Renal tumor biopsy does not increase the risk of surgical complications of minimally invasive partial nephrectomy.

BACKGROUND: For patients with cT1 renal lesions, Partial Nephrectomy (PN) is the gold standard treatment. However, 20% of small renal masses are benign, situation in which the PN is an overtreatment. The percutaneous Renal Tumor Biopsy (RTB) may lower the risk of overtreatment as there is a 90% concordance rate on histotype between the RTB and the final pathology. It has been suggested that the RTB could increase the difficulty of the PN and increase the risk of surgical complications. OBJECTIVE: To compare surgical outcomes and complications of PN with or without previous RTB. DESIGN, SETTING, AND PARTICIPANTS: monocentric retrospective review of patients who underwent laparoscopic or robotic-assisted PN between January 2012 and December 2019. MEASUREMENTS: perioperative complications were recorded using Clavien-Dindo classification, peroperative data included operative time, clamping time and blood loss, and histological outcomes of RTB and PN. RESULTS AND LIMITATIONS: In total, 163 patients were included in our study. There were significantly less benign lesions in PN with prior RTB: 7% (4/56) vs. 20% (22/107) without prior RTB (P=0.03). There were no significant differences regarding Clavien-Dindo>2 perioperative complications with respectively 7% (4/56) vs. 10% (11/107) (P=0.57). Same goes for peroperative data such as duration of surgery (P=0.81), warm ischemia (P=0.07) and blood loss (P=0.13). CONCLUSIONS: RTB does not increase the risk of surgical complications of PN and may reduce the risk of small renal masses overtreatment.

[The circulating PD-L1: An emerging predictive biomarker for immune checkpoint inhibitors response]. / Le taux circulant de PD-L1 : un biomarqueur émergent de réponse aux inhibiteurs de checkpoints immunitaires.

Immune checkpoint inhibitors (ICI) have recently become the standard of care for many metastatic solid tumors, with considerable improvements in patient prognosis. However, a non-negligible proportion of patients does not respond to this type of treatment, making it essential to identify predictive factors of this response in order to better adapt the therapy. Among the biomarkers that have been most extensively studied in recent years, tumor PD-L1 levels come out on top, with controversial results for predicting response to ICI. The determination of circulating PD-L1 (or soluble PD-L1) in peripheral blood seems to be an interesting emerging biomarker. Indeed, several studies have investigated its prognostic value, and/or its potential predictive value of response to immunotherapy, and it would appear that there is a correlation between the level of soluble PD-L1 and the level of tumor aggressiveness and therefore prognosis. Furthermore, the results suggest that higher PD-L1 levels are associated with a poorer response to immunotherapy, although this remains to be confirmed in large-scale studies.

[CAR-T cells development in solid tumors]. / Développement des CAR-T cells dans les tumeurs solides.

CAR-T cells have produced very promising results in the field of onco-hematology and have been rapidly approved for marketing in France for several years now. In solid tumors, current results are more disappointing. Indeed, many hurdles come in the way. Tumor vascularization, the strongly immunosuppressive microenvironment, the loss of the target antigen as well as T cell exhaustion are part of the explanation of those results. Hence many researchers are working to develop strategies to counteract these resistance mechanisms. Arming CAR-T cells with BiTEs, with immune checkpoint inhibitors or with interleukins seem to be effective ways to improve antitumor efficacy. Other strategies including vaccines association or local delivery of the CAR-T cells look very promising. Many Phase I studies are investigating these new strategies and are expected to improve the previous results obtained to date in this area.

[T cell-based immunotherapies in solid tumors]. / Approches d'immunothérapie cellulaire T dans les tumeurs solides.

In solid tumors, adoptive T cell therapies based on ex vivo amplification of antitumor T cell are represented by three main complementary approaches : (i) tumor infiltrating lymphocytes (TILs) which are amplified in vitro before reinjection to the patient, (ii) chimeric antigen receptor (CAR) engineered T cells and (iii) T cell receptor (TCR) engineered T cells. Despite encouraging results, some obstacles remain, such as optimal target selection and tumor microenvironment. In this Review, we discuss pros and cons of these different therapeutic strategies that may open new perspectives in the treatment of solid tumors.

