Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2016

01-04-2016 | Melanomas

Australian Multicenter Study of Isolated Limb Infusion for Melanoma

Authors: Hidde M. Kroon, MD, PhD, Brendon J. Coventry, BMBS, PhD, FRACS, FACS, FRSM, Mitchell H. Giles, BMBS, Michael A. Henderson, MDDS, MD, BMed Sci, David Speakman, MDDS, FRACS, Mark Wall, BMBS, Andrew Barbour, MBBS, PhD, FRACS, Jonathan Serpell, MDDS, MD, FRACS, Paul Paddle, MBBS, Alexander G. J. Coventry, BMBS, Thomas Sullivan, MsC, Bernard Mark Smithers, MBBS, FRACS, FRCS, John F. Thompson, MBBS, BSC(Med), MD, FRACS, FACS

Published in: Annals of Surgical Oncology | Issue 4/2016

Login to get access

Abstract

Purpose

Isolated limb infusion (ILI) offers a less invasive alternative to isolated limb perfusion (ILP) for the treatment of locally advanced extremity melanoma. In Australia, ILI has essentially completely replaced ILP. The aim of this study was to collect and evaluate the results of ILI in an Australian multicenter setting.

Patients and Methods

The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were collectively analyzed, with all five institutions using the same protocol. Melphalan was circulated in the isolated limb for 20–30 min (±actinomycin D). Response was determined using the World Health Organization criteria, and limb toxicity was assessed using the Wieberdink scale.

Results

The median patient age was 74 years (range 28–100) and 59 % of patients were female. Overall response rate was 75 % (complete response [CR] 33 %; partial response 42 %). Stable disease was seen in 18 % of patients and progressive disease in 7 %. Wieberdink grade III or higher was seen in 30 % of the cases. No toxicity-related amputations occurred, and median survival was 44 months. In patients with a CR, median survival was 80 months (p = 0.014). On multivariate analysis, Breslow thickness, lower-limb ILI, and a procedure performed at the Melanoma Institute Australia remained significant predictors for response, although not for survival.

