Combined radiohormonotherapy in node positive lymph node prostate cancer

Purpose: Pelvic radiation therapy (RT) represents a therapeutic option in the treatment of node-positive prostate cancer but it remains controversial, because of its high rate toxicities. New radiation technique such as IMRT may reduce these complications. In this study, we aimed to assess the rate of toxicities according to CTC-NCI.v3 in such patients treated with either 3DCRT or IMRT (Tomotherapy).Methods and Materials: From January 2008 to December 2010, data were analyzed from 30 consecutive patients including 29 node-positive prostate cancer undergoing definitive or adjuvant RT (IMRT and/or 3DCRT) after radical prostatectomy and lymphadenectomy combined to hormonal therapy. Median age was 66 years (range : 52-83). Median preoperative PSA value was 12 ng/ml (range: 2.72-165). According to the pT-classification, there were 4 pT2, 7 pT3a, 10 pT3b, and 1 pT4 patients. Pathologic positive lymph nodes were found in 23 patients. Radiologic positive lymph nodes were found in 5 patients. Two patients were node negative. Gleason score was ranging between 7 to 10. Twelve patients were treated by Tomotherapy including 4 with simultaneous integrated boost (SIB). Eighteen patients were treated by Tomotherapy including 2 with SIB to the whole pelvis and 3DCRT boost to the prostate. V50% for bladder and rectum were recorded. Acute and late toxicities were assessed according to CTC-NCI.v3 classification.Results: With a median follow-up of 17 months, only one patient presented nodal and metastatic failure. Urinary incontinence was graded 1 after surgery for 6 patients and grade 2 in two. Sexual impuissance was noted in 3 patients. Acute toxicities during RT were proctitis grade 0 in 23 patients (76.5%), grade 1 in 7 (23.5%). Nocturia grade 1 in 9 patients. Interruption of treatment was seen in only case because of grade 3 urinary incontinence. Late effects included erectile dysfunction in 5 patients (83%) and one patient had grade 3proctitis requiring colostomy 3 months after RT. Median Dose-Volume Histogram according to radiation techniques V50% bladder V50% rectum Tomotherapy (IMRT) 36.25 Gy 39 Gy Tomotherapy + 3DCRT 41.26 Gy 39.18 GyConclusion: Based on our above-mentioned findings, there is no a significant difference in morbidity in patients treated with Tomotherapy or Tomotherapy with 3DCRT boost.

Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Colorectal cancer and thoracic surgeons: close encounters of the third kind.

Resection of lung metastases from colorectal cancer (CRC) is increasingly performed with a curative intent. This strategy was made possible in the 1990s by the development of new chemotherapeutic approaches, improved surgical techniques and better imaging modalities. However, evidence-based data showing clinical benefits of lung metastasectomy in this setting are nonexistent, and there are no prospective randomized trials to support the routine performance of these procedures for stage IV CRC. Current evidence suggests that resection of pulmonary metastases in combination with new cytotoxic agents, such as oxaliplatin, irinotecan and bevacizumab, may result in prolonged survival for many, and cure for a small minority of CRC patients who experienced tumor spread beyond the limits of the abdomen. This review focuses on the results of surgical management of CRC patients with lung metastases: we report the outcome of published series according to the presence or the absence of liver metastasis (and hepatic resection) prior to lung resection.

Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975.

BACKGROUND: To update the pattern of cancer mortality in Europe. Materials and methods: We analysed cancer mortality in 34 European countries during 2000-2004, with an overview of trends in 1975-2004 using data from the World Health Organization. RESULTS: From 1990-1994 to 2000-2004, overall cancer mortality in the European Union declined from 185.2 to 168.0/100 000 (world standard, -9%) in men and from 104.8 to 96.9 (-8%) in women, with larger falls in middle age. Total cancer mortality trends were favourable, though to a variable degree, in all major European countries, including Russia, but not in Romania. The major determinants of these favourable trends were the decline of lung (-16%) and other tobacco-related cancers in men, together with the persistent falls in gastric cancer, and the recent appreciable falls in colorectal cancer. In women, relevant contributions came from the persistent decline in cervical cancer and the recent falls in breast cancer mortality, particularly in northern and western Europe. Favourable trends were also observed for testicular cancer, Hodgkin lymphomas, leukaemias, and other neoplasms amenable to treatment, though the reductions were still appreciably smaller in eastern Europe. CONCLUSION: This updated analysis of cancer mortality in Europe showed a persistent favourable trend over the last years.

