Search

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Huit nouveaux traitements ont été commercialisés dans le mélanome métastatique en cinq ans. Le profil de tolérance des combinaisons de thérapies ciblées est meilleur que celui des inhibiteurs de BRAF (qui ne sont plus utilisés en monothérapie) et largement acceptable. Les effets indésirables (EI) problématiques au quotidien sont la photosensibilité pour le vemurafenib et la fièvre pour la combinaison dabrafenib + trametinib. Les EI immuns de l'ipilimumab et de l'association anti-CTLA4 + anti-PD1 (éruptions cutanées, endocrinopathies, pneumopathies interstitielles, etc.), dont la gestion nécessite une expertise, doivent être anticipés, les colites et les hépatites étant les EI le plus souvent à l'origine d'arrêts de traitement. Une prise en charge multidisciplinaire est souvent nécessaire du fait de la variété des effets immuns. Le meilleur profil de tolérance est celui des anti-PD1, dont l'utilisation requiert moins d'expérience que celle des anti-CTLA-4. La vigilance reste cependant de rigueur pour repérer précocement des complications rares, mais potentiellement graves. [ABSTRACT FROM AUTHOR]

The number of drugs available to clinicians, especially targeted therapies, grows continuously. Some drugs are known to cause frequent digestive adverse effects, which may affect the gastro-intestinal tract in a diffuse or localized manner. Some treatments may leave relatively pathognomonic deposits, but histological lesions of iatrogenic origin are mostly non-specific. The diagnostic and etiological approach is often complex because of these non-specific aspects and also because (1) a single type of drug may cause different histological lesions, (2) different drugs may cause identical histological lesions, (3) the patient may receive different drugs, and (4) drug-induced lesions may mimic other pathological entities such as inflammatory bowel disease, celiac disease, or graft versus host disease. The diagnosis of iatrogenic gastrointestinal tract injury therefore requires close anatomic-clinical correlation. The iatrogenic origin can only be formally established if the symptomatology improves when the incriminating drug is stopped. This review aims to present the different histological patterns of gastrointestinal tract iatrogenic lesions, the potentially incriminate drugs, as well as the histological signs to look for in order to help the pathologist to distinguish an iatrogenic injury from another pathology of the gastrointestinal tract., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) are common for men with a poor prognosis in case of recurrent or metastatic disease. There are several rationales for the use of immunotherapies in this indication. Indeed, human papilloma virus-related cancers are particularly immunogenic and provide many interesting therapeutic targets. The vaccination, as developed in cervical cancer, may be very effective in the prevention of HNSCC dysplasia. There is currently no data for curative vaccination. The rapid immune checkpoints inhibitors development in other cancers seem to arise in HNSCC also. Some trials are recruiting to evaluate anti-PD-1 in association with chemoradiotherapy for advanced tumors. In recurrent or metastatic HNSCC, the results presented in international meetings are overwhelmingly in favor of nivolumab with a significative improvement of overall survival in second line of treatment. The association with cetuximab is also studied but the skin toxicity seems to be limiting. [ABSTRACT FROM AUTHOR]

