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International audience; Background: We previously reported a 35-gene expression classifier identifying four clear-cell renal cell carcinoma groups (ccrcc1 to ccrcc4) with different tumour microenvironments and sensitivities to sunitinib in metastatic clear-cell renal cell carcinoma. Efficacy profiles might differ with nivolumab and nivolumab-ipilimumab. We therefore aimed to evaluate treatment efficacy and tolerability of nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors (VEGFR-TKIs) in patients according to tumour molecular groups.Methods: This biomarker-driven, open-label, non-comparative, randomised, phase 2 trial included patients from 15 university hospitals or expert cancer centres in France. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had previously untreated metastatic clear-cell renal cell carcinoma. Patients were randomly assigned (1:1) using permuted blocks of varying sizes to receive either nivolumab or nivolumab-ipilimumab (ccrcc1 and ccrcc4 groups), or either a VEGFR-TKI or nivolumab-ipilimumab (ccrcc2 and ccrcc3 groups). Patients assigned to nivolumab-ipilimumab received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by intravenous nivolumab 240 mg every 2 weeks. Patients assigned to nivolumab received intravenous nivolumab 240 mg every 2 weeks. Patients assigned to VEGFR-TKIs received oral sunitinib (50 mg/day for 4 weeks every 6 weeks) or oral pazopanib (800 mg daily continuously). The primary endpoint was the objective response rate by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1. The primary endpoint and safety were assessed in the population who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02960906, and with the EU Clinical Trials Register, EudraCT 2016-003099-28, and is closed to enrolment.Findings: Between June 28, 2017, and July 18, 2019, 303 patients were screened for eligibility, 202 of whom were randomly assigned to treatment (61 to nivolumab, 101 to nivolumab-ipilimumab, 40 to a VEGFR-TKI). In the nivolumab group, two patients were excluded due to a serious adverse event before the first study dose and one patient was excluded from analyses due to incorrect diagnosis. Median follow-up was 18·0 months (IQR 17·6-18·4). In the ccrcc1 group, objective responses were seen in 12 (29%; 95% CI 16-45) of 42 patients with nivolumab and 16 (39%; 24-55) of 41 patients with nivolumab-ipilimumab (odds ratio [OR] 0·63 [95% CI 0·25-1·56]). In the ccrcc4 group, objective responses were seen in seven (44%; 95% CI 20-70) of 16 patients with nivolumab and nine (50% 26-74) of 18 patients with nivolumab-ipilimumab (OR 0·78 [95% CI 0·20-3·01]). In the ccrcc2 group, objective responses were seen in 18 (50%; 95% CI 33-67) of 36 patients with a VEGFR-TKI and 19 (51%; 34-68) of 37 patients with nivolumab-ipilimumab (OR 0·95 [95% CI 0·38-2·37]). In the ccrcc3 group, no objective responses were seen in the four patients who received a VEGFR-TKI, and in one (20%; 95% CI 1-72) of five patients who received nivolumab-ipilimumab. The most common treatment-related grade 3-4 adverse events were hepatic failure and lipase increase (two [3%] of 58 for both) with nivolumab, lipase increase and hepatobiliary disorders (six [6%] of 101 for both) with nivolumab-ipilimumab, and hypertension (six [15%] of 40) with a VEGFR-TKI. Serious treatment-related adverse events occurred in two (3%) patients in the nivolumab group, 38 (38%) in the nivolumab-ipilimumab group, and ten (25%) patients in the VEGFR-TKI group. Three deaths were treatment-related: one due to fulminant hepatitis with nivolumab-ipilimumab, one death from heart failure with sunitinib, and one due to thrombotic microangiopathy with sunitinib.Interpretation: We demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma.

International audience; We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of laryngeal cancers. Intensity modulated radiotherapy is the standard of care radiotherapy for the management of laryngeal cancers. Early stage T1 or T2 tumours can be treated either by radiotherapy or conservative surgery. For tumours requiring total laryngectomy (T2 or T3), an organ preservation strategy by either induction chemotherapy followed by radiotherapy or chemoradiotherapy with cisplatin is recommended. For T4 tumours, a total laryngectomy followed by radiotherapy is recommended when feasible. Dose regimens for definitive and postoperative radiotherapy are detailed in this article, as well as the selection and delineation of tumour and lymph node target volumes.

PURPOSE The prevalence of breast cancer is increasing in low- to middle-income countries such as Senegal. Our prospective study assessed the quality of life (QoL) of patients with breast cancer undergoing chemotherapy in Senegal. PATIENTS AND METHODS Our study included women with breast cancer undergoing chemotherapy as initial treatment at the Center Aristide Le Dantec University Hospital in Dakar. Clinical, sociodemographic, and QoL data were collected and analyzed at three different times: baseline, 3 months, and 6 months after the start of systemic therapy. Health-related QoL was assessed using a Functional Assessment of Cancer Therapies-Breast (FACT-B) questionnaire after translation into the Wolof language. Linear mixed-effects models were performed to assess the changes in QoL scores. RESULTS Between July 2017 and February 2018, 120 patients were included in the study. Their median age was 45 years. Most patients (n = 105; 92%) had locally advanced disease (T3 to T4 stage) and lymph node involvement (n = 103; 88%), and half had metastatic disease. The FACT-B total scores significantly improved over time (β = 1.58; 95% CI, 0.50 to 2.67; P < .01). Nausea and vomiting were significantly associated with a decrease in FACT-B total scores (β = −16.89, 95% CI, −29.58 to −4.24, P = .012; and β = −13.44, 95% CI, −25.15 to −1.72, P = .028, respectively). CONCLUSION Our study confirmed the feasibility of standardized QoL assessment in Senegalese patients with breast cancer. Our results indicated a potential improvement of QoL over the course of chemotherapy. Optimizing nausea and vomiting prevention may improve QoL.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; pMethods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing.Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab (n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8-16·9) at the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in the pembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable over time. The difference in average GHQ score between the two groups over the 2 years was -2·2 points (95% CI -4·3 to -0·2). The difference in average score during treatment was -1·1 points (95% CI -3·2 to 0·9) and the difference in average score after treatment was -2·2 points (-4·8 to 0·4). These differences are within the 5-point clinical relevance threshold for the QLQ-C30 and are therefore clinically non-significant.Interpretation: Pembrolizumab does not result in a clinically significant decrease in HRQOL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting.

