The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial).

OBJECTIVE: ILP has shown to achieve high response rates in patients with melanoma ITM. Possibly there is a synergistic mechanism of action of ILP and anti-PD1. The aim of this trial was to investigate the safety and efficacy of adding a single dose of systemic anti-PD1 to isolated limb perfusion (ILP) for patients with melanoma in-transit metastases (ITM). METHODS: In this placebo controlled double-blind phase Ib/II trial, patients with melanoma ITM were randomized 1:1 to either a single systemic dose of nivolumab or placebo one day prior to ILP. The primary endpoint was complete response (CR) rate at three months, and safety in terms of incidence and severity of adverse events (AEs). RESULTS: A total of 20 patients were included. AEs of any grade occurred in 90% of patients in the nivolumab arm and in 80% in the placebo arm within three months after ILP. Grade 3 AEs were reported in 40% and 30% respectively, most commonly related to wound infection, wound dehiscence, or skin necrosis. There were no grade 4 or 5 AEs reported. The CR rate was 75% in the nivolumab arm and 60% in the placebo arm. The 1-year local progression-free rate was 86% in the nivolumab arm and 67% in the placebo arm. The 1-year OS was 100% in both arms. CONCLUSION: For patients with melanoma ITM, the addition of a single systemic dose of nivolumab the day before ILP is considered safe and feasible with promising efficacy. Accrual will continue in a phase 2 trial.

Efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours: systematic review.

BACKGROUND: Accurate tumour localization is crucial for precise surgical targeting and complete tumour removal. Indocyanine green fluorescence, an increasingly used technique in oncological surgery, has shown promise in localizing non-palpable breast tumours. The aim of this systematic review was to describe the efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours. METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library, including studies from 2012 to 2023. Studies reporting the proportion of breast tumours identified using indocyanine green fluorescence were included. The quality of the studies and their risk of bias were appraised using the Methodological Index for Non-Randomized Studies ('MINORS') tool. The following outcomes were collected: identification rate, clear resection margins, specimen volume, operative time, re-operation rate, adverse events, and complications. RESULTS: In total, 2061 articles were screened for eligibility, resulting in 11 studies, with 366 patients included: two RCTs, three non-randomized comparative studies, four single-arm studies, and two case reports. All studies achieved a 100 per cent tumour identification rate with indocyanine green fluorescence, except for one study, with an identification rate of 87 per cent (13/15). Clear resection margins were found in 88-100 per cent of all patients. Reoperation rates ranged from 0.0 to 5.4 per cent and no complications or adverse events related to indocyanine green occurred. CONCLUSION: Indocyanine green fluorescence has substantial theoretical advantages compared with current routine localization methods. Although a limited number of studies were available, the current literature suggests that indocyanine green fluorescence is a useful, accurate, and safe technique for the intraoperative localization of non-palpable breast tumours, with equivalent efficacy compared with other localization techniques, potentially reducing tumour-positive margins.

A Clinical Validation Study of Anatomical Risk Scoring for Procedural Stroke in Patients Treated by Carotid Artery Stenting in the International Carotid Stenting Study.

OBJECTIVES: Vascular anatomy of the aortic arch and supra-aortic arteries has been suggested as influencing the risk of carotid artery stenting (CAS). The expert opinion based Delphi anatomical risk (DAR) score was developed to predict difficulty of CAS in relation to procedural stroke risk, and thereby aid patient selection. The aim was to validate the DAR score in the context of a randomised clinical trial. METHODS: In this post hoc analysis of the International Carotid Stenting Study (ICSS), only patients treated by CAS with available pre-procedural CT angiography (CTA) were included. Patients with tortuous anatomy unsuitable for stenting were excluded from ICSS. CTA based vascular anatomy was rated by two independent observers. Every possible combination of anatomy resulted in a risk score, divided in four categories of expected risk (low, < 5.0; low-intermediate, 5.0-5.9; high-intermediate, 6.0-6.9; high, ≥ 7.0). Binomial logistic regression was used to assess the relationship between anatomical risk score and procedural risk of any stroke. Differences between predefined age groups were also assessed. RESULTS: A total of 275 patients were included. Interobserver reliability for all anatomical risk factors was high (κ = 0.76-0.84). In total, 16 strokes (6%) occurred in the procedural period. No significant relationship was observed between the DAR score and risk of procedural stroke, with the risk of stroke being 9% in the high risk vs. 4% in the low risk categories (p = .49). A higher mean DAR score was observed in patients ≥70 years compared with younger patients (4.6 ± 1.5 vs. 3.9 ± 1.4, p < .001), which was mainly explained by higher rates of arch atheroma (44% vs. 20%, p < .001). Prolonged intervention duration was significantly associated with increased stroke risk (11% vs. 4%, p < .04), but not with the DAR score. CONCLUSIONS: No statistically significant association was found between anatomical difficulty, as defined in the DAR score, and procedural stroke risk. However, the small sample size potentially rendered the study underpowered to detect group differences, and confirmation with a larger sample is essential.

Editor's Choice - Cerebral Hyperperfusion Syndrome After Carotid Artery Stenting: A Systematic Review and Meta-analysis.

INTRODUCTION: Cerebral hyperperfusion syndrome (CHS) is a preventable cause of stroke after carotid endarterectomy (CEA). There are currently no pooled data available on the incidence of CHS after carotid artery stenting (CAS). The aim of this review was to assess the relevance of CHS in the procedural stroke rate following CAS. METHOD: A systematic search on incidence rates of CHS after CAS was conducted in the MEDLINE, EMBASE, and Cochrane databases in November 2017. A meta-regression analysis was performed on CHS to explain heterogeneity and determine the impact of potential risk factors on observed CHS. The methodological quality of the included studies was assessed using the Cowley criteria. RESULTS: The pooled CHS risk across 33 studies concerning 8731 CAS patients was 4.6% (3.1-6.8%). Stroke occurred in 47% of CHS patients, of which 54% were fatal or disabling. Average time from procedure to symptoms was 12 h (IQR 8-36 h). Impaired cerebrovascular reserve (CVR) was associated with a higher risk of CHS after CAS (RR 5.18; 95% CI 1.0-26.8; p = .049). Symptomatic status was associated with a lower risk of CHS (RR 0.20; 95% CI 0.07-0.59; p = .001). CONCLUSION: CHS is a serious and frequent complication in patients undergoing carotid angioplasty with stenting, and is most likely to occur in the very early post-procedural period. Future studies are encouraged to investigate the effect of intensive haemodynamic monitoring, including blood pressure control and assessment of cerebral blood flow, on the incidence of stroke caused by CHS after CAS.