The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study

Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies. Keywords: Immune checkpoint inhibitor; In-transit metastasis; Ipilimumab; Melanoma; Nivolumab; PD-1; Pembrolizumab

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

Effects of the Introduction of Modern Immunotherapy on the Outcome of Isolated Limb Perfusion for Melanoma In-Transit Metastases

Isolated limb perfusion (ILP) is an effective locoregional treatment for melanoma in-transit metastasis, but the advent of modern effective immunotherapy, such as ICI (immune checkpoint inhibitors), has changed the treatment landscape. The primary aims of this study were to compare the characteristics of the patient population receiving ILP before and after the introduction of modern systemic treatments and to assess if outcomes after ILP were influenced by previous immunotherapy treatment. A single-centre analysis of patients that underwent ILP for melanoma in-transit metastasis between 2010 and 2021 was conducted, with patients grouped and compared by treatment time period: pre-ICI era (2010–2014) and ICI era (2017–2021). 218 patients were included. Patients undergoing ILP in the ICI era were slightly older (median age 73 vs. 68 years) compared to the pre-ICI era, with no other difference found. The overall response rate (ORR) was 83% vs. 84% and the complete response (CR) rate was 52% vs. 47% for the pre-ICI era and the ICI era, respectively. For patients that had received and failed immunotherapy prior to ILP (n = 20), the ORR was 75% and the CR rate was 50%. Melanoma-specific survival has improved, with a 3-year survival rate of 54% in the pre-ICI era vs. 86% in the ICI era. The patient population undergoing ILP for in-transit melanoma is largely unchanged in the current era of effective systemic treatments. Response rates have not decreased, and prior ICI treatment did not affect response rates, making ILP still a valid treatment option for this patient group

Att kommunicera på rätt nivå – 1024Mb vadå? : En studie om upplevda risker och informationssökning vid ett högengagemangsköp

Internet har gett konsumenten en ökad marknadsöverblick, detta har gjort det möjligt för konsumenten att tidseffektivt jämföra varor och priser. Detta innebär att dagens konsument är betydligt mer välinformerad. Medvetenheten om en stor och komplex marknad innebär ett högt engagemang och upplevda risker med köpet som följd. Det höga engagemanget innebär att man som konsument bland annat söker information för att reducera sina upplevda risker. Syftet med denna uppsats är att minska luckan i teorin om konsumenters riskreducerande informationsbeteende då de genomgår köpprocessen i ett högengagemangsköp. Ett annat syfte blir att se vilka faktorer kring informationssökning som är viktiga i ett högengagemangsköp på en högteknologisk marknad 2006. Frågeställningarna rör hur informationskällorna används idag, vilka källor som har störst utvecklingspotential och hur denna utveckling borde se ut. Datainsamlingen har skett genom åtta stycken djupintervjuer med studenter från olika fackhögskolor inom Högskolan i Jönköping. Studenternas köp av bärbar dator de senaste sex månaderna har fungerat som underlag för samtalet. Resultatet av studien visar att de ekonomiska och funktionella riskerna upplevts vara mycket omfattande för våra respondenter. Priset och krav på en viss funktionalitet har varit klart tidigt i köpprocessen, funktionalitetskravet har under köpets gång översatts från behovsbeskrivningar till teknisk specifikation. Översättningen har mestadels inneburit omfattande informationssökning på Internet, vilket i många fall inneburit att respondenten engagerat personliga källor för värdering av informationen. De ekonomiska och funktionella riskerna har varit aktuella växelvis under köpprocessens olika faser. Många upplevelser kring informationssökningen präglas av ineffektivitet. Det icke kommersiella intryck information från jämförelsesajter på nätet och personliga källor ger ser vi ha en stor potential att kunna utvecklas. Detta genom att både i butik och på Internet aktivt arbeta med konsumenternas referenspunkter. Lösningsorienterad information med fokus på att bygga relationer och förtroende har enligt studiens resultat utvecklingsmöjligheter både på Internet och bland säljare.Today Internet has given consumers a greater possibility to have a more complete view over the range of products on a market. This has made it possible to in a time effective way compare products and prices. A greater amount of perceived risks when purchasing a high involvement product is one result of the consumers awareness of a large and complex market. To reduce the risks, that high involvement purchase in hazes, the consumer is in a greater need of information The purpose with this essay is to reduce the gap in the theory about consumers risk reducing information behaviour when following the buyer’s decision process in a high involvement purchase. Another purpose is to identify which factors that is important when seeking information during a high involvement purchase. The ambition with this study is to explain how different information channels are used today, which channels that has the best potentials and how the development of these should be done. Interviews with eight different students from Jönköping University underlie the result of this study. During the six latest months these students have purchased a laptop, this purchase has been the starting-point for the interviews. The result shows that the economical and functional risks are those that have been most frequent perceived among our respondents. Requirements concerning price and functionality where also those things that the respondents early in the buyer’s decision process hade a clear opinion about. Functional requirements was in the beginning spoken out as to solve certain needs. These needs have been translated to technical specifications during the process. This translation has been signified with a lot of time spent on seeking information on the Internet. It has also engaged personal contacts with friends etc for valuation of information. Many experiences of information seeking shows on inefficiency. The non-commercial impression that personal contacts and Internet pages, with product comparison, has given is something that we mean should be taken to account in a larger scale. This could be done by actively working with the consumer’s frame of references to the product. Information that is solution orientated, on Internet and from sellers, and which has the ambition to build long term relations has from this reports result shown to have great possibilities for development

Effects of the Introduction of Modern Immunotherapy on the Outcome of Isolated Limb Perfusion for Melanoma In-Transit Metastases

Isolated limb perfusion (ILP) is an effective locoregional treatment for melanoma in-transit metastasis, but the advent of modern effective immunotherapy, such as ICI (immune checkpoint inhibitors), has changed the treatment landscape. The primary aims of this study were to compare the characteristics of the patient population receiving ILP before and after the introduction of modern systemic treatments and to assess if outcomes after ILP were influenced by previous immunotherapy treatment. A single-centre analysis of patients that underwent ILP for melanoma in-transit metastasis between 2010 and 2021 was conducted, with patients grouped and compared by treatment time period: pre-ICI era (2010–2014) and ICI era (2017–2021). 218 patients were included. Patients undergoing ILP in the ICI era were slightly older (median age 73 vs. 68 years) compared to the pre-ICI era, with no other difference found. The overall response rate (ORR) was 83% vs. 84% and the complete response (CR) rate was 52% vs. 47% for the pre-ICI era and the ICI era, respectively. For patients that had received and failed immunotherapy prior to ILP (n = 20), the ORR was 75% and the CR rate was 50%. Melanoma-specific survival has improved, with a 3-year survival rate of 54% in the pre-ICI era vs. 86% in the ICI era. The patient population undergoing ILP for in-transit melanoma is largely unchanged in the current era of effective systemic treatments. Response rates have not decreased, and prior ICI treatment did not affect response rates, making ILP still a valid treatment option for this patient group

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.</p