TY - JOUR
T1 - Factors predicting toxicity and response following isolated limb infusion for melanoma
T2 - An international multi-centre study
AU - Kenyon-Smith, Timothy J.
AU - Kroon, Hidde M.
AU - Miura, John T.
AU - Teras, Jüri
AU - Beasley, Georgia M.
AU - Mullen, Dean
AU - Farrow, Norma E.
AU - Mosca, Paul J.
AU - Lowe, Michael C.
AU - Farley, Clara R.
AU - Potdar, Aishwarya
AU - Daou, Hala
AU - Sun, James
AU - Farma, Jeffrey M.
AU - Henderson, Michael A.
AU - Speakman, David
AU - Serpell, Jonathan
AU - Delman, Keith A.
AU - Smithers, B. Mark
AU - Barbour, Andrew
AU - Coventry, Brendon J.
AU - Tyler, Douglas S.
AU - Zager, Jonathan S.
AU - Thompson, John F.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology
PY - 2020/11
Y1 - 2020/11
N2 - Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.
AB - Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response. Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres. Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response. Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low.
KW - Isolated limb infusion
KW - Loco-regionally metastatic disease
KW - Melanoma
KW - Multi-centre
KW - Regional chemotherapy
KW - Response
KW - Toxicity
KW - in-transit disease
KW - metastatic melanoma
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U2 - 10.1016/j.ejso.2020.06.040
DO - 10.1016/j.ejso.2020.06.040
M3 - Article
C2 - 32739218
AN - SCOPUS:85088942643
SN - 0748-7983
VL - 46
SP - 2140
EP - 2146
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 11
ER -