NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase 1b outcomes and MRI-based biodistribution.

Background: In glioblastoma (GBM), tumor progression occurs mainly within the irradiated tumor volume. To address this challenge, a radiosensitization strategy with intravenous gadolinium-based theranostic nanoparticles (AGuIX) is being explored in the NANO-GBM phase1b/2R trial (NCT04881032). Here, we present the results of the phase 1b part, which is the first-in-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed GBM. Material and Methods: Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed GBM, with incomplete resection (biopsy or partial surgery). The phase 1b part was a dose escalation approach (Time-to-event Continuous Reassessment Method) with three dose levels: 50, 75, and 100 mg/kg. Patients were treated with RT (60 Gy), and concomitant and adjuvant TMZ, and 4 injections of AGuIX (D-3/-7, D1, D8, and D15). Dose-limiting-toxicity (DLT) was defined as any grade 3-4 adverse event (CTCAE v5.0), excluding alopecia, nausea, and rapidly controlled vomiting. Pharmacokinetic (PK), and biodistribution based on MRI were evaluated. Results: Between March 2022 and March 2023, eight patients were enrolled: 1 at 50 mg/kg, 1 at 75 mg/kg, and 6 at 100 mg/kg. All patients received the four AGuIX injections. Only one patient experienced a DLT (at 100 mg/kg): a grade 3 lymphopenia (related to TMZ). The RP2D of AGuIX was determined as 100 mg/kg. AGuIX mean AUC increased with dose. Regions of GBM with moderate (36-123 µM), and high (123-291 µM) or very high (>291 µM) AGuIX concentrations accounted in average for 38.7 and 26.8 %, respectively. Conclusion: These results confirm the lack of AGuIX-related toxicity and the widespread dispersion of nanoparticles throughout GBM. This supports progression to the randomized phase 2 part, utilizing an RP2D of AGuIX of 100 mg/kg (4 injections).

Evaluation of the impact of pharmaceutical trainings and tools on the proper use of medicines in pediatrics.

Introduction: After six years of medication errors' (MEs) collection and analysis in a pediatric unit of a French University Hospital, the number of MEs was no longer decreasing. We then decided to set up pharmaceutical training and tools and evaluate their impact on the occurrence of ME. Materials and methods: This monocentric prospective study was carried out in the form of audits of prescriptions, preparations, and administrations before and after intervention (A1 and A2). After the analysis of A1 results, feedback was given to the teams, some tools for the proper use of medication (PUM) were distributed, and A2 was conducted. Finally, A1 and A2 results were compared. Results: Each audit included 202 observations. A total of 120 MEs were identified during A1 and 54 for A2 (p < 0.0001). The observation rate with at least 1 ME decreased from 39.11% to 21.29% (p < 0.0001), and no observation had more than two MEs during A2 in contrast to A1 (n = 12). Human factors were responsible for the majority of MEs. The audit feedback allowed professionals to feel concerned about ME. The PUM tools received an average satisfaction rating of 9/10. The staff had never participated in this type of training, and all felt it was useful to apply PUM. Conclusion: This study showed a significant impact of pharmaceutical training and tools on the pediatric PUM. Clinical pharmaceutic actions allowed us to reach our objectives and satisfied all the staff. They must, therefore, be continued to limit human factors' impact and thus contribute to the safety of drug management in pediatrics.

A global perspective on bacterial diversity in the terrestrial deep subsurface.

While recent efforts to catalogue Earth's microbial diversity have focused upon surface and marine habitats, 12-20 % of Earth's biomass is suggested to exist in the terrestrial deep subsurface, compared to ~1.8 % in the deep subseafloor. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and Firmicutes, probably as a function of the diverse metabolic strategies of these taxa. Evidence was also found for a common small consortium of prevalent Betaproteobacteria and Gammaproteobacteria operational taxonomic units across the localities. This implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, depth and other variables, that may play an important role in colonizing and sustaining microbial habitats in the deep terrestrial subsurface. An in silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.

