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Long-term Morbidity After Regional Isolated Perfusion With Melphalan for Melanoma of the Limbs: The Influence of Acute Regional Toxic Reactions

Long-term Morbidity After Regional Isolated Perfusion With Melphalan for Melanoma of the Limbs:... Abstract Objective: To determine the influence of acute regional toxic reactions on the incidence and characteristics of long-term morbidity after regional isolated perfusion with melphalan. Design: Retrospective study. Setting: The Amsterdam and Rotterdam perfusion centers, the Netherlands. Patients: All patients with melanoma who were treated between 1978 and 1990 and had a minimum follow-up of 1 year after perfusion (n=367). Intervention: Fifty-four patients (15%) had perfusion of the upper limb, 313 (85%) had perfusion of the lower limb, and 164 patients (45%) underwent regional lymph node dissection at the time of perfusion. Main Outcome Measure: Incidence and characteristics of morbidity 1 year after perfusion and the influence of acute regional toxic reactions on long-term morbidity. Results: One hundred sixty patients (44%) showed some degree of objective or subjective morbidity; most (104 [28%]) had lymphedema. Other long-term morbidity consisted of muscle atrophy or fibrosis (42 [11%]), limb malfunction (55 [15%]), neuropathy (13 [4%]), pain (28 [8%]), and recurrent infection (11 [3%]). Miscellaneous complications were seen in 14 patients (4%). Seventy-one patients (19%) had more than one complication. Acute regional toxic reactions had a statistically significant effect on the incidence of long-term morbidity (P<.01). Moderate to severe acute regional toxic reactions were strongly linked to the occurrence of muscle atrophy or fibrosis (P<.001) and limb malfunction (P<.001). Regional lymph node dissection was statistically significantly related to lymphedema (P=.05). Conclusion: Improvement of the perfusion technique should be pursued in an effort to reduce acute regional toxic reactions, and thereby long-term morbidity, without compromising the therapeutic effect.(Arch Surg. 1995;130:43-47) References 1. Coit DG. Hyperthermic isolation limb perfusion for malignant melanoma: a review . Cancer Invest . 1992:10:277-284.Crossref 2. Vrouenraets BC, Klaase JM, Van Geel AN, et al. Regional isolated limb perfusion in patients with malignant melanoma . Onkologie . 1993;16:163-169.Crossref 3. Hafström L, Rudenstam C-M, Blomquist E, et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities . J Clin Oncol . 1991:9:2091-2094. 4. Lejeune FJ. A randomized trial on prophylactic isolation perfusion for stage 1 high risk (i.e. 1.5mm thickness) malignant melanoma of the limbs: an interim report . Melanoma Res . 1993;3( (suppl 1) ):95.Crossref 5. Van Geel AN, Van Wijk J, Wieberdink J. Functional morbidity after regional isolated perfusion of the limbs for melanoma . Cancer . 1989;63:1092-1096.Crossref 6. Klaase JM, Kroon BBR, Van Geel AN, Eggermont AMM, Franklin HR, Hart AAM. Patient and treatment related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities . Am J Surg . 1994; 167:618-620.Crossref 7. Skene Al, Bulman AS, Williams TR, Meirion Thomas J, Westbury G. Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb . Br J Surg . 1990;77:765-767.Crossref 8. Krementz ET. Regional perfusion: current sophistication, what next? Cancer . 1986;57:416-432.Crossref 9. Edwards MJ, Soong S-J, Boddie AW, Balch CM, McBride CM. Isolated limb perfusion for localized melanoma of the extremity: a matched comparison of wide local excision with isolated limb perfusion and wide local excision alone . Arch Surg . 1990;125:317-321.Crossref 10. Lee Y-TM. Loco-regional recurrent melanoma, II: non-systemic treatments (1964-1979) . Cancer Treat Rev . 