DIRECTOR PAUL HOFMAN
The IHU RespirERA (Respiratory Health, EnviRonment and Ageing) is a collective project structuring the Nice Sophia Antipolis medical-scientific community around a single pathology centred on respiratory diseases. Continue reading
MFR of Puyloubier Team
It is with great pleasure that we announce the succes of Rural Family Home of Puyloubier (MFR of Puyloubier) which won the TABADO Games 2021-2022!
The TABADO Games are a national competition that mobilises different actors and creates an emulation around the TABADO programme and the opportunity to win prizes in the sports universe!
By participating in the different stages of the programme (detailed below), students score points for their school. At the end of the TABADO Games, a ranking is established: a winning school per region and a national winner are designated. This year, the MFR of Puyloubier, from PACA, is the national champion!
Financed by the combatting addiction Funds and supported by the National Cancer Institute (INCa) at national level, TABADO is coordinated in the PACA region by the OncoAge University Hospital Federation and led by the Nice University Hospital Centre since 2019.
TABADO is a programme helping to prevent and reduce tobacco use among young people by proposing personalised support directly at their school. It involves, in each partner establishment, prevention facilitators and health professionals. Trained in tobacco addiction, they are authorised to prescribe nicotine replacement therapies to the young people registered.
The aim of TABADO is to identify and prevent smoking rather than treat it, and it introduces a shift from an individual issue to collective support. Marked by its desire to mobilise all actors of the project by using the codes of the sporting world, the project is built around three key stages:
TABADO has been proven to double the number of smokers quitting. Early intervention on addiction is effective in reducing health risks. Its ambition is to protect young people as a priority and to fight against social inequalities.
Article in leMag.sante
The Nice University Hospital is setting up the TABADO program, free support for quitting smoking for more than 15 people enrolled in vocational training.
The managers of the TABADO program from left to right: Prof. Paul Hofman, Melissa Manucci and Taycir Skhiri.
The article is available below in French:
Article in leMag.sante
Assessing the response to treatment, adapting it in the event of resistance, early detection of residual disease predicting a relapse:
These are the major challenges of the innovation with which the Nice University Hospital has equipped itself.
The article is available below in French:
Article in Wiley
From: Daniel Kazdal, Véronique Hofman, Petros Christopoulos, Marius Ilié, Albrecht Stenzinger, Paul Hofman
2021 October
Based on superior efficacy and tolerability, targeted therapy is currently preferred over chemotherapy and/or immunotherapy for actionable gene fusions that occur in late-stage non-small cell lung carcinoma (NSCLC). Consequently, current clinical practice guidelines mandate testing for ALK, ROS1, NTRK, and RET gene fusions in all patients with newly diagnosed advanced non-squamous NSCLC (NS-NSCLC). Gene fusions can be detected using different approaches, but today RNA next-generation sequencing (NGS) or combined DNA/RNA NGS is the method of choice. The discovery of other gene fusions (involving, eg, NRG1, NUT, FGFR1, FGFR2, MET, BRAF, EGFR, SMARC fusions) and their partners has increased progressively in recent years, leading to the development of new and promising therapies and mandating the development and implementation of comprehensive detection methods. The purpose of this review is to focus on recent data concerning the main gene fusions identified in NSCLC, followed by the discussion of major challenges in this domain.
Article in Nature Communications
From: Laetitia Douguet, Serena Janho dit Hreich, Jonathan Benzaquen, Laetitia Seguin, Thierry Juhel, Xavier Dezitter, Christophe Duranton, Bernhard Ryffel, Jean Kanellopoulos, Cecile Delarasse, Nicolas Renault, Christophe Furman, Germain Homerin, Chloé Féral, Julien Cherfils-Vicini, Régis Millet, Sahil Adriouch, Alina Ghinet, Paul Hofman & Valérie Vouret-Craviari
2021 January
Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor-bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.