Analytical development for the assessment of pesticide contaminations in blood and plasma of wild birds: The case of grey partridges (Perdix perdix).

In this study, blood and plasma of grey partridges (Perdix perdix) were analyzed to assess their potential contamination by plant protection products (PPP) and especially pesticide compounds. The group of pesticides selected is composed of a huge variety of compounds. Therefore, in this study, two methods were optimized and validated to analyze 104 compounds including herbicides, insecticides, fungicides and photoprotectors or synergists. Various extraction methods found in the literature were compared and adapted for the extraction of pesticides from blood and plasma. After extraction, samples were concentrated then injected for quantification simultaneously in LC-MS/MS and ATD-GC-MS/MS with an automatic thermal desorption step (ATD). Both LC-MS/MS and ATD-GC-MS/MS analyses were performed using the MRM mode with 2 mass transitions for each compound.The two analytical methods achieved a good linearity for the calibration responses in plasma and blood. Methods allowed sensitive detection and quantification in complex biological matrices such as plasma and blood in both LC and GC. For plasma samples and considering all 104 compounds of the study, the average LOD was 0.005 ng mg-1 in LC-MS/MS and 0.035 ng mg-1 in ATD-GC-MS/MS and the average LOQ was 0.017 ng mg-1 and 0.116 ng mg-1 in LC-MS/MS and ATD-GC-MS/MS respectively. Accordingly, the average LOD for blood samples was 0.011 ng mg-1 in LC and 0.028 ng mg-1 in GC whereas the average LOQ was 0.038 ng mg-1 and 0.094 ng mg-1 in LC-MS/MS and ATD-GC-MS/MS respectively. Those analytical methods were then successfully applied to 70 blood samples and 35 plasma samples.

[Impact of IMRT for neoadjuvant rectal cancer?] / Quel apport de la modulation d'intensité pour la radiothérapie des cancers du rectum ?

The standard management of locally advanced rectal tumors as cT3-T4 and/or N0/N1 is based on preoperative treatment combining radiotherapy of 45 to 50Gy and chemotherapy based on 5-fluorouracil. Intensity-modulated radiotherapy has already shown its interest compared to conformal radiotherapy in other locations, like in pelvic cancer. The role of intensity-modulated radiotherapy in the pre/postoperative treatment of rectal cancers is not a standard of care. Published studies showed its feasibility with the objective of less toxicity with equivalent efficacy.

Sustainable neurosurgical training around the globe. A review and outline.

Sharing an equal and quality neurosurgical training across the globe without exclusion may seem utopian. However, such training is possible through educational opportunities and the ongoing digital revolution. The aim is to present the current state of neurosurgery training and education methods indicating strengths, weaknesses and opportunities. The thoughts, comments and suggestions of the authors are based on their academic experiences, training missions around the world and particularly in low- and middle-income countries by pointing out the French experience. The learning must be interactive and programmed over time, integrating varied courses and activities. Virtual reality and neurosurgical simulation need to be developed. The content of the teaching including e-learning must be evidence-based and peer-reviewed. Pedagogical training of trainers is fundamental. It is critical to evaluate the training under real working conditions. The optimization of human resources should create economies of scale that would attenuate the financial burden. The commitment of the teams, tutoring are success factors.

Impact of the method chosen for the analysis of recurrences after radiotherapy for head and neck cancers: volume-based, point-based and combined methods.

Intensity modulated radiation therapy for head and neck is a complex technique. Inappropriate delineation and/or dose distribution can lead to recurrences. Analysis of these recurrences should lead to improve clinical practice. For several years, different methods of analysis have been described. The purpose of this review is to describe these different methods and to discuss their advantages and limitations. The first published methods used a volume-based approach studying the entire volume of recurrence according to initial target volumes, or dose distribution. The main limitation of these methods was that the volume of recurrence studied was dependent on the delay in diagnosis of that recurrence. Subsequently, other methods used point-based approaches, conceptualizing recurrence either as a spherical expansion from a core of radioresistant cells (center of mass of recurrence volume) or using a more clinical approach, taking into account tumor expansion pathways. More recently, more precise combined methods have been described, combining the different approaches. The choice of method is decisive for conclusions on the origin of recurrence.

