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Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort.Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy.A total of 182 patients were included; 179 were analysed. Most patients received platinium-based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2-positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second-line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One- and 2-year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p 0.0001).Our study showed that treatment strategies in France are based on a succession of doublets, making it possible to offer a second and third line of treatment more often. This treatment strategy must be taken into account for future trials with immunotherapy combinations.

Summary Background Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer. Methods In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0–2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m2 from day 1 to day 3]) or oral topotecan (2·3 mg/m2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , NCT02738346 . Findings Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0−37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9–5·5 vs 2·7 months, 2·3–3·2; stratified hazard ratio 0·57, 90% CI 0·41–0·73; p=0·0041). The most frequent grade 3–4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group. Interpretation Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer. Funding Amgen and the French Lung Cancer Group (Groupe Francais de Pneumo-Cancerologie).

Introduction La nephrectomie partielle (NP) apres embolisation des vaisseaux tumoraux en salle hybride (NPESH) combine l’embolisation des vaisseaux tumoraux et l’enucleation de la tumeur sous coelioscopie dans un meme temps operatoire. L’objectif de cette etude etait d’evaluer l’impact de l’utilisation d’une salle hybride sur la prise en charge des patients traites par chirurgie pour une tumeur localisee du rein. Materiel et methodes Nous avons etudie, via la base de donnees uroCCR, tous les patients consecutifs pris en charge par nephrectomie partielle, dans un centre universitaire pour une tumeur du rein. Pendant la periode 1, de 2011 a mai 2015, les patients ont ete traites par nephrectomie partielle coelioscopique (NPC) ou ouverte (NPCO) classique. Pendant la periode 2, de mai 2015 a mai 2019, les patients ont ete traites par NPESH. Nous avons recueilli les caracteristiques des patients, des tumeurs, les donnees peroperatoires et postoperatoires. Ces donnees ont ete comparees par des tests de Student et du Khi2. Resultats Quatre-vingt-sept NP ont ete realisees pendant la periode 1 et 137 pendant la periode 2. Le score ASA des patients de la periode 2 etait plus eleve (p < 0,0001). La complexite tumorale et la taille tumorale mediane etaient similaires dans les deux groupes (p = 0,852 et p = 0,48). Le taux de complications pour les periodes 1 et 2 etait de 55,2 % et 33,6 % (p = 0,002). Les complications etaient moins severes dans le groupe 2 (p = 0,012). La duree mediane d’hospitalisation etait de 8 et 4 jours pour les periodes 1 et 2 (p < 0,0001). Les marges chirurgicales positives etaient de 2 (2,3 %) et 6 (4,6 %) pour les periodes 1 et 2 (p = 0,713). Discussion L’utilisation de la salle hybride a permis le developpement de la NPESH qui est une technique fiable. Elle semble etre une alternative interessante a la nephrectomie partielle standard en permettant de limiter, le taux de complication et la duree de sejour. Summary Introduction Partial nephrectomy (NP) after embolization of tumor vessels (NPESH) in a hybrid room combines embolization of tumor vessels and enucleation of the tumor under laparoscopy in the same operative time. The purpose of this study was to assess the impact of the use of NPESH in the management of patients treated with surgery for a localized kidney tumor. Material and methods Using the uroCCR database, we included all consecutive patients operated in a university hospital for localized kidney tumor. From 2011 to May 2015, patients were treated by Standard Partial Nephrectomy (NPS) Laparoscopic or Open and from May 2015 to May 2019 by NPESH. We evaluated characteristics of patients, tumors, perioperative data and complications. These data were compared by Student and Khi2 tests. Results 87 NPS were performed during Period 1 and 137 NPS were performed during period 2. The ASA score of patients undergoing NPESH was higher than NPS (P < 0.0001). The tumor complexity and median tumor size were similar in the two groups (P = 0.852 and P = 0.48). The complication rate for NPS and NPESH was 55.2% and 33.6% (P = 0.002). There were less severe complications in the NEPSH group (P = 0.012). The median length of stay was 8 and 4 days for the NPS and NPESH groups (P < 0.0001). Positive surgical margins were 2 (2.3%) and 6 (4.6%) for the NPS and NPESH group (P = 0.713). Discussion NPESH is an efficient technique compared to NPS. It seems to be an interesting alternative to limit renal ischemia, complication rate and length of stay for the management of localized kidney tumors.