Advanced nursing role to improve care among breast cancer patients

Background: Breast cancer is a devastating disease for women as it impacts on their intimate, familial, social life. We study the specificities of breast cancer nurse interventions related to demands of support, information and coordination. Material and Methods: More than 300 patients are treated every year in our institution. From 2006 January to 2008 December, the specialist nurse has reported demands of patients and professionals: 1. Patients' needs related to support, information and coordination of care were collected from consultations with her and from their phone calls on using working days help line 2. Demands of breast cancer specialists and general practitioners related to information and coordination for specific patients were collected from their phone calls. Results: The specialist nurse received 679 phone calls respectively 71.5% from patients and 28.5% from professionals. Data are presented in the following table. Table 1: Evolution of number of patients and professionals demands Patients consultations Patients calls Professionals calls 2006 93 45 32 2007 210 200 40 2008 245 240 122 - Seventy percent (70%) of women asked for information about exams and treatments by phone and in nurse consultation. - Forty percent (40%) of women asked for support after announce of diagnosis. The specialist nurse proposed consultations, 2 to 4 consultations were necessary for women to express emotional distress or psychosocial problem. With this specialised nursing support less than 15% of patients were referred to the psycho-oncologist setting. - Forty percent (40%) of professionals asked support for patients and 60% for information and coordination of care. Conclusion: The interventions of the specialist nurse have improved coordination and quality of care. The increase of professionals' demands showed that it was necessary that a nurse assures continuity of information between hospital and extrahospital structures. The breast cancer nurse empowers patients and helps them to get well by providing support to fulfil specific needs.

The histone deactylase SIRT6 is a novel tumor suppressor that regulates cancer metabolism.

Report for the scientific sojourn carried out at the University of Aarhus, Denmark, from 2010 to 2012. Reprogramming of cellular metabolism is a key process during tumorigenesis. This metabolic adaptation is required in order to sustain the energetic and anabolic demands of highly proliferative cancer cells. Despite known for decades (Warburg effect), the precise molecular mechanisms regulating this switch remained unexplored. We have identify SIRT6 as a novel tumor suppressor that regulates aerobic glycolysis in cancer cells. Importantly, loss of this sirtuin in non-transformed cells leads to tumor formation without activation of known oncogenes, indicating that SIRT6 functions as a first-hit tumor suppressor. Furthermore, transformed SIRT6-deficient cells display increased glycolysis and tumor growth in vivo, suggesting that SIRT6 plays a role in both establishment and maintenance of cancer. We provide data demonstrating that the glycolytic switch towards aerobic glycolysis is the main driving force for tumorigenesis in SIRT6-deficient cells, since inhibition of glycolysis in these cells abrogates their tumorigenic potential. By using a conditional SIRT6-targeted allele, we show that deletion of SIRT6 in vivo increases the number, size and aggressiveness of tumors, thereby confirming a role of SIRT6 as a tumor suppressor in vivo. In addition, we describe a new role for SIRT6 as a regulator of ribosome biogenesis by co-repressing MYC transcriptional activity. Therefore, by repressing glycolysis and ribosomal gene expression, SIRT6 inhibits tumor establishment and progression. Further validating these data, SIRT6 is selectively downregulated in several human cancers, and expression levels of SIRT6 predict both prognosis and tumor-free survival rates, highlighting SIRT6 as a critical modulator of cancer metabolism. Our results provide a potential Achilles’ hill to tackle cancer metabolism.

The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network.

PURPOSE: The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS: Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS: The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS: The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

Lung cancer mortality in European women: trends and predictions.

Female lung cancer mortality increased by 50% between the mid 1960s and the early 2000s in the European Union (EU). To monitor the current lung cancer epidemic in European women, we analyzed mortality trends in 33 European countries between 1970 and 2009 and estimated rates for the year 2015 using data from the World Health Organization. Female lung cancer mortality has been increasing up to recent calendar years in most European countries, with the exceptions of Belarus, Russia, and Ukraine, with relatively low rates, and the UK, Iceland and Ireland, where high rates were reached in mid/late 1990s to leveled off thereafter. In the EU, female lung cancer mortality rates rose over the last decade from 11.3 to 12.7/100,000 (+2.3% per year) at all ages and from 18.6 to 21.5/100,000 (+3.0% per year) in middle-age. A further increase is predicted, to reach 14/100,000 women in 2015. Lung cancer mortality trends have been more favorable over the last decade in young women (20-44 years), particularly in the UK and other former high-risk countries from northern and central/eastern Europe, but also in France, Italy, and Spain where mortality in young women has been increasing up to the early 2000s. In the EU as a whole, mortality at age 20-44 years decreased from 1.6 to 1.4/100,000 (-2.2% per year). Although the female lung cancer epidemic in Europe is still expanding, the epidemic may be controlled through the implementation of effective anti-tobacco measures, and it will probably never reach the top US rates.

Fried potatoes and human cancer.

A considerable public concern about cancer risk from acrylamide-rich foods followed the announcement that high concentrations of acrylamide are found in fried potatoes and potato chips and, more generally, in starch-containing foods cooked at high temperatures. From a series of hospital-based case-control studies conducted in Italy and Switzerland between 1991 and 2000, we have analyzed the relation between intake of fried/baked potatoes and cancer risk. The cancer sites considered were oral cavity and pharynx (749 cases, 1772 controls), esophagus (395 cases, 1066 controls), larynx (527 cases, 1297 controls), large bowel (1225 colon and 728 rectum cases, 4154 controls), breast (2569 cases, 2588 controls) and ovary (1031 cases, 2411 controls). All cancer cases were incident and histologically confirmed. Controls were subjects admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. All the odds ratios (OR) for the highest vs. the lowest tertile of intake ranged between 0.8-1.1. We found no evidence of interaction with age, gender, alcohol and tobacco use. Our data provide reassuring evidence for the lack of an important association between consumption of fried/baked potatoes and cancer risk.

