Predictors of circulating INTERLEUKIN-6 levels in head and neck cancer patients

Abstract Background Circulating interleukin-6 (IL-6) improves outcome prediction for second primary cancer (SPC) in head and neck cancer (HNC) patients. This study aimed to identify factors associated with IL-6 serum levels in HNC patients. Methods This study was conducted as part of a phase III chemoprevention trial. IL-6 was measured using chemiluminescent immunometric assay on pretreatment serum sample obtained from 527 stage I-II HNC patients. Patients’ lifestyle habits, sociodemographic, medical and tumor characteristics were evaluated before radiation therapy (RT). Factors independently associated with IL-6 levels before RT were identified using multiple linear regression. Results The median IL-6 serum level was 3.1 ng/L. In the multivariate analysis, eight factors were significantly associated (p <  0.05) with IL-6: age, gender, marital status, body mass index, tobacco consumption, comorbidities, Karnofsky Performance Status and HNC site. Smoking duration and lifetime pack-years were positively associated with IL-6 serum levels in a dose-response relationship (p-value for trend ≤0.03). Conclusions Circulating IL-6 is a strong predictor of the occurrence of SPC in HNC patients. We identified eight factors independently associated with serum IL-6 levels in 527 stage I-II HNC patients. The dose-response relationship between lifetime smoking and IL-6 serum levels suggested a causal role of tobacco exposure on IL-6 production. Further studies are needed to establish whether the effect of tobacco exposure on SPC could be partly mediated by IL-6, a pro-inflammatory cytokine

Factors Influencing the Prescription of Cardiovascular Preventive Therapies in Patients with Peripheral Arterial Disease.

BACKGROUND:Guidelines recommend that patients with peripheral arterial disease should be medically treated to reduce the occurrence of serious cardiovascular events. Despite these recommendations, studies conducted in the early 2000s reported that medical therapies for secondary cardiovascular prevention are not given systematically to patients with peripheral arterial disease (PAD). We identified factors associated with the prescription of preventive therapies in patients with symptomatic PAD. METHODS AND FINDINGS:Consecutive patients with symptomatic peripheral arterial disease (n = 362) treated between 2008 and 2010 in one tertiary care center (CHU de Quebec, Canada) were considered. Data were collected from the medical charts. The main outcome was the combined prescription of three therapies: 1) statins, 2) antiplatelets, 3) angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. The mean age was 70 years and 43% had a pre-existing coronary artery disease. Antiplatelet therapy was the most prescribed drug (83%). A total of 52% of the patients received the three combined therapies. Less than 10% of patients had a known contraindication to one class of medication. Having at least three cardiovascular risk factors (Odds Ratio (OR) = 4.51; 95% CI: 2.76-7.37) was the factor most strongly associated with the prescription of the combined therapies. Pre-existing coronary artery disease (OR = 2.28; 95% CI: 1.43-3.65) and history of peripheral vascular surgery (OR = 2.30; 95% CI: 1.37-3.86) were two factors independently associated with the prescription of the combined therapies. However, peripheral arterial disease patients with chronic critical limb ischemia were less likely to receive the combined therapies (OR = 0.53; 95% CI: 0.32-0.87) than those with claudication. The retrospective nature of this study, not allowing for an exhaustive report of the contraindication to medication prescription, is the main limitation. CONCLUSION:About half of the patients with peripheral arterial disease were not optimally managed. Patients with multiple cardiovascular risk factors were more likely to receive the combined therapies. We still need to better understand the barriers and facilitators to the application of the guidelines

A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer

Abstract Background Cisplatin-induced hearing loss is frequent and severe. Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. Methods Eligible participants were newly diagnosed patients with stage III or IV squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or larynx and scheduled to be treated by concurrent chemoradiation (CCR). Patients with asymmetric hearing were not eligible. The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43. A baseline pre-treatment complete audiometric evaluation (pure tone at frequencies ranging from 0.5 to 14 kHz, bone conduction at 0.5–4 kHz and DPOAEs) was performed. Adverse effects were noted according to CTCAE. On the day before the beginning of CCR, eligible and consenting patients were randomized to receive a trans-tympanic injection of the gel either in the left ear or in the right ear. A final post-treatment complete audiometric evaluation was scheduled to be performed 1 month after the end of CCR by audiologists kept blind to the ear assignment. For the main outcome, the permanent threshold shift (PTS) in decibel (dB) was calculated as the difference between the final and baseline measures at all pure tone frequencies at 0.5–14 kHz for each patient and for each ear. The main outcome was assessed blindly in a mixed linear model with the PTS as the dependent variable and intervention, frequency, their interaction and radiation dose to the cochlea as independent variables. Results Between January 2015 and April 2016, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. Conclusions Our trial suggests that STS deposited on the round window was safe for the middle and inner ears. More work is needed to improve the efficacy of trans-tympanic injections of cisplatin antidotes. Trial registration ClinicalTrials.gov, NTC02281006, Registered 3 November 2014