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This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON).In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS).Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 μm and 66.4 μm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p lt; 0.001), respectively.We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.

Purpose The incidence of retinal displacement after rhegmatogenous retinal detachment (RRD) surgery is variable and its clinical consequences are unclear. The aim of this study was to assess the incidence and clinical features of retinal displacement after RRD surgery by using ultra-widefield (UWF) imaging. Methods Retrospective observational study including all consecutive patients who underwent RRD surgery at the Rothschild Foundation Hospital. Postoperative data included the visual acuity and symptoms of visual impairment. Macular retinal displacement occurrence and its features were assessed and measured by using the autofluorescence images. Results A total of 123 eyes were included. UWF fundus autofluorescence revealed the presence of macular retinal displacement in 14 (11%) eyes. All displacements were inferior, with a mean angle of 3.8°. Patients with and without macular displacement did not differ in postoperative visual acuity. The retinal detachment extent and preoperative macular involvement were not significantly associated with the occurrence of retinal displacement. Conclusion In this representative cohort of eyes that underwent RRD surgery with systematic screening for postoperative retinal displacement by UWF fundus autofluorescence, 11% of eyes experienced an inferior retinal shift. As in other cohorts, the presence of metamorphopsia was not associated with the occurrence of retinal shift.

Background Cabozantinib, a potent multi-tyrosine kinases inhibitor (TKI), has demonstrated overall survival (OS) benefit over everolimus in patients previously treated with VEGFR TKI for metastatic Renal Cell Carcinoma (mRCC). The efficacy of systemic treatments after cabozantinib failure has not been investigated. Methods We conducted a retrospective study on patients receiving systemic treatment after cabozantinib failure in heavily pre-treated patient with mRCC. We assessed Time to Treatment Failure (TTF), OS and objective response rate (ORR). Results Among 150 patients treated with cabozantinib in our institution, 56 (37.3%) received subsequent systemic therapy and were eligible for the analysis. IMDC prognostic group was good, intermediate and poor in 11 (19.6%), 24 (42.9%) and 11 (19.6%) patients, respectively. Cabozantinib was administered mainly as a second (41.1%), or third (33.9%) line treatment. axitinib or immune-checkpoint inhibitors were the subsequent treatment in 18 (34.8%) patients for each everolimus (n:16, 28.6%), other angiogenesis inhibitors (n:4, 7.1%) TTF and OS from subsequent systemic therapy after cabozantinib failure were 2.8 months (95%CI 1.9-3.7) and 7.7 months (95%CI 4.4-10.8), respectively. ORR was 8.7% and two patients with axitinib and two patients treated with Immune checkpoint inhibitors achieved a partial response. Conclusions Overall, activity of systemic therapies after cabozantinib was limited. Micro abstract We performed a retrospective analysis on 56 patients with metastatic renal cell carcinoma who received at least 1 systemic treatment line after cabozantinib. Median OS after cabozantinib was 7.7 months, while median TTF after cabozantinib was 2.8 months. Further investigation is needed in this clinical context

PURPOSE: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic. METHODS AND MATERIALS: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination. RESULTS: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8). CONCLUSIONS: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.

Genetic predisposition to acute myeloid leukemia (AML) concerns a minority of adult patients. Development of high-throughput sequencing technologies over the last ten years allowed identification o...

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INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions "(ABL). Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, p

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PurposeIn March 2020, the sudden rise in number of SARS-CoV2 infections in France let the government to impose a strict lockdown during which all non-urgent medical consultations were postponed. From March 17 to May 10, 2020, private medical practices were closed and telemedicine was encouraged. The consequences on ophthalmic care were dramatic with over 90% of scheduled consultations canceled. The aim of this study was to report the consultation during the 2-month strict lockdown in Paris and to analyze its impact on the visual outcomes of patients consulting in the ophthalmology emergency department (OED) Methods :Data of patients who presented to the OED of the A. de Rothschild Foundation Hospital (RFH), a tertiary ophthalmology center in Paris, France, during the lockdown period and its immediate aftermath were analyzed. The results were compared to the same time periods in the years of 2018 and 2019. Four time periods were defined and numbered chronologically: March 17 to May 10, 2018 (Period 1) ; March 17 to May 10, 2019 (Period 2); March 17 to May 10, 2020 (Period 3, the lockdown period); May 11 to June 9, 2020 (Period 4, the post-lockdown period)Results :The number of consultation was reduced by more than 50% during the lockdown period (n=2909 patients) and by 30% during the post-lockdown period (n=2622) when compared to periods 1 (n=7125) and 2 (n=8058) Even though LP4 saw an increase in the number of consulting patients, there was no raise in the rate of severe diseases (12.8% during LP3 vs 11.1% during LP4) and the proportion of patients who were padmitted was statistically similar (4.3% VS 3.6%). Neuro-ophthalmic -diseases were the most common during LP3 and LP4. Neovascular glaucoma were twice as common during post LP4 (p=0.08). We highlighted a significant increase in patients with a graft reject consulting in our OED during the post LP4 (p

