Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

Preclinical development of a docetaxel nanocarrier to enhance prostate cancer radiosensitivity.

International audienceBackground: From 30% to 50% of high risk prostate cancer patients who undergo radiation therapy (RT) will have a biochemical failure. Combining chemotherapy, such as Docetaxel (DXL), with RT can enhance its efficiency. Multidrug resistance mechanisms often limit drug efficacy by decreasing tumor cell intracellular concentration of drugs. There is interest to develop nanocarrier of DXL to maintain drug inside cancer cells by improving its efficacy. The purpose of this study was to develop a titanate-nanotube (TiONt)-DXL nanocarrier (nanohybrid) and to evaluate its in vivobiodistribution as well as its radiosensitizing efficacy in association with RT on a hormone-independent prostate cancer model. Methods: DXL molecules were grafted on TiONts using PEG-3000 molecules to generate the nanohybrid. In vitrocytotoxic activity of the nanohybrid was evaluated on PC-3 cell line using MTS assay. After intratumoral injection, biodistribution analysis was performed by SPEC-CT imaging of mice bearing subcutaneous PC-3 human prostate tumors. To evaluate the benefit of nanohybrid and RT association, tumors were irradiated using 3 fractions of 4Gy administrated after the injection of nanohybrids. Nine groups of 7 mice were used to evaluate nanohybrid and RT association efficacy : untreated, control with buffer IT injection, +/- RT, free DXL, +/- RT, TiONt +/- RT and TiONt-DXL +/- RT. Mice behavior, health status and tumor volume were monitored twice a week until tumor growth recovery. Results: Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT exhibited a significant tumor growth delay to reach a volume of 1,000mm 3 compared to mice receiving free DXL-RT: 73.7 days (median, [58.9-89]) vs 56 days (median, [31.5-74]) (p=0.0127). Conclusions: TiONt-DXL improves RT efficacy compared to free DXL. These results suggest that local control might be enhanced by TiONt-DXL. TiONt-DXL can be injected as a radiosensitizer in men harboring high risk localized prostate cancer with needles during prostate brachytherapy procedure

Baseline circulating soluble factors as predictors of immune-related adverse events (irAEs) in patients (pts) with metastatic clear cell renal carcinoma (mRCC) treated with nivolumab: A translational NIVOREN GETUG-AFU 26 study.

International audienc

Serum soluble MAdCAM-1: A new biomarker for cancer immunotherapy.

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Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer

Netrin-1 is upregulated in cancers as a protumoural mechanism1. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC. As best response we observed 8 stable disease (8 out of 14, 57.1%) and 1 objective response as RECIST v.1.1 (partial response, 1 out of 14 (7.1%), 51.16% reduction in target lesions at 6 weeks and up to 54.65% reduction during the following 6 months). To evaluate the NP137 mechanism of action, mouse tumour gene profiling was performed, and we observed, in addition to cell death induction, that NP137 inhibited epithelial-to-mesenchymal transition (EMT). By performing bulk RNA sequencing (RNA-seq), spatial transcriptomics and single-cell RNA-seq on paired pre- and on-treatment biopsies from patients with EC from the NP137 trial, we noted a net reduction in tumour EMT. This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment. Given the importance of EMT in resistance to current standards of care2, we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone. Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition, thus potentially alleviating resistance to standard treatments