Eilber FR, Morton DL, Eckhardt J, et al. Limb salvage for skeletal and soft tissue sarcomas: multidisciplinary preoperative therapy. Cancer 1984; 53:2579–2584PubMedCrossRef Eilber FR, Morton DL, Eckhardt J, et al. Limb salvage for skeletal and soft tissue sarcomas: multidisciplinary preoperative therapy. Cancer 1984; 53:2579–2584PubMedCrossRef
7.
Zurück zum Zitat Pisters PWT, Ballo MT, Patel SP. Preoperative chemoradiation treatment strategies for localized sarcoma. Ann Surg Oncol 2002; 9(6):535–542PubMedCrossRef Pisters PWT, Ballo MT, Patel SP. Preoperative chemoradiation treatment strategies for localized sarcoma. Ann Surg Oncol 2002; 9(6):535–542PubMedCrossRef
8.
Zurück zum Zitat Creech O, Krementz E, Ryan R. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg 1958; 148:616–632PubMedCrossRef Creech O, Krementz E, Ryan R. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg 1958; 148:616–632PubMedCrossRef
9.
Zurück zum Zitat Thompson JF, Kam PC, Waugh RC, et al. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol 1998: 14(3):238–247PubMedCrossRef Thompson JF, Kam PC, Waugh RC, et al. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol 1998: 14(3):238–247PubMedCrossRef
10.
Zurück zum Zitat Linder P, Doubrovsky A, Kam PC, Thompson JF. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol 2002; 9(2):127–136 Linder P, Doubrovsky A, Kam PC, Thompson JF. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol 2002; 9(2):127–136
11.
Zurück zum Zitat Wieberdink J, Benchuysen 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; 18:905–910PubMedCrossRef Wieberdink J, Benchuysen 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; 18:905–910PubMedCrossRef
12.
Zurück zum Zitat O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs: A randomized trial. Lancet 2002; 359:2235–2241PubMedCrossRef O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs: A randomized trial. Lancet 2002; 359:2235–2241PubMedCrossRef
13.
Zurück zum Zitat Rossi CR, Foletto M, Alessio S, et al. Limb sparing treatment for soft tissue sarcomas: Influence of prognostic factors. J Surg Oncol 1996; 63:3–8PubMedCrossRef Rossi CR, Foletto M, Alessio S, et al. Limb sparing treatment for soft tissue sarcomas: Influence of prognostic factors. J Surg Oncol 1996; 63:3–8PubMedCrossRef
14.
Zurück zum Zitat Brennan MF, Caspar ES, Harrison KB, et al. The role of multimodality therapy in soft tissue sarcoma. Ann Surg 1991; 214:328–336PubMedCrossRef Brennan MF, Caspar ES, Harrison KB, et al. The role of multimodality therapy in soft tissue sarcoma. Ann Surg 1991; 214:328–336PubMedCrossRef
15.
Zurück zum Zitat Schary MF, Gunderson LL, Sim FH, et al. Soft tissue sarcoma; integration of brachytherapy, resection and external irradiation. Cancer 1990; 66:451–456CrossRef Schary MF, Gunderson LL, Sim FH, et al. Soft tissue sarcoma; integration of brachytherapy, resection and external irradiation. Cancer 1990; 66:451–456CrossRef
16.
Zurück zum Zitat Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft tissue sarcomas of the extremities: prospective randomized study evaluation of (1) limb sparing surgery plus irradiation compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982: 196:305–315PubMedCrossRef Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft tissue sarcomas of the extremities: prospective randomized study evaluation of (1) limb sparing surgery plus irradiation compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982: 196:305–315PubMedCrossRef
17.
Zurück zum Zitat Pisters PW, Harrison LB, Leung DH, et al. Long term results of as prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996; 14:859–868PubMed Pisters PW, Harrison LB, Leung DH, et al. Long term results of as prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996; 14:859–868PubMed
18.
Zurück zum Zitat Rooser B, Gustafson P, Rydholm AS. Is there no influence of local control on the rate of metastases in high grade soft tissue sarcoma? Cancer 1990; 65:1727–1729PubMedCrossRef Rooser B, Gustafson P, Rydholm AS. Is there no influence of local control on the rate of metastases in high grade soft tissue sarcoma? Cancer 1990; 65:1727–1729PubMedCrossRef
19.