Summary Background GRECCAR 2 was the first multicentre, randomised trial to compare local excision with total mesorectal excision in downstaged low rectal cancer. Encouraging oncological results were noted at 3 years' follow-up but needed to be corroborated with longer follow-up. In this study, we aimed to report the 5-year oncological outcomes, including local recurrence, metastatic disease, and survival. Methods Patients age 18 years and older with T2T3 low rectal cancer, of maximum size 4 cm, who were clinically good responders after chemoradiotherapy (residual tumour ≤2 cm) were randomly assigned before surgery to either local excision or total mesorectal excision. Randomisation was centralised and not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was performed if pathological tumour stage was ypT2–3. The primary objective of this study was to assess the 5-year oncological outcomes of local recurrence, metastatic disease, disease-free survival, overall survival, and cancer-specific mortality, which were the secondary endpoints of GRECCAR 2. We used Kaplan-Meier estimates and Cox modelling to estimate and compare recurrence and survival in modified intention-to-treat and as-treated populations. This trial was registered with ClinicalTrials.gov , number NCT00427375 . Findings Between March 1, 2007, and Sept 24, 2012, 148 patients who were good clinical responders were randomly assigned to treatment, three patients were excluded after randomisation (because they had metastatic disease, tumour >8 cm from anal verge, or withdrew consent), leaving 145 for analysis: 74 in the local excision group and 71 in the total mesorectal excision group. Median follow-up was 60 months (IQR 58–60) in the local excision group and 60 months (57–60) in the total mesorectal excision group. 23 patients died and five were lost to follow-up. In the local excision group, 26 had a completion total mesorectal excision for ypT2–3 tumour. In the modified intention-to-treat analysis, there was no difference between the local excision and total mesorectal excision groups in 5-year local recurrence (7% [95% CI 3–16] vs 7% [3–16]; adjusted hazard ratio [HR] 0·71 [95% CI 0·19–2·58]; p=0·60), metastatic disease (18% [CI 11–30] vs 19% [11–31]; 0·86 [0·36–2·06]; p=0·73), overall survival (84% [73–91] vs 82% [71–90]; 0·92 [0·38–2·22]; p=0·85), disease-free survival (70% [58–79] vs 72% [60–82]; 0·87 [0·44–1·72]; p=0·68), or cancer-specific mortality (7% [3–17] vs 10% [5–20]; 0·65 [0·17–2·49]; p=0·53). Interpretation The 5-year results of this multicentre randomised trial corroborate the 3-year results, providing no evidence of difference in oncological outcomes between local excision and total mesorectal excision. Local excision can be proposed in selected patients having a small T2T3 low rectal cancer with a good clinical response after chemoradiotherapy. Funding National Cancer Institute of France.

ObjectiveDiagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.DesignWe have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.ResultsWithin the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; pConclusionThese findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients’ prognosis.

International audience; This review discusses the clinical applications of magnetic resonance imaging (MRI) for the assessment of neo-adjuvant chemotherapy (NAC) indication, axillary lymph node status, preNAC cancer prognosis, early and intermediate response to NAC, and post-NAC residual disease in patients with breast cancer. Contrast-enhanced MRI with analysis of the tumor morphological features and qualitative enhancement kinetics must be considered as the standard method for pre-NAC breast cancer staging and post-NAC residual disease assessment. Diffusion-weighted imaging (DWI) is easy to perform and may increase the specificity of breast MRI for tumor staging, and also for the assessment of tumor multifocality and multicentricity and lymph node status. It also provides an ancillary added value in the early and post-NAC response evaluation. Changes in the functional tumor volume are the main criterion for the early response analysis. Other MRI methods, such as quantitative perfusion analysis, MR spectroscopy and texture analysis, are still under study.

International audience; BACKGROUND:Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)-positive, postmenopausal patients not eligible for primary breast-conserving surgery (BCS).METHODS:This was a multicenter, phase 2, randomized trial designed to evaluate as its primary objective the clinical response rate after up to 6 months of neoadjuvant endocrine therapy (NET) alone in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative patients with 1 mg of anastrozole (arm A) or 500 mg of fulvestrant (arm B). Secondary objectives included the BCS rate, tumor response assessment (breast ultrasound and magnetic resonance imaging), pathological response (Sataloff classification), safety profile, relapse-free survival (RFS), and predictive markers of responses and outcomes.RESULTS:From October 2007 to April 2011, 116 women (mean age, 71.6 years) with operable infiltrating breast adenocarcinoma (T2-T4, N0-N3, M0) were randomized to receive anastrozole or fulvestrant. The clinical response rates at 6 months were 52.6% (95% confidence interval [CI], 41%-64%) in arm A and 36.8% (95% CI, 25%-49%) in arm B. BCS was performed for 57.6% of arm A patients and 50% of arm B patients. The RFS rates at 3 years were 94.9% in arm A and 91.2% in arm B. The Preoperative Endocrine Prognostic Index status was significantly predictive of RFS. Both treatments were well tolerated.CONCLUSIONS:Both drugs are effective and well tolerated as NET in postmenopausal women with HR-positive/HER2-negative breast cancer. NET could be considered a treatment option in this subpopulation. Cancer 2016;122:3032-3040. © 2016 American Cancer Society.

International audience; HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C > G polymorphisms. The mutations were identified with PCR and PCR-RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C > G polymorphism (p = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008-0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C > G polymorphism is maintained in young patients (< 50 years, p = 0.0006) and in early-diagnosed BC patients (< 50 years, p = 0.0033). In addition, an association was found between the haplotypes inferred by both HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081-0.895, p = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL (p < 0.0001). We demonstrated also that sHLA-G is closely associated with advanced stages of BC without significance. sHLA-G is increased in TNM IV and SBR III subgroups. It is also enhanced in patients with a tumor size over 20 mm and in triple-negative patients. Taken together, our findings demonstrate, for the first time, the association of HLA-G +3142 C > G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.

