Carbon ion therapy (C12) for high-grade malignant salivary gland tumors (MSGTs) of the head and neck: do non-ACCs profit from dose escalation?

PURPOSE: To evaluate the use of high-dose radiotherapy using carbon ions (C12) on non-adenoid cystic malignant salivary gland tumors (MSGT). PATIENTS AND METHODS: Between 2009 and 2013, patients with biopsy-proven non-ACC MSGT histologies of the head and neck received a combined regimen of IMRT plus C12 boost. Treatment toxicity (CTC v3), response (RECIST 1.1), control and survival rates were retrospectively analyzed. RESULTS: 40 patients with pathologically confirmed non-ACC MSGT (T4: 45 %; N+: 40 %; gross residual: 58 %; mucoepidermoid carcinoma (MEC): 45 %; adenocarcinoma: 20 %) were treated with a median of 74 GyE (80 Gy BED). Chemoradiation was given in 5 patients with MEC. Grade III acute toxicity was observed in up to 15 % (mucositis, dermatitis, dysphagia), no higher-grade late toxicity occurred to date. At a follow-up of 25.5 months, LC, and PFS at 2 and 3 years are 81.5 % (LC) and 66.8 % (PFS), OS at 2 and 3 years is 83.6 % and 72.8 %. Most frequent site of disease progression was distant metastasis. Histologic subtype correlated with LC and PFS. Resection status (gross vs microscopic disease) had no significant effect on LC, PFS, or OS. CONCLUSION: The treatment is well tolerated, no higher grade late effects were observed. Considering the negative pre-selection, LC, PFS and OS are promising. While histology and site of origin significantly influenced control and survival rates, resection status did not, potentially due to the effect of dose escalation.

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension.

BACKGROUND AND AIMS: Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. METHODS AND RESULTS: In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g(-1), p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s(-1), p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the 'independent correlates' of ACR (R(2) = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the 'independent correlates' of c-f PWV (R(2) = 0.428, p < 0.0001). CONCLUSION: In hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage.

The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives.

The data regarding the role of serum uric acid (SUA) along with subclinical inflammation in the context of hypertensive vascular damage are rather scarce and controversial. Towards this end, we assess the links between SUA, high-sensitivity CRP (hs-CRP), adiponectin and carotid to femoral pulse wave velocity (c-f PWV) in 292 subjects with never-treated stage I-II essential hypertension. On the basis of the median SUA levels (0.31 mmol l(-1)), the study population was divided into subjects with low (n=149) and high (n=143) SUA values. By multiple regression analysis, it was revealed that SUA was independently associated with log hs-CRP (R(2)=0.098; P=0.02), log adiponectin (R(2)=0.102; P=0.03), waist circumference (R(2)=0.049; P=0.04), 24-h systolic blood pressure (SBP) (R(2)=0.179; P=0.001) and estimated glomerular filtration rate (R(2)=0.156; ß (s.e.)=-0.169 (0.023); P=0.02). In addition, c-f PWV was independently associated with age (R(2)=0.116; P<0.0001), waist circumference (R(2)=0.088; P<0.0001), 24-h SBP (R(2)=0.167; P=0.001), log adiponectin (R(2)=0.07; P=0.006) and log hs-CRP (R(2)=0.06; P=0.034). In conclusion, SUA levels are independently associated with hs-CRP and adiponectin levels but not with c-f PWV in essential hypertensive patients. Increased SUA levels are accompanied by a state of pronounced inflammatory activation and hypoadiponectinemia that significantly impairs the arterial stiffness accelerating the vascular ageing process in this setting.