[Intra and extra hepatic cholangiocarcinomas radiation therapy]. / Place de la radiothérapie des cholangiocarcinomes intra- et extrahépatiques.

Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

Hypofractionated stereotactic radiotherapy for large brain metastases: Optimizing the dosimetric parameters.

PURPOSE: Stereotactic radiotherapy plays a major role in the treatment of brain metastases (BM). We aimed to compare the dosimetric results of four plans for hypofractionated stereotactic radiotherapy (HFSRT) for large brain metastases. MATERIAL AND METHODS: Ten patients treated with upfront NovalisTx® non-coplanar multiple dynamic conformal arcs (DCA) HFSRT for≥25mm diameter single BM were included. Three other volumetric modulated arc therapy (VMAT) treatment plans were evaluated: with coplanar arcs (Eclipse®, Varian, VMATcEclipse®), with coplanar and non-coplanar arcs (VMATncEclipse®), and with non-coplanar arcs (Elements Cranial SRS®, Brainlab, VMATncElements®). The marginal dose prescribed for the PTV was 23.1Gy (isodose 70%) in three fractions. The mean GTV was 27mm3. RESULTS: Better conformity indices were found with all VMAT techniques compared to DCA (1.05 vs 1.28, P<0.05). Better gradient indices were found with VMATncElements® and DCA (2.43 vs 3.02, P<0.001). High-dose delivery in healthy brain was lower with all VMAT techniques compared to DCA (5.6 to 6.3 cc vs 9.4 cc, P<0.001). Low-dose delivery (V5Gy) was lower with VMATncEclipse® or VMATncElements® than with DCA (81 or 94 cc vs 110 cc, P=0.02). CONCLUSIONS: NovalisTx® VMAT HFSRT for≥25mm diameter brain metastases provides the best dosimetric compromise in terms of target coverage, sparing of healthy brain tissue and low-dose delivery compared to DCA.

Impact of the polycarbonate strippers used in assisted reproduction techniques on embryonic development.

STUDY QUESTION: Do daily manipulations of preimplantation embryos with polycarbonate (PC)-made bisphenol A (BPA)-releasing strippers influence embryo development? SUMMARY ANSWER: Compared to glass strippers, PC strippers enhance the blastocyst development rate but this does not seem to be BPA-related. WHAT IS KNOWN ALREADY: PC strippers have been shown to release tiny amounts (around 0.5 ng/ml BPA) of BPA in routine human IVF procedures. A chronic exposure to BPA either in vivo or in vitro during the preimplantation period can impact post-implantation and post-natal development. BPA can act rapidly by binding to membrane receptors and inducing rapid non-genomic effects. STUDY DESIGN, SIZE, DURATION: This experimental study using mouse embryos had a balanced design and blinded evaluations of the endpoints. PARTICIPANTS/MATERIALS, SETTING, METHODS: In vivo fertilized zygotes were obtained from outbred Swiss CD1 mice crossings after an ovarian stimulation. The zygotes were allocated to three daily handling conditions (HCs) and cultured until Day 4 in a single human commercial medium. Each day, the embryos were handled for 20 s either in a PC stripper (HC1) or in a glass stripper (HC2). In HC3, the embryos were pre-exposed to 0.5 ng/ml BPA before being handled for 20 s in a glass stripper. Handling operations were repeated on Days 1, 2 and 3. Embryo development was assessed blindly on Day 4. Expanded blastocysts were selected for a transcriptomic analysis using Agilent Sureprint G3 Mouse GE v2 microarrays and the retrotransposon LINE1-Orf2 expression was analysed using qRT-PCR, as a proxy for a global evaluation of the epigenetic status. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to the embryos manipulated in HC2 (n = 243), those in HC1 (n = 228) developed significantly more often to the blastocyst stage (55 vs 46%; P < 0.05). It appears the effect of these PC strippers was not BPA-related because embryos pre-exposed to BPA (HC3, n = 230) showed no difference in the blastocyst rate when compared to HC2 (43 vs 46%). When analysing same-stage blastocysts, we noticed no difference in the embryo gene expression between the three HC groups. LARGE SCALE DATA: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148868. LIMITATIONS, REASONS FOR CAUTION: Our results using a mouse model designed to mimic human conditions (outbred strain, human commercial IVF dishes and a unique commercial human embryonic culture media) are reassuring since no gene was found to be differentially expressed, including LINE-1 genes, as a proxy for a global evaluation of the epigenetic status. However, no global epigenetic analysis of the genome has been performed. Furthermore, we did not evaluate post-implantation events, although BPA exposure during peri-conception could affect foeto-placental and post-natal development. WIDER IMPLICATIONS OF THE FINDINGS: Based on the precautionary principle, several European countries banned the use of BPA in baby bottles and food packaging several years before European Agencies took an official position. The question of applying this principle to plastics in closed contact with human embryos is raised. Further studies are needed for a decision to be made. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Agence de Biomédecine (AOR 2016). The authors declare no competing interest.