Copyright of Biologie Aujourd'hui is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé Les progrès scientifiques de cette dernière décennie ont permis de démontrer le rôle important du système immunitaire de l’hôte dans la lutte contre les cancers. La meilleure connaissance des voies de signalisation a permis le développement de nouvelles stratégies d’immunothérapie. La découverte des mécanismes du rétrocontrôle négatif faisant suite à l’activation lymphocytaire a incité au développement de nouveaux anticorps ciblant des molécules inhibitrices telles PD1, PDL1 et CTLA-4. Les résultats les plus spectaculaires ont été obtenus avec le mélanome. Les immunomodulateurs (pembrolizumab et ipilimumab) ont de nombreux avantages en termes de taux de réponses objectives et de survie. Des études récentes en recherche translationnelle ont pour vocation la compréhension et l’analyse des mécanismes d’action de ces anticorps immunomodulateurs anti-PD1 et anti-PDL1. Ainsi, il semblerait que l’expression de PDL1 au niveau tumoral soit associée à une probabilité d’obtenir une réponse objective plus importante (analyse immuno-histochimique). Néanmoins, les limites de l’analyse immuno-histochimique des tumeurs incitent les scientifiques à chercher de nouveaux biomarqueurs. D’autres approches d’immunothérapie basées sur les thérapies cellulaire et génique permettent également d’envisager des résultats significatifs pour les patients. Plus contraignantes (coût, procédé de fabrication), ces thérapies pourraient être utilisées en cas d’inefficacité des anticorps immunomodulateurs ou lorsque l’infiltrat lymphocytaire intra-tumoral est absent. L’objectif serait alors de reprogrammer ex vivo le système immunitaire du patient en restaurant la capacité des lymphocytes T à reconnaître et détruire les cellules tumorales. Les deux outils de reprogrammation génique actuellement en développement étant le récepteur antigénique chimérique et le TCR transgénique. Scientific advances in the last decade have demonstrated the critical role of host immune system in the elimination and suppression of cancer cells. Better knowledge of signaling pathways has enabled the development of new cancer immunotherapy. The discovery of negative feedback mechanisms following the lymphocyte activation has promoted the development of new antibodies targeting molecule inhibitors such as PD1, PDL1 or CTLA-4. Dramatic results were obtained with melanoma. Checkpoint inhibitors (pembrolizumab and ipilimumab) have many advantages in terms of rate of objective response and overall survival. Recent studies in translational research aimed to understand and analyze mechanisms of action of anti-PD1/anti-PDL1. Expression of PDL1 in the tumor is associated with a significantly greater objective response rate (immunohistochemistry). Nevertheless, limits with tumor immunohistochemical analysis encourage new biomarkers research. Other immunotherapy approaches, such as cell and gene therapies using engineered T cells call for further advancements to broaden their applicability. However, these therapies are very expensive and their manufacturing process very restrictive, which could lately limit their use in case of inefficiency of checkpoint inhibitors or when lymphocytic infiltration in tumor is absent. In this case, the objective would be to engineer ex vivo the patient's immune system by restoring the ability of T cells to identify and suppress tumor cells. Currently, two gene-reprogramming tools are under development: chimeric antigen receptor and TCR modified T cells. [ABSTRACT FROM AUTHOR]

The most commonly reported pattern of anti-PD-1 induced colitis is an active colitis characterized by neutrophilic inflammation and prominent apoptosis. On the other hand, reports of collagenous colitis (which is a microscopic colitis) are exceptional. In this report, we describe an unusual case of anti-PD1-associated collagenous colitis in a 76-year-old man, treated with pembrolizumab for a stage IV cutaneous melanoma. Fourteen months after the start of pembrolizumab, the patient developed a grade 3 diarrhea (up to 9 stools per day) associated with profound hypokalemia. No bacterial, viral or parasitological infectious agents were found from stool analysis. The rectosigmoidoscopy showed colonic diffuse congestion with no ulceration. Systematic biopsies were performed during endoscopy. Histologically, the fragments analyzed revealed a moderately thickened subepithelial collagen layer (20-30μm thick) associated with a mild mixed inflammatory infiltrate within the lamina propria. There were no granuloma lesions, ulcerations or viral inclusion bodies. The patient was initially successfully treated with corticosteroids (prednisone) and temporary interruption of pembrolizumab. However, during corticosteroids tapering, a relapse was observed. The treatment was switched to budesonide, leading to a complete and definitive resolution of diarrhea. To date, budesonide has been stopped and pembrolizumab has not been restarted. Currently, there is a bone progression treated by radiotherapy alone. In case of a more important progression, a systemic treatment will be secondarily discussed., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Checkpoint inhibitors immunotherapy is more and more prescribed in oncology, causing new immune related endocrine adverse events. Hypophysitis occurs in approximately 10 % of patients treated with anti-CTLA4. It occurs two to three months after initiation of the immunotherapy. The initial presentation is characterized, in typical forms, by the association of headache, asthenia and hyponatremia. Hormonal exploration usually shows ACTH, gonadotropic and thyrotropic deficiencies. ACTH deficiency may be life-threatening and requires urgent supplementation, without awaiting for biological results. MRI is warranted in order to exclude differential diagnoses, such as pituitary metastases. Hypophysitis induced by anti-PD1/PDL1 seems to be a different nosologic entity characterized by a later onset and a less symptomatic presentation. Biologically ACTH deficiency seems to be constant and permanent, and often isolated. Treatment requires high-dose steroids only in case of severe tumor syndrome (resistant headache, visual disturbance) or acute decompensation of ACTH deficiency. Patients always need lifelong hormonal supplementation of pituitary deficits and must be followed and educated specifically. Immunotherapy can be delayed during the acute phase, but can be secondarily continued if there is an oncological benefit. As it is a pauci-symptomatic but potentially life-threatening complication, biological screening must be systematic in patients treated with checkpoint inhibitors., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Use of checkpoint inhibitors to treat cancer was one of the most important revolution these last years and an increasing number of new types of tumors is currently under investigation with these new treatments. However, immune-related adverse events associated with these agents frequently affect various organs, mimicking auto-immune or inflammatory diseases. Some of these effects can be severe, often requiring hospitalization and specialized treatment (immunosuppression). Most known agents are ipilimumab (anti-CTLA-4 antibody) nivolumab and pembrolizumab (anti-PD-1 antibodies). New molecules are now approved or in development as anti-PD-L1 antibodies, anti-LAG-3 or anti-TIM-3 antibodies, increasing the probability and new description of immune-related adverse events. With his experience in auto-immune diseases, the immunologist/internal medicine specialist has an important role in the management of these toxicities. The goal of this review is to focus on the incidence, diagnostic assessment and recommended management of the most relevant immune-related adverse events., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Checkpoints inhibitors are known to induce striking tumor responses in advanced MSI colorectal cancers, which used to be related to a poor clinical outcome. The incidence of the MSI phenotype is highly heterogeneous across non-colorectal cancers. The highest incidence rates are found in endometrioid forms of uterine cancers and in gastric tumors (20 to 40 % and 10 to 33 %, respectively). The association between a "MSI" tumor phenotype and other clinical or biological tumor characteristics is still under debate. Its prognostic value has not been determined yet. The deficiency of the DNA mismatch repair (dMMR) system of such tumor cells increases their mutational load and induces the production of so-called neo-antigens. Therefore, checkpoint inhibitors are a target therapeutic class for this molecular group of tumors. For example, response rates reach more than 50 % in pre-treated advanced endometrial cancers and in metastatic gastric tumors in association with a first line of chemotherapy. Those promising results imply the development of reliable biomarkers predictive of tumor response to immunotherapy. The present article summarizes the clinical outcomes related to the administration of checkpoint inhibitors in non-colorectal cancers. The ongoing clinical trials of such therapeutic class in this patient population are displayed., (Copyright © 2019. Published by Elsevier Masson SAS.)

