[Therapeutic impact of molecular diagnosis in metastatic non-small cell lung cancer: targeted therapies in 2013]. / Impact thérapeutique du diagnostic moléculaire des carcinomes bronchiques non à petites cellules métastatiques : les traitements ciblés en 2013.

Recent advances in the molecular characterization of metastatic unresectable lung cancers have markedly improved the management of patients. Today, molecular tests should be performed routinely in all patients with non-squamous non-small cell lung cancer, and in case of squamous cell carcinoma occurring in a non-smoker. In the presence of EGFR mutation or ALK rearrangement, specific inhibitors have shown superior efficacy to chemotherapy in first-line treatment for anti-EGFR (erlotinib and gefitinib) and in second-line treatment for anti-ALK (crizotinib). We will report the most recent clinical trials that aimed to identify effective therapeutic alternatives in case of acquired resistance to first-generation inhibitors (erlotinib, gefitnib, crizotinib), which inevitably occur in a median of 11-13 months at the first line setting and 7 months at the second line setting. Finally, we will describe more recently known molecular alterations such as ROS1 or RET rearrangements and HER2, BRAF, PIK3CA, DDR2 mutations. Some of these alterations are already elegible for dedicated targeted therapies within clinical trials or temporary use authorization (ATU).

[New techniques in thoracic radiation therapy]. / Apport des nouvelles techniques en radiothérapie thoracique.

Advanced technologies have led to an improvement of target volume delineation and a higher accuracy in dose delivery. Stereotactic body radiotherapy, intensity-modulated radiotherapy and respiratory gating allow new therapeutic perspectives along with an improvement of the therapeutic ratio. Ongoing trials aim to show the magnitude of gains in patient care with technical improvements.

Statistical thermodynamics of adsorption of dye DR75 onto natural materials and its modifications: double-layer model with two adsorption energies.

In this article, adsorption modelling was presented to describe the sorption of textile dye, Direct Red 75 (DR75), from coloured wastewater onto the natural and modified adsorbent, Posidonia oceanica. The formulation of the double-layer model with two energy levels was based on statistical physics and theoretical considerations. Thanks to the grand canonical ensemble in statistical physics some physico-chemical parameters related to the adsorption process were introduced in the analytical model expression. Fitting results show that the dye molecules are adsorbed in parallel position to the adsorbent surface. The magnitudes of the calculated adsorption energies show that the DR75 dye is physisorbed onto Posidonia. Both Van der Waals and hydrogen interactions are implicated in the adsorption process. Despite its simplicity, the model fits a wide range of experimental data, thereby supporting the underlying data that the grafted groups facilitate the parallel anchorage of the anionic dye molecule. Thermodynamic parameters, such as adsorption energy, entropy, Gibbs free adsorption energy and internal energy were calculated according to the double-layer model. Results suggested that the DR75 adsorption onto Posidonia was a spontaneous and exothermic process.

[Tolerance and efficacy of preoperative radiation therapy for elderly patients treated for rectal cancer]. / Tolérance et efficacité de la radiothérapie préopératoire chez les patients âgés atteints d'un cancer du rectum.

PURPOSE: To retrospectively assess the impact of age on tolerance and oncologic outcomes treated by neoadjuvant treatment for patients of 70 years old or above with locally advanced rectal cancer. PATIENTS AND METHODS: Ninety-one consecutive patients were divided into three groups: group 1 from 70 to 75 years (n=31); group 2: 76 to 79 years (n=31) and group 3, patients aged 80 years or above (n=29). Radiation therapy was delivered according two schemes: 25Gy in five fractions (short scheme) or 45 to 50Gy with a classical fractionation (long scheme). Long scheme patients received a concomitant chemotherapy with 5-fluoro-uracile alone or associated with oxaliplatin. RESULTS: The three groups were comparable for performance status, Charlson's score and T staging. Long scheme radiation therapy and chemotherapy were performed in 77.5, 74.5 and 48.3% of patients (P=0.03) and 77.4, 71 and 41.4% (P=0.006) in the groups 1, 2 and 3, respectively. All patients treated with the short scheme irradiation received the treatment without any acute toxicity. In the long scheme group, 65% of patients received the treatment on time and grade 3 or above toxicity was observed in 12% of patients who did not receive oxaliplatin and in 48% of patients who received oxaliplatin. The overall survival rate at 3 and 5 years was 66.9% and 60.8% in the group 1, 90.5% and 75.9% in the group 2 and 80.5% and 73.8% in the group 3 (P=0.15). CONCLUSION: Neoadjuvant treatment is feasible with encouraging survival rates for patients aged 70 years and older. Short scheme radiation therapy seems to be an interesting option in this population.

Removal of lead and yellow 44 acid dye in single and binary component systems by raw Posidonia oceanica and the cellulose extracted from the raw biomass.

