Search

To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20.Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash.Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Aim. To compare the immediate and long-term results of robot-assisted and open resection of the liver and bile ducts for portal cholangiocarcinoma.Materials and methods. The retrospective study was based upon the results of open and robot-assisted resections in 2013–2021. Patients without signs of the tumor invasion into the great vessels requiring resection and reconstruction were selected for the robot-assisted resection of the liver and bile ducts. Propensity score matching was carried out within the immediate environment in the ratio 1:2 for five covariates.Results. The results of 147 open resections of the liver and bile ducts and 17 robot-assisted resections were compared. After propensity score matching, the authors compared 33 open and 17 robot-assisted resections. Before and after propensity score matching, statistically significant differences were obtained only in the longer duration of robotassisted resections. Right hepatectomy and caudal resection were performed more frequently in the group of patients with robot-assisted interventions, but without significant differences. The authors noted a tendency to a higher frequency of R0 and a lower 90-day mortality rate after robot-assisted interventions, with no differences in the rate and nature of complications, as well as in duration of hospitalization. Survival did not differ before and after propensity score matching. After open and robot-assisted interventions the overall five-year survival rates before propensity score matching were 32% and 67%, after propensity score matching the overall four-year survival rates accounted for 62% and 63%.Conclusion. Analysis of the first experience shows a tendency to improve some immediate outcomes without worsening survival. Robot-assisted resection of the liver and bile ducts can be applied, without limitation of oncologic principles, in selected patients with portal cholangiocarcinoma if the resection is performed in specialized hepatological centers, where specialists have experience in minimally invasive surgery.

Objective To investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone. Methods We conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) were included. Two groups of 30 women were matched and compared: “CRS + HIPEC” which used HIPEC after CRS, and “CRS only” which did not use HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS). Results In “CRS plus HIPEC” group, 96.7% of women were treated for recurrence, while in “CRS only” 83.3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p = 0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p = 0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p = 0.511). Conclusion The use of HIPEC combined to CRS did not have any significance as regard the DFS and OS over CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.

Background MicroRNAs (miRNAs) are promising biomarkers in ovarian cancer. Their kinetics during treatment might be useful for monitoring disease burden, and guiding treatments in patients treated with neoadjuvant chemotherapy and interval debulking surgery (IDS). Methods Serial blood samples of patients enrolled in the randomized phase II CHIVA trial, comparing neo-adjuvant carboplatin-paclitaxel +/- nintedanib (NCT01583322), were investigated to assess the kinetics of 11 relevant miRNAs compared to CA125 kinetics, using C-index & survival tests for predictive and prognostic values. MiRNAs were extracted and quantified by qRT-PCR. The selection of the final 11 miRNAs was based on the expression levels found with a large explorative panel of 84 miRNAs in 8 patients, and on the literature: miR-15b-5p, miR-16-5p, miR-20a-5p, miR-21-5p, miR-93-5p, miR-122-5p, miR-150-5p, miR-195-5p, miR-200b-3p, miR-148b-5p and miR-34a-5p. Results 756 serial blood samples done every 3 weeks from 119 patients were analyzed for a total of 8172 miRNA assays, and 1299 CA-125 values. About 82% of miRNA concentrations were above the limits of quantification. The time courses of the miRNAs expressions were highly heterogeneous, and were not parallel with the CA-125 time changes. The miRNAs kinetics during treatment were not found associated with disease bulk changes, RECIST tumor response, or cytoreductive surgery outcomes (optimal vs non-optimal IDS). However, for 6 of them (miR-15b-5p; miR-16-5p; miR-20a-5p; miR-21-5p; miR-93-5p; and miR-195-5p), significant increases at disease progressions were found (median 40%). Decreases of miR-34a-5p and miR-93-5p were associated with PFS benefit (13.7 vs 24.8 months; p = 0.009) and OS benefits (34.3 months vs Not reached; p Conclusions The longitudinal kinetics of miRNA expressions during neo-adjuvant treatment in ovarian cancer patients were inconsistent, and were not found to be associated with tumor burden changes. Although some prognostic value could be discussed, no predictive value regarding tumor responses or IDS quality could be identified. Clinical trial identification EudraCT: 2011-006288-23. Legal entity responsible for the study ARCAGY-GINECO. Funding Boehringer Ingelheim. Disclosure I.L. Ray-Coquard: Honoraria (self): AstraZeneca; Honoraria (self): Clovis; Honoraria (self): Tesaro; Honoraria (self): Pharma Mar; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: pharma Mar; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): MSD; Travel / Accommodation / Expenses: AstraZeneca. J. Florence: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): BMS; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: BMS. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. A. Leary: Advisory / Consultancy: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Gamamab; Advisory / Consultancy: Gridstone; Advisory / Consultancy: Seattle Genetics; Travel / Accommodation / Expenses: Clovis; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

