F-FDG PET/CT plays an increasingly pivotal role in the staging and post-treatment monitoring of high-risk melanoma patients, augmented by the introduction of therapies, including tyrosine kinase ...inhibitors (TKI) and immune checkpoint inhibitors (ICIs), that have novel modes of action that challenge conventional response assessment. Simultaneously, technological advances have been regularly released, including advanced reconstruction algorithms, digital PET and motion correction, which have allowed the PET community to detect ever-smaller cancer lesions, improving diagnostic performance in the context of indications previously viewed as limitations, such as detection of in-transit disease and confirmation of the nature of small pulmonary metastases apparent on CT.This review will provide advice regarding melanoma-related PET protocols and will focus on variants encountered during the imaging of melanoma patients. Emphasis will be made on pitfalls related to non-malignant diseases and treatment-related findings that may confound accurate interpretation unless recognized. The latter include signs of immune activation and immune-related adverse events (irAEs). Technology-related pitfalls are also discussed, since while new PET technologies improve detection of small lesions, these may also induce false-positive cases and require a learning curve to be observed. In these times of the COVID 19 pandemic, cases illustrating lessons learned from COVID 19 or vaccination-related pitfalls will also be described.
Abstract
Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. ...Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber’s alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.
Cemiplimab is a monoclonal antibody targeting the PD-1, and phase II trials have shown its efficacy in the treatment of advanced cutaneous squamous cell carcinoma in patients who are not candidates ...for curative surgery or radiation therapy as a first- or later-line treatment. A synergistic antitumoral response has been demonstrated with concurrent radiotherapy and PD1-immunotherapy. However, no real-life study has demonstrated this effect in advanced cutaneous squamous cell carcinoma.
We conducted a real-life retrospective cohort study to investigate the benefit of concomitant therapy in 33 patients treated with cemiplimab at the University Hospital of Caen, alone (C group) or concomitant to radiotherapy (C/RT group). Our primary objectives were to evaluate the best overall response and objective response rate. Our secondary objectives were the disease control rate, median time to response, progression-free survival, overall survival, clinical benefit of radiotherapy, and safety data. After stopping cemiplimab administration, we performed a follow-up of our patients and performed a descriptive study.
We reported an objective response rate of 45.5%, including 47.6% in the cemiplimab group versus 41.6% in the concomitant group. The addition of radiotherapy to cemiplimab enables an earlier clinico-radiological response, with a median duration of 5.5 months in the cemiplimab group versus 3 months in the concomitant therapy group. The response to treatment was prolonged despite discontinuation of cemiplimab, with 91.6% (
= 11/12) and 83.3% (
= 10/12) patients in complete or partial remission at 6 months and 1 year after cessation of cemiplimab and no switch to another oncological treatment, respectively. Radiation therapy also provided a therapeutic effect in 83.3% of the patients in the concomitant group, without increasing the occurrence of adverse events.
Our study confirms the efficacy of cemiplimab and radiotherapy in the management of advanced cutaneous squamous cell carcinoma. Concomitant therapy permitted to obtain an earlier radiological response, a beneficial local therapeutic effect of radiotherapy, without any safety alert.
In metastatic stage, therapeutic approach for malignant melanoma is particularly based on performance status, metastatic sites, and BRAF V600 status (BRAF V600E/V600K or V600R (class I BRAF ...mutations). In most cases, BRAF mutations and NRAS mutations are mutually exclusive to each other. However, some rare BRAF mutations class III are preferentially associated with a NRAS mutation, leading to the MAP Kinase pathway activation and subsequent cell proliferation. Melanomas with this double mutation are rare and difficult to treat because of the lack of codified therapeutic options. We report a patient with metastatic melanoma, harboring class III BRAF mutation (N581K) associated to NRAS mutation (Q61L) with treatment failure. He was treated in second line, after immunotherapy, by monotherapy of MEK inhibitor (MEKi), which underline the interest of NGS (Next Generation Sequencing) to early identify all mutations and enabling onco-dermatologist to discuss a treatment. Rare BRAF non V600 mutations represent 3 to 14% of melanoma mutants and the aim of this communication is to promote the next generation sequencing to extend the paradigm of individually therapeutic approach with target therapy into different spectrum of melanoma patients.
This study aimed to provide an updated analysis of the different prognostic trajectories of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies.
Among a cohort of 70 ...patients, baseline characteristics and phenotypes, treatments and outcomes were analyzed. A Cox proportional hazards model was used to identify factors associated with poor outcomes, i.e., death or progressive disease at the last follow-up.
Among the 70 patients, 45 were women, and 54 were Caucasian. A dermatologic involvement was observed in 58 (83%) patients, including 40 with MDA5 vasculopathy-related skin lesions. Muscular involvement was observed in 39 (56%) patients. Interstitial lung disease (ILD) was observed at baseline in 52 (74%) patients, including 23 (44%) who developed rapidly progressive (RP) ILD. Seven (10%) patients showed thromboembolic complications within the first weeks of diagnosis, and eight (11%) other patients developed a malignancy (4 before the diagnosis of anti-MDA5 disease). Poor outcomes were observed in 28 (40%) patients, including 13 (19%) deaths. Among the 23 patients with RP-ILD, 19 (79%) showed poor outcomes, including 12 (63%) who died. In multivariate analyses, RP-ILD (hazard ratio (HR), 95% CI: 8.24 3.21-22, p<0.0001), the occurrence of thromboembolic events (HR: 5.22 1.61-14.77, p=0.008) and the presence of any malignancy (HR: 19.73 6.67-60, p<0.0001) were the three factors independently associated with poor outcomes.