[Concurrent chemoradiotherapy for head neck cancers. Should organs at risk dose constraints be revisited ?] / Chimioradiothérapie concomitante des cancers des voies aérodigestives supérieures. Faut-il revoir les contraintes de dose dans les organes à risque ?

Concurrent chemoradiotherapy improves the outcome of locally advanced head and neck cancers and the current reference chemotherapy is cisplatin. These results are obtained at the cost of increased toxicities. To limit the risk of toxicity, organ at riskdose constraints have been established starting with 2D radiotherapy, then 3D radiotherapy and intensity-modulated radiotherapy. Regarding grade ≥3 acute toxicities, the scientific literature attests that concurrent chemoradiotherapy significantly increases risks of mucositis and dysphagia. Constraints applied to the oral mucosa volume excluding the planning target volume, the pharyngeal constrictor muscles and the larynx limit this adverse impact. Regarding late toxicity, concurrent chemoradiotherapy increases significantly the risk of postoperative neck fibrosis and hearing loss. However, for some organs at risk, concurrent chemotherapy appears to increase late radiation induced effect, even though the results are less marked (brachial plexus, mandible, pharyngeal constrictor muscles, parotid gland). This additional adverse impact of concomitant chemotherapy may be notable only when organs at risk receive less than their usual dose thresholds and this would be vanished when those thresholds are exceeded as seems to be the situation for the parotid glands. Until the availability of more robust data, it seems appropriate to apply the principle of delivering dose to organs at risk as low as reasonably achievable.

Intersphincteric resection for low rectal cancer: the risk is functional rather than oncological. A 25-year experience from Bordeaux.

AIM: There are few data evaluating the long-term outcomes of intersphincteric resection (ISR), especially the impact of inclusion of more juxtapositioned and intra-anal tumours on oncological and functional outcomes. We compared the oncological and functional results of patients treated by total mesorectal excision and ISR for low rectal cancer over a 25-year period. METHOD: This is a retrospective study from a single institution evaluating results of ISR over three periods: 1990-1998, 1999-2006 and 2007-2014. Patients treated by partial or total ISR, with or without neoadjuvant chemoradiotherapy, for low rectal cancer (≤ 6 cm from the anal verge) were included. We compared postoperative morbidity, quality of surgery and oncological and functional outcomes in the time periods studied. RESULTS: Of 813 patients operated on for low rectal cancer, 303 had ISR. Tumour stage did not differ; however, the distance of the tumour from the anorectal junction decreased from 1 to 0 cm (P < 0.001) and the distal resection margin shortened from 25 to 10 mm (P < 0.001) from 1990 to 2014. The postoperative morbidity and quality of surgery did not change significantly over time. The 5-year local recurrence (4.3% vs 5.9% vs 3.5%; P = 0.741) and disease-free survival (72% vs 71% vs 75%; P = 0.918) did not differ between the three time periods. Functional results improved during the last period; however, overall 42% of patients experienced major bowel dysfunction. CONCLUSION: Pushing the envelope of sphincter-saving resection in ultra-low rectal cancer reaching or invading the anal sphincter did not compromise oncological and functional outcomes. The main limitation of the ISR procedure appears to be functional rather than oncological, suggesting that bowel rehabilitation programmes should be developed.

