Serious Long-Term Effects of Head and Neck Cancer from the Survivors’ Point of View

The long-term problems of head and neck cancer survivors (HNCS) are not well known. In a cross-sectional international study aimed at exploring the long-term quality of life in this population, 1114 HNCS were asked to state their two most serious long-term effects. A clinician recorded the responses during face-to-face appointments. A list of 15 example problems was provided, but a free text field was also available. A total of 1033 survivors responded to the question. The most frequent problems were ‘dry mouth’ (DM) (n = 476; 46%), ‘difficulty swallowing/eating’ (DSE) (n = 408; 40%), ‘hoarseness/difficulty speaking’ (HDS) (n = 169; 16%), and ‘pain in the head and neck’ (PHN) (n = 142; 14%). A total of 5% reported no problems. Logistic regression adjusted for age, gender, treatment, and tumor stage and site showed increased odds of reporting DM and DSE for chemo-radiotherapy (CRT) alone compared to surgery alone (odds ratio (OR): 4.7, 95% confidence interval (CI): 2.5–9.0; OR: 2.1, CI: 1.1–3.9), but decreased odds for HDS and PHN (OR: 0.3, CI: 0.1–0.6; OR: 0.2, CI: 0.1–0.5). Survivors with UICC stage IV at diagnosis compared to stage I had increased odds of reporting HDS (OR: 1.9, CI: 1.2–3.0). Laryngeal cancer survivors had reduced odds compared to oropharynx cancer survivors of reporting DM (OR: 0.4, CI: 0.3–0.6) but increased odds of HDS (OR: 7.2, CI: 4.3–12.3). This study provides evidence of the serious long-term problems among HNCS. © 2023 by the authors

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society