Immunotherapy in Head and Neck Cancers: Immunotherapy wave has also touched head and neck cancer. In recurrent or metastatic disease, checkpoint inhibitors (anti PD-1/PD-L1) are approved in 2 nd line with a clear benefit on overall survival and quality of life. Multiple clinical studies are in progress in both palliative and curative intent, combined or not with other checkpoint inhibitor (anti-CTLA4) or other standard therapies (radiotherapy, chemotherapy). It is essential to define which patients will benefit from immunotherapy, according to robust biomarkers, in order to increase risk benefit balance by decreasing side effects and selecting those who respond the most. Here we present an overview of immunotherapy in 2018 in head and neck squamous cell cancer., (© 2018 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Novel Strategy in Oncoimmunology: Recent advances in immuno-oncology with the development of anti-PD1/PD-L1 antibodies are revolutionizing oncological management. Immuno-oncology I currently developing in most histological types of cancer. However, the rate of success of anti-PD1/PD-L1 antibodies in monotherapy is limited by a limited to a subpopulation of patients accounting for about 25-30 % of patients in most indications. The development of new strategies is based on this observation with the aim to predict response or enhancing response rate. Thus, we note the development of different strategies aimed at better selecting patients or combining inhibitory checkpoints with other therapies in order to increase their effectiveness. This review will study therapeutic test strategies to validate these new associations., (© 2018 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

Radiotherapy is known for its action on local tumoral control. However, it is also able to induce immunomodulatory effects at a systemic level. The abscopal effect (from latin ab scopus which means «away from the target») is an illustration of this phenomenon. It is defined as a tumor regression observed outside and at a distance of the irradiation fields. The potential application of this effect of treatment in disseminated cancers is a fast-growing field of research. The optimal therapeutic strategy to achieve this effect remains unknown.

Introduction: Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated., Observation: We report here the case of an unexpected good response after pembrolizumab failure obtained with paclitaxel in a 68-year-old patient with stage IV lung adenocarcinoma. Moreover, the response duration with paclitaxel was more than fourteen months., Conclusion: Our case suggests a mutual potentiation of chemotherapy and immunotherapy, and raises the issue of the treatment sequence to favor., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)