New article in OncoImmunology
From: Marius Ilié, Elisabeth Lantéri, Emmanuel Chamorey, Brice Thamphya, Marame Hamila, Henri Montaudié, Alexandra Picard-Gauci, Sophie Gardrat, Thierry Passeron, Sandra Lassalle, Elodie Long-Mira, Julien Cherfils-Vicini, Eric Gilson, Véronique Hofman & Paul Hofman
2021 March
The outcome of patients with cutaneous melanoma has been strongly modified by recent advances obtained with Immune Checkpoint Inhibitors (ICIs). However, despite this breakthrough, durable response to ICIs is limited to a subset of patients. We investigated whether the expression of TRF2, which preserves telomere integrity, and have an effect on tumor immunosurveillance notably by directly recruiting and activating myeloid-derived suppressor cells (MDSCs), could be a prognostic biomarker in patients with relapsed or metastatic melanoma based on different treatment regimens. We evaluated retrospectively the association of TRF2 expressed in melanoma cells in combination with intratumoral CD33+ CD15+ CD14- MDSCs, as detected by immunohistochemistry and quantified by digital analysis, to clinicopathological features and overall survival (OS) among 48 patients treated with ICIs and 77 patients treated with other treatment options. The densities/mm2 of TRF2+ cells (P=.003) and CD33+ cells (P=.004) were individually significantly related to poor OS. In addition, only the combined expression of CD33+/CD15+/CD14- cells/mm2 was significantly correlated to poor OS (P=.017) in the whole study population as well as in patients treated by ICIs (P=.023). There was no significant difference in OS when analyzing the other markers individually or in combination according to the treatment regimen. The pre-treatment assessment of TRF2 expression and CD33+ cells/mm2 along with the density of CD33+/CD15+/CD14- cells/mm2 could assess OS and better predict clinical response of patients with melanoma treated by ICIs.
New article in Journal of Thoracic Oncology
From: Marius Ilié, MD, PhD, Julien Mazières, MD, PhD, Emmanuel Chamorey, MD, PhD, Simon Heeke, PhD, Jonathan Benzaquen, MD, PhD, Brice Thamphya, MSc, Jacques Boutros, MD, Angélica Tiotiu, MD, PhD, Julien Fayada, MSc, Jacques Cadranel, MD, PhD, Michel Poudenx, MD, Denis Moro-Sibilot, MD, PhD, Fabrice Barlesi, MD, PhD, Juliette Thariat, MD, PhD, Christelle Clément-Duchêne, MD, PhD, Pascale Tomasini, MD, PhD, Véronique Hofman, MD, PhD, Charles-Hugo Marquette, MD, PhD, Paul Hofman, MD, PhD
2021 May
Introduction: Patients with advanced-stage NSCLC whose tumors harbor an ALK gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsy samples contain insufficient tissue for successful ALK molecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALK tissue analysis and as a function of the response to ALKi.
Methods: We conducted a multicenter, prospective observational study (NCT02372448) of 203 patients with stage IIIB/IV NSCLC across nine French centers, of whom 81 were ALK positive (immunohistochemistry or fluorescence in situ hybridization [FISH]) and 122 ALK negative on paraffinembedded tissue specimens. Blood samples were collected at baseline and at 6 and 12 weeks after ALKi initiation or at disease progression. ALK gene rearrangement was evaluated with CTCs using immunocytochemistry and FISH analysis after enrichment using a filtration method.
Results: At baseline, there was a high concordance between the detection of an ALK rearrangement in the tumor tissue and in CTCs as determined by immunocytochemistry (sensitivity, 94.4%; specificity 89.4%). The performance was lower for the FISH analysis (sensitivity, 35.6%; specificity, 56.9%). No significant association between the baseline levels or the dynamic change of CTCs and overall survival (hazard ratio ¼ 0.59, 95% confidence interval: 0.24–1.5, p ¼ 0.244) or progression-free survival (hazard ratio ¼ 0.84, 95% confidence interval: 0.44–1.6, p ¼ 0.591) was observed in the patients with ALK-positive NSCLC.
