Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are ...available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival.
This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese).
Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks.
This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.
The clinical features and the prognostic relevance of vitiligo lesions in melanoma patients are still controversial. This prospective observational study was designed to characterise the clinical ...features of melanoma-associated vitiligo, to analyse the association with other autoimmune manifestations and to ascertain whether the development of vitiligo lesions carries a prognostic relevance on the clinical course of melanoma.
A total of 2954 consecutive patients have been included; multivariate analyses of distant metastasis-free survival (DMFS) and overall survival (OS) were carried out to ascertain the independent prognostic role of vitiligo as a time-dependent covariate.
Vitiligo was demonstrated in 83 of 2954 melanoma patients (2.8%). A significantly higher percentage of autoimmune diseases was demonstrated in vitiligo patients (7 of 83) with respect to patients without vitiligo (80 of 2871) (P=0.004). Multivariate analyses selected the time-dependent covariate vitiligo as the favourable independent prognostic variable associated to a longer DMFS in stage III and a higher OS in both stage III and stage IV.
Melanoma-associated vitiligo should be considered as a distinct clinical entity, separate from vitiligo vulgaris, and identifies a subgroup of patients characterised by a high prevalence of immune-mediated diseases and by a favourable prognosis.
Background
Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti‐IgE antibody effective in refractory CSU, ...but its mechanism of action and markers predictive of response remain not completely defined.
Objectives
To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d‐dimer (bd‐dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal.
Methods
In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd‐dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2‐ and 3‐month interval after a first and a second course of treatment, respectively.
Results
bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non‐responders (P = 0.0002). Conversely, bd‐dimer did not correlate to response. There was no correlation between both bIgE and d‐dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023).
Conclusions
Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd‐dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.
Background
Sentinel lymph node biopsy (SLNB) is currently recommended for patients with intermediate-thickness melanomas (T2–T3). Historically, T4 melanoma patients have not been considered good ...candidates for SLNB because of the high risk of distant progression. However, some authors suggest that T4 melanoma patients could be considered as a heterogeneous group that could benefit from SLNB.
Methods
We retrospectively analyzed 350 patients with thick (>4 mm) melanomas between 1999 and 2011. Patients were stratified into three groups depending on the results of SLNB: (1) 94 SLNB-negative; (2) 84 SLNB-positive; and (3) 172 SLNB not performed (observation group). The associations of clinical-pathologic features with the result of SLNB, disease-free interval (DFI), and disease-specific survival (DSS) were analyzed.
Results
Multivariate analyses confirmed a better prognosis for SLN-negative patients compared with patients in the observation group (DSS hazard ratio HR 0.62,
p
= 0.03; DFI HR 0.47,
p
< 0.001). The observation group was shown to have the same prognosis as the positive-sentinel lymph node group, when adjusted for principal confounders in the model.
Conclusions
We confirmed that thick-melanoma patients are a heterogeneous group with different prognosis. In our experience, SLNB allowed for an appropriate stratification of patients in different survival groups. On the basis of our results, we strongly recommend the routine execution of SLNB in cases of primary melanoma thicker than 4 mm.
Summary
Background
The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front‐line treatments and ...quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF).
Objectives
To identify (i) differences in first‐line approaches according to tumour‐nodes‐metastasis‐blood (TNMB) staging; (ii) parameters related to a first‐line systemic approach and (iii) response rates and QoL measures.
Methods
In total, 395 newly diagnosed patients with early‐stage MF (stage IA–IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review.
Results
The most common first‐line therapy was skin‐directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA–IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first‐line SDT was 73%, while the ORR to first‐line systemic treatments was lower (57%) (P = 0·027). Health‐related QoL improved significantly both in patients with responsive disease and in those with stable disease.
Conclusions
Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early‐stage MF need to address these issues.
What is already known about this topic?
Early‐stage mycosis fungoides is characterized by a good prognosis.
The first‐line treatment approach is typically stage based and is usually skin‐directed therapy.
What does this study add?
This multicentre prospective international study reports that real‐life treatment decisions are not limited to a stage‐based approach but are also influenced by the presence of plaques and folliculotropic mycosis fungoides.