Conclusions

This Australian multicenter study of ILI is the largest reported to date. ILI is a useful technique that can be safely and effectively performed across tertiary referral centers for the successful management of advanced extremity melanoma. Increased optimization of perioperative factors might allow response rates to be raised further, while maintaining acceptable toxicity.
Literature
1.
Australian Institute of Health and Welfare, and Australasian Association of Cancer Registries 2012. Cancer in Australia: an overview, 2012. Australian Cancer Incidence and Mortality Workbooks-Melanoma. Cancer series no. 74. Cat. no. CAN 70. Canberra: Australian Institute of Health and Welfare; 2012.
2.
Francken AB, Accortt NA, Shaw HM, et al. Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma. Ann Surg Oncol. 2008;15:1476–84.CrossRefPubMed
3.
Testori A, Faries MB, Thompson JF, et al. Local and intralesional therapy of in-transit melanoma metastases. J Surg Oncol. 2011;104:391–6.CrossRefPubMed
4.
Moreno-Ramirez D, de la Cruz-Merino L, Ferrandiz L, et al. Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety. Oncologist. 2010;15:416–27.CrossRefPubMedPubMedCentral
5.
Thompson JF, Waugh RC, Saw RPM, et al. Isolated limb infusion with melphalan for recurrent limb melanoma: a simple alternative to isolated limb perfusion. Reg Cancer Treat. 1994;7:188–92.
6.
7.
Kroon HM, Lin DY, Kam PC, et al. Efficacy of repeat isolated limb infusion with melphalan and actinomycin-D for recurrent melanoma. Cancer. 2009;115:1932–40.CrossRefPubMed
8.
Kroon HM, Huismans AM, Kam PCA, et al. Isolated limb infusion with melphalan and actinomycin D for melanoma: a systematic review. J Surg Oncol. 2014;109:348–51.CrossRefPubMed
9.
Kroon HM, Moncrieff M, Kam PC, et al. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15:3003–13.CrossRefPubMed
10.
Beasley GM, Caudle A, Petersen RP, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg. 2009;208:706–15.CrossRefPubMed
11.
12.
Klaase JM, Kroon BB, van Geel AN, et al. Limb recurrence-free interval and survival in patients with recurrent melanoma of the extremities treated with normothermic isolated perfusion. J Am Coll Surg. 1994; 178:564–72.PubMed
13.
Thompson JF, Kam PCA, de Wilt JHW, et al. Isolated limb infusion for melanoma. In: Thompson JF, Morton DL, Kroon BBR, editors. Textbook of melanoma. London: Martin Dunitz; 2004: pp. 429–37.
14.
Kroon HM, Huismans AM, Kam PCA, et al. Isolated limb infusion: technical aspects. J Surg Oncol. 2014;109:352–6.CrossRefPubMed
15.
Giles MH, Coventry BJ. Isolated limb infusion chemotherapy for melanoma: an overview of early experience at the Adelaide Melanoma Unit. Cancer Manag Res. 2013;5:243–9.PubMedPubMedCentral
16.
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.CrossRefPubMed
17.
Lai DTM, Ingvar C, Thompson JF. The value of monitoring serum creatine phosphokinase values following hyperthermic isolated limb perfusion for melanoma. Reg Cancer Treat. 1993;6:36–9.
18.
World Health Organization. WHO handbook for reporting results of cancer treatments. WHO Offset Publication No. 48. Geneva: World Health Organization; 1979.
19.
Kaplan L, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1985;53:457–81.CrossRef
20.
Cox DR. Regression models and life table. J Stat Soc. 1972;34:187–220.
21.
Huismans AM, Kroon HM, Kam PC, et al. Does increased experience with isolated limb infusion for advanced limb melanoma influence outcome? A comparison of two treatment periods at a single institution. Ann Surg Oncol. 2011;18:1877–83.CrossRefPubMed
22.
Coventry BJ, Kroon HM, Giles MH, et al. Australian multi-center experience outside of the Sydney Melanoma Unit of isolated limb infusion chemotherapy for melanoma. J Surg Oncol. 2014;109:780–5.CrossRefPubMed
23.
Beasley GM, Sharma K, Wong J, et al. A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion. Cancer. 2012;118:6136–43.CrossRefPubMed
24.
Barbour AP, Thomas J, Suffolk J, et al. Isolated limb infusion for malignant melanoma: predictors of response and outcome. Ann Surg Oncol. 2009;16:3463–72.CrossRefPubMed
25.
Sanki A, Kroon HM, Kam PCA, et al. Isolated limb perfusion and isolated limb infusion for malignant lesions of the extremities. Curr Probl Surg. 2011;48:371–430.CrossRefPubMed
26.
Vrouenraets BC, Kroon BBR, Nieweg OE, et al. Isolated limb perfusion for melanoma: results and complications, toxicity. In: Thompson JF, Morton DL, Kroon BBR, editors. Textbook of melanoma. London: Martin Dunitz; 2004: pp. 410–28.