PURPOSE The aim of this study was to evaluate the effectiveness of a disposable uniplanar pupil expansion device in small-pupil cataract surgery. METHODS This is a feasibility study carried out at the Rothschild Foundation, Paris, France. Patients undergoing routine cataract surgery with a dilated pupil size

IMPORTANCE: Retinoblastoma (RB) is the most common pediatric intraocular neoplasm. RB is a complex model in which atypical pathogenic variants, modifier genes, imprinting, and mosaicism are known to be associated with the phenotype. In-depth understanding of RB therefore requires large genotype-phenotype studies. OBJECTIVE: To assess the association between genotype and phenotype in patients with RB. DESIGN, SETTING, AND PARTICIPANTS: This single-center, retrospective cohort study, conducted from January 1, 2000, to September 30, 2017, enrolled 1404 consecutive ascertained patients with RB who consulted an oncogeneticist. All patients had their genotype and phenotype recorded. Statistical analysis was performed from July 1, 2018, to December 31, 2018. MAIN OUTCOMES AND MEASURES: RB1 germline and somatic pathogenic variant types, family history, and disease presentation characteristics (ie, age at diagnosis, sex, laterality, and International Intraocular Retinoblastoma Classification group). RESULTS: Among 1404 patients with RB (734 [52.3%] female; mean [SD] age, 20.2 [21.2] months), 866 cases (61.7%) were unilateral and 538 cases (38.3%) were bilateral. Loss of function variants were found throughout the coding sequence, with 259 of 272 (95.2%) somatic pathogenic variants and 537 of 606 (88.6%) germline pathogenic variants (difference, 6.6%; 95% CI, 4.0%-9.2%; P

To collect information about the retinal blood flow variations and other choroidal and retinal parameters during a prolonged effort such as marathon running.Non-randomized prospective cohort study.Patients were recruited through an information campaign at the Rothschild Foundation Hospital (Paris, France). A first visit (V1) was planned in the month before the marathon. All participants underwent blood pressure measurement, fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A). A second visit (V2) was scheduled within one hour of crossing the finish line. The same tests were repeated, using the same equipment.Of the 31 runners who were included, 29 finished the marathon and attended V2. At baseline, various ophthalmological abnormalities were found in 45.2% of the 58 eyes, among which almost a third concerned the optic nerve and a quarter the pachychoroid spectrum. A significant decrease in retinal vascular plexus density was found between V1 and V2 (p0.01). While median macular and retinal nerve fiber layer (RNFL) thicknesses significantly increased after the marathon (p0.01), median choroidal thickness significantly decreased (p0.01). Both systolic and diastolic blood pressures significantly decreased (p0.01 and p=0.021 respectively).Prolonged physical effort impacts the structure and vascularization of the retina and the choroid. Hypoxia and dehydration due to such an effort may induce a low ocular blood flow rate resulting in a choroidal thinning, contrasting with a transient subclinical ischemic edema of the inner retina and optic nerve head.NCT03864380.

International audience; Living tissues, heterogeneous at the microscale, usually scatter light. Strong scattering is responsible for the whiteness of bones, teeth, and brain and is known to limit severely the performances of biomedical optical imaging. Transparency is also found within collagen-based extracellular tissues such as decalcified ivory, fish scales, or cornea. However, its physical origin is still poorly understood. Here, we unveil the presence of a gap of transparency in scattering fibrillar collagen matrices within a narrow range of concentration in the phase diagram. This precholesteric phase presents a three-dimensional (3D) orientational order biomimetic of that in natural tissues. By quantitatively studying the relation between the 3D fibrillar network and the optical and mechanical properties of the macroscopic matrices, we show that transparency results from structural partial order inhibiting light scattering, while preserving mechanical stability, stiffness, and nonlinearity. The striking similarities between synthetic and natural materials provide insights for better understanding the occurring transparency.

