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Nice, France

De Nardo L.,University of Padua | Colautti P.,Viale dellUniversit 2 | Herault J.,Center cassagne | Conte V.,Viale dellUniversit 2 | And 2 more authors.
Radiation Measurements | Year: 2010

In this study we have investigated the radiation quality of proton beams used to treat conjunctival melanomas at the Biomedical Cyclotron in Nice. To quantify radiation quality we have used a mini tissue-equivalent proportional counter (TEPC). Microdosimetric spectra have been measured at different depths and lateral positions in a Plexiglas eye phantom. A weighting function, which was derived from evaluations of the early effects on the mouse intestine, was applied to the spectra to obtain the microdosimetric assessment of relative biological effectiveness (RBEμ). Data show that RBEμ varies significantly in the eye phantom, from 1.1 to 1.7. However, within the conjunctiva the RBE-weighted dose varies in a similar fashion to the absorbed, although it is up to 20% higher than the corresponding absorbed dose. © 2010 Published by Elsevier Ltd. All rights reserved.

Doyen J.,Center cassagne | Trastour C.,Archet II Hospital | Ettore F.,Center cassagne | Peyrottes I.,Center cassagne | And 8 more authors.
Biochemical and Biophysical Research Communications | Year: 2014

Background 18Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (70%), followed by Her-2 (50%) and RH-positive cancers (30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H+ symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors. © 2014 Elsevier Inc. All rights reserved.

Thariat J.,Oncopharmacology Unit EA 3836 | Thariat J.,Center cassagne | Vignot S.,rue Claude Bernard | Lapierre A.,University of Lyon | And 4 more authors.
Critical Reviews in Oncology/Hematology | Year: 2015

Head and neck squamous cell carcinomas (HNSCC) represent a multifactorial disease of poor prognosis. They have lagged behind other cancers in terms of personalized therapy. With expansion and high throughput sequencing methods, recent landmark exonic studies and Cancer Genome Atlas data have identified genes relevant to carcinogenesis and cancer progression. Mutational profiles and rates vary widely depending on exposure to carcinogens, anatomic subsites and human papilloma virus (HPV) infection. Tumors may exhibit specific, tissue-specific, not exclusively HPV-related, gene alterations, such those observed in oral cavity cancers in Asia or Occident. Except for the PI3K pathway, the rate of mutations in HPV+ cancers is much lower than in tobacco/alcohol-related cancers. Somatic driver mutation analyses show that relatively few driver genes are druggable in HNSCC and that tumor suppressor gene alterations prevail. More mature for therapeutic applications is the oncogenic PI3K pathway, with preclinical human xenograft models suggesting that PI3KCA pathway mutations may be used as predictive biomarkers and clinical data showing efficacy of mTOR/Akt inhibitors. Therapeutic guidance, to date, relies on classical histoprognostic factors, anatomic subsite and HPV status, with integration of hierarchized supervised mutational profiling to provide additional therapeutic options in advanced HNSCC in a near future. Unsupervised controlled genomic analyses remain necessary to unravel potentially relevant genes. © 2015 Elsevier Ireland Ltd.

Lutz M.P.,CaritasKlinikum St. Theresia | Zalcberg J.R.,Monash University | Glynne-Jones R.,Mount Vernon Cancer Center | Ruers T.,Netherlands Cancer Institute | And 26 more authors.
European Journal of Cancer | Year: 2016

Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care. © 2016 The Authors.

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