Asthme difficile (définition et mise en évidence de différents profils de patients)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients

Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival

Management of patients with synchronous head-and-neck and lung cancers: SYNCHRON GFPC 15-01 study

Few data have been published on the management of patients with synchronous head-and-neck cancer (HNC) and lung cancer (LC). This observational study was undertaken to describe the management of these patients in multiple centers

PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients.

International audienceThymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival

Role of the YAP-1 Transcriptional Target cIAP2 in the Differential Susceptibility to Chemotherapy of Non-Small-Cell Lung Cancer (NSCLC) Patients with Tumor RASSF1A Gene Methylation from the Phase 3 IFCT-0002 Trial

CERVOXYInternational audienceRASSF1 gene methylation predicts longer disease-free survival (DFS) and overall survival(OS) in patients with early-stage non-small-cell lung cancer treated using paclitaxel-based neoadjuvant chemotherapy compared to patients receiving a gemcitabine-based regimen, according tothe randomized Phase 3 IFCT (Intergroupe Francophone de Cancérologie Thoracique)-0002 trial. To better understand these results, this study used four human bronchial epithelial cell (HBEC) models(HBEC-3, HBEC-3-RasV12, A549, and H1299) and modulated the expression of RASSF1A or YAP1. Wound healing, invasion, proliferation and apoptosis assays were then carried out and the expression of YAP-1 transcriptional targets was quantified using a quantitative polymerase chain reaction. This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of early-stage lung cancer patients receiving perioperative paclitaxel-based treatment compared to gemcitabine-based treatment, identifying IAP-2 as a novel biomarker indicative of YAP-1-mediated modulation of chemosensitivity in lung cancer

Alveolar hemorrhage in anti-basement membrane antibody disease : A series of 28 cases

Anti-basement membrane antibody disease is a rare disorder characterized by the presence of autoantibodies binding to the alveolar and glomerular basement membranes, and mediating both alveolar hemorrhage and acute glomerulonephritis. We retrospectively analyzed 28 cases of anti-basement membrane antibody disease with alveolar hemorrhage proven by bronchoalveolar lavage. The median age of patients at diagnosis was 23 years; 68% were male, 89% were active smokers, and 36% were exposed to some other inhaled agent. At diagnosis, 46% had predominant pulmonary involvement with normal initial serum creatinine. Lung function tests disclosed a restrictive ventilatory defect in 28% (n = 11) and hypoxemia (moderate in 29% and severe in 29%, n 2 1). Carbon monoxide transfer factor was elevated in only 25% (n = 12). Bronchoalveolar lavage was more sensitive than any other criterion for detecting alveolar hemorrhage. After onset of treatment. new hemoptysis or transient worsening of hypoxemia occurred in 29% but did not affect pulmonary outcome. In contrast, worsening of renal function occurred in 33% and adversely affected renal outcome. At last follow-up (median, 2.6 yr; n = 24), all patients were alive and a complete cure was achieved in 50%. Long-term dialysis or renal transplantation was required in 42%, and 8% had mild chronic renal insufficiency. Last chest X-ray was normal in all cases, and no patient had respiratory insufficiency. All patients with predominant pulmonary involvement at presentation maintained independent renal function. In summary, this cohort was characterized by frequent exposure to tobacco smoking and other inhaled agents, and a constantly favorable pulmonary outcome contrasting with frequent chronic renal failure. Renal outcome was excellent in the subgroup of patients with predominant pulmonary involvement

Venous thrombotic events and impact on outcomes in patients treated with first-line single-agent pembrolizumab in PD-L1 ≥ 50% advanced non small cell lung cancer

International audienceBackgroundFew data are available on the impact of venous thrombotic events (VTE) in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunotherapy.MethodsThis is a secondary analysis of the ESKEYP study, a national, retrospective, multicenter study that consecutively included all PD-L1 ≥ 50% mNSCLC patients who initiated first-line treatment with pembrolizumab monotherapy. From May 2017 to November 2019, 845 patients were included (from availability of pembrolizumab in this indication in France to the authorization of the combination with chemotherapy). Impact of VTE and patient characteristics were analyzed.ResultsOf the 748 patients (88.5%) with available data, the incidence of VTE was 14.8% (111/748). At pembrolizumab initiation, Khorana score was ≥ 2 for 55.0% (61/111) of them. Recurrence of VTE was reported for 4 of the 111 patients and 5 had bleeding complications. Patients with VTE were significantly younger, had more frequently long-term corticosteroids treatment and more often liver metastases. Progression-free survival (PFS) was significantly shorter in patients with VTE compared to patients without VTE: 6.1 (95% CI 4.1–9.0) months vs. 8.3 (6.9–10.3) months (p = 0.03). VTE did not significantly impact overall survival (OS): 15.2 (10.0–24.7) months with VTE and 22.6 (18.4–29.8) months without VTE (p = 0.07). In multivariate analysis for PFS and OS, HRs for VTE were 1.3 (0.99–1.71), p = 0.06 and 1.32 (0.99–1.76), p = 0.05.ConclusionThe incidence of VTE appears to be as high with in first-line immunotherapy as with chemotherapy in patients with mNSCLC, with in patient with VTE, a no significant trend for lower PFS and OS in multivariate analysis. more marked impact on PFS than on OS