Background Patients (pts) with RM SCCHN progressing after platinum have a median overall survival (OS) of 7-8 months with nivolumab or pembrolizumab. No other drug has shown meaningful activity in this setting. HLA-E is a non-classical MHC molecule that is highly expressed in 70% of SCCHN. By binding to the NKG2A receptor expressed on NK cells and T-lymphocytes, HLA-E inhibits their cytotoxic function. Monalizumab (mona) is a human IgG4 antibody targeting the NKG2A receptor. Methods The UPSTREAM trial is a biomarker-driven umbrella trial of several targeted therapies and immunotherapy for RM SCCHN (post platinum, ECOG 0-1, measurable disease). The immunotherapy 1 (I1) cohort was a phase II, single arm, proof-of-concept substudy evaluating the efficacy of single agent mona. Non-eligible pts for the biomarker-driven cohorts were included in the I1 cohort. Mona was given as an infusion (10 mg/kg) on day 1 of each cycle (14 days). The primary endpoint was objective response rate (RECISTv1.1) during the first 16 weeks. A two-stage Simon design was used (H1 15%, H0 3%, α 8%, power 90%) with planned interruption of accrual if no response was seen after 25 pts. Secondary endpoints included toxicity (CTCAEv4.03), progression-free survival (PFS), response duration and OS. Results 27 RM SCCHN pts were included in the 1st stage (median age: 62 yrs, oral cavity (26%), oropharynx (41%), hypopharynx (26%), larynx (7%)). 16 (59%) were pretreated with anti-PD(-L)1 compounds. No objective response was recorded. Stable disease was observed in 6 pts (22%). Disease progression was recorded in all but one patient and the median PFS was 7.4 wks (95% CI: 6.6-7.9 wks). Based on 16/27 deaths currently recorded, median OS was 27.7 wks (95% CI: 13-53.9 wks). Mona showed a favorable safety profile: 59% pts reported grade >/= 3 adverse events, none of them treatment-related. The final results of these preliminary data will be presented at ESMO. Conclusions The substudy of mona in monotherapy did not meet its primary objective and was closed at interim for futility. Median PFS was 7.4 wks. Mona has a favorable safety profile and is under investigation in combination with durvalumab within the UPSTREAM trial. Clinical trial identification NCT03088059. Legal entity responsible for the study EORTC. Funding EORTC, Innate Pharma. Disclosure R. Galot: Advisory / Consultancy: Innate Pharma; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Astellas. C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: BMS; Advisory / Consultancy: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: GSK; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix. C. Even: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Innate Pharma. L.F. Licitra: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution): EISAI; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Debiopharm; Advisory / Consultancy, Research grant / Funding (institution): Sobi; Honoraria (self), Advisory / Consultancy, For teaching in medical meetings: Incyte Biosciences Italy srl; Advisory / Consultancy: Doxa Pharma; Honoraria (self), For public speaking in medical meetings: Amgen; Advisory / Consultancy: Nanobiotics; Advisory / Consultancy: GSK; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): IRX Therapeutics; Research grant / Funding (institution): Pfizer. M. Kaminsky-Forrett: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): AstraZeneca; Advisory / Consultancy: EMD Serono. J. Machiels: Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Innate Pharma; Honoraria (institution), Research grant / Funding (institution): Merck Serono; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Research grant / Funding (institution): Novartis; Honoraria (institution), Research grant / Funding (institution): Janssen; Honoraria (institution), Research grant / Funding (institution): Incyte; Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Data safety monitoring board with honoraria: Debio; Advisory / Consultancy, Data safety monitoring board with honoraria: Nanobiotix; Non-remunerated activity/ies, investigator and study coordinator: EORTC. All other authors have declared no conflicts of interest.