Background A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. Patients and methods Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. Results A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. Conclusion A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. Clinical trial number NCT01480869.

International audience; Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies.

International audience; This study aimed to compare the relative survival of patients with invasive breast cancer between women from French Guiana (a French territory in South America) and metropolitan France. No study hadever compared survival of breast cancer on the basis of immigrant status in France. Our study underlined that access to care for migrants is challenging whichwgenerates health inequalities. Background The prognosis of breast cancer in French Guiana is worse than in France with 23 deaths per 100 incident cases against 17 per 100 in metropolitan France. This study aimed to compare relative survival of patients with invasive breast cancer (IBC) between women from French Guiana and metropolitan France and to determine risk factors influencing breast cancer survival in French Guiana.Materials and methods Data were collected from the Cancer registry of French Guiana. We comparedthe relative survival of women with IBC between French Guiana and metropolitan France. We used Cox's proportional hazard regression to evaluate the effect of prognostic factors on cancer-specific mortality in French Guiana. Results We included all 269 cases of IBC in women diagnosed in French Guiana between 2003 and 2009. The overall 5-year relative survival rate of patients with IBC was 79% in French Guiana and 86% in metropolitan France. The place of birth (foreign country versus French territory), the tumor stage at the time of diagnosis, the mode of diagnosis (symptoms versus screening), the presence of hormone receptors in the tumor and the histologic type were the variables associated with survival differences. None of the other study variables were significantly associated with prognosis. Conclusion Access to care for migrants is challenging,which leads to health inequalities. Early detection through prevention programs is crucial to increaseIBC survival notably for foreign-born patients.

IF 2.415; International audience; The haemoglobin concentration measured by faecal immunochemical tests (FIT) may be decreased in cases of delayed sample return or high temperature. It is an issue of great importance. The aim of this study was to investigate the effects of sample return time and of season on the performance of an FIT (FOB-Gold) with a new buffer. The study included 20 371 participants involved in the French organized colorectal cancer (CRC) screening programme. The probability of a positive screening test, detection rates and positive predictive values for CRC and advanced adenoma were analysed according to sample return time and season of screening. A sample of positive FIT was stored for 7 days in an incubator at 20°C or 30°C. The positivity rate was 4.1% for a sample return time of up to 3 days, 4.1% for 4-5 days and 4.6% for 6-7 days (P=0.25). In multivariate analysis, there was no association between positivity rates, detection rates and positive predictive values for CRC and advanced adenoma and the sample return time or the season of screening. At a constant temperature of 20°C, there was a decrease in the haemoglobin concentration of 5.1% after 7 days. The decrease reached 20.5% at a temperature of 30°C. It was only 4.5% during the first 4 days of storage in the incubator. With the new buffer, delay in sample return or season did not affect the clinical outcome. When temperatures reach 30°C, the faecal sample must be returned promptly.

BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical trials is an active area of investigation, but the factors that determine clinical trial enrollment following a molecular prescreening program have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal cancer at the MD Anderson Cancer Center were offered screening in the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility for companion phase I or II clinical trials with a therapy targeted to an aberration detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010 and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and 157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected clinical trials was ninefold higher for predefined ATTACC-companion clinical trials as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial enrollment in multivariate analysis were higher performance status, older age, lack of standard of care therapy, established patient at MD Anderson, and the presence of an eligible biomarker for an ATTACC-companion study. Early molecular screening did result in a higher rate of patients with remaining standard of care therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical trials resulted in an increase rate of trial enrollment of nonrefractory patients, the majority of patients enrolled on clinical trials were refractory to standard of care therapy. Within molecular prescreening programs, tailoring screening for preidentified and open clinical trials, temporally linking screening to treatment and optimizing both patient and physician engagement are efforts likely to improve enrollment on biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is NCT01196130.

IF 2.719; International audience

Background: EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel. Methods: HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated. Results: Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p, SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction The evidence on the association between anthropometric measures quantifying body fatness and prostate cancer (PCa) risk is not entirely consistent. Associations among waist circumference (WC), waist-hip ratio, body mass index (BMI), and PCa risk were assessed in a population-based case-control study. Patients and methods The study included 1933 incident PCa cases diagnosed between 2005 and 2009. Population controls were 1994 age-matched (±5 y) Montreal residents selected from electoral lists. Information on sociodemographics, medical history including PCa screening, height, weight, and waist and hip circumferences was collected through interviews. Logistic regression was used to assess odds ratios (ORs) for the association between anthropometric measures, and overall and grade-specific PCa. Results After adjustment for BMI, an excess risk of high-grade PCa (Gleason≥7) was associated with a WC ≥102 cm (OR = 1.47 [1.22–1.78]) and with a waist-hip ratio >1.0 (OR = 1.20 [1.01–1.43]). Men with a BMI≥30 kg/m 2 had a lower risk of PCa, regardless of grade. Restricting to subjects recently screened for PCa did not alter findings. Conclusion Elevated BMI was associated with a lower risk of PCa, regardless of grade. Contrastingly, abdominal obesity, when adjusted for BMI, yielded results in the opposite direction. Taken together, our observations suggest that the specific body fat distribution (abdominal), for a given BMI, is a predictor of PCa risk, whereas BMI alone is not. BMI and abdominal obesity, especially when measured by the WC, should be examined conjointly in future studies on this issue and may require consideration at patient counseling.

International audience; BACKGROUND:Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.METHODS:Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FINDINGS:Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p

Background Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) may cause damage to the hepatic artery (HA) and impact the postoperative course of the liver transplantation (LT). We aim to describe the relationship between preoperative TACE and the occurrence of histological and radiological hepatic artery complications (HAC). Methods All cirrhotic patients with HCC undergoing LT between January 2009 and October 2012 were included and divided in two groups: TACE (group 1) and No TACE (group 2). HA histological complications were reviewed and compared. Results Sixty-seven patients were reviewed, 32 in group 1 and 35 in group 2. Both groups were similar in gender, age, cirrhosis origin, and American Society of Anesthesiology (ASA) score. After a mean follow-up of 17 months, 10 radiological HAC occurred: seven in group 1 and three in group 2 (p = 0.02). There was one thrombosis in each group: six non-thrombotic complications in group 1 and two in group 2. Histological screening showed 12 HA injuries in group 1 (three HA wall edemas, five fibrosis, one edema + fibrosis, one hemorragic necrosis + thrombosis, two thrombosis) and three in group 2 (two HA wall edemas, one fibrosis) (p = 0.01). All these injuries were found at the proper HA and at the right/left HA bifurcation level. Conclusions Despite the limits of our study, we found a higher incidence of radiological and histological injury in patients underwent TACE.

