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Background: Breast cancer (BC) is the most frequent cancer and the second leading cause of cancer death for women. Although there is a need of new treatments to improve BC outcome, patients with BC are still under-represented in early phase trials, possibly because of the availability of numerous approved treatments and widely recruiting phase II and III trials. We aim to characterize the molecular profile, outcome and prognostic factors of patients with BC treated in a phase I trial at our institution. Methods: We retrospectively analyzed medical records of every BC patients treated consecutively in a phase I trial in the Early Drug Development Department (DITEP) at Gustave Roussy Cancer Center. Multivariate logistic regression models were used to determine the association between known prognostic factors such as ECOG, LDH or albumin levels, number of previous lines of treatment, metastatic sites and duration of treatment. When available, molecular profile was also reviewed. Results: Between April 1st 2008 and December 31th 2021, 4682 patients were enrolled and treated in a phase I trial in our department. Among them, 272 were treated for BC (5.8%): 271 women and 1 man, in 74 different trials. The median number of BC patients treated per year was 16.5 (min 1; max 33). Median time between consented date and C1D1 was 14 days (min 1; max 63). Median age at C1D1 was 50 years old (min 24; max 82). 5 patients (1.8%) were treated in an adjuvant setting (therapeutic vaccine) while all the others were metastatic. 12 patients (4.5%) had brain metastases and 127 patients (47.6%) had liver metastases. 186 patients (70%) had only 1 or 2 metastatic sites, and 81 (30%) had three or more sites. Triple negative was the most common subtype, representing 132 patients (48.5%), 125 (46%) were ER+ and 15 (5.5%) Her2+. Patients received a median number of 3 prior lines before enrollment (min 0; max 19). Overall, only 78 patients (28%) had a genetic testing: 30.7% had a germline BRCA1/2 mutation. 146 patients (54%) had a molecular profile (liquid biopsy or tissue sample) before their enrollment and among them 32,9% were oriented in a trial according to their specific profile. Regarding the type of treatments received: 21.7% were immunotherapy, 73.6% were targeted therapies (46.7% in monotherapy, 26.9% in different combinations with immunotherapy, chemotherapy, radiotherapy or endocrine treatments), 2.9% were chemotherapy and 1.8% endocrine therapy. The overall response rate was 11.1% (0.4% complete response, 10.7% partial response, 37.5% stable disease, 43.8% progressive disease and 7.6% not evaluable). Main reasons for discontinuation of treatment were: progressive disease (80.5%), toxicity (9.6%) and end of trial (6.6%). Median duration of treatment was 2 months (min 0; max 44), only 28.6% of patients were still treated after 3 months of trial and 10% at 6 months. At data cut off (June 21st 2022) median overall survival was 11 months. All patients had discontinued the trial by the time of the analysis: median number of lines of subsequent treatment was 2 (min 0; max 10) and 31 patients (11%) were enrolled in another phase I trial in our center. In a multivariate analysis, there was no prognostic factor associated with duration of treatment whether it was albumin (p=0.76) or LDH levels (p=0.68), ECOG (p=0.67), number of prior lines of treatment (p=0.79) or number of metastatic site (p=0.05). Conclusion: These results are consistent with prior published data as only few patients with BC are addressed for inclusion in a phase I trial, despite response rates and survival rates similar to other phase I patients. We did not find any specific factor associated with duration of treatment. It is likely that a thorough molecular profile could open more treatment options and access to phase I trials. Citation Format: Lauren Seknazi, Arthur Geraud, Vincent Goldschmidt, Capucine Baldini, Stéphane Champiat, Christophe Massard, Sophie Postel-Vinay, Aurelien Marabelle, Rastilav Bahleda, Antoine Hollebecque, Cristina Smolenschi, Anas Gazzah, Jean-Marie Michot, Patricia Martin-Romano, Aurore Vozy, Perrine Vuagnat, François-Xavier Danlos, Arnaud Bayle, Linda Mahjoubi, Barbara Pistilli, Yohann Loriot, Santiago Ponce-Aix, Kaissa Ouali. COBRA: Characteristics and Outcomes of patients with BReast cancer in phAse I trials at Gustave Roussy Cancer center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-02.

Research aim and purposeThe benefits of Electronic Patient -Reported Outcomes (e-PRO) for telemonitoring are well established, allowing early detection of illnesses and continuous monitoring of patients. The primary objective of the PROTECTY study was to assess the compliance with patient use of the telemonitoring platform Cureety. An exploratory objective was to assess if the first-month health status is a prognostic factor of progression free-survival (PFS) and overall survival (OS) for prostate cancer patient.MethodsThis prospective study was conducted at the Military Hospital Bégin on prostate cancer patients. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluates the health status of the patient based on the reported adverse events, with a classification into 2 different states: Good Health Status (GHS) and Poor Health status (PHS).ResultsSixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 74.0 (range 58.0–94.0). 78% presented a metastatic stage, and the most represented cancer was mHSPC. Overall, 2,457 questionnaires were completed by the patients, 4.0% resulted in a health classification in to monitor or critical state. 87% of patients were classified in the GHS group. The compliance was 72% in the overall population during the first month, 71% in GHS group and 75% in PHS group. The median follow-up was 8 months. PFS at 6 months was 84% in GHS group vs. 57% in PHS group, p = 0.19. OS at 6 months was 98% in GHS group vs. 83% in PHS group, p = 0.31.ConclusionsOur study showed that compliance was satisfactory. The feasibility of remote monitoring for prostate cancer patients means that they should benefit from its implementation. Our study is also the first to assess the correlation between treatment tolerance and survival. The initial results suggest that e-PRO assessment could help identify in the early stages the patients that require further health assessment and potential therapeutic changes. While further follow-up of more patients will be required, our study highlights the importance of e-PRO in cancer patient care.

