Adjuvant Chemotherapy and Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Clinical Practice Guideline.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.

High insulin levels in newly diagnosed breast cancer patients reflect underlying insulin resistance and are associated with components of the insulin resistance syndrome.

BACKGROUND: High insulin levels have been associated with poor outcomes in breast cancer. Our goal was to investigate whether hyperinsulinemia was associated with insulin resistance in a cohort of newly diagnosed locoregional breast cancer patients and to examine associations of hyperinsulinemia with the broader insulin resistance syndrome (IRS). METHODS: Five hundred and four women with T1-3, N0-1, M0 breast cancer provided fasting blood that was analyzed for glucose, insulin and lipids. They underwent anthropomorphic measurements and provided information on diet, exercise and sleep. Relationships of insulin with three validated indices of insulin resistance and with attributes of the IRS were examined. RESULTS: High insulin levels were strongly correlated with insulin resistance calculated using the three indices of insulin resistance/sensitivity (Spearman r=0.83-0.98). Hyperinsulinemia was also associated with other components of the IRS (obesity, high waist-hip ratio, lipid profile). CONCLUSIONS: High insulin levels in women with locoregional breast cancer reflect the presence of insulin resistance and are associated with other components of the IRS. These observations have implications for the development of therapies that target hyperinsulinemia in early stage breast cancer and for the long-term management of breast cancer survivors.

Tolerability of the Intergroup 0099 (INT 0099) regimen in locally advanced nasopharyngeal cancer with a focus on patients' nutritional status.

PURPOSE: The Intergroup 0099 trial (INT 0099) for locally advanced nasopharyngeal cancer (NPC) has set a standard of practice. This retrospective review documents our institutional experience with this regimen. METHODS AND MATERIALS: For all NPC patients treated between January 1998 and December 2002 with the INT 0099 regimen, compliance, toxicity, weight change, and feeding tube use were recorded. Patients were grouped by therapy completion status and by feeding tube status. RESULTS: Of 78 consecutive patients, 75 were evaluable. Compliance with radiotherapy was excellent. Only 43% and 61% of patients received all cycles of concurrent and adjuvant chemotherapy, respectively. Patients who successfully completed therapy had a higher average baseline weight and were more likely to have had a prophylactic feeding tube. Forty of 75 patients had a feeding tube inserted and were analyzed as two groups. Patients with prophylactic insertion (n = 23) had a more gradual drop in weight, and recovered to a greater degree at 1 year (93.6% vs. 87.2%), than those with a feeding tube inserted therapeutically during treatment (n = 17). CONCLUSIONS: The INT 0099 regimen was generally delivered with modifications to the chemotherapy component, as in the original trial. The prophylactic insertion of a feeding tube may facilitate therapy completion and weight recovery in some patients.

Plasma amino acid profiles of breast cancer patients early in the trajectory of the disease differ from healthy comparison groups.

This study describes and compares fasting plasma amino acid profiles of breast cancer patients near the initiation of chemotherapy with those of healthy age- and body mass index-matched females (HM), as well as young healthy females (HY). Breast cancer patients had significantly greater glutamate and histidine concentrations and significantly lower threonine concentrations compared with HM and HY females independent of protein or caloric intake. These differences may be related to metabolic perturbations associated with the disease.

A comprehensive metabolic evaluation reveals impaired glucose metabolism and dyslipidemia in breast cancer patients early in the disease trajectory.

