Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan.
BACKGROUND
The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNF alpha) and melphalan.


METHODS
Forty-eight patients with melanoma (n = 14) or soft tissue sarcoma (n = 34) of an extremity underwent 51 perfusions. Perfusion was performed at the iliac level in 22 cases, at the popliteal level in 16 cases, at the femoral level in 7 cases, and at the axillary level in 6 cases. Leakage rates and perfusion circuit and systemic levels of TNF alpha, interleukin-6, and C-reactive protein were determined, as were systemic hematological and metabolic profiles and tumor response.


RESULTS
The mean isotopically measured leakage was 2.9%. Systemic leakage was < or = 2% in 28 perfusions and >2% in 23 perfusions. The correlation between the maximal monitored leakage and maximal systemic TNF alpha levels was.7114. The area under the curve for TNF alpha in the perfusion circuit, indicating the exposure of the perfused limb to TNF alpha, was 18.7% lower in the >2% leakage group. No significant differences in tumor response were found between groups. The area under the curve for systemic TNF alpha, indicating the exposure of the patient to TNF alpha, was 18.1 times higher in the >2% leakage group, resulting in a significant decrease in leukocyte and platelet count, hyperbilirubinemia, hypocholesterolemia, and proteinemia. No beneficial effect of the systemically leaked TNF and melphalan was seen on the occurrence of distant metastasis during follow-up. There was a significant difference between perfusions performed at the iliac and femoral levels compared with leakage values at the popliteal level.


CONCLUSIONS
A good correlation between RISA leakage measurement and TNF alpha exposure during and after hyperthermic isolated limb perfusion with TNF alpha and melphalan was demonstrated. RISA leakage measurement serves as a good guide for the effectiveness of isolation during perfusion. If leakage exceeds the 2% limit during perfusion, less exposure of the tumor-bearing limb to TNF alpha, increased exposure of the patient systemic circulation to TNF alpha, and more systemic side effects can be expected.
van Ginkel
Robert J
RJ
Department of Surgical Oncology, Groningen University Hospital, Groningen, The Netherlands.
Limburg
Pieter C
PC
Piers
D Albertus
DA
Koops
Heimen Schraffordt
HS
Hoekstra
Harald J
HJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000097:blood; D019540:Area Under Curve; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D005121:Extremities; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007457:Iodine Radioisotopes; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy*; D008558:Melphalan / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy*; D012709:Serum Albumin; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000627:therapeutic use*
D018906:Antineoplastic Agents, Alkylating; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; C107869:technetium Tc 99m serum albumin; D008558:Melphalan