Background: Talazoparib (TALA) is a highly potent PARP inhibitor that has demonstrated clinical benefit in the phase III EMBRACA trial for patients with germline BRCA1 or BRCA2-mutation and a locally advanced or metastatic HER2 negative (HER2-) breast cancer (BC). Methods: ViTAL is an ambispective, multi-center longitudinal, phase IV study that aims to ensure the effectiveness and safety of TALA in the real-world setting among patients with locally advanced or metastatic HER2- BC, with somatic or germline BRCA mutation (sBRCA or gBRCA). This study includes two cohorts: - Cohort 1: patients treated through the French Early Access Program from November 2018 to September 2019. Inclusion of patients with sBRCA mutation was allowed. - Cohort 2: patients treated according to the European Marketing Approval granted 21/09/2021. The primary endpoint is Time to Treatment Discontinuation (TTD) for TALA defined as Time between the date of first dose of TALA and the date of last dose or death. Results: We present the results of Cohort 1 in which includes 85 patients. Patients’ characteristics are as follows: median age 50 years; 46% triple negative BC and 54% ER+ BC; 47% BRCA1-mutated and 53% BRCA2-mutated; 94% gBRCA and 6% sBRCA; 95% ECOG PS 0 or 1; 31% premenopausal status; 40% de novo metastatic BC (mBC). Visceral, bones and central nervous system metastases were found in 61%, 54% and 11% of patients, respectively. No breast or ovarian cancer in first degree relative was found in 35 patients (41%). The median number of prior cytotoxic regimen was 2, 15% were chemo-naïve for mBC; 35% received prior platinum in the neoadjuvant, adjuvant or metastatic setting. For patients with ER+/HER2- mBC the median number of prior endocrine therapy was 2 and 74% of these patients received a CDK4/6 inhibitor prior to TALA. The median follow-up was 17.4 months [range 15.7-20.5]. Of 85 treated patients, 66 patients (78%) experienced permanent discontinuation of TALA due to progressive disease (88%), toxicity (8%), cancer-related death (3%), or other reasons (1.5%). The median TTD for TALA was 9.0 months [range 6.0-11.0] with 35% of patients still in under treatment at 12 months. At least one adverse event (AEs) was recorded in 71% of patients. Hematologic AEs (any grade) occurred in 44% of patients (anemia for 26%, thrombocytopenia for 9%, neutropenia for 8%). The most common non-hematologic AEs were alopecia (6%) and asthenia (5%). Related serious hematologic AEs occurred in 7 (8%) patients including 6 (7%) with anemia. Related serious non-hematologic AEs (vomiting, pyelonephritis) were seen in 2 patients (2%). AEs associated with temporary drug interruption, dose modification and permanent drug discontinuation occurred in 32 (38%), 16 (19%), and 5 (8%) patients respectively. After discontinuation of TALA, 83% of patients received a subsequent treatment with a TTD of 2.4 months [range 1.7-3.3]. The most common subsequent treatments were non-platinum chemotherapy (64%) and platinum therapy (24%). Conclusions: The TTD of 9 months is consistent with the outcomes and safety results of the EMBRACA study. ViTAL, the first real-word study with TALA confirms its interest in locally advanced or metastatic HER2- BC. Analysis of Cohort 2 will occur when data are mature. (Ref Litton JK, Rugo HR, Ellt J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018; 379:753-763. Citation Format: Delphine Loirat, Marie Duboys de Labarre, Christine Essner, Ioana Hrab, Jean-Christophe Thery, Christelle Jouannaud, Cristian Villanueva, Perrine Vuagnat, Pauline Soibinet-Oudot, Anne Creisson, Audrey Mailliez, Jean-Loup Mouysset, Laura Salabert, Nadine Dohollou, Jean-David Fumet, Thibault De La Motte Rouge, Jean-Michel Vauthier, Maylis Decrop, Pascal Pujol. Phase IV study evaluating effectiveness and safety of talazoparib in patients with locally advanced or metastatic HER2 negative breast cancer and a BRCA1 or BRCA2 mutation (ViTAL) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-28.

Introduction Studies regarding coronavirus disease 2019 (COVID-19) were mainly performed in the initial wave, but some small-scale data points to prognostic differences for patients in successive waves. We therefore aimed to study the impact of time on prognosis of ICU-admitted COVID-19 patients. Method We performed a national retrospective cohort study, including all adult patients hospitalized in French ICUs from March 1, 2020 to June 30, 2021, and identified three surge periods. Primary and secondary outcomes were in-hospital mortality and need for invasive mechanical ventilation, respectively. Results 105,979 critically ill ICU-admitted COVID-19 patients were allocated to the relevant three surge periods. In-hospital mortality for surges 1, 2, and 3 was, respectively, 24%, 27%, and 24%. Invasive mechanical ventilation was the highest level of respiratory support for 42%, 32%, and 31% (p Conclusion In this large database of ICU patients admitted for COVID-19, we observed a decline in invasive mechanical ventilation, vasopressors, and RRT use over time but a high risk of in-hospital death. Vaccination was identified as protective against the risk of invasive mechanical ventilation and in-hospital death.

Immunotherapy alone or in combination has clearly improved the survival of patients with lung cancer. However, it may also be responsible for adverse events impacting these patients' quality of life. The ToxImmune study aims to identify prognostic factors that can help to predict immune-related adverse events.We included all patients aged 18 years and older who had received at least one dose of immune checkpoint inhibitors, with or without other therapy, between June 2015 and December 2020 and were diagnosed with nonsmall cell lung cancer or small-cell lung cancer. Patients' baseline demographic characteristics, biological blood markers, and imaging by PET-scanner were collected from electronic medical records. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Events V.5.0).Sixty-four patients were included, of whom 60 (94%) presented at least one irAE. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and grade 3-4 was 34% and 8% respectively. Female sex, Primitive Tumor Standardized Uptake Value Max (SUVmax)5, number of metastases ≥3 and immunotherapy received after the first line were found to be significant risk factors for immune-related adverse events. Based on the number of risk factors, the ToxImmune score predicts the risk of having a grade ≥2 adverse event (primitive tumor SUV ≥ 5 = 0 vs. primitive tumor SUV5 = 1, number of metastases3 = 0 vs. number of metastases ≥3 = 1 and L1 = 0 vs. L1 ≥ 1). The incidence of grade ≥2 adverse events was 20%, 55% and 90% with ToxImmune scores 0, 1 and = 2 respectively (p = .003). Median progression-free survival (PFS) times were 19.2 months, 6.64 months and 2.63 months for ToxImmune scores 0, 1 and = 2 respectively, p = .13. Median overall survival times were 22.6 months, 16.4 months and 9.8 months for ToxImmune scores 0, 1 and ≥2 respectively, p = .24. The disease control rate (DRR) was 78% in ToxIummune score 0 group, and 50% in ToxImmune score 1 and ≥2 groups (p = .363).The ToxImmune score, which is grounded on objective clinical parameters, indicates that cases with a high score had an advanced threat of severe adverse events. The ToxImmune score could therefore be used in clinical practice to identify patients treated for lung cancer with immunotherapy and at risk of severe AE.