International audience; Background: The global risk of hepatocellular carcinoma (HCC) is largely due to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years, however, an increased prevalence of non-viral HCC has been noted. The clinical impact of the presence/absence of viral infections in HCC remains controversial. The present study aimed to assess the effect of hepatitis viruses on demographics, clinical and pathological features and long-term outcome in a large cohort of Romanian patients who underwent surgery for HCC.Methods: The study included 404 patients with HCC who had undergone resection, transplantation or radiofrequency ablation at a single institution between 2001 and 2010. The patients were divided into four groups: 85 patients with hepatitis B virus infection (HBV group), 164 patients with hepatitis C virus infection (HCV group), 39 patients with hepatitis B and C virus co-infection (HBCV group), and 116 patients without viral infection (non-BC group).Results: The patients of both HBV (56.0+/-11.3 years) and HBCV groups (56.0+/-9.9 years) were significantly younger than those of the HCV (61.0+/-8.5 years, P=0.001) and non-BC groups (61.0+/-13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis was significantly lower in the non-BC group (47%) than in any other subsets (72%-90%, P

Purpose: Despite research efforts to develop more effective diagnostic and therapeutic approaches, malignant pleural mesothelioma (MPM) prognosis remains poor. The assessment of tumor response to therapy can be improved by a deeper phenotypical classification of the tumor, with emphasis on its clinico-biological heterogeneity. The identification of molecular profiles is a powerful approach to better define MPM subclasses and targeted therapies. Experimental Design: Molecular subclasses were defined by transcriptomic microarray on 38 primary MPM cultures. A three-gene predictor, identified by quantitative reverse transcription PCR, was used to classify an independent series of 108 frozen tumor samples. Gene mutations were determined in BAP1, CDKN2A, CDKN2B, NF2, and TP53. Epithelial-to-mesenchymal transition (EMT) markers were studied at the mRNA and protein levels. Results: Unsupervised hierarchical clustering on transcriptomic data defined two robust MPM subgroups (C1 and C2), closely related to prognosis and partly to histologic subtypes. All sarcomatoid/desmoplastic MPM were included in the C2 subgroup. Epithelioid MPM were found in both subgroups, with a worse survival prognosis in the C2 subgroup. This classification and its association with histologic subtypes and survival were validated in our independent series using the three-gene predictor. Similar subgroups were found after classification of other MPM series from transcriptomic public datasets. C1 subgroup exhibited more frequent BAP1 alterations. Pathway analysis revealed that EMT was differentially regulated between MPM subgroups. C2 subgroup is characterized by a mesenchymal phenotype. Conclusions: A robust classification of MPM that defines two subgroups of epithelioid MPM, characterized by different molecular profiles, gene alterations, and survival outcomes, was established. Clin Cancer Res; 20(5); 1323–34. ©2014 AACR.

International audience; BACKGROUND:Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity.PATIENTS AND METHODS:An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemotherapy between the elderly (≥70 years; n=142) and younger patients (

International audience; It has recently been suggested that the percentage of smudge cells on blood smears from patients with chronic lymphocytic leukemia (CLL) could predict overall survival. However, smudge cells are a cytological artifact influenced by multiple physical factors not related to CLL. To identify simple parameters reflecting CLL cell fragility, we studied CD45 expression in a series of 66 patients with Binet stage A CLL. Decreased CD45 expression was specific for CLL cells when compared to 44 patients with a leukemic phase of B-cell non Hodgkin lymphoma and 42 control B-cells. CD45 expression was markedly decreased for all patients with CLL with high percentages of smudge cells. CLL cells with the lowest CD45 expression were the most sensitive to osmotic shock. Very low levels of CD45 expression were significantly associated with lack of CD38 expression, absence of trisomy 12, and with increased treatment free survival time. Altogether, these results demonstrate that low levels of CD45 expression are specific to CLL cells and reflect cell fragility, suggesting that this is an important intrinsic biological feature that determines disease course.

International audience; Prostate cancer can usually be treated at a clinically localized stage by radical prostatectomy. Unfortunately, within 10 years following surgery, 30% of patients experience local or distant relapse. Few data exist on the association of markers of angiogenesis and distant relapse after radical prostatectomy. By immunohistochemistry in tissue microarray, we compared the expression pattern of hypoxia inducible factor 1, alpha subunit (HIF1α) and vascular endothelial growth factor (VEGF) and its receptors in 45 patients with distant relapse and 68 patients without relapse after radical prostatectomy. Expressions of HIF1α and VEGF were assessed in prostate tumor cells and those of VEGFR1, VEGFR2 and neuropilin 1 in tumor and endothelial cells. The five molecules studied were expressed by all tumors, with the exception of neuropilin 1 in endothelial cells for one tumor. Strong endothelial expression of VEGFR1 appeared to be an independent predictor of distant relapse. A moderate to strong endothelial expression of neuropilin 1 was in turn an independent predictor of absence of distant relapse. No significant difference was found for HIF1α, VEGF, VEGFR1, VEGFR2 and neuropilin 1 expression in tumor cells, nor for VEGFR2 in endothelial cells, between the two groups. To our knowledge, this is the first study to evaluate the prognostic value of VEGFR1, VEGFR2 and neuropilin 1 in endothelial cells in prostate cancer after radical prostatectomy. The evaluation by immunohistochemistry of endothelial expression of neuropilin 1 and VEGFR1 could be an additional tool in the assessment of tumor aggressiveness of clinically localized prostate cancer to better identify patients at high risk of distant relapse.