International audience; Background: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting.- methods: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model.Results: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers.Conclusion: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH.

Choroidal thickness can undergo considerable variations in response to different substances. The aim of this study was to assess the change in choroidal thickness after the ingestion of taurine and caffeine contained in the Red Bull energy drink.Enhanced Depth Imaging - Spectral Domain Optical Coherence Tomography was used to measure subfoveal choroidal thickness (SFCT) variations in healthy volunteers at several time points after drinking a Red Bull can (25 cl).Forty eyes of 20 volunteers were enrolled. A significant reduction in SFCT (-14 μm, p 0.0001) occurred at 1 h after the Red Bull intake, and was even more important (-20.14 μm, p 0.0001) in eyes with particularly thick choroids (≥ 395 μm). SFCT measurements at 4 h were comparable to baseline.A concomitant ingestion of caffeine and taurine can induce a transient choroidal thinning that is more marked in eyes with thick choroids.NCT02856256.

Introduction Clonal selection is one of the mechanisms leading to therapy-related myeloid neoplasms (TRMN). A preexisting somatic mutation in hematopoietic stem cell (defined as clonal hematopoiesis [CH]) emerges under pressure of chemotherapy or radiotherapy, leading to TRMN development. Most of these mutations belong to the DNA damage response (DDR) pathway as TP53 or PPM1D mutations and are known to confer a dismal prognosis. Recently authorized for the treatment of ovarian cancers (OC), the poly (ADP-ribose) polymerase inhibitors (PARPi) represent a promising targeted therapy. However, by inducing DNA damage and altering DNA repair process, PARP inhibition could represent a challenge for the genetic stability of the healthy tissues. Thus, we assessed the effect of PARP inhibition on the development of CH and TRMN after PARPi treatment for OC (TRMN-PARPi) in combination with chemotherapies. Methods Firstly, we performed a targeted 77 genes mutational analysis using Next Generation Sequencing (NGS) in 13 patients exposed to PARPi without TRMN. Secondly, we retrospectively identified, with the help of the UNIHEM group of Unicancer, 17 patients who experienced TRMN-PARPi. Clinical, biological and survival data were collected and compared to 23 OC patients with TRMN not treated with PARPi (Gustave Roussy institutional database). Lastly, NGS was performed for 3 patients with TRMN-PARPi with sequential sampling. Patient's samples were obtained with informed consent. Results Thirteen OC patients during maintenance treatment with PARPi without TRMN were explored by NGS. Median age at NGS was 64.5 years old (yo) (40.5-75.3). 4/13 (31%) patients harbored BRCA1/2 germline mutation. Time between OC diagnosis and NGS was 4.3 y (1-11.6). The median number of chemotherapy line at PARPi initiation was 2 (1-3). 7 received Olaparib, 5 Niraparib and 1 Rucaparib. The median duration of PARPi treatment before NGS was 4.7 months (1.1-25.1). 12/13 patients experienced hematological toxicities during the PARPi treatment. CH was found in 10/13 (77%) patients (Figure 1a), including mutations of DDR genes in 8/10 (80%). 6/8 (75%) patients had 2 or more gene mutations. Next we identified 17 cases of TRMN occurring during or after PARPi administration for OC (6/17 [35%] t-AML and 11/17 [65%] t-MDS). 12/17 (71%) patients had BRCA germline mutations (7 BRCA1 and 5 BRCA2). All received Olaparib with a median dose of 600mg/d (400-1200). Median duration of Olaparib treatment was 1.7 years (0.2-4.6). TRMN-PARPi were described 1.4 months (0-10.9) after the end of PARPi administration. We compared these patients to a cohort of TRMN post OC not treated by PARPi. Number of therapy lines for OC, time between TRMN and OC diagnosis, median age at TRMN, were, for TRMN-PARPi, 2 (1-8), 5.9 y (0.9-20.8), 64.4 yo (46-74); respectively, compared to 3 (1-8), 4.9 y (1.7-36.9), 59.3 yo (35.7-85.7); (p=ns). TRMN-PARPi cytogenetic was unfavorable for 16/17 (94%) (including 11/17 [65%] complex karyotype) compared to 16/23 (70%) (11/23 [48%] complex karyotype). C Median survival was significantly lower in the TRMN-PARPi group 3.9 months 95%CI [2.0-9.7] and 6.1 months 95%CI [4.1-15.8] respectively, p=0.046, Fig 1b). However, median survival from OC diagnosis was not different between the two groups 6.2 y 95%CI [5.6-NA] for TRMN-PARPi vs 5.6 y 95%CI [5.0-11.6]. NGS was available for 8/17 TRMN-PARPi and revealed mutations in DDR genes in 7/8 patients (6 patients with TP53 mutation, 2 with PPM1D mutation). For 3 patients, we had samples from OC stage, before PARPi administration. We found that mutations from TRMN stage were present at lower frequency, confirming clonal selection by PARPi treatment (Figure 1c). Conclusions Here we described, for the first time, a cohort of TRMN patients previously treated with PARPi for an OC. Intriguingly, most of these TRMN occurred with a short latency at the end of PARPi treatment, with unfavorable cytogenetic and very short OS. Moreover, we found a very high percentage of CH involved in the DDR pathway (62%) in patients under PARPi treatment without TRMN suggesting a potential clonal selection which could lead ultimately to TRMN. PARPi are now indicated in 1rst line high grade OC regardless of BRCA status, which should expand indications. Benefit for OC patients is not questionable; however, caution will be warranted for patients with CH before PARPi treatment, especially implicating DDR mutations. Disclosures Etienne: Incyte: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.

