Early nutritional intervention improves treatment tolerance and outcomes in head and neck cancer patients undergoing concurrent chemoradiotherapy

Goals of work

Patients with head and neck cancer (HNC) undergoing chemoradiotherapy are at high risk of malnutrition, which is related to complication rate. The aim of this study was to investigate the impact of an early intensive nutritional intervention on nutritional status and outcomes in patients undergoing chemoradiotherapy for HNC.

Materials and methods

We analysed retrospectively the clinical documentation of 33 HNC patients who were referred for early nutritional intervention (nutrition intervention group, NG) before they were submitted to chemoradiotherapy. The outcome of these patients was compared to that of 33 patients who received chemoradiotherapy without receiving a specifically designed early nutrition support programme (control group, CG).

Main results

NG patients lost less weight during chemoradiotherapy compared to CG patients (?4.6?±?4.1% vs ?8.1?±?4.8% of pre-treatment weight, p?<?0.01, at the completion of treatment). Patients in the NG experienced fewer radiotherapy breaks (>5 days) for toxicity (30.3% vs 63.6%, p?<?0.01); the mean number of days of radiation delayed for toxicity was 4.4?±?5.2 in NG vs 7.6?±?6.5 in CG (p?<?0.05); a linear correlation was found between percentage of weight lost from baseline to chemoradiotherapy completion and days of radiation delays (p?<?0.01). There were less patients who had an unplanned hospitalisation in the NG relative to the CG (16.1% vs 41.4%, p?=?0.03). In the NG, symptoms having an effect on the nutritional status developed early and were present in the nearly totality of patients at chemotherapy completion; 60.6% of NG patients needed tube feeding.

Conclusions

Early nutrition intervention in patients with HNC receiving chemoradiotherapy resulted in an improved treatment tolerance and fewer admissions to hospital. This result suggests that nutritional intervention must be initiated before chemoradiotherapy, and it needs to be continued after treatment completion.     

Improving sun-protection behavior among children: results of a cluster-randomized trial in Italian elementary schools. The "SoleSi SoleNo-GISED" Project

A history of sunburns in early life nearly doubles the risk of developing malignant melanoma in adulthood. From 2001 to 2004, we conducted a cluster-randomized trial of an educational intervention to reduce sunburn rates (primary outcome) and improve sun-protection behavior (secondary outcome) in schoolchildren. A total of 122 Italian primary schools (grades 2 and 3) were randomized to receive, or not, an intervention consisting of an educational curriculum at school, conducted by trained teachers, which included the projection of a short video and the distribution of booklets to children and their parents. Behavior while in the sun was assessed at baseline and 14-16 months after baseline. In a subgroup (44% of the total sample), melanocytic nevi were also counted. Of the 11,230 children enrolled, 8,611 completed the study. A total of 1,547 children (14%) reported a history of sunburns at baseline. At follow-up, no difference in sunburn episodes was documented between the study groups (odds ratio 0.97, 95% confidence interval 0.84-1.13) and similar sun-protection habits were reported. No significant impact of the proposed educational program was documented at 1-year follow-up. Innovative strategies need to be developed to increase the effectiveness of future educational interventions in this area.     

Alcohol and endometrial cancer risk: a case–control study and a meta-analysis

To evaluate the association between alcohol consumption and endometrial cancer risk, we analyzed data from a hospital-based case–control study, conducted in Italy between 1992 and 2006, on 454 endometrial cancer cases and 908 controls, and performed a meta-analysis updated to October 2009. Compared to never alcohol drinkers, the odds ratio was 1.03 (95% confidence interval, CI, 0.76–1.41) for ≤7, 1.27 (95% CI 0.86–1.87) for 8–14, and 1.19 (95% CI 0.80–1.77) for ≥15 drinks/week, with no trend in risk. No association emerged for wine, beer, and spirit consumption analyzed separately. The meta-analysis included 20 case–control and seven cohort studies, for a total of 13,120 cases. Compared to non/low drinkers, the pooled relative risks for drinkers were 0.90 (95% CI 0.80–1.01) for case–control studies, 1.01 (95% CI 0.90–1.14) for cohort studies, and 0.95 (95% CI 0.88–1.03) overall, with no heterogeneity between study design (p = 0.156). The overall estimate for heavy versus non/low drinkers was 1.12 (95% CI 0.87–1.45). The results were consistent according to selected study characteristics, including geographic area, definition of alcohol drinkers, and type of controls in case–control studies. Our findings provide evidence that alcohol drinking is not associated with endometrial cancer risk, although a weak positive association for very high drinkers cannot be excluded.     