International audience; In this study, a practical and straightforward synthesis of β-( E )-trifluoromethylstyrenes by ruthenium-catalyzed C-H bond activation was developed. The readily available and inexpensive 2-bromo-3,3,3-trifluoropropene (BTP), a non-ozone depleting reagent, was used as a reservoir of 3,3,3-trifluoropropyne. With this approach, the monofunctionalization of a panel of heteroarenes was possible in a safe and scalable manner (23 examples, up to 87% yield). Mechanistic investigations and density functional theory (DFT) calculations were also conducted to get a better understanding of the mechanism of this transformation. These studies suggested that 1) a cyclometallated ruthenium complex enabled the transformation, 2) this latter exhibited high efficiency in this transformation compared to the commercially available [RuCl 2 ( p -cymene)] 2 and 3) the mechanism proceeded through a bis-cyclometallated ruthenium intermediate for the carboruthenation step

Chronic wounds, ie, non-healing ulcers, have a prevalence of ~1% in the general population. Chronic wounds strongly affect the quality of life and generate considerable medical costs. A fraction of chronic wounds will heal within months of appropriate treatment; however, a significant fraction of patients will develop therapy-refractory chronic wounds, leading to chronic pain, infection, and amputation. Given the paucity of therapeutic options for refractory wounds, cell therapy and in particular the use of adipose-derived stromal cells (ASC) has emerged as a promising concept. ASC can be used as autologous or allogeneic cells. They can be delivered in suspension or in 3D cultures within scaffolds. ASC can be used without further processing (stromal vascular fraction of the adipose tissue) or can be expanded in vitro. ASC-derived non-cellular components, such as conditioned media or exosomes, have also been investigated. Many in vitro and preclinical studies in animals have demonstrated the ASC efficacy on wounds. ASC efficiency appears to occurs mainly through their regenerative secretome. Hitherto, the majority of clinical trials focused mainly on safety issues. However more recently, a small number of randomized, well-controlled trials provided first convincing evidences for a clinical efficacy of ASC-based chronic wound therapies in humans. This brief review summarizes the current knowledge on the mechanism of action, delivery and efficacy of ASC in chronic wound therapy. It also discusses the scientific and pharmaceutical challenges to be solved before ASC-based wound therapy enters clinical reality.

Immunotherapy with immune checkpoint blockers (ICB) represents a valid therapeutic option in older patients for several solid cancer types. However, most of the data concerning efficacy and adverse events of ICB available are derived from younger and fitter patients. Reliable biomarkers are needed to better select the population that will benefit from ICB especially in older patients who may be at a higher risk of developing immune-related adverse events (irAEs) with a greater impact on their quality of life. The Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/[leukocytes − neutrophils]) and lactate dehydrogenase (LDH) and is correlated with outcomes in patients treated with ICB in non-small-cell lung cancer. We aimed to assess the impact of LIPI in ICB outcomes in a dedicated cohort of older patients. The primary objective was to study the prognostic role of LIPI score in patients aged 70 years or above in a real-life population treated with anti-programmed death-(ligand)1 (anti PD-(L)1). dNLR and LDH were collected in a prospective cohort of patients aged 70 years or above treated with PD-(L)1 inhibitors with metastatic disease between June 2014 and October 2017 at Gustave Roussy. LIPI categorizes the population into three different prognostic groups: good (dNLR ≤ 3 and LDH ≤ ULN—upper normal limit), intermediate (dNLR > 3 or LDH > ULN), and poor (dNLR > 3 and LDH > ULN). Anti PD-(L)1 benefit was analyzed according to overall survival (OS), progression free survival (PFS), and overall response rate (ORR) using RECIST v1.1. criteria. In the 191 older patients treated, most of them (95%) were ICB-naïve, and 160 (84%) had an ECOG performance status of 0–1 with a median age at ICB treatment of 77 (range, 70–93). The most common tumor types were melanoma (66%) and non-small-cell lung cancer (15%). The median follow-up duration was 18.8 months (95% CI 14.7–24.2). LIPI classified the population into three different groups: 38 (23%) patients had a good LIPI score, 84 (51%) had an intermediate LIPI score, and 43 (26%) had a poor LIPI score. The median OS was 20.7 months [95% CI, 12.6–not reached] compared to 11.2 months [95% CI, 8.41–22.2] and 4.7 months [95% CI, 2.2–11.3] in patients with a good, intermediate, and poor LIPI score, respectively (p = 0.0003). The median PFS was 9.2 months [95% CI, 6.2–18.1] in the good LIPI group, 7.2 months [95% CI, 5.4–13] in the intermediate LIPI group, and 3.9 months [95% CI, 2.3–8.2] in the poor LIPI group (p = 0.09). The rate of early death (OS < 3 months) was 37% in the poor LIPI group compared to 5% in the good LIPI group (

Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts.Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method.Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups.Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs.