1988;15:105-133.Crossref 11. Ghussen F, Nagel K, Groth W, Müller JM, Stützer H. A prospective randomized study of regional extremity perfusion in patients with malignant melanoma . Ann Surg . 1984;200:764-768.Crossref 12. Lejeune FJ, Deloof T, Ewalenko P, et al. Objective regression of unexcised melanoma in-transit metastases after hyperthermic isolation perfusion of the limbs with melphalan . Recent Results Cancer Res . 1983;86:268-276. 13. Kroon BBR. Regional isolation perfusion in melanoma of the limbs: accomplishments, unsolved problems, future . Eur J Surg Oncol . 1988;14:101-110. 14. Kroon BBR, Klaase JM, Van Geel AN, Eggermont AMM, Franklin HR, Van Dongen JA. Results of a double perfusion schedule with melphalan in patients with melanoma of the lower limb . Eur J Cancer . 1993;29A:325-328.Crossref 15. Kroon BBR, Klaase JM, Van Geel AN, Eggermont AMM. Application of hyperthermia in regional isolated perfusion for melanoma of the limbs . Reg Cancer Treat . 1992;4:223-226. 16. EORTC Malignant Melanoma Cooperative Group. A Randomized Trial on Prophylactic Isolation Perfusion for Stage I High Risk (≥1.5 mm Thickness) Malignant Melanoma of the Limbs. Brussels , Belgium: European Organization for Research and Treatment on Cancer; 1984. Protocol 18832. 17. Wieberdink J, Benckhuysen 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 . 1982; 18:905-910.Crossref 18. Klaase JM, Kroon BBR, Van Slooten GW, Benckhuijsen C. Relation between calculated melphalan peak concentrations and toxicity in regional isolated perfusion for melanoma . Reg Cancer Treat . 1992;4:309-312. 19. Krementz ET, Saha S. Limb perfusion with melphalan for melanoma by increased dose and dilution compared to standard technique: a pilot study . Reg Cancer Treat . 1989;2:233-237. 20. Fontijne WPJ, Mook PH, Schraffordt Koops H, Oldhoff J, Wildevuur CRH. Improved tissue perfusion during pressure regulated hyperthermic regional isolated perfusion: a clinical study . Cancer . 1985;55:1455-1461.Crossref 21. Byrne DS, McKay AJ, Scott RN, et al. Assessment of regional perfusion for melanoma by peroperative transcutaneous oxygen tension measurement . Reg Cancer Treat . 1990;3:88-89. 22. Klaase JM, Kroon BBR, Van de Merwe SA, Van der Zee J, Van Slooten GW, Van Dongen JA. Comparison between the use of whole blood versus a diluted perfusate in regional isolated perfusion by continuous monitoring of transcutaneous oxygen tension: a pilot study . J Invest Surg . 1994;7:249-258.Crossref 23. Scott RN, Kerr DJ, Blackie R, et al. The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma . Br J Cancer . 1992;66:159-166.Crossref 24. Klaase JM, Kroon BBR, Beijnen JH, Van Slooten GW, Van Dongen JA. Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb . Br J Cancer . 1994;70:151-153.Crossref 25. Baas PC, Schraffordt Koops H, Hoekstra HJ, Van Bruggen JJ, Van der Weele LT, Oldhoff J. Groin dissection in the treatment of lower-extremity melanoma: short-term and long-term morbidity . Arch Surg . 1992;127:281-286.Crossref 26. Ames FC, Balch CM, McCarthy WH. Axillary lymph node dissection . In: Balch CM, Houghton AN, Milton GW, Sober AJ, Soong S-J, eds. Cutaneous Melanoma . Philadelphia, Pa: JB Lippincott Co; 1992:384-391. 27. Karakousis CP, Hena MA, Emrich LJ, Driscoll DL. Axillary node dissection in malignant melanoma: results and complications . Surgery . 1990;108:10-17. 28. Vrouenraets BC, Eggermont AMM, Klaase JM, Van Geel BN, Kroon BBR. Long-term neuropathy after regional isolated perfusion with melphalan for melanoma of the extremities. Eur J Surg Oncol. In press. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Long-term Morbidity After Regional Isolated Perfusion With Melphalan for Melanoma of the Limbs: The Influence of Acute Regional Toxic Reactions