Learning Objectives Describe the effect of worsening fatigue after breast cancer surgery on physical functioning and psychological distress. Better identify women at risk for developing cancer-related fatigue. Direct target interventions to patients most in need. Purpose. Fatigue is one of the most frequent symptoms in patients with cancer. However, the precise determinants of fatigue are still unknown. This study was conducted to investigate factors correlated with cancer-related fatigue before surgery and just before subsequent adjuvant therapy. Methods. Patients completed the Multidimensional Fatigue Inventory (MFI-20), the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire before and after surgery, the Trait Anxiety Inventory and the Life Orientation Test before surgery, and the State Anxiety Inventory before the start of adjuvant therapy. Multiple regression analysis of determinants of change in MFI-20 total score after surgery was conducted. Results. A series of 466 eligible patients with stage I–III breast cancer with planned surgery were recruited. An increase in MFI-20 total score after surgery was significantly correlated with higher preoperative fatigue and lower role functioning before surgery; a decrease in role functioning, physical functioning, and cognitive functioning after surgery; an increase in insomnia after surgery; and a higher state anxiety after surgery. Disease stage, lymph node metastases, surgical procedure, and demographic characteristics (e.g., age, marital status, having children, educational level) were not correlated with fatigue in multivariate analysis. Conclusion. These results suggest that worsening fatigue after surgery for breast cancer is associated with a decrease in physical functioning and an increase in psychological distress rather than with the cancer characteristics. Therefore, screening measures should be implemented at the time of diagnosis—before starting treatment—to identify psychologically vulnerable patients and to offer them professional support.

International audience; Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin. Mesorectal excision was performed 6 weeks after treatment. Impact of clinical, pathological and surgical variables on positive CRM (≤1 mm) were analysed by multivariate analysis. Of 565 randomised patients, CRM was recorded in 390 cases and was positive in 8% (30/390). Patients with 50 Gy plus capecitabine and oxaliplatin had a 6% rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10% rate (p=0.128). Three independent predictive factors of positive CRM were identified: abdominoperineal resection (APR) (odds ratio OR=3.24; p=0.004), vascular tumour invasion (OR=2.78; p=0.026) and poor histological response (modified Dworak 0-2) (OR=9.01; p=0.003). Significant predictive factors of positive CRM are related to type of surgery, especially APR, and poor histological prognostic factors. Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study.

International audience; Differences in postoperative outcome and recovery between patients subjected to laparoscopic-assisted versus open surgery for colorectal cancer (CRC) resection have been widely documented, though not specifically for right-sided tumors. We investigated the immunological responses to the different surgical approaches, by comparing postoperative data simultaneously obtained at systemic, local and cellular levels. A total of 25 right-sided CRC patients and controls were managed, assessing -in the immediate followup- the conventional perioperative parameters and a large panel of cytokines on plasma, peritoneal fluids and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) tissue cultures. A general better recovery for patients operated with laparoscopy compared to conventional procedure, as indicated by the analysis of typical pre- and post-surgical parameters, was observed. The synchronous evaluation of 12 cytokines showed that preoperative plasma levels of the proinflammatory cytokines IL-6, IL-8, IL-1β, TNFα were significantly lower in healthy donors versus CRC patients and that such differences progressively increase with tumor stage. After surgery, the IL-6 and IL-8 increases were significantly higher in open compared to laparoscopic approach only in CRC at early stages. The postsurgical whole panel of cytokine levels were significantly higher in peritoneal fluids compared to corresponding plasma, but with no significant differences depending on kind of surgery or stage of disease. Then we observed that, pre- compared to the corresponding post-surgery derived LPS-stimulated PBMC cultures, produced higher supernatant levels of the whole cytokine panel. In particular IL-6 in vitro production was significantly higher in PBMC derived from patients subjected to laparoscopic versus open intervention, but -again- only in CRC at early stages of disease. Our results thus show that laparoscopy compared to open right resection is associated with a shorter compromission of the immunological homeostasis, mainly in early stages of right-CRC patients.

Purpose To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer. Patients and Methods Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2 bolus followed by 2,400 mg/m2 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks. Results Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin. Conclusion FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.

International audience; PURPOSE: To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. A total of 148 patients (25 %) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence. RESULTS: The median time from RNU to disease recurrence was 12 months (interquartile range 5-22). A total of 491 (82 %) of 597 patients died from UTUC, and 8 patients (1.3 %) died from other causes. The median time from disease recurrence to death of UTUC was 10 months. Actuarial cancer-specific survival estimate at 12 months after disease recurrence was 35 %. On multivariable analysis that adjusted for the effects of standard clinicopathologic characteristics, higher tumor stages [hazard ratio (HR) pT3 vs. pT0-T1: 1.66, p = 0.001; HR pT4 vs. pT0-T1: 1.90, p = 0.002], absence of lymph node dissection (HR 1.28, p = 0.041), ureteral tumor location (HR 1.44, p < 0.0005) and a shorter interval from surgery to disease recurrence (p < 0.0005) were significantly associated with cancer-specific mortality. The adjusted 6-, 12- and 24-month postrecurrence cancer-specific mortality was 73, 60 and 57 %, respectively. CONCLUSIONS: Approximately 80 % of patients who experience disease recurrence after RNU die within 2 years after recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor more quickly than their counterparts. These factors should be considered in patient counseling and risk stratification for salvage treatment decision making.

Background The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable. Objectives The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients. Design, setting, and participants From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue). Intervention RNU. Measurements Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses. Results and limitations Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study. Conclusions Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.