2049 Background: Low intensity pulsed ultrasound (LIPU) in conjunction with intravenous microbubbles can transiently and reversibly disrupt the blood-brain barrier (BBB), allowing for an increase in the tissue concentration of chemotherapy agents in the brain. Mass spectrometry data from preclinical models (mouse, swine) showed a > 5x enhancement in carboplatin brain concentrations, which correlated well with the spatial distribution of a Gadolinium (Gd) contrast agent used for magnetic resonance imaging (MRI). Methods: The primary objective of this phase I/IIa study (NCT03744026) was to demonstrate the safety of BBB disruption using LIPU in patients with recurrent glioblastoma. This study was a 3+3 design using escalating numbers (3, 6, 9) of activated 1 MHz ultrasound emitters. Nine patients were treated in the escalation phase and another 12 patients were treated with 9 emitters in the expansion phase. Eligibility included recurrent GBM (any recurrence) with a maximum tumor size of < 70 mm. The SonoCloud-9 device (CarThera, Paris, France) was implanted during tumor debulking/resection surgery and replaced the bone flap, with the device targeting the tumor and surrounding peritumoral brain. The device was activated every four weeks for a duration of 270 seconds, concomitantly with IV DEFINITY microbubbles (10 ml/kg), to disrupt the BBB prior to administration of carboplatin (AUC 4-6). MRI was performed to verify safety and evaluate efficacy of BBB disruption with Gd enhancement. Results: No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with two transient, manageable grade 3 wound infections and one grade 1 acquired meningocele event considered as probably related to the overall procedure. The most frequent neurologic adverse events were grade 1 blurred vision (5%) and dizziness (5%). Conclusions: Significant Gd enhancement was observed after more than 90% of sonication sessions, suggesting effective BBB disruption and carboplatin enhancement. Clinical trial information: NCT03744026.

The incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing sharply. The survival of patients with metastases is usually about a year. However, the occurrence of isolated lung metastases after resection of the primary tumor, although rare, seems to indicate a better prognosis, with an average survival ranging from 40 to 80 months. KRAS, TP53, CDK2NA, and SMAD4 are the most common driver genes in pancreatic adenocarcinoma. Our objectives were to determine whether a link exists between survival and mutations of driver genes in patients with isolated pulmonary metastases. All patients who underwent curative surgery in our institution between 2010 and 2018 were included in the study. From these, we identified patients for whom recurrence was only pulmonary and those with metastases at other sites. KRAS, TP53, CDK2NA, and SMAD4 were analyzed on the primary tumor of patients with pulmonary metastases. Among 233 patients diagnosed with PDAC in our institution over 8 years, 41 (17.5%) underwent curative surgery. Of these, seven (3%) developed isolated pulmonary metastases, 32 developed other metastases, and two did not recur. Median survival was 59 months for patients with isolated lung metastases and 25.3 months for patients with metastases at other sites. An absence of mutations of two driver genes in primary tumors (CDK2NA and SMAD4) was observed in patients with isolated pulmonary metastases. The absence of mutations in the CDK2NA and SMAD4 tumor-suppressor genes in patients with isolated pulmonary metastases contrasts with the commonly observed high rates of driver gene mutations and suggests a link with overall survival.

