Management and Outcomes of Pancreatic Cancer in French Real-World Clinical Practice.

Background: Our objective was to describe real-world patterns of care and outcomes in pancreatic cancer. Methods: 912 patients diagnosed with pancreatic cancer from 2014 to 2017 were registered by the population-based cancer registry of Burgundy (France). Progression-free and net survival were estimated.

Is There a Role for Large Exome Sequencing in the Management of Metastatic Non-Small Cell Lung Cancer: A Brief Report of Real Life.

Introduction: Non-small-cell lung cancer (NSCLC) is one of the main causes of death by cancer worldwide. With the rise of targeted therapies, the search for molecular abnormalities is becoming a crucial step in the management of lung cancer. Whole exome sequencing (WES) is developing rapidly and is now accessible in routine care.

Targeting PD-L1 and TIGIT could restore intratumoral CD8 T cell function in human colorectal cancer.

Microsatellite stable colorectal cancers (MSS-CRC) are resistant to anti-PD-1/PD-L1 therapy but the combination of immune checkpoints inhibitors (ICI) could be a clue to reverse resistance. Our aim was to evaluate ex vivo the capacity of the combination of atezolizumab (anti-PD-L1) and tiragolumab (anti-TIGIT) to reactivate the immune response of tumor infiltrating lymphocytes (TILs) in MSS-CRC. We analysed CRC tumor tissue and the associated blood sample in parallel.

MER4 endogenous retrovirus correlated with better efficacy of anti-PD1/PD-L1 therapy in non-small cell lung cancer.

Background: Endogenous retroviruses (ERVs) are highly expressed in various cancer types and are associated with increased innate immune response and better efficacy of antiprogrammed death-1/ligand-1 (anti-PD1/PD-L1)-directed immune checkpoint inhibitors (ICI) in preclinical models. However, their role in human non-small cell lung cancer (NSCLC) remains unknown.

Methods: We conducted a retrospective study of patients receiving ICI for advanced NSCLC in two independent cohorts.

Custom multi‑tumor next‑generation sequencing panel for routine molecular diagnosis of solid tumors: Validation and results from three‑year clinical use.

Molecular testing is extremely important in cancer care, starting as early as at diagnosis. In order to address the challenge of providing reliable results within the timeframe adapted to patient management and suitable to guide clinical decisions, a capture‑based next‑generation sequencing (NGS) panel focusing on ten genes known to harbor genetic variations which may be targeted by approved drugs in patients with cancer was designed and validated. Very favorable analytical performances were obtained for both solid and liquid biopsies.

Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses.

Tumors poorly infiltrated by T cells are more resistant to immunogenic chemotherapies and checkpoint inhibition than highly infiltrated tumors. Using murine models, we found that CCR6 type 3 innate lymphoid cells (ILC3s) can trigger an increase in the number of T cells infiltrating a tumor. Shortly after administration of cisplatin chemotherapy, production of the chemokine CCL20 and proinflammatory cytokine IL-1β at the tumor site led to the recruitment and activation of ILC3s.

Using a convolutional neural network for classification of squamous and non-squamous non-small cell lung cancer based on diagnostic histopathology HES images.

Histological stratification in metastatic non-small cell lung cancer (NSCLC) is essential to properly guide therapy. Morphological evaluation remains the basis for subtyping and is completed by additional immunohistochemistry labelling to confirm the diagnosis, which delays molecular analysis and utilises precious sample. Therefore, we tested the capacity of convolutional neural networks (CNNs) to classify NSCLC based on pathologic HES diagnostic biopsies.

Phase I Dose-Escalation Trial of an Innovative Chemotherapy Regimen Combining a Fractionated Dose of Irinotecan Plus Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Folinic Acid (bFOLFIRINOX-3) in Chemorefractory Metastatic Colorectal Cancer.

The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient's molecular biology and general condition. Irinotecan bifractionation showed efficacy in chemorefractory patients in a previous study, FOLFIRI-3, but a desynchronized triplet has never been tested.

Utility of exome sequencing in routine care for metastatic colorectal cancer.

Metastatic colorectal cancer (mCRC) is a heterogenous disease and its prognosis depends on clinical features, such as tumor sidedness, and whether it is metachronous or synchronous. However, little is known about the overall genomic characterization of mCRC in these clinical subtypes. This single-center observational study included 77 patients with mCRC who underwent somatic and germline exome analysis during the first or second line of therapy in 2018.

Does large NGS panel analysed using exome tumour sequencing improve the management of advanced non-small-cell lung cancers?

Introduction: Non-small-cell lung cancer (NSCLC) is one of the most common and deadly cancers. Several molecular drivers of oncogene addiction are now known to be strong predictive biomarkers for target therapies. Advances in large Next Generation Sequencing (LNGS) have improved the ability to detect potentially targetable mutations.

TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer.

Purpose: Immune infiltration is a prognostic factor in high-grade serous ovarian carcinoma (HGSC) but immunotherapy efficacy is disappointing. Genomic instability is now used to guide the therapeutic value of PARP inhibitors. We aimed to investigate exome-derived parameters to assess the tumor microenvironment according to genomic instability profile.

Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1.

Anti-PD1/PD-L1-directed immune checkpoint inhibitors are game changers in advanced non-small-cell lung cancer, but biomarkers are lacking. The aim of our study was to find clinically relevant biomarkers of the efficacy of ICI in non-squamous NSCLC. We conducted a retrospective study of patients receiving ICI for advanced non squamous NSCLC in two cohorts.

Splenic Volume as a Surrogate Marker of Immune Checkpoint Inhibitor Efficacy in Metastatic Non Small Cell Lung Cancer.

