Évaluation du taux de polynucléaires éosinophiles et de sa variation comme facteur prédictif de réponse au nivolumab dans le cancer du rein métastatique

CONTEXTE : Malgré l’amélioration de la stratégie thérapeutique dans le cancer du rein métastatique grâce à l’immunothérapie, seuls 25% des patients seront répondeurs. Des biomarqueurs prédictifs de réponse sont actuellement étudiés mais restent insuffisants.OBJECTIF : Étudier le taux de PNE et sa variation sous nivolumab comme facteurs prédictif et pronostique de réponse dans le cancer du rein métastatique.MÉTHODES : Il s’agissait d’une étude rétrospective incluant les patients atteints d’un cancer du rein métastatique traités par nivolumab. Le taux de PNE et sa variation sous ICI à 6 semaines ont été relevés. Le changement relatif a été catégorisé en trois groupes ≥10% baisse, pas de changement, et ≥10% hausse. Des analyses univariées et multivariées ont été conduites pour déterminer l’impact de ces facteurs sur la réponse à la première évaluation, la SSP et la SG.RÉSULTATS : Soixante-cinq patients ont été inclus dans cette étude. Le suivi médian était de 16.6 mois. Une hausse des PNE et du changement relatif étaient associés à une bonne réponse au nivolumab (p=0.012 et p=0,024). Pour les patients présentant une diminution de 10% du changement relatif, la SSP était réduite significativement par rapport aux deux autres groupes (p=0.0044 et p=0,03). L’augmentation relative des PNE était un facteur indépendant de meilleure SG par rapport aux paramètres de l’IMDC (HR=3.3 [1.45-7.4] ; p=0.004). CONCLUSION : Les variations de PNE à 6 semaines de nivolumab étaient associées à un meilleur pronostique, et pourraient être des biomarqueurs efficients de réponse au nivolumab pour les patients atteints d’un cancer du rein métastatique

Eosinophil counts as a relevant prognostic marker for response to nivolumab in the management of renal cell carcinoma: a retrospective study

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Mutation of Tp53 in a Patient with Aggressive Central Nervous System Solitary Fibrous Tumor/Hemangiopericytoma

International audienceIntroduction: Central Nervous System (CNS) Solitary Fibrous Tumor (SFT) / Hemangiopericytoma (HPC) is a fibroblastic mesenchymal tumor of the meninges that accounts for < 1% of intracranial tumours. The natural history of CNS SFT / HPC is characterized by a high rate of local (60%) and distant (20%) failure following gross total resection (GTR), and treatment options are limited. The identification of new genomic markers could be of interest to improve the understanding and management of CNS SFT / HPC. We present the results of a search for molecular alterations by next-generation sequencing (NGS) in a patient diagnosed with CNS SFT / HPC who experienced rapid distant failure. Case Description: A 64-year-old Caucasian man was diagnosed with a right hemisphere extra-axial frontal tumor after being referred for persistent headaches in October 2017. The patient underwent surgical resection followed by adjuvant radiation therapy of the operative cavity. A diagnosis of grade III HPC of the CNS was established. A diffuse metastatic recurrence with multiple bone lesions occurred rapidly after the initiation of radiation therapy. In July 2018, a CT-guided biopsy of the left iliac crest confirmed a highly proliferative metastatic recurrence and a FoundationOne CDx TM test was performed, which showed a somatic mutation of the tumor suppressor gene TP53 (Tumor Protein p53) (R175H). The microsatellite status was stable and the Tumor Mutational Burden (TMB) was low (1 Muts/Mb). A massive disease evolution of the disease occurred in September 2018. The patient died in November 2018 after neurological decline. Conclusion: This case report shows that an anatomopathological examination alone is insufficient to correctly classify these rare tumors and predict their aggressiveness. In this case report, the somatic mutation of TP53 (R175H) was associated with a very poor prognosis (survival of 13 months). Further studies including systematic NGS of CNS SFT / HPC are warranted to investigate the role of TP53 in prognostic assessment to adapt future treatment strategies

Body Mass Index, Sarcopenia and Their Variations in Predicting Outcomes for Patients Treated with Nivolumab for Metastatic Renal Cell Carcinoma

International audienceIntroduction : The advent of immune checkpoint inhibitors (ICI) such as nivolumab has enabled outcomes for metastatic renal cell carcinoma (mRCC) to be improved. Although, only around 25% of patients respond to these therapies without being able to formally identify them. Datas on relevant predictive markers are still laking. The obesity paradox has been shown as a relevant prognostic marker in mRCC with better outcomes for obese patients. Nevertheless, the impact of weight variation and the presence of sarcopenia during ICI is not known for now. Methods : In a retrospective study, weight and its variations were collected at first day of ICI and at 6 weeks of treatment. Scanographic imagery was used to define the skeletal muscle index (SMI) as a reflect of sarcopenia. The impact of these parameters as predictive and prognostic factors for mRCC with nivolumab was evaluated. Results : A higher BMI at baseline was significantly associated with response at the first scan (p=0.036). Longer OS was observed for patients with a weight gain compared to the group with weight loss (p=0.00028). Median OS for sarcopenic patients was 17.2 months, and 31.6 months for the non-sarcopenic group of patients, but there was no statistical difference. Conclusion : This trial showed that a higher BMI and weight gain during nivolumab treatment were good predictive markers for outcomes in mRCC with nivolumab. Sarcopenia and variations in SMI could thus be of interest, but further studies are required