Purpose: To improve the tumor localization during laparoscopic surgery, we describe an innovative technique involving superselective intra-arterial injection of blue dye in tumoral vessels to color the tumor before surgical enucleation. Materials and Methods: The dye injection was performed at the same time as superselective embolization, immediately before laparoscopic surgery in a hybrid operating room. We used this new treatment sequence on 50 consecutive patients. Results: The selective intra-arterial injection of an emulsion of blue dye and lipiodol was feasible in 46 (92%) cases and well tolerated, followed by superselective embolization of the tumor vessels with glue or coils. The tumor was easily localized during surgery due to the blue coloration. Tumor coloration was not associated with postoperative complication, especially allergic reaction or renal failure. Pathologic analysis of the tumor was not modified by the coloration and all tumors had negative surgical margins. Conclusions: The preoperative dye localization is a feasible, safe, and accurate procedure. This combined approach reduces the difficulty of surgery and increases patient safety.

International audience; BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.

International audience; Background: Gemcitabine is a standard treatment for pancreatic adenocarcinoma. Many mechanisms are involved in gemcitabine resistance, such as reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) membrane transporter, deoxycytidine kinase deficiency, and changes in the signal transmission of mitogen-activity protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K) pathways.Aim:To evaluate the anti-tumor efficiency of blocking signaling pathways using combined action of gemcitabine, everolimus and zoledronic acid versus gemcitabine alone in a mouse subcutaneous xenograft.Methods: Implantations of two human pancreatic adenocarcinoma cells lines (PANC1, K-ras mutated and gemcitabine-resistant; and BxPc3, wild-type K-ras and gemcitabine-sensitive) were performed on male athymic nude mice. The mice received different treatments: gemcitabine, gemcitabine plus everolimus, everolimus, gemcitabine plus zoledronic acid, everolimus plus zoledronic acid, or gemcitabine plus everolimus and zoledronic acid, for 28 days. We measured the tumor volume and researched the expression of the biomarkers involved in the signaling pathways or in gemcitabine resistance.Results: In wild-type K-ras tumors, the combinations of gemcitabine plus everolimus; zoledronic acid plus everolimus; and gemcitabine plus zoledronic acid and everolimus slowed tumor growth, probably due to caspase-3 overexpression and reduced Annexin II expression. In mutated K-ras tumors, gemcitabine plus everolimus and zoledronic acid, and the combination of zoledronic acid and everolimus, decreased tumor volume as compared to gemcitabine alone, inhibiting the ERK feedback loop induced by everolimus.Conclusion: The combination of zoledronic acid and everolimus has an antitumor effect and could increase gemcitabine efficacy.

International audience; CONTEXT: Nivolumab, an anti-PD1immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated.OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area.DOCUMENTARY SOURCE: A systematic review of the literature was performed in PubMed/Medline database and Meeting Library Asco by searching for articles in French or English published on immunotherapy in renal cell carcinoma. The research was limited to abstracts and articles published from 2014to 2017.SELECTION OF TRIALS: We identified 349publications and abstracts and selected 17references from prospective studies.RESULTS: Recent data on checkpoint inhibitors, as well as their combination with tyrosine kinase inhibitors or with anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1in renal cell carcinoma and the latest advances in vaccine therapy have been reported.CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to lead to a paradigm shift in the clinical management of patients. The combination of nivolumab and ipilimumab in the first line will revolutionize the therapeutic management of patients with metastatic renal cell carcinoma.; ContexteEn 2015, le nivolumab, un inhibiteur du point de contrôle immunitaire ciblant les récepteurs PD1a été le premier traitement qui a amélioré la survie globale des patients atteints d’un cancer rénal métastatique après une première ligne. Depuis deux ans un grand nombre d’essais sur les traitements ciblant les lymphocytes T et l’intérêt des associations thérapeutiques est en cours d’évaluation.ObjectifDans cet article, nous nous proposons de résumer le développement clinique des inhibiteurs des points de contrôle immunitaire pour évaluer les avancées de la recherche clinique dans ce domaine.Sources documentairesUne revue systématique de la littérature a été réalisée dans la base de données Meeting Library Asco et PubMed/Medline sur l’immunothérapie dans le cancer du rein. La recherche s’est limitée aux abstracts et articles publiés en langue anglaise ou française de 2014à 2017.Sélection des étudesNous avons identifié 349publications et abstracts et avons retenu 17références correspondant à des études prospectives.RésultatsLes données récentes sur les inhibiteurs de points de contrôle ainsi que leur combinaison avec des inhibiteurs de la tyrosine kinase ou avec les anti-angiogéniques ou avec l’indoléamine 2,3-dioxygénase 1dans le cancer du rein et les dernières avancées par thérapie par vaccination ont été rapportées.ConclusionEn 2017, l’immunothérapie associée avec d’autres traitements entraînera vraisemblablement un changement de paradigme dans la prise en charge clinique des patients. L’association du nivolumab et de l’ipililumab en première ligne va révolutionner le traitement du cancer du rein métastatique.