Background High tumor uptake of fluorodeoxyglucose (FDG) is associated with an unfavorable outcome in patients with cancer. We evaluated FDG uptake as a prognostic factor in patients with head and neck squamous cell carcinoma. Methods Maximum standardized uptake values (SUVmax) of tumor, liver, and pulmonary artery were recorded. Ratios of SUVmax from tumor to liver (T/L) and from tumor to pulmonary artery (T/PA) were calculated for each patient. Clinical data, tumor, and SUVmax ratios were compared with disease-free survival (DFS) and overall survival (OS). Results Eighty-nine patients were included: 48 presented a local recurrent disease or distant metastases and 42 died. For both DFS and OS, tumor SUVmax value of 7 was the best cutoff value and 4 and 5 for T/L and T/PA ratios. Multivariate analysis confirmed the independent prognostic value of these 3 thresholds for DFS and OS. Conclusions FDG uptake has a significant and independent relationship with recurrence and survival. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

International audience; BACKGROUND: This prospective phase II study assessed the efficacy and safety of bevacizumab plus chemotherapy regimens commonly used in the second-line treatment of metastatic colorectal cancer (mCRC). METHODS: Patients with mCRC who progressed or relapsed after first-line oxaliplatin-based or irinotecan-based treatment received bevacizumab 2.5 mg/kg/week plus chemotherapy until disease progression. The primary endpoint was disease-control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. RESULTS: Fifty-three patients (66% men; median age, 62 years old) received second-line bevacizumab plus folinic acid, fluorouracil, and irinotecan (FOLFIRI; 57%), folinic acid, fluorouracil, oxaliplatin (FOLFOX; 26%), irinotecan (15%), or capecitabine plus irinotecan (XELIRI; 2%). The DCR was 87% (95% CI, 77%-97%); ORR was 32% (95% CI, 19%-46%). Median PFS was 6.5 months (95% CI, 5.8-7.8 months) and median OS 19.3 months, (95% CI, 14.2-25.1 months).The most frequent grade 3/4 adverse events included neutropenia (21%), diarrhea (15%), asthenia, and vomiting (9% each). Five patients (9%) had grade 3/4 targeted toxicities: grade 3 hypertension (n = 2), grade 3 venous thromboembolism (n = 2), and grade 4 arterial thromboembolism (n = 1). None of these events led to death during the study. CONCLUSION: Bevacizumab plus standard second-line chemotherapy is highly active in patients with mCRC and has an acceptable safety profile.

Learning Objectives After completing this course, the reader will be able to: Evaluate the therapeutic impact of hysterectomy after chemoradiation therapy in locally advanced cervical cancer.Evaluate the rate of histologic residual disease in patients with complete clinical and radiologic response after chemoradiation therapy. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery. Methods. A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6–8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003–2006) and are reported on here. Results. Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively. Conclusions. Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power).

Chantier qualité GA; International audience; Apoptosis has to be drastically controlled in organs with important cell turnover such as the colon. Deregulation of this process is often present in tumor progression. Tissues of 82 patients treated for colorectal cancer (CRC) were analyzed using antibodies against AIF, p53, DR4, DR5, cleaved caspase-3 and the TUNEL method to detect apoptosis; whereas staining of Ki-67 was used as a proliferation marker. In situ immunohistochemical analyses were compared in non-tumor (NT) cells from normal adjacent mucous membranes with tumor (T) cells from patients with Stage I (n=6), Stage II (n=35), Stage III (n=27) and Stage IV (n=14) CRC. Results were correlated with the tumor stages and the treatment response of patients to improve the understanding of CRC development. p53 and DR5 expression decreased progressively with CRC stage, suggesting that these proteins are important markers of advanced tumor stages. Moreover, p53 appears as a prognostic factor to predict recurrence-free survival. Including the detection of p53 and DR5 for establishing the diagnosis of CRC and adapting the treatment to each patient is strongly suggested by our work.

International audience; The introduction of molecularly targeted therapies has ushered in a considerable transformation in the management of gastrointestinal stromal tumors (GIST) that currently defines the paradigm of targeted therapy for solid tumors. Indeed, in the past decade the management of GIST has evolved from a disease only effectively treatable by surgery to the archetype of a tumor treatable with a molecularly targeted therapy. Better understanding of the molecular and genetic characteristics that underlie the aberrant behavior of GIST has increased the accuracy of its diagnosis and allowed for the identification of distinct genetic hallmarks, prognostic groups, and treatment strategies. Collectively, this has resulted in the development of the targeted tyrosine kinase inhibitors (TKIs) imatinib and sunitinib, and continues to prompt studies of novel agents in this disease. Since approval in 2002, imatinib has been shown to provide a high level of clinical efficacy in patients with advanced GIST, including a median progression-free survival (PFS) of 2 years and median overall survival approaching 5 years, with some patients progression-free after 10 years of treatment. Imatinib is now also approved in adult patients following resection of KIT-positive GIST. In 2006, sunitinib was approved for the treatment of advanced GIST after failure of imatinib. Sunitinib provides significant benefit in this setting, with a median PFS close to 6 months after imatinib failure. Following progression on these agents, patients have limited treatment options. This critical unmet need is being addressed by the development of new TKIs and the use of novel regimens with approved agents.

International audience; BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

International audience; Abstract PURPOSE: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). METHODS AND MATERIALS: A total of 72 men (mean age, 67.8 ± 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratio of the most pathologic voxels and the MRSI-based TV were also determined. RESULTS: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 ± 13.60 vs. 2.31 ± 5.65 (p = .018), 8.98 ± 14.58 vs. 2.56 ± 5.70 (p = .016), and 10.32 ± 15.47 vs. 3.55 ± 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 ± 2.62 cm(3) vs. 1.26 ± 2.06 cm(3), respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). CONCLUSION: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.