Approximately half of the patients with early‐stage disease experienced a moderate or severe impact on their quality of life at diagnosis.
This study suggests that treatment guidelines in patients with early‐stage disease should incorporate high‐risk features and quality‐of-life evaluation.
Linked Comment: Porcu and Nikbakht. Br J Dermatol 2021; 184:594–595.
Different protocols have been used to follow up melanoma patients in stage I–II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals ...between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up.
Analysis of two prospectively collected cohorts of melanoma patients in stage IB–IIA from two tertiary referral centres in Barcelona (clinical-based follow-up C-FU) and Turin (ultrasound-based follow-up US-FU). Kaplan–Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS).
A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range IQR 41.5–65.2) with a median follow-up time of 4.14 years (IQR 1.2–7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14–4.04) for skin metastases, 1.32 (IQR 0.57–3.29) for lymph node metastases and 2.84 (IQR 1.32–4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts.
Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB–IIA.
•Ultrasonography (US) of the regional lymph nodes and US of the abdomen do not improve melanoma-specific survival.•Ultrasound-based follow-up does not increase survival of melanoma patients in stage IB–IIA.•Our recommendation for patients in stage IB–IIA after negative sentinel lymph node biopsy is to perform clinical follow-up.
Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in adults even in developed countries. Several lifestyle factors and comorbidities have been linked to an increased ...risk, although their prevalence has not been well documented in the primary care setting. The aim of this study is to assess the incidence, risk factor and comorbid conditions distribution of CAP in adults in primary care in Spain.
Retrospective observational study in adults (>18 years-old) with CAP diagnosed and attended at primary care in Spain between 2009 and 2013, using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP).
Twenty-eight thousand four hundred thirteen patient records were retrieved and analyzed. Mean age (standard deviation): 60.5 (20.3) years, 51.7 % males. Global incidence of CAP in adults was estimated at 4.63 per 1000 persons/year. CAP incidence increased progressively with age, ranging from a 1.98 at 18-20 years of age to 23.74 in patients over 90 years of age. According to sex, global CAP incidence was slightly higher in males (5.04) than females (4.26); CAP incidence from 18 to 65 year-olds up was comparable between males (range: 2.18-5.75) and females (range: 1.47-5.21), whereas from 65 years of age, CAP incidence was noticeable higher in males (range: 7.06-36.93) than in females (range: 5.43-19.62). Average prevalence of risk factors was 71.3 %, which increased with age, doubling the risk in males by the age of 75 (females 20 % vs males 40 %). From 55 years of age, at least one risk factor was identified in 85.7 % of cases: one risk factor (23.8 %), two risk factors (23.4 %), three or more risk factors (38.5 %). Major risk factors were: metabolic disease (27.4 %), cardiovascular disease (17.8 %) and diabetes (15.5 %).
The annual incidence of CAP in primary care adults in Spain is high, comparable between males and females up to 65 years of age, but clearly increasing in males from that age. CAP risk increases with age and doubles in males older than 75 years. The majority of CAP cases in patients over 55 years of age is associated to at least one risk factor. The main risk factors associated were metabolic disease, cardiovascular disease, and diabetes.
Starting from the revolutionary Retinex by Land and McCann, several further perceptually inspired color correction models have been developed with different aims, e.g. reproduction of color ...sensation, robust features recognition, enhancement of color images. Such models have a differential, spatially-variant and non-linear nature and they can coarsely be distinguished between white-patch (WP) and gray-world (GW) algorithms. In this paper we show that the combination of a pure WP algorithm (RSR: random spray Retinex) and an essentially GW one (ACE) leads to a more robust and better performing model (RACE). The choice of RSR and ACE follows from the recent identification of a unified spatially-variant approach for both algorithms. Mathematically, the originally distinct non-linear and differential mechanisms of RSR and ACE have been fused using the spray technique and local average operations. The investigation of RACE allowed us to put in evidence a common drawback of differential models: corruption of uniform image areas. To overcome this intrinsic defect, we devised a local and global contrast-based and image-driven regulation mechanism that has a general applicability to perceptually inspired color correction algorithms. Tests, comparisons and discussions are presented.
PDF