Purpose In order to limit ischemia and operative bleeding during and after partial nephrectomy we developed a clampless laparoscopic technique, in a hybrid operating room, immediately after super-selective arterial embolization of the renal tumor. We evaluated feasibility and morbidity of this new approach of zero ischemia in partial nephrectomy. Methods We included prospectively 50 consecutive patients treated in a hybrid operating room by this new technique for a localized renal tumor in a university hospital between May 2015 and January 2017. We evaluated perioperative data, postoperative complications, surgical margin and modification of renal function one month after surgery. Renal tumor complexity was evaluated by the R.E.N.A.L. score. Results We included 30 (60%) men and 20 (40%) women with a median age of 61 years (32–84) and a median BMI of 26.85 kg/m2 (20.1–46.4). Tumors were at low, median and high complexity in respectively 11 (22%), 32 (64%) and 7 (14%) cases. Median endovascular and surgical procedures durations were 43 min (16–120) and 80 min (32–150). Median blood loss was 100 mL (10–850). Two Clavien II complications occurred. Median length of hospital stay was 3 days (2–7). Renal function was not modified one month after partial nephrectomy. Median tumor size was 3 cm (1.2–8). Forty tumors (80%) were malignant and surgical margins were positive in one (2%). Conclusions Clampless laparoscopic partial nephrectomy in a hybrid operating room without pedicular dissection after previous tumoral embolization is a technically safe and carcinologically efficient mini-invasive alternative for the management of localized renal tumors.

Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T‐lymphocyte antigen‐4 and those that target programmed cell death‐protein 1, have been approved for use in melanoma, non‐small‐cell lung cancer, and renal cell carcinoma as first‐line or second‐line therapy. Their adverse events are primarily regarded as immune‐related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors. We have identified areas of uncertainty and unmet requirements, including essential interaction between endocrinologists and oncologists. Five issues have been identified for discussion: (1) diagnosis of endocrine toxicity, (2) assessment of toxicity severity, (3) treatment of toxicity, (4) withdrawal or continuation of immunotherapy, (5) preventive action.

Resume L’etude des comorbidites, des facteurs de risque de pathologies organiques ou de la baisse de l’esperance de vie des patients atteints de pathologies mentales, notamment psychotiques, fait l’objet de nombreuses publications. La prise en charge, l’accompagnement, notamment en soins palliatifs, de ces patients, mais egalement le vecu tant des patients que des soignants dans ce type de situation sont plus rarement abordes. A partir de l’histoire de Pierre, patient suivi pour une schizophrenie paranoide et atteint d’un cancer du poumon au pronostic letal a court terme, nous evoquons l’accompagnement, la prise en charge de ces patients dans le cadre de soins palliatifs en secteur specialise psychiatrique et la complexite que cela peut representer, tant pour les patients que pour les equipes soignantes. Ainsi, le lieu de prise en charge mais egalement l’evaluation du comportement ou de la douleur s’averent a l’origine de reflexions complexes que nous discutons. Nous initions par la suite une reflexion autour des enjeux de cet accompagnement singulier avec les notions de travail du trepas et, plus generalement, des enjeux legaux et ethiques autour des refus de traitements dans ce cadre precis.

Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age>18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Analysis used all enrolled patients. Results: 50 patients suffering from PCNSL, including 9 primary vitreoretinal lymphoma (PVRL) were included from July, 2017 to October, 2019. Median age was 72 years (range: 43 to 83), Median PS (ECOG) was 1 (range 0-1). The median number of cycles was 4 (range 1-35). At 84 days from start of treatment, 6 patients responded (4 CR+2PR). Overall, 3 patients whose response was not assessed were considered as failures, and the rates of ORR (CR+PR), stable disease (SD), progressive disease (PD) were 26% (13/50, 8 CR + 5 PR), 10% (5/50), 58% (29/50), respectively. ORR was 29% (12/41) and 11% (1/9) in primary cerebral lymphoma and PVRL respectively. After a median follow-up of 6.7 months (range 0.2-27.4), median PFS was 2.6 months, with 6-month PFS of 29.8% and 6-month OS of 60.4%. In responders, median duration of response was estimated at 10 months (95%CI, 2.7 to 12.5). Grade III and IV toxicities related to the drug were observed in 4 patients (8%) and one patient (2%) respectively. No related toxic death was reported. Conclusion: Pembrolizumab shows moderate activity in relapsed/ refractory PCNSL with acceptable toxicity, supporting further studies evaluating its use in combination therapies. Disclosures Hoang-Xuan: BTG: Consultancy, Research Funding. Houot:Bristol-Myers Squibb: Honoraria; MSD: Honoraria; Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Schmitt:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen: Honoraria. Ahle:Roche: Honoraria; Novartis: Honoraria; Biogene: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria. Bories:Abbvie: Consultancy; Celgen: Consultancy; Gilead: Consultancy; BMS: Honoraria; Novartis: Honoraria. Houillier:BTG: Consultancy.

Low intensity pulsed ultrasound (LIPU), in combination with systemic injection of microbubbles, can be used to transiently disrupt the blood-brain barrier (BBB) and increase brain-drug concentrations. In pre-clinical models, carboplatin can be enhanced by a factor of 5x in the brain using LIPU and increase the survival of GBM-bearing mice. In clinical studies, a single emitter, implantable ultrasound device (SonoCloud-1) was used to disrupt the BBB in 19 rGBM patients prior to carboplatin chemotherapy (NCT02253212). The feasibility of this approach was demonstrated, and safe acoustic parameters were determined. The primary objective of this subsequent Phase 1/2a study (NCT03744026) was to demonstrate the safety of BBB disruption over a larger volume, including the tumor and surrounding peritumoral region using a nine-emitter version of the device (SonoCloud-9). This study was a 3 + 3 design using escalating numbers of activated 1-cm diameter emitters (3, 6, 9). GBM patients at any recurrence, with a maximum tumor size of < 70 mm were included. The SonoCloud-9 device was implanted during tumor debulking/resection surgery and replaced the bone flap. The device was activated every four weeks for 270 seconds, concomitantly with DEFINITY® microbubbles to disrupt the BBB prior to administration of carboplatin. Magnetic resonance imaging was performed to verify safety and the extent of BBB disruption. As of June 2020, the escalation phase of the study (9 patients) was complete, with a median of four monthly cycles of sonication and carboplatin chemotherapy per patient. No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with only a few, transient, and manageable related adverse events. The safety of administration of multiple repeat treatments of BBB opening using nine emitters of the device at an acoustic pressure of 1.03 MPa will be confirmed in an additional 12 patients to be included in the ongoing expansion phase.