27.
Kroon HM, Moncrieff M, Kam PC, et al. Factors predictive of acute regional toxicity after isolated limb infusion with melphalan and actinomycin D in melanoma patients. Ann Surg Oncol. 2009;16:1184–92.CrossRefPubMed
28.
Santillan AA, Delman KA, Beasley GM, et al. Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol. 2009;16:2570–8.CrossRefPubMed
29.
Scott RN, Blackie R, Kerr DJ, et al. Melphalan in isolated limb perfusion for malignant melanoma, bolus or divided dose, tissue levels, the pH effect. In: Jakesz R, Rainer H, editos. Progress in regional cancer therapy. Berlin: Springer; 1990: pp. 195–200.CrossRef
30.
Klaase JM, Kroon BBR, Beijnen JH, et al. Melphalan tissue concentrations in patients treated with regional isolated perfusion for melanoma of the lower limb. Br J Cancer. 1994;70:151–3.CrossRefPubMedPubMedCentral
31.
Huismans AM, Kroon HM, Haydu LE, et al. Is melphalan dose adjustment according to ideal body weight useful in isolated limb infusion for melanoma? Ann Surg Oncol. 2012;19:3050–6.CrossRefPubMed
32.
McMahon N, Cheng TY, Beasley GM, et al. Optimizing melphalan pharmacokinetics in regional melanoma therapy: does correcting for ideal body weight alter regional response or toxicity? Ann Surg Oncol. 2009;16:953–61.CrossRefPubMed
33.
Siemann DW, Chapman M, Beikirch A. Effects of oxygenation and pH on tumor cell response to alkylating chemotherapy. Int J Radiat Oncol Biol Phys. 1991;20:287–9.CrossRefPubMed
34.
Wu ZY, Smithers BM, Parsons PG, et al. The effects of perfusion conditions on melphalan distribution in the isolated perfused rat hindlimb bearing a human melanoma xenograft. Br J Cancer. 1997;75:1160–6.CrossRefPubMedPubMedCentral
35.
Koops HS, Vaglini M, Suciu S, et al. Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. J Clin Oncol. 1998;16:2906–12.PubMed
36.
Wong J, Ann Chen Y, Fisher KJ, et al. Resection of residual disease after isolated limb infusion (ILI) is equivalent to a complete response after ILI-alone in advanced extremity melanoma. Ann Surg Oncol. 2014;21:650–5.CrossRefPubMedPubMedCentral
37.
Thompson JF, Agarwala SS, Smithers BM, et al. Phase 2 study of intralesional PV-10 in refractory metastatic melanoma. Ann Surg Oncol. 2015;22:2135–42.CrossRefPubMedPubMedCentral
38.
Damian DL, Saw RP, Thompson JF. Topical immunotherapy with diphencyprone for in transit and cutaneously metastatic melanoma. J Surg Oncol. 2014;109:308–13.CrossRefPubMed
39.
Muilenburg DJ, Beasley GM, Thompson ZJ, et al. Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin d in melanoma. Ann Surg Oncol. 2015;22:482–8.CrossRefPubMedPubMedCentral
40.
Beasley GM, Coleman AP, Raymond A, et al. A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity. Ann Surg Oncol. 2012;19:3896–905.CrossRefPubMedPubMedCentral
41.
Beasley GM, Riboh JC, Augustine CK, et al. Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma. J Clin Oncol. 2011;29:1210–5.CrossRefPubMedPubMedCentral
42.
Coventry BJ, Ashdown ML. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation. Cancer Manag Res. 2012;4:137–49.CrossRefPubMedPubMedCentral
43.
Metadata
Title
Australian Multicenter Study of Isolated Limb Infusion for Melanoma
Authors
Hidde M. Kroon, MD, PhD
Brendon J. Coventry, BMBS, PhD, FRACS, FACS, FRSM
Mitchell H. Giles, BMBS
Michael A. Henderson, MDDS, MD, BMed Sci
David Speakman, MDDS, FRACS
Mark Wall, BMBS
Andrew Barbour, MBBS, PhD, FRACS
Jonathan Serpell, MDDS, MD, FRACS
Paul Paddle, MBBS
Alexander G. J. Coventry, BMBS
Thomas Sullivan, MsC
Bernard Mark Smithers, MBBS, FRACS, FRCS
John F. Thompson, MBBS, BSC(Med), MD, FRACS, FACS
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4969-2

Other articles of this Issue 4/2016

Annals of Surgical Oncology 4/2016 Go to the issue

Gastrointestinal Oncology

Is There Any Role of Adjuvant Chemotherapy for T3N0M0 or T1N2M0 Gastric Cancer Patients in Stage II in the 7th TNM but Stage I in the 6th TNM System?

Hepatobiliary Tumors

Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma

Hepatobiliary Tumors

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases

Gastrointestinal Oncology

Is All Advanced Gastric Cancer Suitable for Laparoscopy-Assisted Gastrectomy With Extended Lymphadenectomy? A Case–Control Study Using a Propensity Score Method

Gastrointestinal Oncology

Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma

Gastrointestinal Oncology

Noncurative Resection for Gastric Cancer Patients: Who Could Benefit?