International audience; Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated.Methods: Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available.Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4–4.7]) and 11.3 months (95% CI [8.3–25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a TOP2A/ERBB2 co-amplification. No statistically significant correlation was found between outcome and TOP2A/ERBB2 co-amplification.Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

Mesenchymal stem cell-based therapies are emerging as innovative approaches to treat chronic wounds. A common administration route used in clinical trials consists of local injections leading to uncontrolled/sub-optimal delivery. This study reports a comprehensive pre-clinical evaluation program on the mechanism of action, efficacy and safety of an easy-to-use patch that concentrates Adipose-derived Stem Cells (ASCs) in a clinical-grade sponge of porcine crosslinked-gelatin. ASCs were prepared from the fat of ischemic patients. Transcriptome and proteome of ASC-patches and ASC monolayers were assessed by microarrays, bio-arrays and mass spectrometry. Tumorigenesis was investigated in immunosuppressed mice according to the European Pharmacopeia. Angiogenesis was assessed in vivo in the chick chorioallantoic membrane model. Efficacy of the ASC-patch was tested in a rat model of ischemic full-thickness skin defect. Cell stability was assessed by luminescence using ASC-patches generated from ASCs stably transduced with firefly luciferase. ASCs from ischemic patients upregulated the transcription of multiple genes involved in skin wound healing when cultured within the ASC-patch formulation. The patch was not only a concentrator, but also a reservoir of both ASC-derived regenerative factors and sponge-derived soluble fragments having healing capacity. The secretome of the ASC-patch promoted dermal fibroblast survival and epidermal epithelialization. No tumor formation was observed in immunodeficient Nude mice subcutaneously transplanted with the ASC-patch. Transplanted patches were early invaded by new vessels in vivo, and a marked angiogenesis was confirmed in two independent animal models. Finally, ASC-patches prepared from syngeneic rats promoted faster healing and re-vascularization of full-thickness skin defects in a rat animal model. Of note, ASCs were viable and locally stable for at least two weeks in vivo. We provide here compelling pre-clinical evidence that patches concentrating ASCs within crosslinked gelatin may represent a convenient and effective tool for the management of chronic wounds.

Background: The TOP2A and ERBB2 genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by TOP2A), has demonstrated clinical activity in metastatic breast cancer (MBC). However, the clinical benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not been evaluated.Methods: Patients treated at Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in-silico search. Trained medical oncologists retrospectively assessed progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as a duration of at least 6 months), 6 months clinical benefit rate and toxicity. Co-amplification of ERBB2 and TOP2A was assessed by shallow whole genome sequencing on tumor tissue whenever available.Results: Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Three patients had a complete response while 12/40 (30%) had a clinical benefit. Only 3 patients stopped treatment for toxicity. Median PFS in the population with and without TOP2A/ERBB2 co-amplification was respectively 4.7 months (95% CI [2.3-NA]) and 2.9 months (95% CI [1.2-NA]; p=0.36).Conclusion: Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.

Background Early phase clinical trials usually include patients with advanced disease who have failed standard therapies. Early palliative care for these patients has shown to improve quality of life and even survival. PALLIA 10 score (ranging from 1 to 10) is a tool developed by the French Palliative Care Society to identify the best time to introduce palliative care. Methods We assessed the PALLIA 10 score and other prognostic factors (age, ECOG, Royal Marsden Hospital (RMH) score, LDH and albumin levels, number of prior systemic treatments and metastatic sites) in patients enrolled in phase I trials at Gustave Roussy Cancer Center prospectively during 2 periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the PALLIA 10 score was done during 15 days by a member of the palliative care unit in C2. A PALLIA 10 > 3 motivated a dedicated palliative care consultation. Results From July 1st 2018 to November 1st 2018 (C1) and from December 1st 2020 to April 16th 2021 (C2), a total of 86 patients were assessed in C1 and 302 in C2. No difference was observed between the two cohorts regarding prognostic factors. Median PALLIA 10 was also similar and very low (median 1, range 1-5 in C1 and 1-8 in C2). On C1 and C2, 12% and 5% of patients had a dedicated palliative consultation. Overall, 77% and 74% of patients in C1 and C2 were still alive beyond 3 months after discontinuation of the trial (p=0.78), followed by at least one subsequent treatment in 63% and 70% of pts. In C2, assessment of PALLIA 10 score was significantly different between palliative care physician (median 5, range 3-8), phase I physician (median 1, range 1 -6) and phase I nurse (median 3, range 1-8) (p

Additional file 2: Supplementary Fig. 2. Evolution of plasma soluble cytokines between after the first pembrolizumab infusion, between cycle 1 and cycle 2. Tests were paired Wilcoxon signed rank test (paired samples) (representation of p-value: ns > 0.05, * ≤ 0.05). Abbreviations: PD = Progressive disease; SD = Stable disease; PR = Partial response; Ninte. = nintedanib; DCB = Durable clinical benefit; D-7 = day − 7; C1D1 = Cycle 1 day 1; MIP = Macrophage Inflammatory Protein; MCP1 = Monocyte Chemoattractant protein; MDC = Macrophage Derived Chemokine.

Additional file 3: Supplementary Fig. 3. Illustration of multiplex chromogenic staining dedicated to myeloid cells. A Representative image displays a 500umx669um image after multispectral imaging and spectral unmixing (merged image). B All markers. C CD68 (pseudocoloured white). D DAPI nuclear marker (pseudocoloured blue). E CD163 (pseudocoloured green). F DC-LAMP (pseudocoloured magenta). G IDO1 (pseudocoloured yellow). H CD163 measurement was undertaken using Inform v2.2 software segmentation by pixel-based threshold. I CD163+ density in biopsies of patients with DCB or without DCB at baseline and C2D1 were not significantly different (Wilcoxon rank-sum test).