6011 Background: The neoadjuvant setting is an excellent opportunity to study ‘ in vivo’ the biological impact of treatment on tumor cells and the immune TME. Both chemotherapy and anti-angiogenics may have immunomodulatory properties which could prime the TME and increase effectiveness of immunotherapeutic agents. We performed comprehensive multiplexed immune biomarker analyses on paired tumor samples at diagnosis and after 3 cycles of neoadjuvant carboplatin+paclitaxel (CP) +/- the anti-angiogenic tyrosine kinase inhibitor nintedanib (N) in the randomized CHIVA trial. Methods: Patients were randomized 2:1 to CP + N or placebo for 3 cycles prior to interval debulking, samples were evaluable for immune profiling for 124 pts at diagnosis and 107 at surgery from the CHIVA trial. For 86 patients matched paired samples were available. Multiplexed IF or IHC panels were performed for CD4, CD3, CD8, CK, Granzyme B, FOXP3, CD68, CD163 and DC-Lamp. Wilcoxon tests were used to compare measurements. Results: At diagnosis the most abundant cells were CD8+ and CD4+ cells (median=118 and 119cells/mm2, respectively) compared to Foxp3+ TRegs (median=30/mm2). Among the myeloid lineage, the proportion of CD68+ (M1) and CD163+ (M2) macrophages was balanced, while mature dentritic cells (DC) represented

Objectives The aim of this study was to assess efficacy, tolerability, and the impact of comorbidities on outcomes in older women treated by radiation therapy (RT) for non-metastatic breast cancer. Materials and Methods Women aged ≥70 years at diagnosis who received postoperative RT for primary non-metastatic BC between 2003 and 2009 were retrieved from the Institut Curie registry. We calculated the Charlson Comorbidity Index (CCI) for each patient. We analyzed overall survival (OS), progression free survival (PFS), and acute and late toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results A total of 752 patients were included in this study. Median age at diagnosis was 75 years [70–93.3]. With a median follow-up of 7.3 years [0.4–12.9], OS and PFS at 5 years were 87.2% CI95%[84.8–89.8] and 85.7% CI95%[83.1–88.3], respectively. OS at 5 years was statistically different according to the CCI: 90.7% CI95%[87.6–93.9] for a CCI of 0, 85.8% CI95%[81.8–90.1] for a CCI of 1, and 79.1% CI95%[71.1–87.9] for a CCI ≥ 2 (p Conclusion Postoperative RT for non-metastatic BC in older women is effective and well-tolerated. Outcome is impacted by age and comorbidities, which are clear independent prognostic factors.