[Preoperative intensity-modulated radiotherapy of rectal cancers: Relevance and modalities]. / Radiothérapie avec modulation d'intensité préopératoire des cancers rectaux : intérêt et application.

Preoperative radiotherapy boosted by chemotherapy is a recommended treatment in locally advanced rectal cancers. This treatment is delivered by three dimensional conformal irradiation, which is usually well tolerated but can induce potential toxicity such as rectitis, cystitis and hematologic adverse effects. Intensity-modulated radiotherapy, widely available nowadays, allows optimization of volume covering and sparing of organs at risk such as bladder and bone marrow. This review presents relevant clinical situations and requirements for a beneficial and safe preoperative irradiation of rectal cancers by intensity-modulated technique. This technique is compared to three-dimensional conformal radiotherapy.

Delayed coloanal anastomosis: an alternative option for restorative rectal cancer surgery after high-dose pelvic radiotherapy for prostate cancer.

AIM: Restorative total mesorectal excision (TME) for rectal cancer after high-dose pelvic radiotherapy for prostate cancer has been reported to provide an unacceptable rate of pelvic sepsis. In a previous publication we proposed that delayed coloanal anastomosis (DCAA) should be performed in this situation. The present study aimed to assess the feasibility and outcomes of this strategy. METHOD: Between 2000 and 2018, 1094 men were operated on for rectal cancer in our institution. All men with T2/T3 mid and low rectal cancer with preoperative radiotherapy and restorative TME were considered for this study (n = 416). Patients with external-beam high-dose radiotherapy (EBHRT) for prostate cancer (70-78 Gy) were identified and compared with patients with conventional long-course chemoradiotherapy (CRT) followed by TME. We compared our already published historical cohort (2000-2012), including arm A (CRT + TME; n = 236) and arm B (EBHRT + TME; n = 12), with our early cohort (2013-2018), including arm C (CRT + TME; n = 158) and arm D (EBHRT + TME-DCAA; n = 10). The end-points were morbidity, pelvic sepsis, reoperation rate and quality of the specimen. RESULTS: Overall morbidity was not significantly different between groups. Pelvic sepsis decreased from 50% (arm B) to 10% (arm D) with the use of DCAA (P = 0.074), and was similar between arms A, C and D. Quality of the specimen was not significantly different between the four groups. CONCLUSION: Our results suggest that TME with DCAA in patients with previous EBHRT is feasible, with the same postoperative pelvic sepsis rate as conventional CRT.

Management of gestational trophoblastic diseases in a low resource country: establishment of a national center and its results.

To describe the process of establishing a reference center for gestational trophoblastic diseases (GTD) in Senegal and to report its main results so far. We describe the history and establishment of the center, which is based on the experience of the main international centers. The adaptations made to patient follow-up are detailed, while we follow FIGO and WHO diagnostic and management criteria. Finally, we report our main results. Between 2011 and 2017, 878 files were registered at the Center. More than half of the women had no histological confirmation of GTD (60.8 %). The diagnosis was then based on ultrasound images or macroscopic examination of molar vesicles. Spontaneous remission occurred in 64.5 % of the cases, while gestational trophoblastic neoplasia developed in 23.5 %. The FIGO criteria were slightly adapted for hCG monitoring. Methotrexate was the drug of choice in the low-risk group (97.8 %), while the EMACO protocol was financially difficult for nearly half of the high-risk group. The overall remission rate was 83 % and the specific lethality 11.6 %. Our center has demonstrated the efficiency of centralizing the management of GTDs. Difficulty in access to hCG and antimitotic drugs makes management difficult. However, we have introduced alternative solutions that we are working to improve.

