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01-12-2017 | Melanomas

Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions

Authors: Cristina O’Donoghue, MD, MPH, Matthew C. Perez, MD, John E. Mullinax, MD, Danielle Hardman, BS, Sean Sileno, BS, Syeda Mahrukh Hussnain Naqvi, MD, Youngchul Kim, PhD, Ricardo J. Gonzalez, MD, Jonathan S. Zager, MD, FACS

Published in: Annals of Surgical Oncology | Issue 13/2017

Abstract

Background

Isolated limb infusion (ILI) is a minimally invasive technique for delivering regional chemotherapy to an extremity for patients with locally advanced cutaneous malignancies and sarcoma.

Methods

A single-institution, prospectively collected database was analyzed for intention-to-treat with ILI.

Results

From 2007 to 2016, 163 patients underwent 205 procedures (201 were successfully completed), and four malignancies were treated: melanoma (72.1% of all ILIs), sarcoma (23.4%), squamous cell carcinoma (SCC; 2.0%) and Merkel cell carcinoma (MCC; 2.5%). A median grade II regional Wieberdink toxicity score was observed, with 88.1% of patients experiencing grade II or less. Median follow-up was 21.8 months, and overall response rate (ORR) was 59.0% for melanoma, 48.9% for sarcoma, 50.0% for SCC, and 60.0% for MCC. A significant difference (p = 0.04) between upper (76.9%) and lower extremity (55.1%) ORR was observed in patients with melanoma. When comparing responders with nonresponders, patients with melanoma had significantly longer in-field progression-free survival (IPFS; 14.1 vs. 3.2 months, p < 0.001), distant metastatic-free survival (DMFS; not reached vs. 25.8 months, p = 0.006), and overall survival (OS; 56.0 vs. 26.7 months, p = 0.0004). Sarcoma responders had a significantly longer IPFS (13.0 vs. 2.7 months, p < 0.0001), but no significant distant metastatic or OS advantage. Over a median follow-up of 19.3 months, sarcoma patients had an overall limb salvage rate of 68.4%.

Conclusion

ILI is a well-tolerated procedure for patients with locally advanced melanoma, sarcoma, and other cutaneous malignancies. ILI responders had a significantly longer time to IPFS, while melanoma responders also had a DMFS and OS advantage.

Specenier P. Pembrolizumab use for the treatment of advanced melanoma. Expert Opin Biol Ther. 2017;17(6):765–80.CrossRef

Mullinax JE, Kroon HM, Thompson JF, et al. Isolated limb infusion as a limb salvage strategy for locally advanced extremity sarcoma. J Am Coll Surg. 2017;224(4):635–42.CrossRefPubMed

Thompson JF, Kam PC, Waugh RC, Harman CR. Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion. Semin Surg Oncol. 1998;14(3):238–47.CrossRefPubMed

Thompson JF, Hunt JA, Shannon KF, Kam PC. Frequency and duration of remission after isolated limb perfusion for melanoma. Arch Surg. 1997;132(8):903–7.CrossRefPubMed

Sanki A, Kam PC, Thompson JF. Long-term results of hyperthermic, isolated limb perfusion for melanoma: a reflection of tumor biology. Ann Surg. 2007;245(4):591–6.CrossRefPubMedPubMedCentral

Grunhagen DJ, de Wilt JH, van Geel AN, Verhoef C, Eggermont AM. Isolated limb perfusion with TNF-alpha and melphalan in locally advanced soft tissue sarcomas of the extremities. Recent Results Cancer Res. 2009;179:257–70.CrossRefPubMed

Kroon HM, Moncrieff M, Kam PC, Thompson JF. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15(11):3003–13.CrossRefPubMed

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(5):706–15 (Discussion 715–707).CrossRefPubMed

Wong J, Chen YA, Fisher KJ, Zager JS. Isolated limb infusion in a series of over 100 infusions: a single-center experience. Ann Surg Oncol. 2013;20(4):1121–7.CrossRefPubMedPubMedCentral

10.

Barbour AP, Thomas J, Suffolk J, Beller E, Smithers BM. Isolated limb infusion for malignant melanoma: predictors of response and outcome. Ann Surg Oncol. 2009;16(12):3463–72.CrossRefPubMed

11.

Turaga KK, Beasley GM, Kane JM 3rd, et al. Limb preservation with isolated limb infusion for locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms. Arch Surg. 2011;146(7):870–5.CrossRefPubMedPubMedCentral

12.

Moncrieff MD, Kroon HM, Kam PC, Stalley PD, Scolyer RA, Thompson JF. Isolated limb infusion for advanced soft tissue sarcoma of the extremity. Ann Surg Oncol. 2008;15(10):2749–56.CrossRefPubMed

13.

Zeitouni NC, Giordano CN, Kane JM 3rd. In-transit Merkel cell carcinoma treated with isolated limb perfusion or isolated limb infusion: a case series of 12 patients. Dermatol Surg. 2011;37(3):357–64.CrossRefPubMed

14.

Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMed

15.

Wieberdink J, Benckhuysen C, Braat RP, van Slooten EA, Olthuis GA. 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(10):905–10.CrossRefPubMed

16.

Kroon HM, Coventry BJ, Giles MH, et al. Australian Multicenter Study of Isolated Limb Infusion for Melanoma. Ann Surg Oncol. 2016;23(4):1096–103.CrossRefPubMed

17.

Muilenburg DJ, Beasley GM, Thompson ZJ, Lee JH, Tyler DS, Zager JS. Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma. Ann Surg Oncol. 2015;22(2):482–8.CrossRefPubMed

18.

Dossett LA, Ben-Shabat I, Olofsson Bagge R, Zager JS. Clinical response and regional toxicity following isolated limb infusion compared with isolated limb perfusion for in-transit melanoma. Ann Surg Oncol. 2016;23(7):2330–5.CrossRefPubMed

19.

Wong J, Chen YA, Fisher KJ, Beasley GM, Tyler DS, Zager JS. 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(2):650–5.CrossRefPubMed

20.

Chai CY, Deneve JL, Beasley GM, et al. A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities. Ann Surg Oncol. 2012;19(5):1637–43.CrossRefPubMed

21.

Kroon HM, Lin DY, Kam PC, Thompson JF. Efficacy of repeat isolated limb infusion with melphalan and actinomycin D for recurrent melanoma. Cancer. 2009;115(9):1932–40.CrossRefPubMed

Title: Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions
Authors: Cristina O’Donoghue, MD, MPH
Matthew C. Perez, MD
John E. Mullinax, MD
Danielle Hardman, BS
Sean Sileno, BS
Syeda Mahrukh Hussnain Naqvi, MD
Youngchul Kim, PhD
Ricardo J. Gonzalez, MD
Jonathan S. Zager, MD, FACS
Publication date: 01-12-2017
Publisher: Springer International Publishing
Published in: Annals of Surgical Oncology / Issue 13/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-017-6107-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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