BACKGROUND & AIMS: Weight gain in breast cancer patients during treatment is prevalent; the metabolic implications of this weight gain are poorly understood. We aimed to characterize glucose metabolism in breast cancer patients near the initiation of chemotherapy. METHODS: Stage I-II breast cancer patients (n = 8) were evaluated near the initiation of chemotherapy and compared with a group of age- and body mass index-matched, as well as a group of young healthy, non-malignant females. Fasting blood samples (analyzed for lipids and cytokines) were taken and an oral glucose tolerance test was performed. Body composition, waist circumference, diet, cardiovascular fitness and muscle strength were evaluated. RESULTS: Breast cancer patients were abdominally obese (mean ± SD: 94.6 ± 14.0 cm), overweight (28.8 ± 6.0 kg/m(2)) and dyslipidemic (triacylglycerides: 1.84 ± 1.17 mM; high-density lipoprotein cholesterol: 1.08 ± 0.23 mM). Compared to non-malignant matched females, fasting glucose and insulin concentrations were similar but fasting c-peptide was greater in patients (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater extent in patients during the oral glucose tolerance test compared with all non-malignant females. During the glucose tolerance test, c-peptide, but not insulin, remained elevated in patients compared with all non-malignant females. No differences in body composition, serum cytokines, nutrition or exercise capacity between patients and matched, non-malignant females emerged. CONCLUSIONS: Breast cancer patients present with unhealthy metabolic features early in the disease trajectory. Future investigations need to examine the underlying mechanisms and the potential longitudinal changes following chemotherapy.

Bibliometrics of global malaria vaccine research.

OBJECTIVES: This study evaluates malaria vaccine research carried out in different parts of the world during 1972-2004 using different bibliometric indicators. METHOD: Data have been downloaded from PubMed for the period 1972-2004 using the keywords (malaria* or plasmodium or falciparum) and (vaccine*) in the title and abstract fields. The study examined the pattern of growth of the output, its geographical distribution, profile of different countries in different subfields and pattern of citations using GOOGLE Scholar. RESULTS: Malaria vaccine research output is gradually increasing. The USA, followed by the UK and Australia contributed the highest number of papers. Publication activity has decreased in Switzerland and Sweden, but has increased in Brazil and China. The majority of the countries have focused on the development of asexual blood stage malaria. Citations per paper and incidence of high-quality papers for the USA, the UK, Papua New Guinea and Denmark are more than the average. The majority of the prolific institutions are located in the USA, the UK, France and Australia. CONCLUSION: The last two decades have witnessed considerable growth in research output in this field, while a successful malaria vaccine still remains elusive. Interestingly, the countries like the USA, the UK and Australia that lead in the quantity, quality and citation of this output are often not those directly affected by malaria.

Serum lipids and outcome of early-stage breast cancer: results of a prospective cohort study.

PURPOSE: The prognosis of women with early-stage breast cancer is influenced by insulin and body mass index (BMI). High levels of serum insulin and obesity often coexist with dyslipidemia in the insulin resistance syndrome (IRS), but the contribution of lipids to breast cancer outcome is unclear. Here, we examine whether serum levels of total cholesterol (TC) and triglycerides (TG) influence breast cancer outcome. PATIENTS AND METHODS: A cohort of 520 women without known hyperlipidemia or diabetes, with stage T1-T3, N0-N1, M0 breast cancer, was assembled from July 1989 to June 1996. Fasting blood was collected at baseline. Subjects were followed prospectively, for recurrence (local, regional, distant) and death. Cox models were used to calculate the prognostic effect of TC and TG levels. Two-sided significance levels were set at 0.025. RESULTS: TC was correlated with age (Spearman's r = 0.44) and low tumor grade (p = 0.01), while TG was correlated with insulin (r = 0.43) and BMI (r = 0.45). At a median follow-up of 8.7 years, TC and TG were not associated with breast cancer recurrence or death before of after adjustment for age, tumor-related variables, BMI or fasting insulin levels. In multivariate analysis adjusting for age, tumor-related variables and BMI, a trend towards an adverse effect of TC on disease recurrence was seen (HR recurrence = 1.62 for the 4th versus. 1st quartile, 2-sided p = 0.03). CONCLUSIONS: Fasting TG was not associated with outcome. A trend towards risk of recurrence was seen with higher TC in multivariate analysis. This potential association should be explored in future studies.