Background We aimed to determine the safety and efficacy of nintedanib, an oral anti-angiogenic tyrosine kinase inhibitor, in combination with pembrolizumab, an anti-PD1 immunotherapy, in patients with advanced solid tumors (PEMBIB trial; NCT02856425). Methods In this monocentric phase Ib dose escalation cohort, we evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg bid [bis in die, as twice a day]; DL2 = 200 mg bid, oral delivery) in combination with pembrolizumab (200 mg Q3W, IV). Patients received a 1-week lead-in dose of nintedanib monotherapy prior starting pembrolizumab. The primary objective was to establish the maximum tolerated dose (MTD) of the combination based on dose limiting toxicity (DLT) occurrence during the first 4 weeks. Secondary objectives were to assess the anti-tumor efficacy and to identify the associated immune and angiogenic parameters in order to establish the recommended nintedanib dose for expansion cohorts. Flow cytometry (FC), Immuno-Histo-Chemistry (IHC) and electrochemiluminescence multi-arrays were prospectively performed on baseline & on-treatment tumor and blood samples to identify immune correlates of efficacy. Results A total of 12/13 patients enrolled were evaluable for DLT (1 patient withdrew consent prior receiving pembrolizumab). Three patients at 200 mg bid experienced a DLT (grade 3 liver enzymes increase). Four patients developed grade 1–2 immune related adverse events (irAE). Eight patients died because of cancer progression. Median follow-up was 23.7 months (95%CI: 5.55–40.5). Three patients developed a partial response (PR) (ORR = 25%) and five patients (42%) had durable clinical benefit (DCB), defined as PR or stable disease (SD) ≥ 6 months. At baseline, patients with DCB had higher plasma levels of Tie2, CXCL10, CCL22 and circulating CD4+ PD1+ OX40+ T cells than patients without DCB. Patients with DCB presented also with more DC-LAMP+ dendritic cells, CD3+ T cells and FOXP3+ Tregs in baseline tumor biopsies. For DCB patients, the nintedanib lead-in monotherapy resulted in higher blood CCL3, Tregs and CCR4+ CXCR3+ CXCR5− memory CD4 T cells. After the first pembrolizumab infusion, patients with DCB showed lower IL-6, IL-8, IL-27 plasma levels. Conclusion Nintedanib 150 mg bid is the recommended dose for combination with pembrolizumab and is currently investigated in multiple expansion cohorts. Early tumoral and circulating immune factors were associated with cancer outcome under nintedanib & pembrolizumab therapy. Trial registration ClinicalTrials.gov, NCT02856425. Registered August 4, 2016 — Prospectively registered.

International audience; The synthesis of bench-stable electrophilic thiocyanating reagents was depicted in two steps from readily available starting materials in good yields. These newly-designed electrophilic reagents were successfully applied for the thiocyanation of different nucleophiles under mild and transitionmetal-free conditions. Preliminary experiments for the asymmetric C3-thiocyanation of an oxindole derivative were also conducted leading to the expected product with no induction of chirality, although opening possibilities for accessing chiral compounds.

Urothelial carcinoma (UC) is the second most frequent urogenital malignancy with high incidence in the United States and Europe. Despite poor prognosis, new treatments have emerged with great efficacy and safety such as immune checkpoint inhibitors. Durvalumab, an anti Programmed Death Ligand 1, has been given breakthrough in UC in 2017 in patients who have disease progression during or following platinum-containing chemotherapy or who have disease progression

ObjectivePhase I clinical trials usually include patients with advanced disease who have failed standard therapies and should benefit from early palliative care. We try to assess whether PALLIA 10, a score developed in France to help identify patients who might benefit from a palliative care referral, could be used in a phase I department trial.MethodsWe assessed PALLIA 10 score and other prognostic factors in patients enrolled in phase I trials at Gustave Roussy Cancer Center prospectively during two periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the PALLIA 10 score was done in C2 by a palliative care specialist and a nurse.ResultsFrom 1 July 2018 to 1 November 2018 (C1) and from 1 December 2020 to 16 April 2021 (C2), 86 patients were assessed in C1 and 302 in C2. Median PALLIA 10 was very low in both cohorts (median 1, range 1–5 in C1 and 1–8 in C2). On C1 and C2, 12% and 5% of patients had a dedicated palliative consultation. In C2, assessment of PALLIA 10 score was significantly different between palliative care physician (median 5, range 3–8), phase I physician (median 1, range 1–6) and phase I nurse (median 3, range 1–8) (pConclusionMedian PALLIA 10 score was low when assessed by the phase I physician, which suggests the need for a better tool and appropriate clinician’s education to implement early palliative care in clinical practice and trials.

BackgroundClinical studies have highlighted the efficacy of anti-programmed death 1 (αPD-1) monoclonal antibodies in patients with DNA mismatch repair-deficient (MMRD) tumors. However, the responsiveness of MMRD cancers to αPD-1 therapy is highly heterogeneous, and the origins of this variability remain not fully understood.Methods4T1 and CT26 mouse tumor cell lines were inactivated for the MMRD geneMsh2,leading to a massive accumulation of mutations after serial passages of cells. Insertions/deletion events and mutation load were evaluated by whole exome sequencing. Mice bearing highly mutated MMRD tumor or parental tumors were treated with αPD-1 and tumor volume was monitored. Immune cell type abundance was dynamically assessed in the tumor microenvironment and the blood by flow cytometry. Neutrophils were depleted in mice using αLY6G antibody, and regulatory T (Treg) cell population was reduced with αCD25 or anti-cytotoxic T-lymphocytes-associated protein 4 (αCTLA-4) antibodies. Patients with MMRD tumors treated with immune checkpoint blockade-based therapy were retrospectively identified and neutrophil-to-lymphocyte ratio (NLR) was evaluated and examined for correlation with clinical benefit.ResultsBy recapitulating mismatch repair deficiency in different mouse tumor models, we revealed that elevated circulating tumor-induced neutrophils (TIN) in hypermutated MMRD tumors hampered response to αPD-1 monotherapy. Importantly, depletion of TIN using αLy-6G antibody reduced Treg cells and restored αPD-1 response. Conversely, targeting Treg cells by αCD25 or αCTLA-4 antibodies limited peripheral TIN accumulation and elicited response in αPD-1-resistant MMRD tumors, highlighting a crosstalk between TIN and Treg cells. Thus, αPD-1+αCTLA-4 combination overcomes TIN-induced resistance to αPD-1 in mice bearing MMRD tumors. Finally, in a cohort of human (high microsatellite instability)/MMRD tumors we revealed that early on-treatment change in the NLR ratio may predict resistance to αPD-1 therapy.ConclusionsTIN countered αPD-1 efficacy in MMRD tumors. Since αCTLA-4 could restrict TIN accumulation, αPD-1+αCTLA-4 combination overcomes αPD-1 resistance in hosts with hypermutated MMRD tumors displaying abnormal neutrophil accumulation.

