Published March 29, 2018 | Version v1

Perfusion and Oxygenation Changes after Isolated Limb Perfusion with TNF - α in Lower Limb Sarcoma: A Case Report

  • 1. Computational BioMedicine Laboratory (CBML), Foundation for Research & Technology, Greece
  • 2. Department of Pathology, University Hospital of Crete, Greece
  • 3. Department of Radiology, School of Medicine, University of Crete, Greece
  • 4. Department of Surgical Oncology, School of Medicine, University of Crete, Greece

Description

Abstract

Tumor necrosis factor alpha (TNF-α) is known to cause selective destruction of tumor neovascularisation. Perfusion changes in tumor microenvironment were studied in a young patient with a high-grade myxoid liposarcoma after isolated limb perfusion with TNF-α and melphalan, using advanced MR imaging. Quantitative and semi-quantitative evaluation of perfusion metrics included ktrans/f/T2* shift and automatic extraction of enhancement patterns. Strong agreement between different methods is consistent with response to therapy, specifically reduced perfusion (mean ktrans shifted from 0.424 to 0.099 mL/g/min, mean f from 33.5 to 7.3%), reduced hypoxia indication (mean T2* increased from 72 to 82 ms) and prevalence of necrotic areas.

Abbreviations

(TNF-α) : Tumor Necrosis Factor Alpha

ILP : Isolated limb perfusion

DCE : Dynamic Contrast Enhanced

DWI : Diffusion Weighted Imaging

IVIM : Intravoxel Incoherent Motion

T2*r : T2* Relaxometry

BOLD : Blood Oxygen Level-Dependent

PK : Pharmacokinetic

ktrans : Transendothelial permeability

dHb : Deoxyhemoglobin

IMVD : Intratumoral Microvessel Density

FISH : Fluorescence In situ Hybridization

PR : Pattern Recognition

Notes

Biomedical Research and Reviews (ISSN:2631-3944)

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References

  • Jakob J, Hohenberger P. Role of isolated limb perfusion withrecombinant human tumor necrosis factor α and melphalan inlocally advanced extremity soft tissue sarcoma. Cancer. 2016May;22(17):2624-2632.
  • Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptorsuperfamilies: Integrating mammalian biology. Cell. 2001Feb;104(4):487-501.
  • Lienard D, Ewalenko P, Delmotte JJ, Renard N, Lejeune FJ. Highdose recombinant tumor necrosis factor alpha in combinationwith interferon gamma and melphalan in isolation perfusionof the limbs for melanoma and sarcoma. J Clin Oncol.1992Jan;10(1):52-60.
  • Folli S, Pelegrin A, Chalandon Y, Yao X, Buchegger F, et al.Tumor-Necrosis-Factor Can Enhance Radio-Antibody Uptakein Human Colon-Carcinoma Xenografts by Increasing VascularPermeability.Int J Cancer.1993 Mar;53(5):829-836.
  • Jahr J, Grande PO. In vivo effects of tumor necrosis factor-alpha on capillary permeability and vascular tone in a skeletal muscle. Acta Anaesthesiol Scand. 1996 Feb;40(2):256-261.
  • de Wilt JH, ten Hagen TL, de Boeck G, van Tiel ST, de BruijnE a, et al. Tumour necrosis factor alpha increases melphalanconcentration in tumour tissue after isolated limb perfusion. Br JCancer.2000 Mar;82(5):1000-1003.
  • Ruegg C, Yilmaz A, Bieler G, Bamat J, Chaubert P, et al. "Evidencefor the involvement of endotheliai cell integrin αVβ3 in the disruption of the tumor vascuiature induced by TNF and IFN-γ.Nat Med. 1998 April;4:408-414.
  • Sujlana P, Skrok J, Fayad LM. Review of dynamic contrastenhanced MRI: Technical aspects and applications in themusculoskeletal system. Journal of Magnetic ResonanceImaging.2018 Apr;47(4):875-890.
  • Rumley CN, Lee MT, Holloway L, Rai R, Min M , et al. Multiparametricmagnetic resonance imaging in mucosal primary head and neckcancer: A prospective imaging biomarker study. BMC Cancer.2017 Jul;17(1):475.
  • Venianaki M, Salvetti O, de Bree E, T. Maris, A. Karantanas, et al.Pattern recognition and pharmacokinetic methods on DCE-MRIdata for tumor hypoxia mapping in sarcoma. Multimedia Toolsand Application 2017 Aug;1-23.
  • Kuhl CK, Mielcareck P, Klaschik S, Leutner C, Wardelmann E, et al.Dynamic breast MR imaging: are signal intensity time course datauseful for differential diagnosis of enhancing lesions? Radiology.1999 Apr;211(1):101-110.
  • Tofts PS, Kermode AG. Measurement of the blood-brain barrierpermeability and leakage space using dynamic MR imaging. 1.Fundamental concepts. Magn Reson Med.1991 Feb;17(2):357-367.
  • Federau C. Intravoxel incoherent motion MRI as a means tomeasure in vivo perfusion: A review of the evidence. NMRBiomed. 2017 Nov;30(11).
  • Howe FA, Robinson SP, McIntyre DJO, Stubbs M, Griffiths JR. Issuesin flow and oxygenation dependent contrast (FLOOD) imaging oftumours. NMR Biomed. 2001 Nov-Dec;14(7-8):497-506.
  • Preda A, Wielopolski Pa, Ten Hagen TLM, van Vliet M, VeenlandJF, et al. Dynamic contrast-enhanced MRI using macromolecularcontrast media for monitoring the response to isolated limbperfusion in experimental soft-tissue sarcomas. MAGMA. 2004Dec;17(3-6):296-302.
  • Kontopodis E, Karatzanis I, Sakkalis V, Francesca B, Marias K. ADCE-MRI analysis workflow. In: CGI '16:Proceedings of the 33rdComputer Graphics International Conference. 2016:101-104.
  • Manikis GC, Nikiforaki K, Papanikolaou N, Marias K. DiffusionModelling Tool (DMT) for the analysis of Diffusion WeightedImaging (DWI) Magnetic Resonance Imaging (MRI) data. In: CGI'16:Proceedings of the 33rd Computer Graphics InternationalConference. 2016:97-100.
  • Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesisand metastasis--correlation in invasive breast carcinoma. N EnglJ Med. 1991 Jan;324:1-8.
  • Chalkley HW. Method for the quantitative morphologic analysis oftissues. J Natl Cancer Inst. 1943 Aug;4(1):47-53.