Conclusions: CTCs can be used as a complementary tool to a tissue biopsy for the detection of ALK rearrangements. Longitudinal analyses of CTCs revealed promise for realtime patient monitoring and improved delivery of molecularly guided therapy in this population
New article in ESMO Open
From: E. Heitzer, D. van den Broek, M. G. Denis, P. Hofman, M. Hubank, F. Mouliere, L. Paz-Ares, E. Schuuring, H. Sültmann, G. Vainer, E. Verstraaten, L. de Visser & D. Cortinovis
2022 April
Background: Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its
way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived
material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not
limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others.
Patients and methods: The objective of this paper, devised by international experts from various disciplines, is to
review current challenges as well as state-of-the-art applications of ctDNA mutation testing in metastatic non-smallcell
lung cancer (NSCLC). We consider pragmatic scenarios for the use of ctDNA from blood plasma to identify
actionable targets for therapy selection in NSCLCs.
Results: Clinical scenarios where ctDNA mutation testing may be implemented in clinical practice include complementary
tissue and LB testing to provide the full picture of patients’ actual predictive profiles to identify resistance mechanism (i.e.
secondary mutations), and ctDNA mutation testing to assist when a patient has a discordant clinical history and is
suspected of showing intertumor or intratumor heterogeneity. ctDNA mutation testing may provide interesting
insights into possible targets that may have been missed on the TB. Complementary ctDNA LB testing also provides
an option if the tumor location is hard to biopsy or if an insufficient sample was taken. These clinical use cases
highlight practical scenarios where ctDNA LB may be considered as a complementary tool to TB analysis.
Conclusions: Proper implementation of ctDNA LB testing in routine clinical practice is envisioned in the near future. As
the clinical evidence of utility expands, the use of LB alongside tissue sample analysis may occur in the patient cases
detailed here.
New article in ERJ Open Research
From : Jacques Boutros, Jonathan Benzaquen, Charles Hugo Marquette, Marius Ilié, Mickelina Labaky, Didier Benchetrit, Thibaut Lavrut, Sylvie Leroy, Richard Chemla, Michel Carles, Virginie Tanga, Charlotte Maniel, Olivier Bordone, Maryline Allégra, Virginie Lespinet, Julien Fayada, Jennifer Griffonnet, Véronique Hofman, and Paul Hofman
Background The current diagnostic standard for coronavirus disease 2019 (COVID-19) is reverse
transcriptase-polymerase chain reaction (RT-PCR) testing with nasopharyngeal (NP) swabs. The
invasiveness and need for trained personnel make the NP technique unsuited for repeated community-based
mass screening. We developed a technique to collect saliva in a simple and easy way with the sponges that
are usually used for tamponade of epistaxis. This study was carried out to validate the clinical performance
of oral sponge (OS) sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.
Methods Over a period of 22 weeks, we collected prospectively 409 paired NP and OS samples from
consecutive subjects presenting to a public community-based free screening centre. Subjects were referred
by their attending physician because of recent COVID-19 symptoms (n = 147) or by the contact tracing
staff of the French public health insurance because they were considered as close contacts of a laboratoryconfirmed
COVID-19 case (n = 262).
Results In symptomatic subjects, RT-PCR SARS-CoV-2 testing with OS showed a 96.5% (95% CI: 89.6–
94.8) concordance with NP testing, and a 93.2% (95% CI: 89.1–97.3) sensitivity when using the IdyllaTM
platform and a sensitivity of 76.3% (95% CI: 69.4–83.2) on the Synlab Barla laboratory platform. In close
contacts the NP-OS concordance (93.8%, 95% CI: 90.9–96.7) and OS sensitivity (71.9%, 95% CI: 66.5–77.3)
were slightly lower.
Conclusion These results strongly suggest that OS testing is a straightforward, low-cost and highthroughput
sampling method that can be used for frequent RT-PCR testing of COVID-19 patients and
mass screening of populations.