Purpose The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity. Results Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 139 %). The median duration of progression-free survival was 82 days (95 % CI 41140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 727 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected. Conclusions The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

Background Tumour Microvessel density (MVD) is often used as a surrogate marker for tumoral angiogenic activity. In the randomized phase II neo-adjuvant CHIVA trial, ovarian cancer patients (pts) treated with standard chemotherapy plus Nintedanib (Ni) compared to chemotherapy alone had a reduced rate of complete surgical resection at interval debulking surgery (IDS), worse PFS and OS. To explain these results we assessed the predictive/prognostic value of MVD at baseline and the MVD decrease from baseline to IDS. Methods Paired tumours from baseline and IDS were available from 79/188 randomized pts. A total of 158 virtual slides of immunostained tumor section with anti-CD31 were analysed. MVD was quantified by an image processing on whole tumor section. MVD high level was defined as MVD > 33.5 vessel/mm² which is the highest Youden index on the ROC curve for PFS. The relationship between MVD at baseline and PFS and OS was evaluated using Kaplan-Meier survival estimates. Results Main characteristics of the 79 pts were similar to the overall CHIVA population: mean age (62 years), ECOG performance status = 0 (34%), high-grade serous histology (75%). At baseline, MVD was similar in both arms and was low for 35% and 30% of the pts in the Ni and control arm respectively. The rate of complete resection (CC0) was 56% in the Ni arm versus 70% in the control arm. In the low MVD group median PFS was 13.3 months (95%CI 11 – 22.2) versus 17 months (95%CI 13.7 – 20.5) in the high MVD group (p = 0.85). In the low MVD group, PFS in the Ni and control arm were 12.8 (95%CI 10.7-22.2) and 21.3 months (95%CI 12.5-NA) respectively (p = 0.08). The corresponding PFS in the high MVD group were 18.0 (95%CI 14.4-21.6) vs 14.5 months (95%CI 12.4-22.5) (p = 0.22). No difference was observed for OS. Baseline MVD was not associated with the rate of CC0. There was no significant difference in the decrease of MVD at IDS between the Ni arm (38% of the pts) and the control arm (48%, p = 0.4). Conclusions The negative impact of Nintedanib in patients with low baseline MVD tumours may be one explanation of the poor PFS rate observed in the Nintedanib arm of the CHIVA trial. Clinical trial identification 2011-006288-23. Legal entity responsible for the study ARCAGY-GINECO. Funding Health ministry grants( PHRC). Disclosure C. Blanc-Fournier: Honoraria (self): Roche. N. Raban: Travel / Accommodation / Expenses: Roche. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche. A. Floquet: Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. J. Alexandre: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. C. Louvet: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca. J. Florence: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Travel / Accommodation / Expenses: Janssen. All other authors have declared no conflicts of interest.

Background Bevacizumab (bev) is approved in Europe (EU) for first line therapy of OC patients (pts). This study aimed to evaluate the use of Bev in real life, with a focus on toxicity. Methods Representative centers in France of French regions and of mode of practice were asked to participate. From 04/13 to 02/15, among the consecutive OC pts treated in each center, were selected those who were newly diagnosed and planned to receive Bev. An independent CRA captured the clinical data at baseline, 6, 12, 18 and 36 months. Results A total of 104 centers participated: Private practice (44%), non-academic hospital (31%), academic (11%), anticancer center (14%). 1290 pts were screened, 500 registered and 468 were evaluable. Pts characteristics at baseline were: median age 65 yrs, antihypertensive therapy (26%), anticoagulant (10%), cardiac history (5%), serous histology (83%), interval surgery (47%), complete surgical debulking (74%) and carboplatin-paclitaxel chemotherapy (98%). Only 3.4% were not FIGO stage IIIB-IV. Pts received Bev at 15 mg/kg (80%) during a median of 18 cycles (10-21) and 7.8% stopped treatment for toxicity. Main toxicity was HTA requiring new therapy (38%), PRES (1.3%), venous thrombosis (5%), proteinuria (9.8%) and nephrotic syndrome (2.6%). Other toxicities mostly reported include low grade epistaxis, gingivorrhagia, arthralgia, headache and dysphonia. Gastrointestinal perforation, fistula, arterial events and grade 3-4 bleeding were very low: 0.2%, 0.8%, 0,1% and 0.2% respectively. No pts developed congestive heart failure nor died from toxicity. Median PFS was 17.4 months (IC95% [16.4-19.1]) and % of pts alive at 3 years was 62.4% (IC95 % [58.1-67.1]). Conclusions In routine practice among French centers, first-line Bev administration is consistent with the EU label in most of the cases. Efficacy and safety in the real life were in line with that reported in trials excepted for a higher incidence of observed HTA and complications, suggesting the importance of increased education on HTA monitoring. Legal entity responsible for the study ARCAGY-GINECO. Funding Roche. Disclosure A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. O. Tredan: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): BMS; Honoraria (self): MSD. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. C. Garnier Tixidre: Honoraria (self): Lilly; Honoraria (self): AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Pfizer. P. Follana: Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Tesaro. C. Levache: Travel / Accommodation / Expenses: Sanofi. E. Pujade-Lauraine: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Tesaro. F. Selle: Honoraria (self): Roche; Honoraria (self): MSD France; Honoraria (self): PharmaMar; Honoraria (self): Tesaro; Honoraria (self): Clovis; Honoraria (self): AstraZeneca; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD France; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca. All other authors have declared no conflicts of interest.

