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Published in: Annals of Surgical Oncology 7/2018

Open Access 01-07-2018 | Melanomas

The Effect of Temperature and Perfusion Time on Response, Toxicity, and Survival in Patients with In-transit Melanoma Metastases Treated with Isolated Limb Perfusion

Published in: Annals of Surgical Oncology | Issue 7/2018

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Abstract

Background

Isolated limb perfusion (ILP) is used to treat in-transit metastases of melanoma of the extremities when surgical excision is not possible. The optimal setting concerning temperature and perfusion time is unknown. The purpose of this study was to analyze these factors concerning their effects on response, toxicity, and survival.

Methods

A retrospective analysis of 284 consecutive stage III melanoma patients treated with melphalan ILP for the first time in our institution, during a 31-year period (July 1986–May 2017), was performed. Our series was divided in four time periods, according to perfusion temperature and duration. Demographical data, stage, number, and size of lesions were retrieved from our prospective database.

Results

Overall response (OR) rate 83% and a complete response (CR) rate of 59%. Significant predictive factors for CR in multivariate analysis were non-bulky tumor, fewer metastases, and a perfusion time of 120 min. Predictive factors for increased local toxicity were femoral ILP and higher perfusion temperatures. The median overall survival was 30 months, and the independent negative prognostic factors were lymph-node status, bulky tumors, response, upper limb perfusion, and 120 min perfusion at 39–40 °C.