In 2000, a 48-year-old man presented with epigastralgia. Computed tomography scan revealed a hypervascular pancreatic tumor with multiple liver and mediastinal lymph node metastases. The diagnosis of metastatic well-differentiated pancreatic islet cell carcinoma (pNET) was made by biopsy of the liver lesions. The mitotic index was 3/10 HPF (x40); Ki67 index was 5%. Serum levels of digestive hormones were within normal limits and chromogranin A levels was 220 μg/l. Octreotide scintigraphy showed high-grade activity in liver and mediastinal metastases. The patient was successively treated with chemotherapy (six cycles of streptozotocin-doxorubicin); surgery (cephalic duo-denopancreatectomy in March 2002, due to the local risk of compression and presence segmental portal hypertension); without any treatment and stable disease until February 2004; alpha-interferon for 15 months; chemotherapy (ten cycles of Folfi ri); and everolimus in December 2006 (RADIANT 1 trial). The treatment resulted in a decrease in tumor size (34% using RECIST criteria) at four months; the dis-ease was controlled for 24 months. Because of occur-rence of two new liver metastases, the patient was then included in a phase 3 trial and received sunitinib throughout 12 months; sunitinib was stopped because of occurrence of portal vein thrombosis under enox-aparin; the disease was stable. The patient was then treated with lanreotide in order to maintain disease stabilization; however, new progression ( after a break in treatment or maybe induced by 10% among RECIST criteria and elevation of Chromogranin A from 1982 to 2932 μg/l) occurred three months later. In June 2010, as the patient refused cytotoxic chemo-therapy and because of the particular initial good response to the everolimus, it was decided to add everolimus in association with lanreotide. Three months after starting the treatment, the weight of the patient had increased by 3 kg, fatigue had disappeared and imaging studies showed a response of 23% on RECIST criteria. His disease remains stable six months after this combination started. To our knowledge, this is the fi rst case showing a second effi cacy of mTOR inhibitor for treatment of solid advanced cancer. It enables us to discuss the reversibility of resistance mechanisms of evero-limus, and potential interest of a combined therapy with somatostatin analogs. It has recently been shown that, in patients with pNET, sunitinib or everolimus signifi cantly increase progression-free survival [1,2]. However, even if a control of the disease is frequently achieved, objective responses, such as the one observed in our case, are rare. How can we explain the second effi cacy of everolimus in combination with somatostatin analogs 18 months after the end of the fi rst treatment, as reported here? Some hypotheses may be discussed: a) syner-getic antitumor effect between everolimus and somatostatin analogs; b) emergence of a predomi-nant tumor cell clone, responding to everolimus

International audience; Among cancers, pancreatic cancer is known to be associated with a higher incidence of venous thromboembolism (VTE). The aim of the study was to determine the implication of circulating tissue factor (TF) in VTE related to active pancreatic cancer. One hundred and sixty-four consecutive patients who participated to the Etude des Determinants et Interactions de la Thrombose veineuse (EDITH) study between January 2005 and August 2007 for symptomatic VTE related to active pancreatic cancer (n = 8), active cancer of other location (n = 42) or classified as unprovoked (n = 114) were included. TF activity (TFa) was measured in a one-stage kinetic chromogenic method. There were no differences of median TFa levels between patients with VTE related to cancer of other type than pancreas [2.01 pmol/l range (0.05-43.92)] and patients with unprovoked VTE [1.78 pmol/l (range 0.05-63.72), P = 0.21]. Median TFa levels were higher in patients with VTE related to pancreatic cancer [12.67 pmol/l (range 0.05-112.04)] than in patients with VTE related to cancer of other type [2.01 pmol/l (range 0.05-43.92), P = 0.02]. Higher levels of circulating TFa during the course of pancreatic cancer may explain the higher incidence of VTE associated with this type of cancer.

International audience; AIM: To seek differences between ductal carcinoma in situ (DCIS) according to the menopausal status of patients and to analyze their repercussions on patient care. PATIENTS AND METHODS: A multicenter retrospective study of 384 patients from 3 centers specialized in breast cancer surgery was carried out based on an analysis of the various characteristics (clinical, therapeutic, histologic, outcome) of DCIS between two groups of post- and pre-menopausal patients. RESULTS: At the time of diagnosis, 58.6% of the patients were menopausal. Compared to these patients, DCIS in premenopausal women was more frequently associated with initial clinical signs (p=0.006), a larger tumor size (p=0.02), involved margins after initial surgery (p=0.005), and surgical re-excision (p=0.03). The mammograms of the menopausal patients indicated a worse prognosis (using the American College of Radiology Classification) (p=0.025), and according to the histology report findings, more marked comedo necrosis (p=0.01). There was no difference in the other criteria (nuclear grade, multifocality, benign lesions associated with malignancy, relapse and its time of occurrence). The use of hormone replacement therapy had no effect on these data. CONCLUSION: The characteristics of DCIS are similar, whether occuring before or after the menopause, but the phenotypic expression is different. Menopausal status should not be a criterion for changing patient care.

Purpose A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. Patients and Methods Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. Results Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). Conclusion High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.

International audience; Folates are the common sources of DNA synthesis and methylation. Cigarette smoking and genetic susceptibility of folate enzymes are two suspected factors most closely associated with bladder cancer development. This study sought to determine the effect of smoking and genetic polymorphisms in folate metabolizing enzymes on the histological stage and grade of bladder tumors in Tunisian patients. A total of 130 patients with urothelial cell carcinomas were examined with respect to smoking status, MTHFR (5,10-methylenetetrahydrofolate reductase), MTR (methionine synthase), MTRR (methionine synthase reductase) and TYMS (thymidylate synthase) genotypes distribution. Our data have reported that tobacco, MTHFR, MTR and MTRR genotypes were not associated with bladder tumor stage. Only TYMS 3R*G/3R*C genotype was associated with increased risk of developing invasive tumors compared to reference group (RR = 1.74; 95% CI: 0.97-3.12). When we studied the superficial bladder tumor group, we have shown a significant statistical differences for the TYMS 3R*G/2R genotype. This genotype presented a 1.68-fold increased risk of developing high grade tumors compared to reference group (RR = 1.68; 95% CI: 1.12-2.54). Moreover, we have shown that patients having at least one copy of 2R allele were at 4.23-fold increased risk for developing high grade tumors compared to reference group (P = 0.022).

International audience; BACKGROUND: There are few data on the cost-effectiveness of second-line chemotherapies for non-small cell lung cancer (NSCLC). The objective of this phase III, randomized, multicenter, prospective study was to compare the cost-effectiveness of docetaxel and pemetrexed, two widely used drugs. METHODS: We compared, from a payer's perspective, the directs costs and effectiveness of docetaxel (75 mg/m, arm A) and pemetrexed (500 mg/m, arm B) administered every 3 weeks to NSCLC patients who had progressed after first-line platinum-based chemotherapy. Monthly health utilities (based on disease states: responding, stable or progressive, and grade 3/4 toxicities) were derived from the literature. Costs were prospectively assessed. RESULTS: One hundred fifty patients were enrolled between February 2006 and June 2008. The patients in the docetaxel and pemetrexed arms had similar clinical characteristics and treatment efficacy (respective objective response rates 10.7% and 12%; median progression-free survival times 2.8 and 2.5 months; median survival times 8.0 and 6.4 months, respectively). Grade 3/4 toxicities were significantly less frequent with pemetrexed (52.0% versus 33.3%, p = 0.02). Docetaxel was associated with lower treatment-period costs (€9709 ± €6272 versus €13,436 ± €6508, p < 0.001). Docetaxel had a more favorable cost-utility ratio than pemetrexed. When compared with best supportive care, the cost-utility was €32,652/quality-adjusted life year for docetaxel and €40,980/quality-adjusted life year for pemetrexed. CONCLUSION: Second-line treatment for NSCLC is more cost-effective with docetaxel than with pemetrexed. Both strategies have acceptable cost-effectiveness ratios compared with commonly used and reimbursed regimens for advanced NSCLC.

