Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Active surveillance of oesophageal cancer after response to neoadjuvant chemoradiotherapy:dysphagia is uncommon

BACKGROUND: Active surveillance is being investigated as an alternative to standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer. It is unknown whether dysphagia persists or develops when the oesophagus is preserved after neoadjuvant chemoradiotherapy. The aim of this study was to assess the prevalence and severity of dysphagia during active surveillance in patients with an ongoing response. METHODS: Patients who underwent active surveillance were identified from the Surgery As Needed for Oesophageal cancer ('SANO') trial. Patients without evidence of residual oesophageal cancer until at least 6 months after neoadjuvant chemoradiotherapy were included. Study endpoints were assessed at time points that patients were cancer-free and remained cancer-free for the next 4 months. Dysphagia scores were evaluated at 6, 9, 12, and 16 months after neoadjuvant chemoradiotherapy. Scores were based on the European Organisation for Research and Treatment of Cancer oesophago-gastric quality-of-life questionnaire 25 (EORTC QLQ-OG25) (range 0-100; no to severe dysphagia). The rate of patients with a (non-)traversable stenosis was determined based on all available endoscopy reports. RESULTS: In total, 131 patients were included, of whom 93 (71.0 per cent) had adenocarcinoma, 93 (71.0 per cent) had a cT3-4a tumour, and 33 (25.2 per cent) had a tumour circumference of greater than 75 per cent at endoscopy; 60.8 to 71.0 per cent of patients completed questionnaires per time point after neoadjuvant chemoradiotherapy. At all time points after neoadjuvant chemoradiotherapy, median dysphagia scores were 0 (interquartile range 0-0). Two patients (1.5 per cent) underwent an intervention for a stenosis: one underwent successful endoscopic dilatation; and the other patient required temporary tube feeding. Notably, these patients did not participate in questionnaires. CONCLUSION: Dysphagia and clinically relevant stenosis are uncommon during active surveillance.</p

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro

Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro. Oostenbrug GS, Mensink RP, Hornstra G. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. Eleven men received a fish oil (2.4 g n-3 fatty acids), fish oil plus vitamin E (300 IU) or no supplement for 3 weeks. Dietary fish oil increased the maximum amount of conjugated dienes formed during copper-catalysed oxidation of LDL in vitro by 18-20%. Fish oil also tended to decrease the lagtime before onset of oxidation, but this effect was counteracted by vitamin E. We conclude that fish oil supplementation increases the oxidizability of LDL in vitro, and vitamin E increases its oxidation resistanc

Lipid peroxidation-associated oxidative stress during percutaneous transluminal coronary angioplasty in humans.

Department of Human Biology, Maastricht University, The Netherlands. Animal studies suggest that myocardial ischemia/reperfusion causes oxidative stress. We, therefore, examined whether routinely performed percutaneous transluminal coronary angioplasty (PTCA) might be a human ischemia/reperfusion model for oxidative stress-induced lipid peroxidation. Fasting antecubital venous blood was sampled from 13 patients on the morning of PTCA, and 2 d after PTCA. Venous and coronary arterial blood were sampled just before and 10 min after the first balloon inflation. Samples were analyzed for plasma and LDL lipid hydroperoxide levels, in vitro oxidation of LDL, and LDL antioxidant levels. Lipid hydroperoxide levels in plasma and LDL remained unchanged throughout the study. During the first 10 min of PTCA, the lag time during oxidation of LDL in vitro did not change, but the maximum rate of oxidation decreased in venous and arterial samples (Wilcoxon signed rank test: p < .002). At the same time, total tocopherol levels in LDL significantly increased by 6.3% (p = .048) in arterial, but not in venous samples. Total carotenoid levels increased by 3.8% (p = .127) in arterial samples and decreased by 2.9% (p = .040) in venous samples. Forty hours after PTCA, LDL oxidation parameters and LDL antioxidant levels were similar to baseline, except for about 17% lower levels of delta-tocopherol (p = .037) and gamma-tocopherol (p = .014). Our results, therefore, do not support that PTCA in humans is associated with oxidative stress-induced lipid peroxidation. Publication Types: Clinical Tria

Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation.

