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University of Technology of Compiègne, France

Levi F.A.,French Institute of Health and Medical Research | Levi F.A.,University Paris - Sud | Levi F.A.,Cancer Chronotherapy Unit | Boige V.,Institute Gustave Roussy | And 24 more authors.
Annals of Oncology | Year: 2016

Background: Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in ~15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. Patients and methods: Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m2), oxaliplatin (85 mg/m2) and 5-fluorouracil (2800 mg/m2) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m2) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat. Results: The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years. Conclusion: The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing. © The Author 2015.

Gouin F.,Nantes University Hospital Center | Gouin F.,University of Nantes | Rochwerger A.R.,University Hospital Of La Conception | Di Marco A.,University of Strasbourg | And 4 more authors.
European Journal of Cancer | Year: 2014

Background: Giant cell tumours (GCT) of bone are benign neoplasms associated with a high rate of local recurrence after extensive intra-lesional curettage. Recently, understanding of the biological molecular availability of strong anti-osteoclastic drugs has suggested their potential value in reducing local recurrences after curettage. Through a phase II clinical trial, we investigated the effect of a short treatment with zoledronic acid (ZOL) after intra-lesional curettage of GCT, as well as local recurrence and tolerance of the treatment. Methods and patients: Twenty-four patients were enrolled in a multicentre, phase 2 study. The patients were treated with extensive intra-lesional curettage followed by five courses of ZOL (4. mg IV every 3. weeks).The clinical and biological tolerance of each patient was assessed. Patients were reviewed clinically and by X-ray every 6. months until the end of the study (36. months). Results: Eighteen out of 20 patients reported side-effects with ZOL, mainly grade 1 and 2 effects. The local recurrence rate was 15%; three patients had a recurrence, one at 4. months (huge GCT of the sacrum), one at 24. months (patient who discontinued the treatment after the first course of ZOL), and one after the observational period, at 58. months. Finally, local relapse-free survival was 82. ±. 9% at 60. months. Conclusion: Short adjuvant treatments with ZOL after extensive intra-lesional curettage of GCT were associated with a low rate of recurrence but did not prevent local recurrence in this study. No serious general adverse effects were observed. More studies are needed to evaluate the potential benefit of medical bisphosphonate injections combined with intra-lesional curettage in the treatment of GCTB. © 2014 Elsevier Ltd.

Muscari F.,Toulouse University Hospital Center | Muscari F.,French Institute of Health and Medical Research | Foppa B.,Toulouse University Hospital Center | Carrere N.,University Hospital of Purpan | And 3 more authors.
World Journal of Surgery | Year: 2011

Background: The aim of this study was to estimate the survival rates and define risk factors for tumor recurrence after resection surgery for single hepatocellular carcinomas (HCCs) ≥ 5 cm (on preoperative imaging) that developed on compensated cirrhosis. Methods: A retrospective review studied patients treated by surgical resection. Overall survival (OS), disease-free survival (DFS), recurrence rates, and risk factors were studied for all patients. Results: A total of 49 patients were treated by resection. The 5-year OS and DFS rates were 52 and 41%, respectively, after 2000. Three independent risk factors were found for OS and DFS: macroscopic vascular invasion, satellite nodules, R1 resection. In the absence of these three factors, the 5-year OS was 59%. Recurrence rates were 63%. Delayed recurrence was significantly related to the 5-year OS. One factor was correlated with early recurrence: the presence of satellite nodules; and one factor was correlated with late recurrence: hepatitis C virus infection. Conclusions: R0 resection for HCC on compensated cirrhosis may offer good long-term survival in the absence of satellites nodules and macrovascular invasion. Thus, a "first approach" resection is proposed with the possibility of "salvage transplantation." In other cases, resection may be a bridge to transplantation ("transplantation de principe"). © 2011 Société Internationale de Chirurgie.

