Durvalumab and tremelimumab in combination with metronomic oral vinorelbine for recurrent advanced cervical cancer: an open-label phase I/II study.

Background: The MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced cervical cancer cohort.

Methods: Patients received tremelimumab (intravenously, 75 mg, every four weeks (Q4W); four cycles max) plus durvalumab (intravenously, 1,500 mg, Q4W; 26 cycles max) and metronomic oral vinorelbine (40 mg, every three weeks (3QW)) until disease progression.

Deep Multiple Instance Learning Model to Predict Outcome of Pancreatic Cancer Following Surgery.

: Pancreatic ductal adenocarcinoma (PDAC) is a cancer with very poor prognosis despite early surgical management. To date, only clinical variables are used to predict outcome for decision-making about adjuvant therapy. We sought to generate a deep learning approach based on hematoxylin and eosin (H&E) or hematoxylin, eosin and saffron (HES) whole slides to predict patients' outcome, compare these new entities with known molecular subtypes and question their biological significance; : We used as a training set a retrospective private cohort of 206 patients treated by surgery for PDAC cancer and a validation cohort of 166 non-metastatic patients from The Cancer Genome Atlas (TCGA) PDAC project.

Efficient Biochemical Method for Characterizing and Classifying Related Amyloidogenic Peptides.

Amyloidosis is a group of proteinopathies characterized by the systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly 40 proteins play a role in these pathologies, and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies.

The effect of tumor downsizing on surgical complexity during nephrectomy after immune checkpoint inhibitors for metastatic renal cell carcinoma.

Purpose: Immune Checkpoints Inhibitors (ICI) have changed the therapeutic landscape of metastatic renal cell carcinoma first-line treatment with complete response (CR) at metastatic sites observed in 10 to 15% of cases. Delayed nephrectomy could be discussed for patients having a clinical benefit from immunotherapy-based treatment. However, it is unclear whether prior immunotherapy exposure adversely influences the complexity of surgery.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

The translocator protein 18 kDa (TSPO) ligand etifoxine in an animal model of anxiety: Line- and sex-dependent effects on emotionality, stress reactivity, spine density, oxytocin receptors, steroids, and microbiome composition.

The treatment of stress-related disorders such as anxiety and depression is still challenging. One potential therapeutical option are neurosteroids. Their synthesis is promoted by ligands of the mitochondrial translocator protein 18 kDa (TSPO).

Efficacy and Safety of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting Transforming Growth Factor-β and Programmed Death-Ligand 1, Plus Chemotherapy in Patients With Stage IV NSCLC.

Introduction: In a phase 1 study, bintrafusp alfa was found to have an encouraging clinical activity in patients with previously treated advanced NSCLC. This study evaluated the safety and efficacy of bintrafusp alfa with chemotherapy in patients with stage IV NSCLC regardless of the programmed death-ligand 1 (PD-L1) expression status.

Methods: In this open-label, phase 1b/2 study (NCT03840915), eligible patients were assigned to one of four cohorts.

Plasma clearance of 5-fluorouracil is more influenced by variations in glomerular filtration rate than by uracil concentration.

Objectives: The use of plasma uracil measurements to detect dihydropyrimidine dehydrogenase (DPD) deficiency is one of the methods for preventing toxicities associated with fluoropyrimidines, including 5-Fluorouracil (5-FU). Unfortunately, this measurement is subject to variations, that may lead to unnecessary dosage reductions and therefore to a reduced efficacy of treatment. Recently, new factors such as hepatic and renal impairment have been proposed as also influencing uracil concentration.

Salvage radiotherapy with volumetric modulated arc therapy (VMAT) for recurrent prostate cancer after high-intensity focused ultrasound (HIFU): A large French retrospective series and literature review.

Background And Purpose: Although not validated as a standard treatment, high-intensity focused ultrasound (HIFU) is increasingly used in the management of localised prostate cancer (PCa). In case of recurrence after HIFU, treatment is currently not standardised. Our aim was to evaluate normofractionated (NFRT) and hypofractionated (HFRT) salvage radiotherapy (RT) using volumetric modulated arc therapy (s-VMAT) with doses used in first-line management of localised PCa.

Overt and hidden polymorphism in the binary system involving the Z- and E- isomers of broparestrol.

Broparestrol has been used as a drug to treat acne in the form of a mixture of its two stereoisomers. Although it has been withdrawn from the market, the binary system is rich in polymorphism and understanding the phase behaviour of the binary system involving the E- and Z-isomers is challenging. Physical mixtures do not immediately give rise to equilibrium phase behaviour, whereas recrystallization often leads to metastable phases and the appearance of stable phases can take years.

Central nervous system complications of immune checkpoint inhibitors: A comprehensive review.

The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management.

Prognostic value of circulating tumor DNA at diagnosis and its early decrease after one cycle of neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer. An ancillary analysis of the CHIVA phase II GINECO trial.

Objective: To evaluate the prognostic impact of circulating tumor DNA (ctDNA) detection at diagnosis (T0) and its early decrease after one cycle (T1) of neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian cancer (EOC) included in the CHIVA trial (NCT01583322).

Methods: Blood samples were collected at T0 and before each administration of NACT. Circulating tumor DNA detection was performed by next-generation sequencing.

Sacituzumab Govitecan in Patients With Relapsed/Refractory Advanced Head and Neck Squamous Cell Carcinoma: Results From the Phase 2 TROPiCS-03 Basket Study.

Purpose: Treatment options for advanced head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and a programmed death-1 (PD-1) inhibitor are limited. Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in HNSCC. Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved for patients with certain previously treated solid tumors.

Local and systemic methotrexate in management of caesarean scar pregnancy.

Study Objective: The aim is to analyze the management of cesarean scar pregnancy (CSP) based on local and systemic Methotrexate, a protocol implemented in a referral center.

Design: This is an observational, retrospective, monocentric, cohort study with a description of the local protocol, treatment results and tolerance profile. Design Classification III.

Prognostic role of extent of resection and adjuvant radiotherapy in de novo anaplastic meningiomas.

Purpose: Grade 3 meningiomas, although rare, are associated with high morbidity and mortality. The respective impacts of extent of surgical resection and adjuvant radiotherapy are still debated. Moreover, anaplastic meningiomas are studied in heterogenous cohort of de novo and progressive anaplastic tumors.