Zurück zum Zitat Skibber JM, Lotz MT, Seipp CA, et al. Limb sparing surgery for soft tissue sarcoma: wound related morbidity in patients undergoing wide local excision. Surgery 1987; 102:447–452PubMed Skibber JM, Lotz MT, Seipp CA, et al. Limb sparing surgery for soft tissue sarcoma: wound related morbidity in patients undergoing wide local excision. Surgery 1987; 102:447–452PubMed
20.
Zurück zum Zitat Spira AI, Ettinger DS. The use of chemotherapy in soft tissue sarcoma. Oncologist 2002; 7:348–359PubMedCrossRef Spira AI, Ettinger DS. The use of chemotherapy in soft tissue sarcoma. Oncologist 2002; 7:348–359PubMedCrossRef
21.
Zurück zum Zitat Abdel-Wahab O, Grubbs E, Viglianti BL, et al. The role of hyperthermia in regional alkylating agent chemotherapy. Clin Cancer Res 2004; 10:5919–5929PubMedCrossRef Abdel-Wahab O, Grubbs E, Viglianti BL, et al. The role of hyperthermia in regional alkylating agent chemotherapy. Clin Cancer Res 2004; 10:5919–5929PubMedCrossRef
22.
Zurück zum Zitat Mian R, Henderson MA, Speakman D, et al. Isolated limb infusion for melanoma: a simple alternative to isolated limb perfusion. Can J Surg 2001: 44:189–192PubMed Mian R, Henderson MA, Speakman D, et al. Isolated limb infusion for melanoma: a simple alternative to isolated limb perfusion. Can J Surg 2001: 44:189–192PubMed
23.
Zurück zum Zitat Rossi CR, Vecchiato A, Foletto M, et al. Phase II study on neoadjuvant hyperthermic antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas. Cancer 1994; 73:2140–2146PubMedCrossRef Rossi CR, Vecchiato A, Foletto M, et al. Phase II study on neoadjuvant hyperthermic antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas. Cancer 1994; 73:2140–2146PubMedCrossRef
24.
Zurück zum Zitat Ginkel RJ, Schraffordt KH, Vries EG, et al. Hyperthermic isolated limb perfusion with cisplatin in four patients with sarcomas of the soft tissue and the bone. Eur J Surg 1996; 22:528–531 Ginkel RJ, Schraffordt KH, Vries EG, et al. Hyperthermic isolated limb perfusion with cisplatin in four patients with sarcomas of the soft tissue and the bone. Eur J Surg 1996; 22:528–531
25.
Zurück zum Zitat Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1995; 13:1537–1545PubMed Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1995; 13:1537–1545PubMed
26.
Zurück zum Zitat Klaase JM, Kroon BB, Benckhuijsen C, et al. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities. Cancer 1989;64:616–621PubMedCrossRef Klaase JM, Kroon BB, Benckhuijsen C, et al. Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities. Cancer 1989;64:616–621PubMedCrossRef
27.
Zurück zum Zitat Rossi CR, Foletto M, Di Filippo F, et al. Soft tissue limb sarcoma: Italian clinical trials with hyperthermic antiblastic perfusion. Cancer 1999; 86:1742–1749PubMedCrossRef Rossi CR, Foletto M, Di Filippo F, et al. Soft tissue limb sarcoma: Italian clinical trials with hyperthermic antiblastic perfusion. Cancer 1999; 86:1742–1749PubMedCrossRef
28.
Zurück zum Zitat Bonifati DM, Ori C, Rossi CR, et al. Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents. Cancer Chemother Pharmacol 2000; 46:517–522PubMedCrossRef Bonifati DM, Ori C, Rossi CR, et al. Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents. Cancer Chemother Pharmacol 2000; 46:517–522PubMedCrossRef
29.
Zurück zum Zitat Huth JF, Eilber FR. Preoperative intra-arterial chemotherapy. Cancer Treat Res 1989; 44:103–110PubMed Huth JF, Eilber FR. Preoperative intra-arterial chemotherapy. Cancer Treat Res 1989; 44:103–110PubMed
30.
