Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 7;9(2):163.
doi: 10.3390/biomedicines9020163.

Molecular Aspects of the Isolated Limb Infusion Procedure

Jüri Teras  1   2 , Michael J Carr  3 , Jonathan S Zager  3   4 , Hidde M Kroon  5   6
Affiliations
Review

Molecular Aspects of the Isolated Limb Infusion Procedure

Jüri Teras et al. Biomedicines. .

Abstract

For decades, isolated limb infusion (ILI) and hyperthermic isolated limb perfusion (HILP) have been used to treat melanoma in-transit metastases and unresectable sarcoma confined to the limb utilizing the effect of loco-regional high-dose chemotherapy to the isolated limb. Both procedures are able to provide high response rates in patients with numerous or bulky lesions in whom other loco-regional treatments are becoming ineffective. In comparison to systemic therapies, on the other hand, ILI and HILP have the advantage of not being associated with systemic side-effects. Although in principle ILI and HILP are similar procedures, ILI is technically simpler to perform and differs from HILP in that it takes advantage of the hypoxic and acidotic environment that develops in the isolated limb, potentiating anti-tumour activity of the cytotoxic agents melphalan +/- actinomycin-D. Due to its simplicity, ILI can be used in both preclinical and clinical studies to test new cytotoxic regimens and combinations with the aim to overcome tumour resistance. In the future, administration of cytotoxic agents by ILI, in combination with systemic treatments such as BRAF/MEK/KIT inhibitors, immunotherapy (CTLA-4 blockade), and/or programmed death (PD-1) pathway inhibitors, has the potential to improve responses further by inducing increased tumour cell death while limiting the ability of the tumour to suppress the immune response.

Keywords: immunotherapy; in-transit metastases; isolated limb infusion; locally advanced melanoma and sarcoma; melanoma; melphalan; molecular aspects; sarcoma.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of the circuit used for isolated infusion of a lower limb (red arrows indicate direction of flow of infusate).
Figure 2
Figure 2
Angiogram of the arterial (A) and venous (V) catheters positioned in a lower limb with the tips reaching into the mid-popliteal vessels just proximal to the knee.
Figure 3
Figure 3
Typical melphalan concentration graph during isolated limb infusion.
Figure 4
Figure 4
Typical temperature graph during isolated limb infusion.
Figure 5
Figure 5
Typical saturation graph of the perfusate during isolated limb infusion.
See this image and copyright information in PMC

References

    1. Beasley G.M., Miura J., Zager J.S., Tyler D.S., Thompson J.F., Kroon H.M. Isolated limb infusion for melanoma. In: Balch C.M., Thompson J.F., Gershenwald J.E., Atkins M.B., Kirkwood J.M., McArthur G., Sober A., Halpern A.C., Garbe C., Scolyer R.A., editors. Cutaneous Melanoma. 6th ed. Springer; Cham, Switzerland: 2020. pp. 827–850. Chapter 30.
    1. Pasquali S., Gronchi A. Neoadjuvant chemotherapy in soft tissue sarcomas: Latest evidence and clinical implications. Ther. Adv. Med. Oncol. 2017;9:415–429. doi: 10.1177/1758834017705588. - DOI - PMC - PubMed
    1. Kepka L., Delaney T.F., Suit H.D., Goldberg S.I. Results of radiation therapy for unresected soft-tissue sarcomas. Int. J. Radiat. Oncol. 2005;63:852–859. doi: 10.1016/j.ijrobp.2005.03.004. - DOI - PubMed
    1. Grünhagen D.J., Kroon H.M., Verhoef C. Perfusion and infusion for melanoma in-transit metastases in the era of effective systemic therapy. Am. Soc. Clin. Oncol. Educ. Book. 2015;35:e528–e534. doi: 10.14694/EdBook_AM.2015.35.e528. - DOI - PubMed
    1. Kroon B.B.R., Kroon H.M., Noorda E.M., Vrouenraets B.C., Klaase J.M., Van Slooten G.W., Nieweg O.E. Isolated limb perfusion for melanoma. In: Aigner K.R., Stephens F.O., editors. Regional Therapy of Malignant Tumors. Springer; Berlin/Heidelberg, Germany: 2016. pp. 355–373. Chapter 25.

LinkOut - more resources