Background Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma. Methods Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated. Results Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p <0.001) in controls compared to melanoma patients. Conclusions Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.

Introduction: For high-risk familial history of breast cancer, risk reducing mastectomy (RRM) is now regarded as one of the management options. The aim of this study is to analyse the outcome of women undergoing RRM from 1994 to 2010 during which surgical techniques evolved and were refined. Methods: A cohort of women undergoing RRM was followed from this single centre. Surgical and further details about demographics, comorbidities, and follow-up were retrieved form medical records. Analysis was carried out using the IBM®-SPSS®-Statistics-19system. Results: Of 154 women 139 had bilateral RRM and 15 had unilateral surgery after earlier contralateral breast cancer. Median age at operation was 39.4 years (22–63years). 54 (45.5%) women were BRCA1/2 gene mutation carriers. Most women had nipple sacrificing (86) skin-sparing mastectomy with immediate reconstruction. 132 (85.7%) had submuscular expander/implant reconstruction, whilst 9 had either LD flap reconstruction or TRAM flap reconstruction. 31 (20.1%) women had some complication including haematoma requiring evacuation, minor skin/nipple necrosis, but implant loss was rare (2). 52 (33.8%) women had revisional surgeries in 5 years post RRM of whom 29 had one unanticipated secondary operation. Complications were more common in the early years of the cohort. On histology, 3 women were identified with lobular carcinoma in-situ and one was associated with 1mm of microinvasion. 4 had ductal carcinoma in-situ and 2 of them were BRCA carriers. Two (1.2%) primary breast cancers were subsequently identified during a mean follow-up period of 9.82 years (2–18 years) but this was substantially less than prediction modelling. Both were BRCA gene mutation carriers - one had nipple sparing RRM and the other did not. Conclusions: In asymptomatic high-risk women, RRM is safe and efficacious in reducing medium term future breast cancer incidence. Surgery carries the risk of complications and cosmetic revisions can be anticipated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-11.