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De Felice F.,Guys and St Thomas NHS Foundation TrustLondon | De Felice F.,University of Rome La Sapienza | Thomas C.,Guys and St Thomas NHS Foundation TrustLondon | Barrington S.,King's College London | And 3 more authors.
Oral Oncology | Year: 2015

Summary Objectives To investigate the anatomical distribution of loco-regional treatment failures (LRF) in patients with head and neck squamous cell carcinoma (HNSCC) in relation to clinical target volume (CTV) delineation. Materials and methods 56 patients with LRF were retrospectively identified. Patients were previously treated with radical intensity modulated radiotherapy (IMRT) +/- chemotherapy. Target volumes include gross tumour volume (GTV), its volumetric expansion of 10 mm (GTV-HD), CTV high dose (CTV-HD) delineated by anatomic expansion from GTV and CTV low dose (CTV-LD) defined to receive a prophylactic dose. LRF were evaluated by PET-CT or CT scan. We analysed the association between sites of LRF and target volumes and dosimetry, using image co-registration. Based on percentage of volume that received 95% of prescribed dose, LRF were classified as in-field, marginal or out-field. Results Median interval time from end of treatment to LRF was 186 days. 65 (95.6%) LRF were classified as in-field. Considering primary target volumes, 40 (58.8%) LRF occurred inside GTV, 13 (19.1%) in GTV-HD and 7 (10.3%) in CTV-HD. The overall 1-year and 2-year post-failure survival (PFS) was 45.8% and 24.2%, respectively. Post radiation LRF managed with salvage surgery had a significantly higher median PFS when compared with palliative treatments (p = 0.003). Conclusions The majority of LRF occurred within GTV/GTV-HD, suggesting it is safe to reduce the CTV to a volumetric expansion. Given the low incidence of geographical misses, future studies should be directed towards dose escalation of high-risk volumes. Potential reduction of RT-related toxicity with volumetric expansion could facilitate salvage surgery. © 2015 Elsevier Ltd.

Boonk S.E.,Leiden University | Zoutman W.H.,Leiden University | Marie-Cardine A.,French Institute of Health and Medical Research | Marie-Cardine A.,University Paris Diderot | And 29 more authors.
Journal of Investigative Dermatology | Year: 2016

Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4+ T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (≥80% CD4+ T cells) and/or CD7 (≥40% CD4+ T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sézary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sézary syndrome versus erythrodermic inflammatory dermatoses. © 2016 The Authors

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