[Some important breakthroughs in oncology and hematology in 2018: A selection by the editorial board of Bulletin du Cancer]. / Retours sur quelques importantes avancées en oncologie et hématologie de 2018 : une sélection du comité de rédaction du Bulletin du Cancer.

The editorial board of Bulletin du Cancer presents some hot topics published or presented in major oncology meetings in 2018. This selection is related to pediatric oncology and to solid and hemato-malignancies in adults, with immunotherapy approaches (checkpoints or CAR-T) as one of the major breakthroughs. Putative impacts on daily practices are discussed, in order to detail what will really change our practice.

Développement des CAR-T dans les tumeurs solides.

DEVELOPMENT OF CAR T-CELLS IN SOLID TUMORS: CHALLENGES AND PERSPECTIVES: While Chimeric Antigen Receptor (CAR) T-cells have shown outstanding results in some hematologic malignancies, studies in solid tumors are less encouraging with poor response rates. Several factors can account for this lack of efficiency in solid tumors: heterogeneous expression or absence of specific target antigen (and so higher risk of toxicity), immunosuppressive microenvironment, homing and tumoral trafficking issues or lack of CAR T-cell persistence. Different approaches can be considered to overcome these resistance mechanisms: bispecific CARs, use of logic gates, combination with immune checkpoint inhibitors, engineered CAR T-cells resistant to immunosuppressive molecules, addition of chemokines or enzymes, combination with oncolytic virus, intra-tumoral administration, selection of memory T cell subpopulations and development of armored CAR T-cells secreting cytokines such as IL-12, -15 or -18. Last generation optimized CAR T-cell design should thus improve therapeutic efficiency. CAR-T cells may represent in a near future a therapeutic breakthrough also in solid tumors, especially in cold tumors and/or tumors lacking MHC class I expression. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.

Traitement par cellules CAR-T : état des lieux de leur utilisation aux États-Unis en 2018.

CAR-T THERAPY: CURRENT USE IN THE UNITED STATES IN 2018: Treatment with T-cells engineered with chimeric antigen receptors (CAR T-cell therapy) has been a field of intense research in the United States since the 1980s. The recent approval in August 2017 of Kymriah (tisagenlecleucel) opened the door to broader access to CAR T-cell therapy outside of clinical trials. Here, we aim to give the reader a practical summary of the current practices in the US when considering a patient for CAR T-cell therapy. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.

ARLTS1, potential candidate gene in familial aggregation of hematological malignancies.

INTRODUCTION: Genetic predisposition to familial hematological malignancies was previously described through several epidemiological analyses, but the genetic basis remains unclear. The tumor-suppressor ARLTS1 gene was previously described in sporadic hematological malignancies and familial cancer context. METHODS: In this study, we sequence the ARLTS1 gene in 100 patients belonging to 88 independent Tunisian and French families. RESULTS: After gene sequencing, we report 8 genetic variations, most of which were previously reported in several cancer forms. The most common variants were W149X and C148R and were previously associated to B-cell chronic lymphocytic leukemia and to high-risk of familial breast cancer. CONCLUSIONS: These results emphasize the fact that ARLTS1 gene mutations can be considered as a potential predisposing factor in familial hematological malignancies and other several cancer forms.

[Tumour sequencing: Evolutions and revolutions]. / Séquençage des tumeurs : évolutions et révolutions.

For some years now, we have entered the genomic age of tumour genotyping from a medical point of view. Technological breakthroughs in both biology and information science now allow a genomic analysis of cancers in everyday medical practice with, in some case, a major impact on patient care not only for the choice of therapy (i.e. EGFR mutations in lung adenocarcinoma), but also for diagnosis and monitoring of the disease. Tumour genotyping is performed from formalin-fixed paraffin-embedded tissues used for diagnosis of cancer. However, new approaches have emerged, with for example the more and more spread use of "liquid biopsies". Genotyping of a gene panel implicated in carcinogenesis is now routinely performed in some cancer types, with the help of high-throughput sequencers, and it is likely that improvement of these machines will make tumour genotyping easier and more accessible in the near future. Nevertheless, the current challenge is not anymore detection of molecular alterations, but their relevant interpretation, so as to be the most useful in patient care.

[High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors]. / Chimiothérapie à hautes doses comme stratégie pour contourner la résistance aux médicaments dans les tumeurs solides.

The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.