During pregnancy, maternal plasma concentrations of the peroxidation-susceptible polyunsaturated fatty acids (polyenes) increase. In addition, the proportion of polyenes is higher in neonatal plasma than in maternal plasma. To study whether these increased amounts of polyenes affect antioxidant levels, we measured lipid-soluble antioxidants in maternal and neonatal plasmas obtained during thirty-five normal pregnancies. These values were then related to the degree of phospholipid-fatty acid unsaturation. Maternal plasma levels of tocopherols and lutein increased during pregnancy, as assessed at 14, 22, and 32 weeks of gestation. However beta-carotene levels decreased, and levels of other carotenoids remained unchanged. Retinol levels were only decreased at 32 weeks of gestation. The value for alpha-tocopherol: phospholipid-polyene unsaturation index (UI) also increased during pregnancy, despite the observed increase in UI. Corresponding ratios for several carotenoids and retinol, however, decreased during pregnancy. After delivery, maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol, as well as beta + gamma-tocopherol: UI values, were lower than values at 32 weeks of gestation. Umbilical-cord plasma antioxidant levels and antioxidant: UI values, except retinol: UI, were significantly lower than maternal values. Significant and consistent cord v. maternal correlations were observed for plasma levels of beta + gamma-tocopherol, lutein and beta-carotene, but not for delta-tocopherol, alpha-tocopherol, lycopene, alpha-carotene, and retinol. In conclusion, although during pregnancy maternal plasma tocopherol levels increased concurrently with, or more than, fatty acid unsaturation in plasma phospholipids, the decrease in carotenoid: UI values during gestation, the decrease in maternal plasma levels of delta-tocopherol and beta + gamma-tocopherol after delivery, and the low neonatal antioxidant levels merit further investigation

Pregnancy-induced hypertension: maternal and neonatal plasma lipid-soluble antioxidant levels and its relationship with fatty acid unsaturation.

TNO Nutrition and Food Research Institute, Food and Non-Food Analysis Department, Zeist, The Netherlands. OBJECTIVE: Our purpose was to investigate whether plasma lipid-soluble antioxidant levels during the third trimester of pregnancy and immediately after birth are altered in women with pregnancy-induced hypertension. DESIGN: Nested case-control study of women with pregnancy-induced hypertension. SUBJECTS: A group of 23 women with (mild) pregnancy-induced hypertension and their neonates, were compared with 23 matched controls with uncomplicated pregnancies. METHODS: Concentrations of vitamin E isomers, several carotenoids, and retinol were determined by HPLC in venous plasma which had been stored for 2-5 y. Antioxidant levels were adjusted for the degree of fatty acid unsaturation in plasma phospholipids as analysed 2-5 y before. RESULTS: In the third trimester of pregnancy, lipid-soluble antioxidant levels were similar in women with pregnancy-induced hypertension and controls. From the third trimester to postpartum, mean (+/- s.e.m.) beta + gamma-tocopherol levels decreased by 0.38 +/- 0.17 mumol/l or 5% (P = 0.038) in the control group. In the pregnancy-induced hypertension group, however, plasma levels of most antioxidants decreased from the third trimester to postpartum, but only the decreases in plasma levels of beta + gamma-tocopherol of 1.08 +/- 0.27 mumol/l or 26% (P = 0.042), of alpha-tocopherol of 2.51 +/- 1.58 mumol/l or 6% (P = 0.024), and of lutein of 0.13 +/- 0.04 mumol/l or 15% (P = 0.013) reached statistical significance as compared with the changes in the control group. At the same time, the polyunsaturated fatty acid unsaturation index of plasma phospholipids (UI) decreased in the pregnancy-induced hypertension group as well. Consequently, antioxidant levels, adjusted for UI, changed similarly in both groups. Umbilical vein plasma antioxidant levels were also similar after complicated and uncomplicated pregnancies. CONCLUSION: Plasma lipid-soluble antioxidant levels in mother and child are affected by mild pregnancy-induced hypertension, but this effect disappears after adjustment for fatty acid unsaturation