International audience; PURPOSE: To estimate the α/β ratio of prostate cancer treated with external beam radiation only by use of a model of long-term prostate-specific antigen (PSA) dynamics. METHODS AND MATERIALS: Repeated measures of PSA from 5,093 patients from 6 institutions treated for localized prostate cancer by external beam radiation therapy (EBRT) without planned androgen deprivation were analyzed. A biphasic linear mixed model described the post-treatment evolution of PSA, rather than a conventional model of time to biochemical recurrence. The model was adjusted for standard prognostic factors (T stage, initial PSA level, and Gleason score) and cohort-specific effects. The radiation dose fractionation effect was estimated from the long-term rate of rise of PSA level. RESULTS: Adjusted for other factors, total dose of EBRT and sum of squared doses per fraction were associated with long-term rate of change of PSA level (p = 0.0017 and p = 0.0003, respectively), an increase of each being associated with a lower rate of rise. The α/β ratio was estimated at 1.55 Gy (95% confidence band, 0.46-4.52 Gy). This estimate was robust to adjustment of the linear mixed model. CONCLUSIONS: By analysis of a large EBRT-only cohort along with a method that uses all the repeated measures of PSA after the end of treatment, a low and precise α/β was estimated. These data support the use of hypofractionation at fractional doses up to 2.8 Gy but cannot presently be assumed to accurately represent higher doses per fraction.

Background The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. Methods The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. Results The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. Conclusions We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.

Background Great variability in breast cancer (BC) treatment practices according to patient, tumour or organisation of care characteristics has been reported but the relation between these factors is not well known. In two French regions, we measured compliance with Clinical Practice Guidelines for non-metastatic BC care management and identified factors associated with non-compliance at clinical and organisational levels. Methods Eligible patients had invasive unilateral BC without distant metastases and at least two contacts with one of the two regional healthcare systems (2003-2004) in the first year after diagnosis. Medical data were collected from patient medical records in all public and private hospitals (99 hospitals). The care process was defined by 20 criteria: clinical decisions for treatment and therapeutic procedures. Each criterion was classified according to level of compliance ("Compliant", "Justifiable" and "Not Compliant") and factors of non-compliance were identified (mixed effect logistic regression). Results 926 women were included. Non-compliance with clinical decisions for treatment was associated with older patient age (OR 2.1; 95%CI: 1.3-3.6) and region (OR 3.0; 95%CI: 1.2-7.4). Non-compliance with clinical decisions for radiotherapy was associated with lymph node involvement or the presence of peritumoural vascular invasion (OR 1.5; 95%CI: 1.01-2.3) and non-compliance with overall treatment (clinical decisions for treatment + therapeutic procedures) was associated with the presence of positive lymph nodes (OR 2.0; 95%CI: 1.2-3.3), grade III versus grade I (OR 2.9; 95%CI: 1.4-6.2), and one region of care versus another (OR 3.5; 95%CI: 1.7-7.1). Finally, heterogeneity of compliance in overall treatment sequence was identified between local cancer units (p < 0.05). Conclusion This study provides interesting insights into factors of non-compliance in non-metastatic BC management and could lead to quality care improvements.

International audience; PURPOSE OF REVIEW: Extranodal natural killer (NK)/T-cell lymphoma, nasal-type is a highly aggressive disease more frequent in Asia than in Western countries. There is no consensus treatment. The outcome depends on disease stage. Localized NK/T-cell lymphomas often respond to radiotherapy. In contrast, patients who have extensive disease or who relapse after radiotherapy have a very poor prognosis. Overall, long-term survival in these lymphomas tends to be inferior to that for other aggressive lymphomas. This review focuses on the new management modalities in light of advances in risk stratification, patient monitoring and treatment strategies. RECENT FINDINGS: Many parameters have been reported to correlate with prognosis and new staging systems have been elaborated. Detecting Epstein-Barr virus (EBV) in the bone marrow is important for staging and measuring EBV DNA in the serum improved monitoring response to therapy. Radiation modalities have been precised and new strategies combining radiation and chemotherapy have been proposed for patients with localized disease. The particular efficacy of L-asparaginase in this disease has been confirmed and L-asparaginase-based regimens have been studied in prospective trials for patients with refractory, relapsing or disseminated disease with good results. Laboratory studies may point the way toward new therapeutic approaches. SUMMARY: Early-stage disease is treated by involved-field radiotherapy with adjuvant chemotherapy. L-Asparaginase-containing regimens are the mainstay of treatment for advanced or disseminated disease. The role of targeted therapies, autologous and allogeneic haematopoietic stem cell transplantation is yet to be clearly defined.

International audience; OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients.

International audience; OBJECTIVES: To test whether tumor necrosis (TN) could improve the prognostic ability of the predictors of 2 established prognostic renal cell carcinoma (RCC) models. Presence of TN within the nephrectomy specimen is considered an important prognostic marker in patients with RCC. However, its added prognostic value along with established cancer-specific mortality (CSM) predictors has never been formally tested. METHODS: We retrospectively analyzed data of 1526 patients with all stages of RCC, who were treated with radical or partial nephrectomy at 6 institutions between 1988 and 2004. Univariate and multivariate Cox-regression models tested the statistical significance of TN in CSM predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size, and symptom classification. The analyses first addressed the entire patient population (n=1526) and then repeated in patients with exclusive clear-cell histology (n=1320). RESULTS: TN was present in 476 patients (31.2%). TN was a statistically significant predictor of CSM (hazard ratio: 2.73; P