Background NACT is increasingly used as a model to explore new targeted therapy in combination with CT in AOC. Whether an intermediate endpoint could be used as surrogate of PFS and/or OS in pts treated with NACT remains currently elusive and was explored retrospectively in the CHIVA trial. Methods Patients (pts) with FIGO stage IIIC-IV AOC considered as unresectable after laparoscopic (Lap) evaluation were treated with 3 to 4 cycles of platinum-taxane NACT + oral nintedanib before interval debulking surgery (IDS). CT (up to 6 cycles in total) and nintedanib were pursued post-operatively. Were measured response rates at the end of NACT according to RECIST (ORR) with CT-scan and to GCIG with CA125, initial Peritoneal Cancer Index (PCI) and its evolution at IDS, complete surgical resection rate (CC0), pathologic complete or near complete response rate (pCR). These covariates in univariate analysis were included together with other prognostic clinical covariates:age, FIGO stage, ECOG, tumor size, ascitis, neutrophil/lymphocyte ratio, platelet and hemoglobin counts and symptoms (pain). Results A total of 163/188 pts included in the CHIVA trial were evaluable for the analysis. Median follow-up is 42. 6 mos (95% CI: 39.9-44.8). In the univariate Cox model, ECOG, ascitis, neutrophil/lymphocyte ratio, PCI at baseline, RECIST ORR, CC0 at IDS, pCR and treatment arm were correlated (p Conclusions Results from the CHIVA trial suggest that the rate of patients who achieve both a RECIST response to NACT and a complete surgical resection (CC0) at IDS could be used as the main primary endpoint for future NACT trials. Clinical trial identification 2011-006288-23. Legal entity responsible for the study ARCAGY-GINECO. Funding Boehringer Ingelheim. Disclosure F. Lecuru: Advisory / Consultancy, Board: AstraZeneca; Advisory / Consultancy, Proctoring: Intuitive Surgical. E. Pujade-Lauraine: Honoraria (self), Self: AstraZeneca; Honoraria (self), Self: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Tesaro. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. C. Louvet: Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

This case report presents a 57 years-old woman treated for a squamous cell carcinoma of the anal canal by radiochemotherapy and brachytherapy. The particularity of this case lays on the fact that she presented a mediastinal and pleural metastatic evolution three years later, which was also treated by radiochemotherapy, leading to a complete remission of 50 months. This observation is interesting for its curative treatment in metastatic cancer of the anal canal. It also illustrates the radiosensibility of anal canal cancers, including metastatic situations, and raises the contribution of PET-scanner to evaluate the response to treatment and detect a recurrence.

Les carcinomes de site primitif inconnu sont de presentation tre s heterogene. La prise en charge diagnostique d’un patient presentant une maladie metastatique est complexe. Le bilan paraclinique comprend des examens systematiques et des explorations adaptees a la presentation clinique, l’analyse anatomopathologique, l’âge, le sexe et les resultats des examens radiologiques. Ce bilan permet la recherche d’un site primitif et l’identification d’entites anatomocliniques particulie res relevant d’un traitement specifique.

