BACKGROUND: As a system of European Reference Networks (ERNs) emerges, the differences in quality of care for patients with rare cancers may increase at national level. We aimed to elucidate the processes and healthcare planning principles through which the reference centres (RCs) for rare cancers are embedded in national health systems. METHODS: We used a multiple case-study design based on the experiences of Czechia, Finland, France, Italy, Lithuania and Spain. Using sarcoma as an example of rare cancer, 52 semi-structured interviews were conducted during on-site visits, including a multidisciplinary group of professionals, Ministry of Health professionals, patient representatives and European policymakers. RESULTS: The comparative analysis showed substantial heterogeneity in the processes for formalizing RCs' status and in their levels of integration in the different health systems, but two models (centre-based and the network-based) can be envisaged at national level. RCs for rare cancers were legally established only in France and Spain. Expert clinicians cooperate in a structured way, using network mechanisms, in France and Italy, and these countries, plus Finland and Lithuania, had a referral system to facilitate patients' access from non-expert centres to RCs. Seven key healthcare planning principles in instituting RCs at the national level were identified. CONCLUSIONS: The conditions governing patient access to treatment centres-whether RCs or not-are decided at the national level. It is advisable to progressively align the European and national levels so that the RCs that participate in the ERNs also play a significant role at the national level.
PURPOSE: Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS: LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 (P < .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P < .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION: VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.
- MeSH
- časové faktory MeSH
- dítě MeSH
- histiocytóza z Langerhansových buněk diagnóza farmakoterapie genetika MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití MeSH
- kojenec MeSH
- léková rezistence MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- předškolní dítě MeSH
- protoonkogenní proteiny B-raf antagonisté a inhibitory genetika MeSH
- signální transdukce MeSH
- stupeň závažnosti nemoci MeSH
- věkové faktory MeSH
- vemurafenib škodlivé účinky terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD, which now belongs to the R group of the 2016 revised histiocytosis classification, is a widely heterogeneous entity with a range of clinical phenotypes occurring in isolation or in association with autoimmune or malignant diseases. Recent studies have found NRAS, KRAS, MAP2K1, and ARAF mutations in lesional tissues, raising the possibility of a clonal origin in some forms of RDD. More than 1000 reports have been published in the English literature; however, there is a lack of consensus regarding approach for the clinical management of RDD. Although in most cases RDD can be observed or treated with local therapies, some patients with refractory or multifocal disease experience morbidity and mortality. Here we provide the first consensus multidisciplinary recommendations for the diagnosis and management of RDD. These recommendations were discussed at the 32nd Histiocyte Society Meeting by an international group of academic clinicians and pathologists with expertise in RDD. We include guidelines for clinical, laboratory, pathologic, and radiographic evaluation of patients with RDD together with treatment recommendations based on clinical experience and review of the literature.
- MeSH
- biopsie MeSH
- genetická predispozice k nemoci MeSH
- histiocyty metabolismus patologie MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- imunoterapie MeSH
- lidé MeSH
- management nemoci MeSH
- mutace MeSH
- prognóza MeSH
- radioterapie MeSH
- sinusová histiocytóza diagnóza genetika patologie terapie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
PURPOSE: Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive GI stromal tumor (GIST) oncogenesis, but the clinical significance of their single mutations is known incompletely. PATIENTS AND METHODS: We identified 11 population-based series of patients with GIST through a literature search and pooled individual data from 3,067 patients treated with macroscopically complete tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed associations between KIT and PDGFRA mutations and recurrence-free survival (RFS) in the subsets in which patients were treated with surgery alone. RESULTS: We identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication mutations recurred. Patients with deletions of only one codon of KIT exon 11 had better RFS than those with another deletion type, and some KIT exon 11 substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated with favorable RFS. Patients with an identical mutation had greatly variable outcomes depending on the standard prognostic factors, notably, mitotic count. Commonly used risk stratification schemes tended to overestimate the risk for recurrence in subgroups with prognostically favorable mutations. CONCLUSION: GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy.
- MeSH
- dítě MeSH
- dospělí MeSH
- gastrointestinální nádory enzymologie genetika chirurgie MeSH
- gastrointestinální stromální tumory enzymologie genetika chirurgie MeSH
- genetická predispozice k nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru enzymologie genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- protoonkogenní proteiny c-kit genetika MeSH
- růstový faktor odvozený z trombocytů - receptor alfa genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