Social status and cardiovascular disease: a Mediterranean case. Results from the Italian Progetto CUORE cohort study

Background  

Social factors could offer useful information for planning prevention strategy for cardiovascular diseases. This analysis aims to explore the relationship between education, marital status and major cardiovascular risk factors and to evaluate the role of social status indicators in predicting cardiovascular events and deaths in several Italian cohorts.     

Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria

Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F(1)beta subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F(1)beta differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.     

Biological markers and DNA flow cytometric analysis in radically resected patients with non-small cell lung cancer. A study of the Perugia Multidisciplinary Team for Thoracic Tumors

AIMS AND BACKGROUND: The aim of this study was to evaluate the relationship between a panel of biological markers (p53, Bcl-2, HER-2, Ki67, DNA ploidy and S-phase fraction) and clinical-pathological parameters and its impact on outcome in non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: Tumor tissue specimens obtained after surgical resection were collected from consecutive patients with NSCLC. We used an immunocytochemical technique for p53, Bcl-2, HER-2 and Ki67 analysis in fine-needle aspirates obtained from surgical samples that were also evaluated by flow cytometric DNA analysis using a FACScan flow cytometer. RESULTS: From April 2000 to December 2005, 136 patients with radically resected NSCLC were recruited. Median age was 66 years (range, 31-84 years), male/female ratio 117/19, ECOG performance status 0/1 127/4, stage I/II/III 76/25/35, squamous/adenocarcinoma/large-cell/mixed histology 62/49/17/8, smokers yes/no 121/11. Positivity of p53, Bcl-2, HER-2 and Ki67 was detected in 51.4%, 27.9%, 25.0% and 55.8% of the samples, respectively; 82.9% of the cases revealed aneuploid DNA histograms and 56.7% presented an S-phase fraction of more than 12%. Statistically significant associations between high Ki67 and poorly differentiated tumors (P = 0.016) and a smoking history (P = 0.053); p53 positivity and high Ki67 (P = 0.002); HER-2 positivity and adenocarcinoma subtype (P = 0.015) and presence of lymph node involvement (P = 0.006); and Bcl-2 positivity and squamous cell carcinoma subtype (P = 0.058) were observed. At univariate analysis, high Ki67 proved to be the only marker associated with disease-free survival (P = 0.047). After adjusting for stage, none of the examined immunocytochemical markers emerged as an independent factor for disease-free and overall survival; only pathological stage was identified as an independent prognostic factor for disease-free survival (P = 0.0001) and overall survival (P = 0.0001). In the group of 76 patients classified as TNM stage I, high Ki67 was the only marker associated with recurrence of disease (P = 0.05). CONCLUSIONS: Our data do not support a relevant prognostic role of immunocytochemical markers in NSCLC, even if the Ki67 index might have particular relevance to identify patients with more aggressive tumors who are at high risk for disease relapse.     

The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia

In the proposed revised World Health Organization (WHO) criteria for the diagnosis of BCR-ABL(-) myeloproliferative diseases (MPDs), exclusion criteria have been replaced by the presence of JAK2 mutations. We applied these criteria to 45 children with MPDs: 13 with polycythemia vera (PV) and 32 with essential thrombocythemia (ET). Among these 45 patients, 12 with ET and 5 with PV had a familial history of MPD, and had been investigated for hereditary mutations of the erythropoietin receptor, thrombopoietin, or MPL genes. We found that the JAK2(V617F) mutation in children occurs less frequently than in adults, and that exon 12 JAK2 mutations are absent. On the basis of the revised WHO criteria, a significant proportion of childhood PVs were misdiagnosed. Furthermore, all familial ET, including patients carrying the hereditary MPL(Ser505Asn) activating mutation, were erroneously diagnosed as MPDs. Our observations suggest that childhood MPDs require a set of specific diagnostic criteria.