Aim Despite unprecedented results of anti-programmed death protein (ligand) 1 (PD-(L)1) immune checkpoint inhibitor in the oncology's armamentarium, immune-related adverse events (irAEs) represent a therapeutic hurdle. Currently, there is no consensual recommendation on a routinely monitored biomarker to early detect irAE. Biological markers such as serum creatine phosphokinase (CPK) are commonly used to measure muscular tissue injury. The potential of routine serum CPK monitoring to predict cardiac or neuromuscular irAE in patients treated with immunotherapy remains unknown. Methods In this retrospective study between January 2016 and December 2018 at Gustave Roussy Cancer Campus, 1151 cancer patients treated with anti-PD–(L)1 immunotherapy were systematically monitored with serum CPK measurements before each immunotherapy cycle. We considered significant CPK increases according to Common Terminology Criteria for Adverse Events v5.0 (CTCAEV5) of grade ≥2 severity. Comparisons were performed in patients with immune-related CPK (ir-CPK) elevations symptomatic versus asymptomatic. Results Overall, 53 of 1151 (4.6%) patients showed a CPK increase. Elevations of CPK were deemed to be immunotherapy-related in 31 of 1151 (2.7%) patients. Among them, 12 of 31 (38.7%) patients experienced symptomatic cardiac or neuromuscular irAE, whereas the other 19 of 31 (61.3%) patients remained asymptomatic. In patients with symptomatic irAE, the mean ir-CPK level was higher compared with asymptomatic patients (1271 versus 771 UI/L, P value = 0.02). In the asymptomatic group, all patients experienced a spontaneous resolution of the ir-CPK increase, and none required medical intervention. Conclusion Most patients with immune-related CPK increase remained asymptomatic. The CPK serum increase did not alter the clinical management of asymptomatic patients. The results of this study did not support a significant clinical interest for a systematic routine CPK monitoring in patients amenable to anti-PD-(L)1 immunotherapy.

ObjectivesIn managing patients with cancer in the COVID-19 era, clinical oncologists and palliative care practitioners had to face new, disrupting and complex medical situations, challenging the quality of the shared decision-making process. During the first lockdown in France, we developed an onco-palliative ethics meeting to enhance the quality of the decision-making process for patients with advanced cancer treated for COVID-19.MethodsA least one of the institutional ethics committee members was present along with oncologists, palliative care teams, psycho-oncologists, radiologists and intensive care specialists. Specific medical parameters were systematically collected to form a standardised framework for the discussions.ResultsThe main raised issues were the definition of new criteria for the implementation of invasive resuscitation techniques, optimal ways to adapt or delay anticancer treatment and best procedures to address terminal respiratory failure and end-of-life care. The main clinical and ethical guidelines that emerged during these debates are presented. The palliative care team played a major role in assessing and reporting patients’ awareness of cancer-related prognosis and their wishes concerning invasive therapies or transfer to intensive care units, enabling an individualised benefit–risk balance assessment. The ethics committee members ensured continuous monitoring during the discussions. Their function was to recall the main ethical principles including dignity, which is conferred on people when there are treated as having equal status.ConclusionsThe onco-palliative ethics meeting provided a powerful avenue for improvement of collegiality and reinforcement of teamwork, which could be a major protection against burnout for healthcare professionals facing an epidemic onslaught.

Additional file 2: Map of intensive care unit (ICU)-transfers of hospitalized patients with COVID-19 patients in France from 1 March to 21 June 2020.

Additional file 2: Supp Mat 2. Kaplan-Meier survival curves corresponding to 2A: Time from first cancer diagnosis until development of MAHA. 2B: Time from first metastasis until development of MAHA.

Additional file 1: Supp Mat 1. Clinical and biological parameters included in statistical analysis. 1A: Data requested from participating centres. 1B: Predictive score construction according to statistical analysis.

Additional file 1: Criteria for inter-regional transferability of a critical care patient between two hospitals.

12045 Background: Contrary to commonly-held beliefs, older patients (OPs, aged 70 or more) in oncology are compliant with the use of a telemonitoring digital platform. Such a tool allows the medical team to gain detailed knowledge of the tolerance profile of patients, and help monitor and maintain their quality of life, which is a particularly important goal for older patients. The EPROFECY study assesses the predictive power of the patient health status in the first month of treatment, evaluated with the digital telemonitoring platform Cureety, on survival. Methods: This prospective study was conducted at the Military Hospital Bégin on OPs. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluated the patient status based on reported adverse events: correct (A), compromised (B), to be monitored (C) and critical state (D). For A/B (good health status), the patient received therapeutic advice to help manage each of the reported adverse events. For C/D (poor health status), the patient was invited to call the hospital. To assess the early tolerance of patience to their treatments, we determined the health status in the 1st month after initiation of treatment, which was classified as “Good health” (GH, majority of A/B reports) or “Poor health” (PH, majority of C/D reports). The primary endpoint was to assess if the first-month tolerance is a predictive factor of progression free-survival (PFS). The secondary endpoint was to assess if the first-month tolerance is a predictive factor of overall survival (OS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 78.0 years (range 70.0 – 99.0), with 81% presenting a metastatic stage, and the most represented cancer being prostate cancer. The median follow-up was 8.2 months. Overall, 2299 ePRO were completed, 89% (n= 2036) corresponding to a "correct" or a "compromised" state and only 11% (n=263) corresponding to a state "to be monitored" or "critical". Based on the first month of questionnaires, 62% of the patients were classified in the GH group, and 38% in the PH group. The PFS ratio at 6 months was 64.6 % in GH vs 23.4 % in PH (HR = 0.1980, 95% CI = 0.04431–0.8845, p = 0.0339). The OS ratio at 6 months was 100% in GH versus 95.5 % in PH (HR: 0.69, 95 % CI = 0.06 – 8.29, p = 0.77). Conclusions: This is the first study that assesses the use of PRO-based tolerance as a predictive factor of treatment response in older individuals. We demonstrated here a significant 80% reduction in the risk of progression in OPs that exhibited a good first-month tolerance. This suggests that e-PRO follow-up might be an effective predictor of response and a tool to treatment plan.

