Search

Niskogradusni serozni karcinom jajnika (LGSOC) manje je agresivan i ima bolji klinički ishod u usporedbi s visokogradusnim seroznim karcinomom jajnika (HGSOC). Kirurško liječenje s pokušajem maksimalne citoredukcije važno je i opravdano zbog relativne kemorezistencije ovog tumora. Stadije bolesti IA-IB trebalo bi klinički pratiti nakon primarne citoredukcije, dok su kliničko praćenje, kemoterapija ili hormonska terapija predložene mogućnosti za stadije bolesti IC-IIA. Bolesnice stadija IIB-IV liječe se kemoterapijom sastavljenom od karboplatina i paklitaksela tijekom 6 ciklusa koju slijedi hormonska terapija, najčešće inhibitorima aromataze, ili pak samom hormonskom terapijom do progresije bolesti ili neprihvatljive toksičnosti. Kirurško liječenje, kemoterapija i hormonska terapija također se koriste za bolesnice s povratom bolesti. U tijeku su klinička istraživanja ciljanom terapijom, posebno s inhibitorima mitogenom-aktiviranih proteinskih kinaza (MEK) i inhibitorima kinaza ovisnih o ciklinu (CDK). Dodatna istraživanja genomike LGSOC-a, u cilju boljeg definiranja aktivacije genskih mutacija uključenih u karcinogenezu, neophodna su radi poboljšanja prognoze ove zloćudne bolesti.

Breast cancer; Cardiotoxicity; Pharmacogenomics Cáncer de mama; Cardiotoxicidad; Farmacogenómica Càncer de mama; Cardiotoxicitat; Farmacogenòmica Pharmacogenomics is an emerging field in oncology, one that could provide valuable input on identifying patients with inherent risk of toxicity, thus allowing for treatment tailoring and personalization on the basis of the clinical and genetic characteristics of a patient. Cardiotoxicity is a well-known side effect of anthracyclines and anti-HER2 agents, although at a much lower incidence for the latter. Data on single-nucleotide polymorphisms related to cardiotoxicity are emerging but are still scarce, mostly being of retrospective character and heterogeneous. A literature review was performed, aiming to describe current knowledge in pharmacogenomics and prediction of cardiotoxicity related to breast cancer systemic therapies and radiotherapies. Most available data regard genes encoding various enzymes related to anthracycline metabolism and HER2 polymorphisms. The available data are presented, together with the challenges and open questions in the field. This study was supported by a grant from Percy Falks Stiftelse to A.P.

Kévin Jean,1,2 Ahmed Tawheed,3 Liem Binh Luong Nguyen,4 Tarek Heikal,5 Usama Eldaly,5 Neveen Elhadidy,6 Ahmed Elghaieb,7 Ahmed Aboudonia,7 Laura Tondeur,1 Amélie Dublineau,4 Arnaud Fontanet,2,4 Mohamed El-Kassas3 1Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France; 2Unité PACRI, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France; 3Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France; 5Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt; 6Pharmaceutical Services Department, Damietta Oncology Center, Damietta, Egypt; 7Radiology Department, Damietta Oncology Center, Damietta, EgyptCorrespondence: Kévin Jean, Laboratoire MESuRS, Conservatoire national des arts et métiers, 292 rue Saint Martin, Paris, 75003, France, Email kevin.jean@lecnam.netIntroduction: We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally.Methods: We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients’ final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan–Meier curves and differences in restricted mean survival time (RMST).Results: Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p< 10− 3). Overall patient’s survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months.Discussion: Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.Keywords: hepatocellular carcinoma, liver cancer, Egypt, staging system, survival, epidemiology

BackgroundOX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949.MethodsPhase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics.ResultsEighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1–9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs.ConclusionNo safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors.Trial registration numberNCT02923349.