This new independent cohort confirms the presence of different clinical phenotypes of anti-MDA5 diseases at baseline and the poor prognosis associated with RP-ILD. Thromboembolic events and malignancies were also identified as prognostic factors.
Aim: To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV ...melanoma. Materials and methods: We conducted a retrospective monocentric observational study over a 3-year period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint (ICIs) as of January 2017. Imaging reports were analyzed by two physicians in consensus. The anatomical site responsible for discordances, as well as induced changes in treatment were noted. Results: Eighty patients were included and 195 pairs of scans analyzed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient’s management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients’ management in 2/13 cases (15%). The most frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. Conclusions: Treatment monitoring with 18F-FDG PET/CT is more efficient than ceCT and has a greater impact in patient’s management.
Prurit associé à la maladie rénale chronique Lanot, Antoine; Kottler, Diane; Béchade, Clémence
Néphrologie & thérapeutique,
December 2021, 2021-12-00, Volume:
17, Issue:
7
Journal Article
Peer reviewed
Le prurit associé à la maladie rénale chronique est un symptôme fréquent et invalidant chez les patients insuffisants rénaux chroniques sévères et traités par dialyse. Il est associé à une diminution ...de la qualité de vie, à une augmentation du risque de comorbidités et même de mortalité. Néanmoins, sa prévalence est sous-estimée par les soignants. La physiopathologie du prurit associé à la maladie rénale chronique est imparfaitement comprise, mais plusieurs mécanismes semblent concourir à son apparition : accumulation et dépôts cutanés de toxines urémiques, neuropathie périphérique activant de manière anormale la voie spécifique pruritogène du Cowhage, micro-inflammation chronique, déséquilibre de la balance des récepteurs opioïdes κ et μ, et xérose cutanée liée à la maladie rénale. L’optimisation du traitement de la maladie rénale chronique et/ou des paramètres de dialyse et les mesures générales de soins cutanés doivent toujours être effectuées avant introduction d’un traitement systémique ciblant un ou plusieurs de ces mécanismes. Les essais thérapeutiques disponibles restent pour la plupart à risque important de biais, avec de faibles effectifs de patients. Les gabapentinoïdes sont les molécules recommandées en première intention. Les agonistes opioïdes périphériques pourraient trouver une place de choix dans le traitement du prurit associé à la maladie rénale chronique et seront prochainement disponibles en France. Le faible niveau de preuve des autres molécules ne permet actuellement pas de préciser un traitement de deuxième intention pour cette indication.
Pruritus associated with chronic kidney disease is a frequent and disabling symptom in patients with severe chronic kidney disease treated by dialysis. It is associated with a poor quality of life, an increased risk of comorbidities and even mortality. Nevertheless, its prevalence is underestimated by nephrologists. The pathophysiology of pruritus associated with chronic kidney disease is not well understood, but several mechanisms seem to contribute to its occurrence: accumulation and skin deposition of uremic toxins, peripheral neuropathy causing an activation of the pruritogenic cowhage pathway, chronic microinflammation, opioid imbalance, and kidney disease-related skin xerosis. Optimization of the treatment of chronic kidney disease treatment, of dialysis parameters, and general skin care measures should always be performed prior to the introduction of systemic therapy targeting one or more of these mechanisms. The available therapeutic trials remain mostly at high risk of bias, with small patient numbers. Gabapentinoids are the molecules recommended as first-line therapy. Peripheral opioid agonists could find a place of choice in the treatment of pruritus associated with chronic kidney disease and will soon be available in France. The low level of evidence for the other molecules does not currently allow us to specify a second-line treatment for this condition.
Pruritus associated with chronic kidney disease is a frequent and disabling symptom in patients with severe chronic kidney disease treated by dialysis. It is associated with a poor quality of life, ...an increased risk of comorbidities and even mortality. Nevertheless, its prevalence is underestimated by nephrologists. The pathophysiology of pruritus associated with chronic kidney disease is not well understood, but several mechanisms seem to contribute to its occurrence: accumulation and skin deposition of uremic toxins, peripheral neuropathy causing an activation of the pruritogenic cowhage pathway, chronic microinflammation, opioid imbalance, and kidney disease-related skin xerosis. Optimization of the treatment of chronic kidney disease treatment, of dialysis parameters, and general skin care measures should always be performed prior to the introduction of systemic therapy targeting one or more of these mechanisms. The available therapeutic trials remain mostly at high risk of bias, with small patient numbers. Gabapentinoids are the molecules recommended as first-line therapy. Peripheral opioid agonists could find a place of choice in the treatment of pruritus associated with chronic kidney disease and will soon be available in France. The low level of evidence for the other molecules does not currently allow us to specify a second-line treatment for this condition.
Background
In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we ...demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation.
Method
We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab.
Results
Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease.
Conclusion
Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.
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