12048 Background: Immunotherapy (Im) improved the survival of patients with lung cancer. It may be responsible for adverse events impacting these patients' quality of life. We have few data on the tolerance of older cancer patients (OP) to immunotherapy. The Toximmune study aims to describe the safety of older lung cancer patients to Im and identify clinical, biological and radiological markers that can help to predict immune-related adverse events for OP. Methods: All patients aged 60 years and older who had received at least one dose of ICI between June 2015 and December 2020 and diagnosed with lung cancer were included. We collected patients' baseline demographic characteristics, biological blood markers and imaging by PET-scanner. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (CTCAE V.5.0). Results: 49 patients were included, median age was 71 (range 61-97). The incidence of grade 2 and grade 3-4 was 34% and 6% respectively. The main irAEs reported were: asthenia in 51% patients after 13.5 months median delay (grade ≥2 in 22%),musculoskeletal disorders in 45% after 21 months median delay (grade ≥2 in 10%), pneumonitis in 37% after 21 months median delay (grade ≥2 in 10%), and colitis in 35% after 21 months median delay (grade ≥2 in 6%). Female sex, primitive tumor SUV max < 5, number of metastases ≥ 3, prior systemic therapy > 1, PLR < 250 were significantly associated with a risk of toxicity in univariate analysis (p < 0.05) We developed the ToxImmune score (0, 1, or ≥2) to predict the risk of having a grade ≥2 adverse event by adding the following risk factors: Primitive Tumor SUV < 5 = 1, Number of metastases ≥3 = 1, And L1 = 0 vs > L1 = 1. The incidence of grade ≥2 adverse events was 31%, 35% and 86% with ToxImmune scores 0, 1 and 2 respectively (p = 0.032). Median overall survival times (OS) & progression-free survival (PFS) were 21.8 & 21 months, 15.1 & 6.6 months, and 9.8 & 2.1 months for ToxImmune scores 0, 1 and ≥ 2 respectively (p = 0.06 & p = 0.001). There was significant association between the ToxImmune score and the risk of "progressive disease" at the first assessment of the disease: 16% for score = 0, 48% for score = 1, and 71% for score = 2, (p = 0.01). Conclusions: The quality of life is our goal for OP care. The ToxImmune score, which is based on objective clinical parameters, identifies OP with a significant higher risk of severe adverse events. Also, this score was significantly associated with patients’ PFS risk of developing rapid tumor progression. It could be used in clinical practice to personalize toxicity surveillance in OP treated for lung cancer with immunotherapy. This score will be validated in larger prospective cohorts.

International audience; Organothiocyanate and organoselenocyanate compounds are of paramount importance in organic chemistry as they are key intermediates to access sulfur-and selenium-containing compounds. Therefore, among the different synthetic pathways to get SCN-and SeCN-containing molecules, original methodologies using electrophilic reagents has recently been explored. This Minireview will showcase the recent advances, which have been made. In particular, the design of several electrophilic sources and their applications for the thiocyanation and the selenocyanation of various classes of compounds will be highlighted and discussed.

Background Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA. Methods Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records. Results Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2−, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0–1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin Conclusions Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.

BackgroundConcerns have emerged about the higher risk of fatal coronavirus disease 2019 (COVID-19) in cancer patients. In this article, we review the experience of a comprehensive cancer center.MethodsA prospective registry was set up at Institut Curie at the beginning of the COVID-19 pandemic. All cancer patients with suspected or proven COVID-19 were entered and actively followed for 28 days.ResultsAmong 9842 patients treated at Institut Curie between March 13 and May 1, 2020, 141 (1.4%) were diagnosed with COVID-19, based on reverse transcription polymerase chain reaction testing and/or computerized tomography scan. In line with our case mix, breast cancer (40.4%) was the most common tumor type, followed by hematological and lung malignancies. Patients with active cancer therapy or/and advanced cancer accounted for 87.9% and 68.9% of patients, respectively. At diagnosis, 78.7% of patients had COVID-19–related symptoms, with an extent of lung parenchyma involvement inferior to 50% in 95.8% of patients. Blood count variations and C-reactive protein elevation were the most common laboratory abnormalities. Antibiotics and antiviral agents were administered in 48.2% and 6.4% of patients, respectively. At the time of analysis, 26 patients (18.4%) have died from COVID-19, and 100 (70.9%) were cured. Independent prognostic factors at the time of COVID-19 diagnosis associated with death or intensive care unit admission were extent of COVID-19 pneumonia and decreased O2 saturation.ConclusionsCOVID-19 incidence and presentation in cancer patients appear to be very similar to those in the general population. The outcome of COVID-19 is primarily driven by the initial severity of infection rather than patient or cancer characteristics.

Background Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the current standard of therapy in several cancer types. Patients (pts) with lung cancer display higher response rates to CT when given after ICIs. Although ICIs have failed to demonstrate antitumour activity in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), little is known about CT effect after ICIs. We aimed to assess whether sequential ICIs followed by CT may be an alternative therapeutic approach in a population of pts with mCRC. Material and methods We retrospectively assessed CT after ICI (CAICI) failure in pts with mCRC. The ICI regimen consisted of anti-PD(L)1 alone or in combination. The primary end-point was objective response rate. Progression-free survival (PFS) and overall survival (OS) were secondary end-points. Results Between 2014 and 2018, 29 pts with mCRC received CAICI (MSS tumours, 27 pts [86%]). The median number of previous lines was 4 (range, 2–7). Regimens included TAS-102 (n = 14), FOLFIRI (irinotecan, leucovorin, and fluorouracil; n = 6) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil; n = 4), regorafenib (n = 3) and carboplatin (1 pt with BRCA mutation). Partial response and stable disease were observed in 4 (19%) and 9 (43%) pts, respectively (disease control rate, 62%). The median PFS and OS were 3.8 months (95% confidence interval [CI] = 1.5–5.4) and 8.0 months (95% CI = 4.2–14.0), respectively. Conclusion ICIs administered before CT might enhance cytotoxic effects even in pts with immunorefractory MSS mCRC. The results of this small cohort need to be validated in independent prospective cohorts. The role of ICIs as modifiers of both tumour cells and microenvironment in mCRC deserves further research.