Resume Objectif de l'etude Evaluer les resultats et les facteurs pronostiques carcinologiques et fonctionnels des patients traites a visee curative et conservatrice par irradiation pour un carcinome epidermoide du canal anal dans une equipe privilegiant la curietherapie. Patients et methodes De 1976 a 2005, 286 patients ont ete traites pour un carcinome epidermoide du canal anal par irradiation seule (180 patients) ou par une association concomitante de radiotherapie et de chimiotherapie (106 patients) suivie d'un complement par curietherapie (233 patients) ou par radiotherapie externe (24 patients). Resultats La duree moyenne de suivi etait de 65 mois (1,3–250 mois). Les taux de survie globale et specifique etaient de 66,4 et 78,1 % a cinq ans. Les facteurs pronostiques de la survie specifique etaient la taille tumorale ( 75 %) [RR = 1,9]. Le taux de controle locoregional etait de 71 % a cinq ans (88 % pour les cancers de stade I (43 patients), 69 % pour ceux de stade II (154 patients), 77 % pour ceux de stade IIIA (31 patients) et 60 % pour ceux de stade IIIB (53 patients). Les facteurs pronostiques du controle local etaient la taille tumorale (RR = 2,5), la reponse majeure a la premiere serie de radiotherapie (RR = 2,9). Les facteurs pronostiques de la survie sans colostomie (71 % a cinq ans) etaient la taille tumorale (RR = 1,9) et la reponse majeure a la premiere serie de radiotherapie (RR = 2,4). Conclusion Les resultats carcinologiques et fonctionnels a long terme sont similaires a ceux d'autres series et la curietherapie ne semble pas deletere. Outre l'extension tumorale initiale, la reponse majeure a la premiere serie de radiotherapie est un facteur pronostique retrouve pour la survie specifique, le controle locoregional et la survie sans colostomie.

Kaminsky-Forrett M-C, Weber B, Conroy T, Spaeth D. Brain metastases from epithelial ovarian carcinoma. Background: Brain metastases from epithelial ovarian carcinoma are rare. We reviewed our experience to evaluate the results of different treatments and their prognosis. Discussion is based on a review of the literature. Methods. From 1974 to 1998, eight of 704 patients treated for epithelial ovarian carcinoma at our large cancer center developed brain metastases. The median time before occurrence of brain metastases was 15 months after the diagnosis of the ovarian cancer. Six patients had a single lesion and two had multiple parenchymal lesions. Brain was the only site of disease in one patient, while seven had concomitant dissemination. Seven out of eight patients underwent a treatment for brain metastases. The treatment consisted of either radiotherapy (2 cases), chemotherapy (2 cases), surgery and radiotherapy (1 case), or combined treatment of the three modalities (2 cases). Results. Median survival from diagnosis of brain lesions was 3 months (range 1–12). One patient without treatment died one month later. Survival after complete surgical resection and radiotherapy was 12 months. One patient treated by complete surgical resection followed by radiotherapy and chemotherapy is still alive (+ 5 months). The patient who underwent partial surgical resection followed by radiotherapy and chemotherapy died 7 months later. Two patients treated by radiotherapy alone died, respectively, 2 and 3 months later. After systemic chemotherapy alone, survival times were 1 and 3 months. Conclusions. The prognosis of patients with brain metastases from ovarian carcinoma is poor. A better outcome might be obtained by a multimodal treatment.

Resume Introduction Malgre les progres chirurgicaux et la reduction de mortalite operatoire, le pronostic du cancer de l'œsophage reste defavorable. Le but de cette revue est de faire le point sur l'apport des techniques non chirurgicales, y compris palliatives. Actualites et points forts Les cancers de l'œsophage sont sensibles a la chimiotherapie mais, en maladie metastatique, la duree de reponse est courte et la toxicite significative. De ce fait, une chimiotherapie palliative devrait etre realisee preferentiellement dans le cadre d'un essai clinique. Par ailleurs, la chimiotherapie utilisee seule n'a pas fait la preuve de son efficacite en complement de la chirurgie. Pour les cancers inoperables, la radiotherapie a visee curative, lorsqu'elle est utilisee comme seul traitement, s'est averee inferieure a une radio-chimiotherapie. Les donnees concernant la radio-chimiotherapie preoperatoire sont encourageantes, mais les resultats des essais randomises sont discordants. Une reponse complete histologique a la radio-chimiotherapie constitue toutefois un facteur pronostique favorable. Les protheses metalliques expansives sont devenues le traitement palliatif endoscopique de premiere intention du fait de leur facilite d'implantation et d'une morbidite faible. Elles trouvent leurs indications optimales dans le traitement des fistules ou de la dysphagie des cancers du bas œsophage. Perspectives et projets Les taxoides devraient etre evalues par des etudes randomisees de chimiotherapie ou de radio-chimiotherapie. Les progres de la radiotherapie (hyperfractionnement, augmentation de la dose delivree, curietherapie associee) devraient permettre d'ameliorer le controle local et la survie. La question de l'interet d'une eventuelle chirurgie seconde chez les patients repondeurs a la radio-chimiotherapie reste ouverte.