Monoclonal antibodies targeting PD1/PD-L1 are game changers in advanced non-small cell lung cancer (NSCLC), but biomarkers are lacking. We previously reported the prognostic role of splenic volume in digestive cancer and its correlation with the presence of immunosuppressive cells. The aim of this study was to evaluate the prognostic role of splenic volume in NSCLC patients treated with immune checkpoint inhibitors (ICIs).

An Algorithm Combining Patient Performance Status, Second Hit Analysis, PROVEAN and Dann Prediction Tools Could Foretell Sensitization to PARP Inhibitors in Digestive, Skin, Ovarian and Breast Cancers.

PARP inhibitors yield interesting outcomes for patients with ovarian tumors harboring or mutation, but also with other tumors with homologous repair (HR) deficiency. About 40% of variants are variants of unknown significance (VUS), blocking the use of PARP inhibitors. In this study, we analyzed NGS data from 78 metastatic patients treated with PARP inhibitors.

Positron Emission Tomography Imaging of Neurotensin Receptor-Positive Tumors with Ga-Labeled Antagonists: The Chelate Makes the Difference Again.

Neurotensin receptor 1 (NTS) is involved in the development and progression of numerous cancers, which makes it an interesting target for the development of diagnostic and therapeutic agents. A small molecule NTS antagonist, named [Lu]Lu-IPN01087, is currently evaluated in phase I/II clinical trials for the targeted therapy of neurotensin receptor-positive cancers. In this study, we synthesized seven compounds based on the structure of NTS antagonists, bearing different chelating agents, and radiolabeled them with gallium-68 for PET imaging.

Targeting BRAF and RAS in Colorectal Cancer.

Colorectal cancer (CRC) is still one of the most frequent forms of cancer in the world in terms of incidence. Around 40% of CRC patients carry a mutation of the Kirsten rat sarcoma (KRAS) gene, while 10% have a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene. These mutations are responsible for dysregulation of the mitogen-associated protein kinase (MAPK) pathway, leading to the proliferation, differentiation, angiogenesis, and resistance to apoptosis of cells.

Using Exome Sequencing to Improve Prediction of FOLFIRINOX First Efficacy for Pancreatic Adenocarcinoma.

Purpose: The first line treatment of advanced pancreatic ductal adenocarcinoma cancer (PDAC) comprises a FOLFIRINOX regimen for most patients with good performance status. However, no biomarker to predict efficacy is currently available. We investigated whether exome sequencing could be used to predict progression-free and overall survival in patients undergoing FOLFIRINOX for PDAC.

Radiotherapy for primary tumor in lung cancer with synchronous metastases: Overview from the past and proposal for the future.

The management of metastatic lung cancers, either of the small-cell (SCLC) or the non-small cell (NSCLC) subtype, largely based on systemic treatments so far, has been the subject of breakthrough advances over the past few years, with notably the wide use of immunotherapy changing the landscape of these harmful prognosis diseases. In parallel with this major progress, the increasing use of radiotherapy (RT) for the treatment of the primary thoracic lesion±the distant lesions, may contribute to improving the condition of these metastatic patients, both in terms of progression-free survival (PFS) and overall survival (OS). This review proposes to summarize and explain the findings provided by the different studies published in the last years experiencing RT of the primary tumor in metastatic lung cancers, either associated or not with the local ablative treatment of a low number of distant lesions.

Implementation and use of whole exome sequencing for metastatic solid cancer.

Background: Genomically-guided clinical trials are performed across different tumor types sharing genetic mutations, but trial organization remains complex. Here we address the feasibility and utility of routine somatic and constitutional exome analysis in metastatic cancer patients.

Methods: Exoma trial (NCT02840604) is a multicenter, prospective clinical trial.

Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors.

Nanohybrids based on titanate nanotubes (TiONts) were developed to fight prostate cancer by intratumoral (IT) injection, and particular attention was paid to their step-by-step synthesis. TiONts were synthesized by a hydrothermal process. To develop the customengineered nanohybrids, the surface of TiONts was coated beforehand with a siloxane (APTES), and coupled with both dithiolated diethylenetriaminepentaacetic acidmodified gold nanoparticles (Au@DTDTPA NPs) and a heterobifunctional polymer (PEG) to significantly improve suspension stability and biocompatibility of TiONts for targeted biomedical applications.

Somatic substitution signature as an innovative tool in lung cancer diagnosis.

Diagnosis of lung cancer can sometimes be challenging and is of major interest since effective molecular-guided therapies are available. Compounds of tobacco smoke may generate a specific substitutional signature in lung, which is the most exposed organ. To predict whether a tumor is of lung origin or not, we developed and validated the EASILUNG (Exome And SIgnature LUNG) test based on the relative frequencies of somatic substitutions on coding non-transcribed DNA strands from whole-exome sequenced tumors.

Functionalization of theranostic AGuIX® nanoparticles for PET/MRI/optical imaging.

A novel trifunctional imaging probe containing a chelator of radiometal for PET, a NIR heptamethine cyanine dye, and a bioconjugatable handle, has been grafted onto AGuIX® nanoparticles a Michael addition reaction. The resulting functionalized nanoparticles have been fully characterized, radiolabelled with Cu, and evaluated in a mice TSA tumor model using multimodal (PET/MRI/optical) imaging.

Modular Assembly of Multimodal Imaging Agents through an Inverse Electron Demand Diels-Alder Reaction.

The combination of two imaging probes on the same biomolecule gives access to targeted bimodal imaging agents that can provide more accurate diagnosis, complementary information, or that may be used in different applications, such as nuclear imaging and fluorescence guided surgery. In this study, we demonstrate that dichlorotetrazine, a small, commercially available compound, can be used as a modular platform to easily assemble various imaging probes. Doubly labeled tetrazines can then be conjugated to a protein through a biorthogonal IEDDA reaction.