Ganci F.,Italian National Cancer Institute |
Sacconi A.,Italian National Cancer Institute |
Bossel Ben-Moshe N.,Weizmann Institute of Science |
Sperduti I.,Biostatistical Unit |
And 12 more authors.
Annals of Oncology | Year: 2013
Background: TP53 mutation is associated with decreased survival rate in head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify microRNAs (miRNAs) whose expression associates with TP53 mutation and survival in HNSCC. Patients and methods: We analyzed TP53 status by direct sequencing of exons 2 through 11 of a prospective series of 121 HNSCC samples and assessed its association with outcome in 109 followed-up patients. We carried out miRNA expression profiling on 121 HNSCC samples and 66 normal counterparts. miRNA associations with TP53 mutations and outcome were evaluated. Results: A TP53 mutation was present in 58% of the tumors and TP53 mutations were significantly associated with a shorter recurrence-free survival. This association was stronger in the clinical subgroup of patients subjected to adjuvant therapy after surgery. The expression of 49 miRNAs was significantly associated with TP53 status. Among these 49, we identified a group of 12 miRNAs whose expression correlates with recurrence-free survival and a group of 4 miRNAs that correlates with cancer-specific survival. The two groups share three miRNAs. Importantly, miRNAs that correlate with survival are independent prognostic factors either when considered individually or as signatures. Conclusions: miRNAs expression associates with TP53 status and with reduced survival after surgical treatment of squamous cell carcinoma of the head and neck. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Truong T.,French Institute of Health and Medical Research |
Truong T.,University Paris - Sud |
Liquet B.,Biostatistical Unit |
Liquet B.,University of Queensland |
And 15 more authors.
Endocrine-Related Cancer | Year: 2014
Night shiftwork has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case - control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene- and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA (rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at thegenelevel. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction between PER1 and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk. © 2014 Society for Endocrinology. Published by Bioscientifica Ltd.
Bellera C.A.,Institute Bergonie |
Bellera C.A.,French Institute of Health and Medical Research |
Bellera C.A.,Clinical Data |
Pulido M.,Institute Bergonie |
And 20 more authors.
European Journal of Cancer | Year: 2013
Introduction: In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. Methods: We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Results: Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). Discussion: The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. © 2012 Elsevier Ltd. All rights reserved.
Carlo-Stella C.,Humanitas Cancer Center |
Rcci F.,Humanitas Cancer Center |
Dalto S.E.,Fondazione IRCCS Instituto Nazionale Tumori |
Mazza R.,Humanitas Cancer Center |
And 9 more authors.
Oncologist | Year: 2015
Background. Brentuximab vedotin (BV) has demonstrated an extraordinary efficacy in heavily pretreated classical Hodgkin lymphoma (cHL) patients, targeting CD30-positive cells; however, limited data have been reported on the efficacy of BV in cHL patients failing allogeneic stem cell transplantation (allo-SCT).The aim of this study was to retrospectively evaluate the efficacy and safety of BV in a multicenter setting of cHL relapsing or progressing after allo-SCT. Methods. Sixteen BV-na¨ve patients with recurrent cHL after allo-SCT were included in a compassionate use program and treated with intravenous BV at the dose of 1.8 mg/kg of body weight every 3 weeks for a maximum of 16 cycles. Results. The objective response rate was 69%. Five patients (31%) had complete remission, and 6 (37%) had partial remission. Stable disease was observed in 4 patients (25%), and progressive disease was observed in 1 (6%). After median follow-up of 26 months (range: 5-30 months), median progression-free survival (PFS), overall survival (OS), and duration of response were 7, 25, and 5 months, respectively. The 2-year PFS and OS were 20% and 61%, respectively. Grade 3-4 hematological adverse events included anemia (15%), thrombocytopenia (12%), and neutropenia (18%). Grade 3 peripheral sensory neuropathy occurred in 2 patients (12%). Conclusion. BV therapy is an effective and safe approach for achieving transient disease control in cHL patients with failed allo-SCT. To improve disease control, future studies should explore the combination of BV with targeted agents. © AlphaMed Press 2015.
Tenti E.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori |
Casadei Gardini A.,IRST IRCCS |
Nanni O.,IRST IRCCS |
Foca F.,Biostatistical Unit |
Cumero S.,University of Bologna
European Journal of Oncology | Year: 2014
Background: The number of cancer patients undergoing anticancer treatment who concomitantly take non-conventional medicines is increasing. Among cancer patients the use of non-conventional medicines, often in the form of self-medication, is intended to counteract the side-effects of cancer treatment, alleviate symptoms or strengthen the immune system. Aim of the work: The present study aimed to evaluate how widespread the practice is and to identify the possible interactions between non-conventional medicines an cancer therapies. Methods: Tis research was an observational prospective study of about 10 weeks. One hundred and forty-three patients undergoing cancer treatment in our day hospital were interviewed about their use of non-conventional medicines. Results: 35.7% (51/143) of patients reported taking vitamin or mineral supplements, 22.4% (32/143) take medicinal herbs and 4.9% (7/143) homeopathic remedies. 75% (24/ 32 using medicinal herbs were <64 years old and 78.1% of such patients (25/32) had a higher level of education These data are in accord with the results from a survey carried out on cancer patients (n=1498) at a hospital in Coventry, UK, where the prevalence of medicinal herb use was 19.7% (95% CI: 17.4–22.1; n= 223). Conclusion: A significant number of cancer patients undergoing treatment with anticancer drugs also make use non-conventional medicines, medicinal herbs being the most commonly used. Clinicians and patients should thus be educated as to the proper use of medicinal herbs to minimise the risk of related interactions. © 2014 Mattioli 1885.