[Reirradiation for head and neck squamous cell carcinoma: Indications and results]. / Réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures : indications et résultats.

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation…) and patient-related factors (comorbidities, sequelae of previous irradiation…), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques.

[Tolerance of hypofractionated stereotactic radiotherapy for hepatic tumours]. / Tolérance de l'irradiation stéréotaxique hypofractionnée des tumeurs hépatiques.

PURPOSE: The purpose of the study was to evaluate the outcomes of stereotactic radiation therapy for primary and secondary liver tumours in Jean-Perrin cancer centre (Clermont-Ferrand, France) in terms of efficacy and safety. MATERIALS AND METHODS: Between December 2013 and June 2016, 25 patients were included. Treatment was performed on a linear accelerator Novalis TX®. The prescription dose was 42 to 60Gy in three to five fractions. Local control at 1 year was evaluated with modified Response Evaluation Criteria in Solid Tumours (mRECIST) and RECIST criteria. Acute and late toxicity were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria. RESULTS: Median follow-up was 10.5 months. Treatment tolerance was good with few side effects grade 3 or above, no acute toxicity and only one late toxicity. We have highlighted that hepatic artery haemorrhage was associated with the presence of a biliary prosthesis in contact with the artery (P=0.006) and in the irradiation field. There was no correlation with the dose delivered to the artery and hepatic artery haemorrhage. CONCLUSION: Stereotactic radiation therapy for liver tumours allows a good local control with few secondary effects. Caution should be exercised when treating patients with biliary prostheses in the vicinity of the target volume because there is a risk of haemorrhage of the hepatic artery in contact with the prosthesis.

[Toxicity of docetaxel, platine, 5-fluorouracil-based induction chemotherapy for locally advanced head and neck cancer: The importance of nutritional status]. / Toxicité de la chimiothérapie d'induction par docétaxel, platine, 5-fluorouracile (TPF) pour les cancers des voies aérodigestives supérieures localement évolués en routine clinique : importance du statut nutritionnel.

PURPOSE: The objective of this study was to identify predictive factors of toxicity of docetaxel, platin, 5-fluorouracil (TPF) induction chemotherapy for locally advanced head and neck cancers. PATIENTS AND METHODS: From July 2009 to March 2015, 57 patients treated consecutively with TPF were included retrospectively. There were 47 males (83%), the median age was 56 years [40-71 years]. Thirty-eight patients (67%) were treated for inoperable cancer (highly symptomatic and/or high tumor burden) and 19 (33%) were treated for laryngeal preservation. There were 47% stage IVa, 32% stage III and 21% stage IVb. At diagnosis, there were 53% stable weight, 28% grade 1 weight loss, 17% grade 2 weight loss and 2% grade 3 weight loss. RESULTS: Forty-seven percent of patients were in partial response after TPF, 28% in complete response, 7% stable, 2% progressing and 2% discordant response. The possibility of oral feeding without a feeding tube was predictive of a better response (P=0.02). Thirty-nine percent of patients increased weight during TPF, 35% were stable, 18% in grade 1 weight loss, 6% in grade 2 and 2% in grade 3. Six of the patients (10.5%) died during chemotherapy: four from febrile neutropenia, one from pneumopathy and one of unknown cause. Age 57years and older was associated with a higher risk of grade≥3 anemia and thrombocytopenia. There was a higher risk of grade≥3 infection for weight loss at diagnosis (P=0.04) and feeding tube (P=0.05). There was a higher risk of grade≥3 neutropenia for weight loss during TPF (P=0.03). CONCLUSION: Induction chemotherapy by TPF has an strong anti-tumor efficacy (75.5% objective response) but an important morbidity with 10% toxic deaths in our very symptomatic population with a very important tumor burden. Age and nutritional status are important factors to consider.

Adalimumab for patients with Crohn's disease complicated by intra-abdominal abscess: a multicentre, prospective, observational cohort study.

doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section.