Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring

Francesco Fiz, Francesco Fiz, Giuseppe Villa, Enrico Ferrari, Elena Pomposelli, Silvia Morbelli, Antonella Alloisio, Daniela Pende, Raffaella Meazza, Cristina Gereloni, Cecilia Marini, Giovanni Battista Ratto, Gianmario Sambuceti

Research output: Contribution to journalArticle

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Abstract

© 2017 Informa UK Limited, trading as Taylor & Francis Group Rationale: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. Methods: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99m Tc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99m Tc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. Results: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p  < 0.01). Conclusions: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.
Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Hyperthermia
DOIs
Publication statusAccepted/In press - Aug 1 2017

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Radioactivity
Perfusion
Lung
Immunosorbents
Erythrocytes
Neoplasm Metastasis
Organized Financing
Physiologic Monitoring
Radioisotopes
Sarcoma
Drug Therapy

Keywords

  • clinical trials-isolated limb perfusion
  • control systems engineering/treatment optimisation
  • ILuP
  • radio-guided surgery
  • TNF-α

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Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring. / Fiz, Francesco; Fiz, Francesco; Villa, Giuseppe; Ferrari, Enrico; Pomposelli, Elena; Morbelli, Silvia; Alloisio, Antonella; Pende, Daniela; Meazza, Raffaella; Gereloni, Cristina; Marini, Cecilia; Ratto, Giovanni Battista; Sambuceti, Gianmario.

In: International Journal of Hyperthermia, 01.08.2017, p. 1-10.

Research output: Contribution to journalArticle

Fiz, F, Fiz, F, Villa, G, Ferrari, E, Pomposelli, E, Morbelli, S, Alloisio, A, Pende, D, Meazza, R, Gereloni, C, Marini, C, Ratto, GB & Sambuceti, G 2017, 'Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring', International Journal of Hyperthermia, pp. 1-10. https://doi.org/10.1080/02656736.2017.1355485
Fiz, Francesco ; Fiz, Francesco ; Villa, Giuseppe ; Ferrari, Enrico ; Pomposelli, Elena ; Morbelli, Silvia ; Alloisio, Antonella ; Pende, Daniela ; Meazza, Raffaella ; Gereloni, Cristina ; Marini, Cecilia ; Ratto, Giovanni Battista ; Sambuceti, Gianmario. / Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring. In: International Journal of Hyperthermia. 2017 ; pp. 1-10.
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author = "Francesco Fiz and Francesco Fiz and Giuseppe Villa and Enrico Ferrari and Elena Pomposelli and Silvia Morbelli and Antonella Alloisio and Daniela Pende and Raffaella Meazza and Cristina Gereloni and Cecilia Marini and Ratto, {Giovanni Battista} and Gianmario Sambuceti",
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AU - Fiz, Francesco

AU - Fiz, Francesco

AU - Villa, Giuseppe

AU - Ferrari, Enrico

AU - Pomposelli, Elena

AU - Morbelli, Silvia

AU - Alloisio, Antonella

AU - Pende, Daniela

AU - Meazza, Raffaella

AU - Gereloni, Cristina

AU - Marini, Cecilia

AU - Ratto, Giovanni Battista

AU - Sambuceti, Gianmario

PY - 2017/8/1

Y1 - 2017/8/1

N2 - © 2017 Informa UK Limited, trading as Taylor & Francis Group Rationale: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. Methods: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99m Tc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99m Tc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. Results: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p  < 0.01). Conclusions: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.

AB - © 2017 Informa UK Limited, trading as Taylor & Francis Group Rationale: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. Methods: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99m Tc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99m Tc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. Results: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p  < 0.01). Conclusions: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.

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