IMRT national audit in Portugal.

PURPOSE: The IAEA newly developed "end-to-end" audit methodology for on-site verification of IMRT dose delivery has been carried out in Portugal in 2018. The main goal was to evaluate the physical aspects of the head and neck (H&N) cancer IMRT treatments. This paper presents the national results. METHODS: All institutions performing IMRT treatments in Portugal, 20 out of 24, have voluntarily participated in this audit. Following the adopted methodology, a Shoulder, Head and Neck End-to-End phantom (SHANE) - that mimics an H&N region, underwent all steps of an IMRT treatment, according to the local practices. The measurements using an ionization chamber placed inside the SHANE phantom at four reference locations (three in PTVs and one in the spinal cord) and an EBT3 film positioned in a coronal plane were compared with calculated doses. FilmQA Pro software was used for film analysis. RESULTS: For ionization chamber measurements, the percent difference was within the specified tolerances of ±5% for PTVs and ±7% for the spinal cord in all participating institutions. Considering film analysis, gamma passing rates were on average 96.9%±2.9% for a criterion of 3%/3 mm, 20% threshold, all above the acceptance limit of 90%. CONCLUSIONS: The national results of the H&N IMRT audit showed a compliance between the planned and the delivered doses within the specified tolerances, confirming no major reasons for concern. At the same time the audit identified factors that contributed to increased uncertainties in the IMRT dose delivery in some institutions resulting in recommendations for quality improvement.

Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1ß and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1ß), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. METHODS: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case-control study. RESULTS: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13-4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. CONCLUSION: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1ß levels produced by this genotype. High IL-1ß levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.

HLA and age of onset in myasthenia gravis.

The aetiology of MG is unknown, but both genetic and environmental factors are important. Over the years association of MG with Human Leucocyte Antigens (HLA) has been described in different populations. We investigated a possible association between HLA-DRB1 alleles and age of onset in MG. One hundred and fourteen MG patients (82 females) and 282 control individuals (CP) were studied. Patients were classified according to the age of onset (early-onset <50, n = 74 and late-onset ≥ 50, n = 20). Patients with thymoma (n = 20) were analyzed separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the early-onset subgroup was considered, this association became even stronger. Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was significantly higher when compared to the CP. These results have shown a strong association of HLA-DRB1*03 with MG, especially for EOMG also in our population. HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for this subgroup of the disease. This study confirms a different genetic background of MG subgroups regarding age of onset.

The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1(∗)15 (OR = 2.17) and HLA-DRB1(∗)03 (OR = 1.81) alleles with MS, HLA-DRB1(∗)03 with SLE (OR = 2.49), HLA-DRB1(∗)01 (OR = 1.79) and HLA-DRB1(∗)04 (OR = 2.81) with RA, HLA-DRB1(∗)07 with Ps + PsA (OR = 1.79), HLA-DRB1(∗)01 (OR = 2.28) and HLA-DRB1(∗)08 (OR = 3.01) with SSc, and HLA-DRB1(∗)03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1(∗)13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1(∗)13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1(∗)13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1(∗)13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.