Orsetti B.,French Institute of Health and Medical Research | Orsetti B.,Institut Universitaire de France | Orsetti B.,Institute Regional du Cancer Montpellier | Selves J.,University Hospital of Purpan | And 20 more authors.
BMC Cancer | Year: 2014

Background: It remains presently unclear whether disease progression in colorectal carcinoma (CRC), from early, to invasive and metastatic forms, is associated to a gradual increase in genetic instability and to a scheme of sequentially occurring Copy Number Alterations (CNAs).Methods: In this work we set to determine the existence of such links between CRC progression and genetic instability and searched for associations with patient outcome. To this aim we analyzed a set of 162 Chromosomal Instable (CIN) CRCs comprising 131 primary carcinomas evenly distributed through stage 1 to 4, 31 metastases and 14 adenomas by array-CGH. CNA profiles were established according to disease stage and compared. We, also, asked whether the level of genomic instability was correlated to disease outcome in stage 2 and 3 CRCs. Two metrics of chromosomal instability were used; (i) Global Genomic Index (GGI), corresponding to the fraction of the genome involved in CNA, (ii) number of breakpoints (nbBP).Results: Stage 1, 2, 3 and 4 tumors did not differ significantly at the level of their CNA profiles precluding the conventional definition of a progression scheme based on increasing levels of genetic instability. Combining GGI and nbBP,we classified genomic profiles into 5 groups presenting distinct patterns of chromosomal instability and defined two risk classes of tumors, showing strong differences in outcome and hazard risk (RFS: p = 0.012, HR = 3; OS: p < 0.001, HR = 9.7). While tumors of the high risk group were characterized by frequent fractional CNAs, low risk tumors presented predominantly whole chromosomal arm CNAs. Searching for CNAs correlating with negative outcome we found that losses at 16p13.3 and 19q13.3 observed in 10% (7/72) of stage 2-3 tumors showed strong association with early relapse (p < 0.001) and death (p < 0.007, p < 0.016). Both events showed frequent co-occurrence (p < 1x10-8) and could, therefore, mark for stage 2-3 CRC susceptible to negative outcome.Conclusions: Our data show that CRC disease progression from stage 1 to stage 4 is not paralleled by increased levels of genetic instability. However, they suggest that stage 2-3 CRC with elevated genetic instability and particularly profiles with fractional CNA represent a subset of aggressive tumors. © 2014 Orsetti et al.; licensee BioMed Central Ltd.

Woisard-Bassols V.,30030 University Hospital of Rangueil Larrey | Alshehri S.,University Hospital of Rangueil Larrey | Simonetta-Moreau M.,University Hospital of Purpan
European Archives of Oto-Rhino-Laryngology | Year: 2013

This prospective, open study was carried out in order to assess changes in the swallowing and dietary status after injection of Botulinum toxin A (BoNT-A) into the upper esophageal sphincter (UES) in a series of patients with cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness during at least 1 year follow-up after treatment. Patients who had a cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness and who were at risk for aspiration were included in the study. The upper border of the cricoid cartilage was identified and the CP muscle localized using a standard electromyogram (EMG). The dose of BoNT-A was determined depending on the results of EMG performed just before the injection. Outcomes were assessed by the penetration-aspiration scale (PAS), the level of residue in the pyriform sinus and the National Institute of Health-Swallow Safety Scale (NIH-SSS) on a video fluoroscopic swallowing (VFSS) assessment, the patient's subjective impressions of their ability to swallow by the Deglutition Handicap Index (DHI), and changes in dietary status by the Functional Oral Intake Scale. Eleven patients underwent the complete assessment of swallowing function at 1, 3, 6, and 12 months. After the first set of treatment, seven patients had a good response and four did not respond. A significant decrease in the PAS score (p = 0.03), the amount of residue (p = 0.04) and the NIH-SSS score (p = 0.03) was observed 3 months after the injection in comparison with the first VFSS before the treatment. A relapse of dysphagia occurred in 3 out of the 11 treated patients; at 3 and 4 months for 2 patients with a Wallenberg syndrome, and at 11 months for a patient with cranial nerve paralysis after a surgery for a glomus tumor. Two of them underwent a second injection. One patient had a good response and remained stable for at least 1 year. The second did not respond either to the second injection or to a myotomy of the cricopharyngeal muscle. The third one is waiting for further surgery (myotomy). Therefore, at the end of the study and after a follow-up of at least 12 months, 5 patients out of the 11 enrolled had a good result. Percutaneous injection of BoNT-A into the UES can be a useful solution to improve cricopharyngeal dysfunction, despite the underlying pharyngo-laryngeal weakness. © 2012 Springer-Verlag.

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