Conclusions

Modern ILP uses diminished perfusion time and lower temperature, leading to a decrease in toxicity. However, our data also show a decrease in response, which indicates that optimal perfusion time and temperature regimen remain to be determined.
Literature
1.
go back to reference Pawlik TM, et al Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol. 2005;12(8):587–96.CrossRefPubMed Pawlik TM, et al Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy. Ann Surg Oncol. 2005;12(8):587–96.CrossRefPubMed
3.
go back to reference Minor DR, et al. A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer, 1985. 55(11):2638–44.CrossRefPubMed Minor DR, et al. A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. Cancer, 1985. 55(11):2638–44.CrossRefPubMed
4.
go back to reference Cavaliere R, et al. Selective heat sensitivity of cancer cells. Biochemical and clinical studies. Cancer. 1967;20(9):1351–81.CrossRefPubMed Cavaliere R, et al. Selective heat sensitivity of cancer cells. Biochemical and clinical studies. Cancer. 1967;20(9):1351–81.CrossRefPubMed
5.
go back to reference Stehlin JS Jr. Hyperthermic perfusion with chemotherapy for cancers of the extremities. Surg Gynecol Obstet. 1969;129(2):305–8.PubMed Stehlin JS Jr. Hyperthermic perfusion with chemotherapy for cancers of the extremities. Surg Gynecol Obstet. 1969;129(2):305–8.PubMed
6.
go back to reference Deroose JP, et al. Isolated limb perfusion for melanoma in-transit metastases: developments in recent years and the role of tumor necrosis factor alpha. Curr Opin Oncol. 2011;23(2):183–8.CrossRefPubMed Deroose JP, et al. Isolated limb perfusion for melanoma in-transit metastases: developments in recent years and the role of tumor necrosis factor alpha. Curr Opin Oncol. 2011;23(2):183–8.CrossRefPubMed
7.
go back to reference World Health Organization, WHO handbook for reporting results of cancer treatment. WHO offset publication No 48. 1979, Geneva: World Health Organization. P. 45. World Health Organization, WHO handbook for reporting results of cancer treatment. WHO offset publication No 48. 1979, Geneva: World Health Organization. P. 45.
8.
go back to reference Wieberdink J, et al. 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 Wieberdink J, et al. 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
9.
go back to reference Olofsson R, et al. Melan-A specific CD8+ T lymphocytes after hyperthermic isolated limb perfusion: a pilot study in patients with in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29(3):234–8.CrossRefPubMed Olofsson R, et al. Melan-A specific CD8+ T lymphocytes after hyperthermic isolated limb perfusion: a pilot study in patients with in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29(3):234–8.CrossRefPubMed
10.
go back to reference Dudek-Peric, A.M., et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 2015; 75(8):1603–1614.CrossRefPubMed Dudek-Peric, A.M., et al. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 2015; 75(8):1603–1614.CrossRefPubMed
11.
go back to reference Martner, A., et al. Melphalan, antimelanoma immunity, and inflammation [letter]. Cancer Res. 2015;75(24):5398–9.CrossRefPubMed Martner, A., et al. Melphalan, antimelanoma immunity, and inflammation [letter]. Cancer Res. 2015;75(24):5398–9.CrossRefPubMed
12.
go back to reference Wieberdink J, et al. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur Jf Cancer Clin Oncol. 1982;18(10):905–10.CrossRef Wieberdink J, et al. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur Jf Cancer Clin Oncol. 1982;18(10):905–10.CrossRef
13.
go back to reference Santillan AA, et al. Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol. 2009;16(9):2570–8.CrossRefPubMed Santillan AA, et al. Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol. 2009;16(9):2570–8.CrossRefPubMed
14.
go back to reference Thompson JF, et al. Determinants of acute regional toxicity following isolated limb perfusion for melanoma. Melanoma Res. 1996;6(3):267–71.CrossRefPubMed Thompson JF, et al. Determinants of acute regional toxicity following isolated limb perfusion for melanoma. Melanoma Res. 1996;6(3):267–71.CrossRefPubMed
15.
go back to reference Klaase JM, et al. Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities. Am J Surg. 1994;167(6):618–20.CrossRefPubMed Klaase JM, et al. Patient- and treatment-related factors associated with acute regional toxicity after isolated perfusion for melanoma of the extremities. Am J Surg. 1994;167(6):618–20.CrossRefPubMed
16.
go back to reference Olofsson R, Mattsson J, Lindner P. Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29(6):551–7.CrossRefPubMed Olofsson R, Mattsson J, Lindner P. Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma. Int J Hyperthermia. 2013;29(6):551–7.CrossRefPubMed
17.
go back to reference Dahl O. Interaction of hyperthermia and chemotherapy. Recent Results Cancer Res. 1988;107:157–69.CrossRefPubMed Dahl O. Interaction of hyperthermia and chemotherapy. Recent Results Cancer Res. 1988;107:157–69.CrossRefPubMed
18.
go back to reference Omlor G, et al. Optimization of isolated hyperthermic limb perfusion. World J Surg. 1992;16(6):1117–9.CrossRefPubMed Omlor G, et al. Optimization of isolated hyperthermic limb perfusion. World J Surg. 1992;16(6):1117–9.CrossRefPubMed
19.
go back to reference Clark J, et al. Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusion of melanoma. Melanoma Res. 1994;4(6):365–70.CrossRefPubMed Clark J, et al. Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusion of melanoma. Melanoma Res. 1994;4(6):365–70.CrossRefPubMed
20.
go back to reference Di Filippo F, et al. The application of hyperthermia in regional chemotherapy. Semin Surg Oncol. 1998;14(3):215–23.CrossRefPubMed Di Filippo F, et al. The application of hyperthermia in regional chemotherapy. Semin Surg Oncol. 1998;14(3):215–23.CrossRefPubMed
21.
go back to reference Ariyan CE, et al. Robust antitumor responses result from local chemotherapy and CTLA-4 blockade. Cancer Immunol Res. 2018;6(2):189–200.CrossRefPubMed Ariyan CE, et al. Robust antitumor responses result from local chemotherapy and CTLA-4 blockade. Cancer Immunol Res. 2018;6(2):189–200.CrossRefPubMed
Metadata
Title
The Effect of Temperature and Perfusion Time on Response, Toxicity, and Survival in Patients with In-transit Melanoma Metastases Treated with Isolated Limb Perfusion
Publication date
01-07-2018
Published in
Annals of Surgical Oncology / Issue 7/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6459-9

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