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

The management of metastatic renal cell carcinoma (mRCC) has been transformed by the use of targeted therapies, ablative therapies and improved surgical techniques. The objective of this study was to identify therapeutic strategies that resulted in complete remission (CR) and to assess survival of patients in CR. In a prospective database, we included all patients treated for mRCC at a university hospital between 2007 and 2015. CR was defined as the absence of metastasis after a full-body computed tomographic scan. We treated 77 patients with mRCC and experienced a CR in 22 (29 %) patients. Patients in CR had, respectively, synchronous and metachronous metastases in 7 (32 %) and 15 (68 %) cases and unique and multiple metastases in 4 (18 %) and 18 (82 %) cases. All patients were treated with cytoreductive nephrectomy and 21 (96 %) had metastasectomy or percutaneous ablation of their metastases. One patient had a CR after systemic treatment with sunitinib. After a median (range) follow-up since metastatic diagnosis of 35 (1–89) months, 12 patients (55 %) had disease recurrence. The median (range) duration of CR before recurrence was 14 (1–39) months. After recurrence, a new CR was obtained in 7 patients (58 %). At the end of follow-up, 16 patients (73 %) were still in CR, 5 (23 %) were undergoing medical treatment, and 1 patient died during the postoperative course. In the era of targeted-therapies, CRs were obtained with multimodal treatment of metastatic kidney cancer. All patients in CR had a nephrectomy and almost all of them had multiple metastasectomies.

Objectifs L’organisation des soins en onco-urologie est variable d’un centre a l’autre. Nous rapportons notre experience de prise en charge des cancers du rein metastatique dans un service universitaire d’urologie. Methodes Nous avons inclus dans cette etude tous les patients traites pour un cancer du rein metastatique de fevrier 2016 a avril 2018. Les patients etaient pris en charge par l’equipe d’urologie aidee par un oncologue. Les donnees cliniques, les effets secondaires des traitements et les resultats oncologiques etaient reportes prospectivement dans la base de donnees uroccr. Pendant la periode d’inclusion, nous avons pris en charge 247 nouveaux cas de cancer du rein, dont 97 etaient metastatiques (67 etaient metastatiques synchrones et 30 metachrones). Nous avons inclus 74 hommes et 23 femmes, dont l’âge median a l’inclusion etait de 66 ans. Resultats La prise en charge des patients a necessite 231 consultations, 198 hospitalisations de jour et 19 traditionnelles. Une nephrectomie de cytoreduction, une metastasectomie et un traitement ablatif des metastases ont ete realises chez 72, 26 et 23 patients. Nous avons inclus 21 patients dans des essais therapeutiques. Un traitement de premiere, de seconde et de troisieme ligne ont ete proposes chez 50, 21 et 8 patients. En premiere ligne, un inhibiteur de tyrosine kinase a mene a 2 reponses completes, 10 reponses partielles, 24 stabilisations, 8 progressions de la maladie et la survie sans progression etait de 8 mois. Les evenements indesirables etaient de grade 1 ou 2. Une immunotherapie etait souvent proposee en deuxieme ligne. Trente-deux patients ont eu une prise en charge palliative et 35 patients sont decedes. Conclusion La prise en charge globale des cancers du rein metastatique au sein d’un service d’urologie est realisable sans importante modification de l’organisation des soins.

But - Le but de cette etude etait de determiner la tolerance et l'efficacite du l'association gemcitabine/oxaliplatine, en premiere ligne therapeutique, chez des malades porteurs de tumeurs du pancreas metastatiques ou loco-regionalement evoluees. Malades et methodes - Les malades ont beneficie de l'administration de gemcitabine a la dose de 1000 mg/m 2 delivree en 10/mg/m 2 /min au jour 1 suivie au jour 2 par l'administration en 2 heures d'oxaliplatine a la dose 100 mg/m 2; l'intervalle entre chaque cycle etait de 15 jours. Tous les malades avaient une tumeur du pancreas histologiquement prouvee avant l'inclusion dans l'etude. Les malades ont ete traites jusqu'a progression de la maladie ou pendant 12 cycles en l'absence de progression. Un bilan tomodensitometrique etait realise tous les 2 mois pour evaluer l'evolution de la maladie. Resultats - Entre janvier 2001 et janvier 2003, 32 malades ont ete eligibles pour entrer dans l'etude. Le taux de reponse objective a ete de 28,1 % avec 12,5 % de reponse complete. La survie sans progression et la survie globale de l'ensemble des malades ont ete respectivement de 7 et 9 mois. Cependant, la survie globale etait significativement plus importante pour les tumeurs loco-regionalement evoluees par rapport au tumeurs metastatiques (25 mois versus 7 mois, P < 0,0007). Onze malades etaient en vie a 1 an (34,4 %), six a 2 ans (18,8 %) et deux a 3 ans (6 %). Quatorze malades (43,8 %) ont presente un benefice clinique selon les criteres d'Anderson. Conclusion - Ces resultats confirment la bonne tolerance de l'association gemcitabine/oxaliplatine et suggerent que cette association peut avoir une activite anti-tumorale durable pour les tumeurs loco-regionalement evoluees.