Zurück zum Zitat Soulen MC, Weismann JR, Sullivan KL, et al. Intra-arterial chemotherapy with limb sparing resection of large soft tissue sarcomas of the extremities. J Vasc Interv Radiol 1992; 3:659–663PubMedCrossRef Soulen MC, Weismann JR, Sullivan KL, et al. Intra-arterial chemotherapy with limb sparing resection of large soft tissue sarcomas of the extremities. J Vasc Interv Radiol 1992; 3:659–663PubMedCrossRef
31.
Zurück zum Zitat Bezwada HP, Granick MS, Long CD, et al. Soft tissue complications of intra-arterial chemotherapy for extremity sarcoma. Ann Plast Surg 1998; 40:382–387PubMedCrossRef Bezwada HP, Granick MS, Long CD, et al. Soft tissue complications of intra-arterial chemotherapy for extremity sarcoma. Ann Plast Surg 1998; 40:382–387PubMedCrossRef
32.
Zurück zum Zitat Temple WJ, Temple CL, Arthur K, et al. Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol 1997; 4:586–590PubMedCrossRef Temple WJ, Temple CL, Arthur K, et al. Prospective cohort study of neoadjuvant treatment in conservative surgery of soft tissue sarcomas. Ann Surg Oncol 1997; 4:586–590PubMedCrossRef
33.
Zurück zum Zitat Nijhuis PH, Pras E, Sleijfer DT, et al. Long term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities. Radiother Oncol 1999; 51:15–19PubMedCrossRef Nijhuis PH, Pras E, Sleijfer DT, et al. Long term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities. Radiother Oncol 1999; 51:15–19PubMedCrossRef
34.
Zurück zum Zitat Rossi CR, Mocellin S, Pilati P, et al. TNF alpha based isolated perfusion for limb threatening soft tissue sarcomas: State of the art and future trends. J Immunother 2003; 26(4):291–300PubMedCrossRef Rossi CR, Mocellin S, Pilati P, et al. TNF alpha based isolated perfusion for limb threatening soft tissue sarcomas: State of the art and future trends. J Immunother 2003; 26(4):291–300PubMedCrossRef
35.
Zurück zum Zitat Lejeune FJ, Pujol N, Lienard D, et al. Limb salvage by neoadjuvant isolated perfusion with TNF alpha and melphalan for non-resectable soft tissue sarcomas of the extremities. Eur J Surg Oncol 2000; 26:669–678PubMedCrossRef Lejeune FJ, Pujol N, Lienard D, et al. Limb salvage by neoadjuvant isolated perfusion with TNF alpha and melphalan for non-resectable soft tissue sarcomas of the extremities. Eur J Surg Oncol 2000; 26:669–678PubMedCrossRef
36.
Zurück zum Zitat Noorda EM, Vrouwenraets BC, Nieweg OE, et al. Isolated limb perfusion with TNF α and melphalan for unresectable soft tissue sarcoma of the extremities. Ann Surg Oncol 2003; 10:S36 Noorda EM, Vrouwenraets BC, Nieweg OE, et al. Isolated limb perfusion with TNF α and melphalan for unresectable soft tissue sarcoma of the extremities. Ann Surg Oncol 2003; 10:S36
37.
Zurück zum Zitat Grunhagen D, Lans TE, de Wilt JHW, et al. Management of local recurrence of soft tissue sarcomas in an irradiated field after prior surgery and radiotherapy: the role of TNF-based isolated limb perfusion to achieve limb salvage. Eur J Cancer Suppl 2003; 1:699CrossRef Grunhagen D, Lans TE, de Wilt JHW, et al. Management of local recurrence of soft tissue sarcomas in an irradiated field after prior surgery and radiotherapy: the role of TNF-based isolated limb perfusion to achieve limb salvage. Eur J Cancer Suppl 2003; 1:699CrossRef
Metadaten
Titel
Preoperative Isolated Limb Infusion of Doxorubicin and External Irradiation for Limb-Threatening Soft Tissue Sarcomas
verfasst von
Mohamed A. F. Hegazy
Sherif Z. Kotb
Hanem Sakr
Ebrahim El Dosoky
Talal Amer
Refaat A. F. Hegazi
Omar Farouk
Publikationsdatum
01.02.2007
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 2/2007
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9138-1

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