Additional file 1.

Objective: Different types of multidisciplinary concepts for treating non-healing wounds have been developed. However, there is insufficient evidence on the quality of multidisciplinary wound centres, and a limited number of evaluation systems have so far been developed. The lack of an international wound centre evaluation/certification system is the basis for the European Wound Management Association (EWMA) Wound Centre Endorsement Project. The project aims to describe the minimum requirements for a wound management centre. These requirements have been defined as a basis for evaluation and endorsement of wound centres inside as well as outside a hospital setting (in- and outpatient clinics). Method: The endorsement programme focused on wound centre characteristics such as: target population; types of centres; and choice of model used. The method used to develop the EWMA wound centre endorsement programme was an evaluation of the quality of the different types of established wound centres across and outside Europe. Criteria and procedures for endorsement of wound centres were developed and pilot projects were performed outside Europe in two in-patient centres in China and one outpatient centre in Brazil. Results: The EWMA endorsement procedure includes the following steps: initial application; review of centre data provided via the application form and follow-up dialogue; visit to the wound centre; final report and endorsement; and re-endorsement. A follow-up visit was arranged in connection with the re-endorsement. Experiences from the pilot studies have so far indicated that the endorsement process is not only a quality declaration, but may also result in positive developments, such as increased visibility, increased patient flow, increased healing rates, and decreased amputation rate. Conclusion: Development of endorsement systems focusing on the minimum requirements for a wound management centre is required to support the development of high-quality wound centres which provide health-care services according to recent evidence of current best practice. The EWMA Wound Centre Endorsement Project is the first international programme of its kind and this may, in the future, support the establishment of international collaboration and knowledge sharing about the development and maintenance of high-quality wound centres.

A national survey carried out in France in June 2013 studied for the first time all emergency department attendances over a 24-hour period. It enables patients' pathways through the emergency department to be described in detail, from their conditions of arrival through to the follow-up care downstream of their attendance.

Background The required duration of antibiotic treatment for prosthetic joint infections (PJI) with debridement and retention of the implant (DAIR procedure) is unknown. Methods Multicenter retrospective study emphasizing the duration of antibiotic therapy in patients treated with by DAIR. Results We included 87 hip or knee PJI episodes in 87 patients from three university hospitals in France and Switzerland. All debridements were performed within 3 weeks of symptom onset. After a mean follow-up of 52.1 months, 60 patients with PJI (69%) remained in remission, with no significant difference between hip and knee cases (73.3% vs. 59.3%, 95% confidence interval (CI), 0.20–1.38), or between patients receiving 6 compared with 12 weeks of antibiotic treatment (70.5% vs.67.4%, 95%CI 0.27–2.10, p =0.60). Methicillin-resistant Staphylococcus aureus was isolated from 13.8% of infections and this was the only variable associated with a poorer outcome (remission in 41.7% vs. 73.3% for those with other pathogens, 95%CI 0.05–0.77, p =0.02). Conclusions In patients undergoing DAIR for hip or knee PJI, the likelihood of long-term remission was not significantly different for those receiving 6 versus 12 weeks of antibiotic therapy. Prospective randomized trials are required to confirm this observation.

Background: adjuvant or neoadjuvant chemotherapy in elderly patients (pts) is currently considered as a toxic treatment and reserved for fit women and high-risk breast cancer; few guidelines are available in this age group. The aim of this study was to evaluate the tolerability of chemotherapy in this patient population. Patients and Methods: We performed a retrospective analysis of the use of adjuvant and neo adjuvant chemotherapy in our Cancer Center in two groups of patients (≥70y-75y and >75 y) with early high-risk breast cancer. Between 2009 and 2014, 116 consecutive breast cancer patients (90pts:70-75y and 26pts:75>y: range70-84) received adjuvant or neoadjuvant chemotherapy; all patients had optimal surgery. The chemotherapy regimens were 3 FEC100 (epirubicine 100mg/m2 + 5-fluorouracil and cyclophosphamide 500mg/m2) + 3 docetaxel100mg/m2 or 4 TC( docetaxel 75mg/m2 + cyclophosphamide 600mg/m2). In case of HER2 positive breast cancer (IHC3+ or Sish+), the patients received trastuzumab for one year. The treatment is considered non optimal when there was a decrease in the number of courses or a dose reduction. However Docetaxel75mg/m2 after 3 FEC100 was considered acceptable as well as weekly administration. A yearly follow-up was performed after the end of the chemotherapy. The association between clinical data and age group (70-75) or (>75) was analyzed with Khi-2 test or Fisher test. Results Pts > 75y had more ≥ 3 co-morbidities: (38.5% vs 18.9% (p= 0.04), had more frequently triple negative breast (TN) breast cancer (53.8% vs 20% (p=0.001), inflammatory breast cancer (19.2% vs 3.3%) (p=0.014). Pts>75y had less frequently RH+ breast cancer (23.1% vs 61.1% (p=0.001); there was no significant differences for N+ between the two groups. The >75y pts received more frequently growth factors: 57.7% vs 35.6% (p=0.043); they had more often comprehensive geriatric assessment: 42.3% vs 11.1% (p75 years old patients, those with ≥3 co morbidities are especially frail, at risk of toxicity, hospitalization, inadequate chemotherapy. These results questioned about the best tools for survey and the value of geriatric intervention along the treatment. Citation Format: Servent V, Tresch E, Vuagnat P, Bonneterre J. Adjuvant and neoadjuvant chemotherapy for elderly patients (≥70 years) with early high-risk breast cancer: A retrospective analysis of 116 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-08.