H G Smith1, J Cartwright2, M J Wilkinson2, D C Strauss2, J M Thomas2, A J Hayes2. 1. The Sarcoma and Melanoma Units, The Department of Academic Surgery, The Royal Marsden Hospital NHS Foundation Trust, London, UK. henrygsmith@doctors.org.uk. 2. The Sarcoma and Melanoma Units, The Department of Academic Surgery, The Royal Marsden Hospital NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: Isolated limb perfusion (ILP) is indicated in locally advanced melanoma and soft tissue sarcoma of the extremities. This series reports the outcome of patients undergoing ILP with melphalan and tumour necrosis factor α (TNFα) at a single centre. METHODS: All patients undergoing ILP from January 2005 to January 2015 were identified from a prospectively maintained database. Those undergoing ILP for in-transit melanoma (ITM) were grouped according to disease burden: low volume and bulky (>2 cm diameter). RESULTS: A total of 143 perfusions were attempted: 9 and 134 in the upper and lower limbs, respectively. A response was assessable in 129 patients with overall response rates for ITM and sarcoma of 81.8 and 61.1 %, respectively. No difference was found in response rates between low-volume and bulky ITM. Limb salvage rates in these cohorts were 97 and 62 %. Regional toxicity following ILP was minimal with 7 grade III (5.4 %), and 1 grade V (0.8 %) reactions. Median progression-free survival was 11 months in the ITM cohort and 12 months in the sarcoma cohort. In the ITM cohort, complete responses were significantly more durable than partial responses (p = 0.0004). Median disease-specific survival was 21 months in the ITM cohort and was not reached in the sarcoma cohort. CONCLUSIONS: TNFα-based ILP is safe and provides excellent palliation of ITM due to rapid progression of systemic disease. It is less effective in sarcoma due to lower initial response rates and a lower incidence of disease dissemination.
BACKGROUND: Isolated limb perfusion (ILP) is indicated in locally advanced melanoma and soft tissue sarcoma of the extremities. This series reports the outcome of patients undergoing ILP with melphalan and tumour necrosis factor α (TNFα) at a single centre. METHODS: All patients undergoing ILP from January 2005 to January 2015 were identified from a prospectively maintained database. Those undergoing ILP for in-transit melanoma (ITM) were grouped according to disease burden: low volume and bulky (>2 cm diameter). RESULTS: A total of 143 perfusions were attempted: 9 and 134 in the upper and lower limbs, respectively. A response was assessable in 129 patients with overall response rates for ITM and sarcoma of 81.8 and 61.1 %, respectively. No difference was found in response rates between low-volume and bulky ITM. Limb salvage rates in these cohorts were 97 and 62 %. Regional toxicity following ILP was minimal with 7 grade III (5.4 %), and 1 grade V (0.8 %) reactions. Median progression-free survival was 11 months in the ITM cohort and 12 months in the sarcoma cohort. In the ITM cohort, complete responses were significantly more durable than partial responses (p = 0.0004). Median disease-specific survival was 21 months in the ITM cohort and was not reached in the sarcoma cohort. CONCLUSIONS: TNFα-based ILP is safe and provides excellent palliation of ITM due to rapid progression of systemic disease. It is less effective in sarcoma due to lower initial response rates and a lower incidence of disease dissemination.
Authors: Michelle J Wilkinson; Henry G Smith; Gráinne McEntee; Joan Kyula-Currie; Tim D Pencavel; David C Mansfield; Aadil A Khan; Victoria Roulstone; Andrew J Hayes; Kevin J Harrington Journal: Oncotarget Date: 2016-12-06
Authors: Michelle J Wilkinson; Henry G Smith; Timothy D Pencavel; David C Mansfield; Joan Kyula-Currie; Aadil A Khan; Gráinne McEntee; Victoria Roulstone; Andrew J Hayes; Kevin J Harrington Journal: Int J Cancer Date: 2016-05-24 Impact factor: 7.396
Authors: Henry G Smith; Kunzah Jamal; Kevin J Harrington; Pascal Meier; Jasbani Hs Dayal; Tencho Tenev; Joan Kyula-Currie; Naomi Guppy; Patrycja Gazinska; Victoria Roulstone; Gianmaria Liccardi; Emma Davies; Ioannis Roxanis; Alan A Melcher; Andrew J Hayes; Gareth J Inman Journal: EMBO Mol Med Date: 2020-05-18 Impact factor: 12.137