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Aide N.,Francois Baclesse Cancer Center | Aide N.,University of Caen Lower Normandy | Visser E.P.,Radboud University Nijmegen | Lheureux S.,University of Caen Lower Normandy | And 4 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2012

Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed. © 2012 The Author(s).

Houede N.,University of Nimes | Pulido M.,Bergonie Cancer Institute | Mourey L.,Claudius Regaud Cancer Center | Joly F.,Francois Baclesse Cancer Center | And 9 more authors.
Oncologist | Year: 2014

Background. Preclinical studies demonstrated that nonnucleoside reverse transcriptase inhibitors used for the treatment of HIV could antagonize tumor development. This led us to assess the efficacy of efavirenz in patients with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter phase II study.Methods. We used a Simon two-stage design and a 3-month prostate-specific antigen (PSA) nonprogression rate of 40% as a primary objective. Patients received 600 mg efavirenz daily with thepossibility of a dose increase in case ofPSAprogression. Exploratory analyses included pharmacokinetics of efavirenz plasma concentrations and correlations with clinical outcomes.Results. Among 53 assessable patients, we observed 15 instances of PSA nonprogression at 3 months, corresponding to a nonprogression rate of 28.3%(95%confidence interval:16.8%–42.3%). The exploratory analysis revealed that for the 7 patients in whom optimal plasma concentration of efavirenz was achieved, PSA progression was observed in only 28.6% compared with 81.8% of patients with suboptimal plasma concentrations of efavirenz.Conclusion. Although 600 mg efavirenz did not statistically improve the PSA nonprogression rate, our exploratory analysis suggests that higher plasma concentrations of this drug (i.e., use of increased dosages) may be of potential benefit for the treatment of mCRPC. © AlphaMed Press 2014.

Vera P.,University of Rouen | Mezzani-Saillard S.,University of Rouen | Edet-Sanson A.,University of Rouen | Menard J.-F.,University of Rouen | And 16 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2014

Purpose: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). Methods: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET1). All included patients had a FDG PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. Results: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77 % received RT with induction chemotherapy and 73 % RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUV max in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95 % CI 1.25 - 3.09, p=0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95 % CI 0.73 - 0.94, p<10-4). A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70 % and a specificity of 92 % for predicting tumour progression or death at 1 year. Conclusion: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study). © 2014 Springer-Verlag Berlin Heidelberg.

Allaoui M.,Francois Baclesse Cancer Center | Hubert E.,Louis Pasteur Hospital | Michels J.-J.,Francois Baclesse Cancer Center
Turk Patoloji Dergisi/Turkish Journal of Pathology | Year: 2014

Malignant pilomatricoma or pilomatrical carcinoma is a rare malignant hair follicle neoplasm. This tumor is locally aggressive with increased tendency to recur, but a low metastatic potential. Its histopathological diagnosis is difficult and based on a detailed evaluation of the infiltrative nature, the importance of the mummified and necrotic cell component, atypical mitoses, and perineural or vascular invasion. Surgical wide resection is the recommended treatment. It reduces the risk of focal recurrence by 50%. Here we report two new cases including one that occurred on a lesion initially diagnosed as benign pilomatricoma.

Palie O.,University of Rouen | Michel P.,University of Rouen | Menard J.-F.,University of Rouen | Rousseau C.,Renee Gauducheau Cancer Center | And 15 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Purpose: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma. Methods: Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84 %) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET1) and on day 21 ± 3 from the start of CRT (d21; PET2). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET 1. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET 1 and PET2 using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40 % and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40 % of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG40 defined as the TLG at 40 % of SUVmax, and TLG p as that defined by a physician). The differences in responses at 3 months and 1 year between PET1 (t0) and PET2 (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA). Results: SUVmax, SUVmean and TLG decreased significantly between PET1 (t0) and PET2 (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV 40 did not decrease significantly. With respect to the predictive value of PET1, only TV40-1 and TVp-1 values, and therefore TLG40-1 and TLGp-1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp-1 and TLGp-1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET2, only TV40-2 and TVp-2 values, and therefore TLG40-2 and TLGp-2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET2 parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV40, TVp, TLG40 and TLGp between PET1 and PET2 had no relationship to patient outcome at 3 months or 1 year. Conclusion: This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET1 are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505). © 2013 Springer-Verlag Berlin Heidelberg.

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