This study examined the sorption behaviour of Pb(II) and C.I. Acid Yellow 44 on Posidonia oceanica, an abundant Mediterranean biomass. A comparison with sorption onto cellulose extracted from the raw material was carried out to identify those site characteristics that play a predominant role in the adsorption of both dye and metal ions. Kinetic and equilibrium studies were performed for single and binary component systems, and the experimental data were analyzed by a non-linear method. The pseudo second-order kinetic model was successfully applied for both dye and metal retention onto sorbents in single and binary systems. Both sorbents were found to be more effective for lead than for Yellow 44 removal. However, lead sorption was more effective on raw P. oceanica suggesting that the metal ions are sorbed into the whole available biomass sites (cellulose and lignin). An opposite behaviour was reported for Yellow 44 sorption, which was found to be more effective on the extracted cellulose than raw P. oceanica. This finding proves that the only available sites for dye sorption are the cellulosic ones. The binary component experimental studies indicated competition between dye and lead for the available sites of raw P. oceanica. However, this competition was found to be less prevalent for sorption by cellulose extracted from raw P. oceanica suggesting that, in binary component systems, the cellulosic sites are equally available for both pollutants, the only limiting parameter being the size of the molecular sorbate. Langmuir and Freundlich isotherms were used to fit the experimental data using the non-linear method for parameter determination.

Specific TP53 mutations predict aggressive phenotype in head and neck squamous cell carcinoma: a retrospective archival study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world in developed countries. Despite the intense research in the area of squamous cell carcinomas of head and neck (HNSCC), long-term survival rate has not changed significantly in this malignancy during recent decades. METHODS: In this study, we focused on TP53 mutations in specific regions, including DNA-binding surface, to determine whether mutations at specific locations of TP53 could be used to help in setting up prognosis and response to therapy of head and neck squamous cell carcinoma patients. We analysed TP53 mutations in 46 HNSCC by PCR-SSCP and sequencing and characterized how different TP53 mutations affect the patient outcome. RESULTS: Tumours containing TP53 mutations in DNA-binding regions (L2, L3 and LSH motif) had a significantly poorer prognosis and response to radiotherapy than tumours outside those regions. Disease-specific 5-year survival of patients with TP53 mutations affecting DNA contacts was 43.5% while it was 77.8% (p < 0.05) in patients with TP53 mutations in other residues not involved in DNA contact. Moreover, nodal metastasis were more prevalent (although not statistically significantly) with TP53 mutations in DNA-binding surface regions. We noticed that the patients with TP53 mutations in L3/LSH motifs had a significantly poorer response (11.4% responding) to radiation than the patients with a wild type p53 (48.6%) or TP53 mutations outside the DNA-binding regions (40%) (p < 0.05). CONCLUSIONS: These data indicate that a TP53 mutation in L2, L3 or LSH is worth pursuing as a marker for predicting prognosis and response to radiation among HNSCC patients.

Male pattern baldness and the risk of prostate cancer.

BACKGROUND: Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life. PATIENTS AND METHODS: A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients. RESULTS: Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors. CONCLUSIONS: This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined.

p53 in head and neck cancer: functional consequences and environmental implications of TP53 mutations.

BACKGROUND: Although TP53 mutations in human tumours generally have been extensively studied, the significance of p53 in the aetiology of head and neck cancers is still incompletely characterized. In recent years, considerable interest has been focused on mutant forms of p53, the abnormal protein product of TP53 alleles with missense mutation that often accumulate in cancer cells. METHODS: We compared the nature of TP53 mutations in primary 46 head and neck squamous cell carcinomas (HNSCC) analyzed by PCR-SSCP and sequencing, immunohistochemistry, and using structural information available at IARC p53 database. RESULTS: Sequencing confirmed 36 TP53 mutations in 23 tumours of the 39 mutations in 26 tumours found by PCR-SSCP. Only half (17) putatively affect the function of p53 protein. Of these 8 were in the L2 domain, three affected the LSH motif and three the L3 domain. Three were in other domains. Codon 259 (GAC > GAA) which is a very rare mutation was found in 4 samples in our study. There were indications of p53 aberrations being associated with the combined effect of smoking, alcohol and work history. Patients with a negative family history of cancer had more often TP53 mutations than patients with a positive family history (71% vs. 46%). CONCLUSIONS: Our study contributes to the knowledge of cumulative chemical exposure and p53 aberrations in head and neck cancer, an area where literature is scarce.

[Clinical and dosimetric analysis of 469 prostate cancer patients treated in France in 2005 by permanent implant brachytherapy using the Iodin 125 seeds IsoSeed Bebig: report to the French Economic committee of health products (CEPS)]. / Analyse clinique et dosimétrique de 469 patients traités en France en 2005 par implantation prostatique de grains d'iode 125 IsoSeed Bebig: rapport pour le Comité économique des produits de santé (CEPS).

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.