The olfactory cleft is a narrow chamber located under the cribriform plate and between the turbinate wall of the ethmoidal labyrinth and the corresponding nasal septum. Nasal adenocarcinomas are mostly described as originating in the ethmoid sinus and operated via external approaches. We designed a prospective study on twenty consecutive woodworkers' adenocarcinomas without intracranial extension to determine the precise site of origin of the tumour. All patients were operated under endoscopic endonasal control according to a methodical surgical procedure as follows: 1) debulking of the tumour and identification of the middle turbinate or conchal lamina, 2) exenteration of the ethmoidal labyrinth according to the nasalisation procedure, and 3) exenteration of the olfactory cleft. Endoscopic endonasal surgery showed that woodworkers' adenocarcinomas constantly originated in the olfactory cleft, appearing as polyp-like neoplasms with well-defined bodies. Over a long period of time, they do not invade, but just displace and push out the surrounding structures, i.e. the nasal septum and the turbinate wall. More than the volume of the tumour, the precise location of the pedicle and especially its connection to the cribriform plate could be of major prognosis value.

Sulfur mustard [bis(2-chloroethyl)sulfide; SM] is a chemical warfare agent that produces edema and blister formation with a severe inflammatory reaction. The mouse ear vesicant model for SM injury has been used to evaluate pharmacological agents for countering SM dermal injury. The vanilloid olvanil reduces SM-induced edema and mRNA expression of cytokines and chemokines, suggesting that blocking the inflammatory effects of neuropeptides, such as substance P (SP), may provide protection against SM-induced dermal injury. This study examined SP expression in mice exposed to SM (0.16 mg) on the inner surface of the right ear, with or without olvanil pretreatment at 1, 10, 30, 60, and 360 min following exposure. In naive skin, SP mRNA localization was associated with blood vessels and sebaceous glands. In SM-exposed skin, SP mRNA was also detected in perivascular dermal cells. Immunohistochemical localization of SP protein was observed in the ear skin of naive, SM-, olvanil/SM-, and vehicle-treated mice. Quantification of SP+ perivascular dermal cells revealed that SM exposure led to a significant increase (P < or = 0.05) in SP+ cells over the observed time period. Olvanil pretreatment significantly reduced (P < or = 0.05) the mean number of SP+ cells at 60 and 360 min. This study demonstrates that SP expression could provide an additional endpoint for evaluating the effectiveness of vanilloid drugs on SM-induced skin inflammation.

Background: Initial cytoreductive surgery followed by 6 cycles of platinum-taxane based chemotherapy (Cx) remains the standard of care for advanced OC. For those patients for whom complete resection is deemed difficult to achieve, IDS after 3 cycles of NACx and followed by 3 others cycles represents an alternative strategy. Three antiangiogenic drugs (AAD) have been shown to be active and to prolong progression-free survival (PFS) in first-line treatment of OC after initial debulking surgery: bevacizumab (BEV, GOG218I F. Joly Lobbedez: Roche; N. Pecuchet: I have received honorarium from Novartis, Amgen, GSK and Roche; J. Alexandre: I am a member of an advisory board concerning bevacizumab. All other authors have declared no conflicts of interest.

5500 Background: Insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the growth and apoptosis of cancer cells, and is overexpressed in squamous cell carcinoma of the head and ...

Analysis of high vibrational level data obtained in modulated population spectroscopy leads to more accurate spectroscopic constants for the A 1Σu+ state of Na2. A new method of solving the RKR integrals leads to quick, accurate calculation of the potential.

Molecular absorption lines from a common lower level are intensity modulated by chopped-laser saturation of another line from that level. Populations of some other levels are also modulated by subsequent fluorescence. Both types of modulated lines are free of Doppler broadening. Also, collisional depopulation modulates absorption from rotational levels near the laser-depleted level. In ${\mathrm{Na}}_{2}$, we have identified 113 lines. Analysis of the $A$ state by Kusch and Hessel is confirmed and extended.

Die Einfuhrung flexibler Fertigungsverfahren setzt die Komrnunikationsfahigkeit der in der Fertigung installierten Automatisierungseinrichtungen voraus. In dem von General Motors initiierten und geforderten MAP-Projekt spezifizieren und erproben Hersteller und Anwender von Automatisierungseinrichtungen gemeinsam ein offenes Kommunikationssystem fur die Fertigungsautomatisierung. Der 5-Stufenplan fur die Realisierung, Stand der Arbeiten und anstehende Aufgaben werden erlautert, die fur Einfuhrung und Verbreitung getroffenen Masnahmen werden vorgestellt.