Trends in smoking and lung cancer mortality in Switzerland.

Patterns of cigarette smoking in Switzerland were analyzed on the basis of sales data (available since 1924) and national health surveys conducted in the last decade. There was a steady and substantial increase in cigarettes sales up to the early 1970s. Thereafter, the curve tended to level off around an average value of 3,000 cigarettes per adult per year. According to the 1981-1983 National Health Survey, 37% of Swiss men were current smokers, 25% were ex-smokers, and 39% were never smokers. Corresponding porportions in women were 22, 11, and 67%. Among men, smoking prevalence was higher in lower social classes, and some moderate decline was apparent from survey data over the period 1975-1981 mostly in later middle-age. Trends in lung cancer death certification rates over the period 1950-1984 were analyzed using standard cross-sectional methods and a log-linear Poisson model to isolate the effects of age, birth cohort, and year of death. Mortality from lung cancer increased substantially among Swiss men between the early 1950s and the late 1970s, and levelled off (around a value of 70/100,000 men) thereafter. Among women, there has been a steady upward trend which started in the mid-1960s, and continues to climb steadily, although lung cancer mortality is still considerably lower in absolute terms (around 8/100,000 women) than in several North European countries or in North America. Cohort analyses indicate that the peak rates in men were reached by the generation born around 1910 and mortality stabilized for subsequent generations up to the 1930 birth cohort. Among females, marked increases were observed in each subsequent birth cohort. This pattern of trends is consistent with available information on smoking prevalence in successive generations, showing a peak among men for the 1910 cohort, but steady upward trends among females. Over the period 1980-1984, about 90% of lung cancer deaths among Swiss men and about 40% of those among women could be attributed to smoking (overall proportion, 85%).

Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Human synthetic lethal inference as potential anti-cancer target gene detection

Background: Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results: In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes) in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases) as well as on existent approved drugs (DrugBank database) supports our selection of cancer-therapy candidates.Conclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.

Characterization of human gene expression changes after olive oil ingestion: an exploratory approach

Olive oil consumption is protective against risk factors for cardiovascular and cancer diseases. A nutrigenomic approach was performed to assess whether changes in gene expression could occur in human peripheral blood mononuclear cells after oli ve oil ingestion at postprandial state. Six healthy male volunteers ingested, at fasting state, 50 ml of olive oil. Prior to intervention a 1-week washout period with a controlled diet and sunflower oil as the only source of fat was followed. During the 3 days before and on the intervention day, a very low-phenolic compound diet was followed. At baseline (0 h) and at post-ingestion (6 h), total RNA was isolated and gene expression (29,082 genes) was evaluated by microarray. From microarray data, nutrient-gene interactions were observed in genes related to metabolism, cellular processes, cancer, and atherosclerosis (e.g. USP48 by 2.16; OGT by 1.68-fold change) and associated processes such as inflammation (e.g. AKAP13 by 2.30; IL-10 by 1.66-fold change) and DNA damage (e.g. DCLRE1C by 1.47; POLK by 1.44- fold change). When results obtained by microarray were verified by qRT-PCR in nine genes, full concordance was achieved only in the case of up-regulated genes. Changes were observed at a real-life dose of olive oil, as it is daily consumed in some Mediterranean areas. Our results support the hypothesis that postprandial protective changes related to olive oil consumption could be mediated through gene expression changes.

Comparative analysis of cancer genes in the human and chimpanzee genomes

Background: Cancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes. Results: This analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene. Conclusion: These data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.

Information provision and information needs in adult survivors of childhood cancer.

BACKGROUND: Knowledge about their past medical history is central for childhood cancer survivors to ensure informed decisions in their health management. Knowledge about information provision and information needs in this population is still scarce. We thus aimed to assess: (1) the information survivors reported to have received on disease, treatment, follow-up, and late effects; (2) their information needs in these four domains and the format in which they would like it provided; (3) the association with psychological distress and quality of life (QoL). PROCEDURE: As part of the Follow-up survey of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all survivors (≥18 years) who previously participated to the baseline survey, were diagnosed with cancer after 1990 at an age of <16 years. RESULTS: Most survivors had received oral information only (on illness: oral: 82%, written: 38%, treatment: oral: 79%, written: 36%; follow-up: oral: 77%, written: 23%; late effects: oral: 68%, written: 14%). Most survivors who had not previously received any information rated it as important, especially information on late effects (71%). A large proportion of survivors reported current information needs and would like to receive personalized information especially on late effects (44%). Survivors with higher information needs reported higher psychological distress and lower QoL. CONCLUSIONS: Survivors want to be more informed especially on possible late effects, and want to receive personalized information. Improving information provision, both qualitatively and quantitatively, will allow survivors to have better control of their health and to become better decision makers.