Alternative Dosing Regimen of Exemestane in a Randomized Presurgical Trial: The Role of Obesity in Biomarker Modulation

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4-6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)\u3c or ≥30 kg/

Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial

IMPORTANCE: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events. OBJECTIVE: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021. INTERVENTIONS: Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery. MAIN OUTCOMES AND MEASURES: Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry. RESULTS: A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was -89%, -85%, and -60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was -3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, -5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of -7.5%, -5.0%, and -4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and -17.0%, -9.0%, and -7.0% for progesterone receptor, respectively. Sex hormone-binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting

Knowledge Graphs Evolution and Preservation -- A Technical Report from ISWS 2019

One of the grand challenges discussed during the Dagstuhl Seminar "Knowledge Graphs: New Directions for Knowledge Representation on the Semantic Web" and described in its report is that of a: "Public FAIR Knowledge Graph of Everything: We increasingly see the creation of knowledge graphs that capture information about the entirety of a class of entities. [...] This grand challenge extends this further by asking if we can create a knowledge graph of "everything" ranging from common sense concepts to location based entities. This knowledge graph should be "open to the public" in a FAIR manner democratizing this mass amount of knowledge." Although linked open data (LOD) is one knowledge graph, it is the closest realisation (and probably the only one) to a public FAIR Knowledge Graph (KG) of everything. Surely, LOD provides a unique testbed for experimenting and evaluating research hypotheses on open and FAIR KG. One of the most neglected FAIR issues about KGs is their ongoing evolution and long term preservation. We want to investigate this problem, that is to understand what preserving and supporting the evolution of KGs means and how these problems can be addressed. Clearly, the problem can be approached from different perspectives and may require the development of different approaches, including new theories, ontologies, metrics, strategies, procedures, etc. This document reports a collaborative effort performed by 9 teams of students, each guided by a senior researcher as their mentor, attending the International Semantic Web Research School (ISWS 2019). Each team provides a different perspective to the problem of knowledge graph evolution substantiated by a set of research questions as the main subject of their investigation. In addition, they provide their working definition for KG preservation and evolution

Chirurgia delle complicanze Linfatiche e dei vasi Chiliferi: l'esperienza della Scuola Genovese.

La stesura di questa Tesi è finalizzata all'inquadramento delle tecniche applicabili alla Chirurgia Generale e Specialistica per la prevenzione e la cura delle complicanze linfatiche e dei vasi chiliferi, quali il Linfedema delle estremità, Chiloperitoneo e Chilotorace

Risk of gonadotoxicity with immunotherapy and targeted agents remains an unsolved but crucial issue

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Microsurgery for groin lymphocele and lymphedema after oncologic surgery

Groin lymphocele (GL) is a frequent complication of inguinal lymph node dissection, and conservative treatment is not always successful. Different surgical methods have been used to treat lymphoceles arising from lymphatics injured during groin surgery. However, they all involve the closure of lymphatics merging at the lymphocele, increasing the risk of postoperative lower limb lymphedema or of worsening lymphedema if already clinically evident. We assessed the efficacy of a diagnostic and therapeutic protocol to manage inguinal lymphoceles using lymphoscintigraphy (LS) and microsurgical procedures. Sixteen GL [seven associated with leg lymphedema (LL)] were studied by LS preoperatively and treated by complete excision of lymphocele and microsurgical lymphatic-venous anastomoses between afferent lymphatics and a collateral branch of great saphenous vein. Lower limb lymphatics were identified intraoperatively using Patent Blue dye injection. Nine patients without lymphedema had complete healing of lymphocele and no appearance of lower limb postoperative lymphedema. The other seven patients with associated secondary lymphedema had complete disappearance of lymphocele and a remarkable reduction of leg volume. Four of them completely recovered without the need of any compression garment, after the first year postoperative. Inguinal lymphocele nonresponsive to conservative treatment can be advantageously studied by LS and successfully treated by microsurgical reconstructive procedures, above all if associated to LL

Update on Pregnancy Following Breast Cancer Diagnosis and Treatment

: Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor-positive disease and BRCA carriers