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American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1995.01430010045009
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Abstract

Abstract Objective: To determine the influence of acute regional toxic reactions on the incidence and characteristics of long-term morbidity after regional isolated perfusion with melphalan. Design: Retrospective study. Setting: The Amsterdam and Rotterdam perfusion centers, the Netherlands. Patients: All patients with melanoma who were treated between 1978 and 1990 and had a minimum follow-up of 1 year after perfusion (n=367). Intervention: Fifty-four patients (15%) had perfusion of the upper limb, 313 (85%) had perfusion of the lower limb, and 164 patients (45%) underwent regional lymph node dissection at the time of perfusion. Main Outcome Measure: Incidence and characteristics of morbidity 1 year after perfusion and the influence of acute regional toxic reactions on long-term morbidity. Results: One hundred sixty patients (44%) showed some degree of objective or subjective morbidity; most (104 [28%]) had lymphedema. Other long-term morbidity consisted of muscle atrophy or fibrosis (42 [11%]), limb malfunction (55 [15%]), neuropathy (13 [4%]), pain (28 [8%]), and recurrent infection (11 [3%]). Miscellaneous complications were seen in 14 patients (4%). Seventy-one patients (19%) had more than one complication. Acute regional toxic reactions had a statistically significant effect on the incidence of long-term morbidity (P<.01). Moderate to severe acute regional toxic reactions were strongly linked to the occurrence of muscle atrophy or fibrosis (P<.001) and limb malfunction (P<.001). Regional lymph node dissection was statistically significantly related to lymphedema (P=.05). Conclusion: Improvement of the perfusion technique should be pursued in an effort to reduce acute regional toxic reactions, and thereby long-term morbidity, without compromising the therapeutic effect.(Arch Surg. 1995;130:43-47) References 1. Coit DG. Hyperthermic isolation limb perfusion for malignant melanoma: a review . Cancer Invest . 1992:10:277-284.Crossref 2. Vrouenraets BC, Klaase JM, Van Geel AN, et al. Regional isolated limb perfusion in patients with malignant melanoma . Onkologie . 1993;16:163-169.Crossref 3. Hafström L, Rudenstam C-M, Blomquist E, et al. Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities . J Clin Oncol . 1991:9:2091-2094. 4. Lejeune FJ. A randomized trial on prophylactic isolation perfusion for stage 1 high risk (i.e. 1.5mm thickness) malignant melanoma of the limbs: an interim report . Melanoma Res . 1993;3( (suppl 1) ):95.Crossref 5. Van Geel AN, Van Wijk J, Wieberdink J. Functional morbidity after regional isolated perfusion of the limbs for melanoma . Cancer . 1989;63:1092-1096.Crossref 6. Klaase JM, Kroon BBR, Van Geel AN, Eggermont AMM, Franklin HR, Hart AAM. Patient and treatment related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities . Am J Surg . 1994; 167:618-620.Crossref 7. Skene Al, Bulman AS, Williams TR, Meirion Thomas J, Westbury G. Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb . Br J Surg . 1990;77:765-767.Crossref 8. Krementz ET. Regional perfusion: current sophistication, what next? Cancer . 1986;57:416-432.Crossref 9. Edwards MJ, Soong S-J, Boddie AW, Balch CM, McBride CM. Isolated limb perfusion for localized melanoma of the extremity: a matched comparison of wide local excision with isolated limb perfusion and wide local excision alone . Arch Surg . 1990;125:317-321.Crossref 10. Lee Y-TM. Loco-regional recurrent melanoma, II: non-systemic treatments (1964-1979) . Cancer Treat Rev . 