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.

The measure number 40 of French Plan against Cancer requires taking into consideration patient's personality and its effect on social relations. However, this psychological impact is different for each cancer. The aim of the present study is to discuss the resulting effects after discovery of breast cancer. Breast cancer is the most common malignancy in women and it's becomes a greater fear of our society. Psychological impact of breast cancer discovery is double: first, it is linked to the bad image of cancer which means suffering and death, then to the good image of breast, symbol of femininity, sexuality and maternity. Considering together these two components can permit to optimize information, listening, help and finally adhesion to treatment. And, if the psycho-oncology is now essential, tomorrow socio-esthetic will come within the framework of more human practice in oncology. Paradoxically, whereas early diagnosis is more frequent and its treatment is improved, breast cancer remains an alarming disease. So, physician can propose since announcement a best utilization of supportive care in order to limit personal and social impact.

Summary Objectives To evaluate long-term survival of patients resected for primarily unresectable colorectal liver metastases downstaged by systemic chemotherapy. Methods Among a group of 82 patients with advanced colorectal cancer, 39 had unresectable liver metastases. After treatment with systemic 3-weekly 5FU/folinic acid/oxaliplatin chemotherapy, the outcome of 11 patients made resectable thanks to chemothe-rapy was compared to that of 28 patients who were not. Criteria for non-resectability consisted of diffuse bilobar invasion with inability to achieve complete resection, unilobar or bilobar invasion plus vascular extension (invasion of inferior vena cava or 2 suprahepatic veins plus continuity with the 3rd) or involvment of hepatic pedicle. Before and after surgery, CT scan evaluation was performed every 2 months. Progression free survival was defined as the time between starting chemotherapy and recurrence of the disease. We used Kaplan-Meier survival curves and log-rank test for comparisons, P values were two-sided and considered significant if Results Progression free survival times were 14 and 6 months, median overall survival were 60 and 18.5 months, respectively, in favour of secondary resected subjects. Conclusion Considering the magnitude of the survival benefit, one may question the need and feasibility for trials to assess more formally the impact of surgery in that setting.

LBA8002 Background: Findings from the SLCG phase II customized chemotherapy trial (NCT00883480) showed that RAP80, a component of the BRCA1 complex, influenced outcome both in p with low BRCA1 expression treated with cisplatin (cis)/gemcitabine (gem) and in p with intermediate/high BRCA1 levels treated with cis/docetaxel (doc) or with doc alone. Together with the French Lung Cancer Group, the SLCG has performed a prospective, randomized phase III trial comparing noncustomized cis/doc with customized therapy in metastatic NSCLC p. A parallel phase II study (ChiCTR-TRC-12001860) is being carried out in China under the auspices of the SLCG. Methods: Since 6 March 2008, 391 p with wild-type EGFR have been randomized 1:1 to the control or experimental arm. p in the control arm receive cis/doc; p in the experimental arm receive treatment according to their BRCA1 and RAP80 levels: p with low RAP80, regardless of BRCA1 levels, cis/gem; p with intermediate/high RAP80 and low/intermediate BRCA1, cis/doc; p with int...