Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.

BACKGROUND & AIMS: Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS: This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS: There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION: Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.

Disparities in guideline-concordant treatment for node-positive, non-small cell lung cancer following surgery.

OBJECTIVES: To examine guideline concordance across a national sample and determine the relationship between socioeconomic factors, use of recommended postoperative adjuvant therapy, and outcomes for patients with resected pN1 or pN2 non-small cell lung cancer. METHODS: All margin-negative pT1-3 N1-2 M0 non-small cell lung cancers treated with lobectomy or pneumonectomy without induction therapy in the National Cancer Database between 2006 and 2013 were included. Use of guideline-concordant adjuvant treatment, defined as chemotherapy for pN1 disease and chemotherapy with or without radiation for pN2 disease, was examined. Multivariable regression models were developed to determine associations of clinical factors with guideline adherence. Survival was estimated using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Of 13,462 patients, 10,113 had pN1 disease and 3349 had pN2 disease. Guideline-concordant adjuvant therapy was used in 6844 (67.7%) patients with pN1 disease and 2622 (78.3%) patients with pN2 disease. After multivariable adjustment, insurance status, older age, pneumonectomy, readmission, and longer postoperative stays were associated with lower likelihood of guideline concordance. Conversely, increased education level, later year of diagnosis, and greater nodal stage were associated with greater concordance. Overall, patients treated with guideline-concordant therapy had superior survival (5-year survival: 51.6 vs 36.0%; hazard ratio, 0.66; 95% confidence interval, 0.62-0.70, P < .001). CONCLUSIONS: Socioeconomic factors, including insurance status and geographic region, are associated with disparities in use of adjuvant therapy as recommended by National Comprehensive Cancer Network guidelines. These disparities significantly impact patient survival. Future work should focus on improving access to appropriate adjuvant therapies among the under insured and socioeconomically disadvantaged.

Validation of a nomogram for selecting patients for chemotherapy after D2 gastrectomy for cancer.

BACKGROUND: According to some guidelines for the management of gastric cancer, adjuvant chemotherapy is recommended for patients with pT3-4 or node-positive disease. The aim of this study was to define low- and high-risk groups in terms of survival, and to predict the benefit of adjuvant fluoropyrimidine plus oxaliplatin (F-OX) chemotherapy. METHODS: Patients with pT3-4 or node-positive gastric cancer after gastrectomy with D2 lymphadenectomy between 2000 and 2013 were included. The performance of a previously published nomogram was assessed by discrimination and calibration. Patients were stratified into risk groups on the basis of the nomogram-predicted overall survival probability. The efficacy of F-OX within each risk subgroup was assessed using the log rank test and Cox regression analysis weighted by inverse propensity score. RESULTS: Some 1464 patients were included. The nomogram showed better discrimination than the seventh AJCC staging classification (concordance index 0·72 versus 0·68 respectively; P = 0·008) and accurate calibration. F-OX was not associated with improved survival in patients in the low-risk group, whereas it reduced the risk of death by over 20 per cent in the intermediate- and high-risk groups (P = 0·036 and P < 0·001 respectively) (P for interaction = 0·014). CONCLUSION: A nomogram can aid in individualized decision-making regarding the administration of F-OX after gastrectomy for cancer.

Influence of early goal-directed therapy using arterial waveform analysis on major complications after high-risk abdominal surgery: study protocol for a multicenter randomized controlled superiority trial.

BACKGROUND: Early goal-directed therapy refers to the use of predefined hemodynamic goals to optimize tissue oxygen delivery in critically ill patients. Its application in high-risk abdominal surgery is, however, hindered by safety concerns and practical limitations of perioperative hemodynamic monitoring. Arterial waveform analysis provides an easy, minimally invasive alternative to conventional monitoring techniques, and could be valuable in early goal-directed strategies. We therefore investigate the effects of early goal-directed therapy using arterial waveform analysis on complications, quality of life and healthcare costs after high-risk abdominal surgery. METHODS/DESIGN: In this multicenter, randomized, controlled superiority trial, 542 patients scheduled for elective, high-risk abdominal surgery will be included. Patients are allocated to standard care (control group) or early goal-directed therapy (intervention group) using a randomization procedure stratified by center and type of surgery. In the control group, standard perioperative hemodynamic monitoring is applied. In the intervention group, early goal-directed therapy is added to standard care, based on continuous monitoring of cardiac output with arterial waveform analysis. A treatment algorithm is used as guidance for fluid and inotropic therapy to maintain cardiac output above a preset, age-dependent target value. The primary outcome measure is a combined endpoint of major complications in the first 30 days after the operation, including mortality. Secondary endpoints are length of stay in the hospital, length of stay in the intensive care or post-anesthesia care unit, the number of minor complications, quality of life, cost-effectiveness and one-year mortality and morbidity. DISCUSSION: Before the start of the study, hemodynamic optimization by early goal-directed therapy with arterial waveform analysis had only been investigated in small, single-center studies, including minor complications as primary endpoint. Moreover, these studies did not include quality of life, healthcare costs, and long-term outcome in their analysis. As a result, the definitive role of arterial waveform analysis in the perioperative hemodynamic assessment and care for high-risk surgical patients is unknown, which gave rise to the present trial. Patient inclusion started in May 2012 and is expected to end in 2016. TRIAL REGISTRATION: This trial was registered in the Dutch Trial Register (registration number NTR3380) on 3 April 2012.

Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages II-IIIA lung cancer: observational cohort study.

OBJECTIVE: To compare the survival and risk of serious adverse events in older patients with stages II-IIIA non-small cell lung cancer treated with or without postoperative platinum based chemotherapy. DESIGN: Observational cohort study. SETTING: Cases of lung cancer in Surveillance Epidemiology and End Results registry linked to Medicare files, 1992-2005, and follow-up data to December 2007. PARTICIPANTS: 3324 patients aged more than 65 years with resected stages II-IIIA lung cancer. MAIN OUTCOME MEASURES: Primary outcome was overall survival and secondary outcome was the rate of serious adverse events among older patients treated with or without adjuvant chemotherapy. RESULTS: Overall, 21% (n = 684) of patients received platinum based chemotherapy. Analyses adjusted, stratified, or matched by propensity scores showed that chemotherapy was associated with improved survival (hazard ratio range 0.78-0.81). The beneficial effect of chemotherapy was also observed among patients treated with radiation therapy (0.75-0.77) or without radiation therapy (0.74-0.77); however, chemotherapy was not beneficial for patients aged 80 or more (1.32-1.46). Adjuvant chemotherapy was associated with an increased odds of serious adverse events (odds ratio 2.0, 95% confidence interval 1.5 to 2.6). CONCLUSIONS: Platinum based adjuvant chemotherapy is associated with reduced mortality and increased risk of serious adverse events in older patients with stages II-IIIA lung cancer. The magnitude of the benefit is similar to that observed in randomised controlled trials carried out among selected patients.