1988;15:105-133.Crossref 11. Ghussen F, Nagel K, Groth W, Müller JM, Stützer H. A prospective randomized study of regional extremity perfusion in patients with malignant melanoma . Ann Surg . 1984;200:764-768.Crossref 12. Lejeune FJ, Deloof T, Ewalenko P, et al. Objective regression of unexcised melanoma in-transit metastases after hyperthermic isolation perfusion of the limbs with melphalan . Recent Results Cancer Res . 1983;86:268-276. 13. Kroon BBR. Regional isolation perfusion in melanoma of the limbs: accomplishments, unsolved problems, future . Eur J Surg Oncol . 1988;14:101-110. 14. Kroon BBR, Klaase JM, Van Geel AN, Eggermont AMM, Franklin HR, Van Dongen JA. Results of a double perfusion schedule with melphalan in patients with melanoma of the lower limb . Eur J Cancer . 1993;29A:325-328.Crossref 15. Kroon BBR, Klaase JM, Van Geel AN, Eggermont AMM. Application of hyperthermia in regional isolated perfusion for melanoma of the limbs . Reg Cancer Treat . 1992;4:223-226. 16. EORTC Malignant Melanoma Cooperative Group. A Randomized Trial on Prophylactic Isolation Perfusion for Stage I High Risk (≥1.5 mm Thickness) Malignant Melanoma of the Limbs. Brussels , Belgium: European Organization for Research and Treatment on Cancer; 1984. Protocol 18832. 17. Wieberdink J, Benckhuysen 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 . 1982; 18:905-910.Crossref 18. Klaase JM, Kroon BBR, Van Slooten GW, Benckhuijsen C. Relation between calculated melphalan peak concentrations and toxicity in regional isolated perfusion for melanoma . Reg Cancer Treat . 1992;4:309-312. 19. Krementz ET, Saha S. Limb perfusion with melphalan for melanoma by increased dose and dilution compared to standard technique: a pilot study . Reg Cancer Treat . 1989;2:233-237. 20. Fontijne WPJ, Mook PH, Schraffordt Koops H, Oldhoff J, Wildevuur CRH. Improved tissue perfusion during pressure regulated hyperthermic regional isolated perfusion: a clinical study . Cancer . 1985;55:1455-1461.Crossref 21. Byrne DS, McKay AJ, Scott RN, et al. Assessment of regional perfusion for melanoma by peroperative transcutaneous oxygen tension measurement . Reg Cancer Treat . 1990;3:88-89. 22. Klaase JM, Kroon BBR, Van de Merwe SA, Van der Zee J, Van Slooten GW, Van Dongen JA. Comparison between the use of whole blood versus a diluted perfusate in regional isolated perfusion by continuous monitoring of transcutaneous oxygen tension: a pilot study . J Invest Surg . 1994;7:249-258.Crossref 23. Scott RN, Kerr DJ, Blackie R, et al. The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma . Br J Cancer . 1992;66:159-166.Crossref 24. Klaase JM, Kroon BBR, Beijnen JH, Van Slooten GW, Van Dongen JA. Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb . Br J Cancer . 1994;70:151-153.Crossref 25. Baas PC, Schraffordt Koops H, Hoekstra HJ, Van Bruggen JJ, Van der Weele LT, Oldhoff J. Groin dissection in the treatment of lower-extremity melanoma: short-term and long-term morbidity . Arch Surg . 1992;127:281-286.Crossref 26. Ames FC, Balch CM, McCarthy WH. Axillary lymph node dissection . In: Balch CM, Houghton AN, Milton GW, Sober AJ, Soong S-J, eds. Cutaneous Melanoma . Philadelphia, Pa: JB Lippincott Co; 1992:384-391. 27. Karakousis CP, Hena MA, Emrich LJ, Driscoll DL. Axillary node dissection in malignant melanoma: results and complications . Surgery . 1990;108:10-17. 28. Vrouenraets BC, Eggermont AMM, Klaase JM, Van Geel BN, Kroon BBR. Long-term neuropathy after regional isolated perfusion with melphalan for melanoma of the extremities. Eur J Surg Oncol. In press.

Journal

Archives of SurgeryAmerican Medical Association

Published: Jan 1, 1995

References