Contexte Les salaries du secteur de la petite enfance sont exposes a de nombreux facteurs de risque de troubles musculosquelettiques (TMS). Une activite physique reguliere pourrait constituer une action de prevention individuelle efficace en complement des interventions ergonomiques et de formations collectives deja en place. Objectif Rechercher une association entre activite physique reguliere et survenue de TMS chez les agents des structures de la petite enfance d’une collectivite territoriale. Methode En 2017, 235 auxiliaires de puericultures (APu), educatrices jeunes enfants et agents techniques de la petite enfance de la fonction publique territoriale ont ete interroges par auto-questionnaire a l’occasion de leur visite de medecine preventive sur leur activite physique, leurs TMS sur l’annee ecoulee et leur satisfaction au travail. Une association entre les TMS et une activite physique reguliere a ete recherchee dans des modeles de regression ajustes sur des facteurs sociodemographiques et professionnels pour l’echantillon total et chez les APu. Resultats Une tendance etait retrouvee dans tous les modeles en faveur d’une protection de la survenue de TMS par la pratique d’une activite physique reguliere. Elle n’atteignait pas le niveau de significativite et etait la plus marquee dans le modele multivarie de l’echantillon total (OR [IC95 %] = 0,6 [0,3–1,1] ; p = 0,074). Les TMS etaient associes a l’insatisfaction au travail (p = 0,003), et a un accident du travail dans les 12 mois (p = 0,005). La satisfaction au travail etait liee a un IMC Discussion Cette etude n’a pas permis de mettre en evidence d’effet protecteur de l’activite physique reguliere sur les TMS. Pour autant, il est vraisemblable que l’activite physique reguliere puisse representer un moyen complementaire de prevention individuelle contre la survenue des TMS. Elle permettrait une reduction conjointe du surpoids, des arrets et accidents de travail qui pourrait contribuer a une amelioration de la satisfaction au travail et au maintien des capacites fonctionnelles. Elle peut etre proposee par l’employeur sous la forme d’etirements ou echauffements en milieu de travail.

650 Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p < 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients. [Table: see text]

647 Background: During the last decade, 10 agents have been approved for the treatment of patients (pts) with mccRCC, and guidelines have been developed up to 3L. The aim of the study is to describe the potential benefit of therapies beyond 3L in clinical practice Methods: Retrospective data analysis was performed using IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes beyond 3L in mccRCC. Kaplan Meier estimation was applied for progression free survival (PFS) and overall survival (OS) Results: Between 2005 and 2016, 825 (80%) pts had mccRCC and were treated with targeted therapies, of which 517 (63%) had 2L, 271 (33%) had 3L, 145 (18%) had 4L and 75 (9%) had 5L of therapy. Baseline characteristics and treatments are displayed in Table 1. With a median follow-up of 29 months (mo) (min: 20 max: 51), for patients receiving 4L, the median PFS is 5 mo (95%CI 4 – 6) and the median OS is 15.5 mo (95%CI 12 – 21). Pts with International Metastatic Renal Cell Cancer Database Consortium (IMDC) score favourable (18%), intermediate (59%), and poor risk (23%) at 4L initiation had a median OS of 24 mo (95%CI 11 – NR), 16 mo (95%CI 12.6 – 24), and 8 mo (95%CI 6 – 15), respectively (p < 0.0036). Partial response (PR) and stable disease (SD) were achieved in 13% and 56% of 122 evaluable pts. With a median follow-up of 16 mo (min: 13 max: 37) in 5L, the median PFS is 4.5 mo (95%CI 3 – 6) and the median OS is 19.5 mo (95%CI 11 - 28). Pts with a poor IMDC score risk at 5L initiation (33%) had a median OS of 7 mo (95%CI 3 – 10) (p < 0.0001). PR and SD were achieved in 16% and 52% of 55 evaluable pts in 5L Conclusions: The approved agents remain active as 4L or 5L options for mccRCC in pts who can reach this situation. Interestingly, both PFS and OS appear to be very similar in 4L and 5L as compared to 3L. Therefore, we believe that selected pts may derive benefit from these treatments beyond the barriers of regulatory or reimbursement approval [Table: see text]