Ospedaliero di Castelfranco Veneto

Epidemiological and retrospective studies suggest that letrozole may improve outcomes in low-grade serous carcinoma of the ovary (LGSCO) by targeting estrogen-driven tumor progression. We designed a multicenter, randomized, open-label, phase III trial to compare letrozole versus standard chemotherapy (carboplatin plus paclitaxel) in prolonging progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), quality of life (MENQoL), and musculoskeletal pain (BPI-SF). Translational objectives explore mutational and expression profiles (NGS, RAD51/BRCA1 foci) and circulating tumor DNA (ctDNA) as markers of treatment response. Eligible patients are postmenopausal women with stage III-IV ER/PgR-positive LGSCO after primary cytoreductive surgery. Patients are randomized 1:1 to letrozole 2.5 mg daily until progression or unacceptable toxicity, or to carboplatin-paclitaxel for 6-8 cycles. Disease progression is assessed by RECIST, CA-125, and imaging every 3-6 months. As of March 2025, 46 patients have been randomized (23 per arm). Preliminary analysis shows a favorable safety profile for letrozole compared with chemotherapy. Early findings suggest letrozole is well tolerated and may represent a viable therapeutic option for hormone receptor-positive LGSCO. Ongoing molecular and clinical analyses will clarify its role in this rare subtype. ClinicalTrials.gov Identifier: NCT05601700; https://clinicaltrials.gov/study/NCT05601700.

511 Background: Local therapy for managing metastatic sites may be a beneficial frontline approach for patients with mRCC. However, existing data are limited to retrospective studies involving patients treated mainly with tyrosine kinase inhibitors (TKIs). This study aims to characterize the initial LT approach prior to the initiation of immuno-TKI combinations. Methods: ProPaxi is a prospective observational study that enrolled pts treated with the Pembrolizumab/Axitinib (Paxi) combination as first-line therapy. We conducted a retrospective analysis of pts characteristics and outcomes when LT was used as a frontline approach. Results: From December 2020 to September 2023 ProPaxi study enrolled 170 pts, of whome 56 (33%) received LT as frontline therapeutic approach. The majority had clear-cell histology (86%). Approximately half of pts (46%) had synchronous metastasis and nephrectomy was performed in 60% of cases. Stratifying by IMDC criteria at the time of the start of systemic treatment, 11 pts (20%) were classified as favorable-risk, 32(59%) as intermediate-risk, and 12 (21%) as poor-risk. Additionally, around half of pts (52%) had time-to-treatment start longer than 1 year as prognostic factors; this was the only prognostic factor in 18% of cases. Bone was the most commonly treated metastatic site, accounting for 50% of cases, followed by the lung (14%) and brain (13%). The types of LT administered were as follows: radiotherapy (46%), surgery (43%), and other (11%). The objectives of treatment included: pain control (30%), curative treatment for local complications (29%), prevention of local complications (29%), and achieving complete response or delaying systemic treatment (30%). In one-fifth of patients (21%), there were multiple objectives for the local therapy. Radiotherapy was the most frequently used treatment for pain control, applied in 94% of cases. For managing local complications, surgery and radiotherapy were also common, accounting for 31% and 38%, respectively. Both treatments were equally utilized (38%) for the prevention of local complications. Surgery was the predominant approach for achieving complete response or delaying systemic treatment, used in 88% of cases. The mean time from metastasis diagnosis to treatment start was 7.9 months (95% CI: 4.1–11.2) for patients who received LT versus 2.5 months (95% CI: 1.9–3.1) for those who did not (p < 0.001). No significant differences were observed in progression-free survival (PFS) or overall survival (OS). Conclusions: This analysis describes for the first time the current approach to implementing LT for the management of mRCC. Thus, LT emerges as a valid and established option even in the era of immuno-TKI combinations. The objective of therapy appears to be the key factor in determining the choice of treatment in clinical practice.

Acute promyelocytic leukemia (APL) now accounts for approximately 10% of acute myeloid leukemias (AML) and is classified among those with specific molecular abnormalities, presenting with the t(15;17) translocation in 98% of cases, which is closely associated with clinical manifestations of the disease. Advances in research and a deeper understanding of the molecular etiopathogenesis of the disease have led to the use of non-chemotherapeutic drugs, such as ATRA (all-trans retinoic acid) and ATO (arsenic trioxide), both of which have significantly improved the prognosis and changed the course of the disease. However, for these therapies to have a positive impact, they must be administered as promptly as possible. Diagnosis, therefore, requires both fast and easily applicable diagnostic analytical methods and healthcare professionals capable of conducting investigations within a very tight time frame, to ensure that the therapeutic efficacy available can be maximized. In this diagnostic pathway, the laboratory plays a crucial role, performing essential tests such as complete blood cell counts (CBC) and the critical identification, recognition and reporting of atypical promyelocytes. These cells, with their peculiar morphological characteristics, are the key markers of the pathology. According to current recommendations, in cases of suspected APL, while waiting for molecular confirmation - essential in the management of the pathology - specific therapy should be started after examining the peripheral blood and bone marrow smear and evaluating the presence of coagulopathy. Thus, while more in-depth investigations and confirmatory tests are being conducted, morphology can provide early clues necessary for a presumptive diagnosis, both for specific cytogenetic/molecular subtypes of APL. This view, shared by leading experts in the field, emphasizes the importance of morphology in providing a high degree of diagnostic accuracy within a very short time frame, especially when corroborated by immunophenotyping studies. This paper deals with the current role of microscopic morphology to the early diagnosis of APL, as well as the importance of trained laboratory personnel capable of recognizing the disease early using and interpreting basic tests, whether in peripheral laboratories, or hub & spoke systems, or integrated multidisciplinary specialist networks. In real-world scenarios, these setups represent both the present and the future, where efforts must focus on improving both the prognosis and the quality of life of patients affected by this severe pathology.

Future Cities and Environment aims to tackle the environmental impact of cities and challenges to their long-term sustainability, on both the local and global scale. Through high quality and multi-disciplinary research on developments being introduced in our existing cities, as well as those which could become reality in the cities of the future, the journal provides a forum for discussion on a more enlightened approach to city design. We publish research in the areas of transport, urban planning, architecture and design, and energy and infrastructure and accept both fundamental and applied research, critical reviews and case studies, including experimental development, demonstration and computer modelling. For more information on our submission and author guidelines. As a fully open access journal, all FCE publications have a broad audience from around the world and are free to read and download.

An efficient treatment plan using a temporary anchorage device should be built following the principle of reducing the number of tads to obtain a multiple biomechanical advantage. The following case report concerns the Biga system, a strategy that supports orthodontists during class II corrections and vertical control through treatment. A 12-year-old girl with a high angle of skeletal class II was selected. A novel biomechanical strategy was effectively applied using two tads on the upper arch to obtain sequential distalization of the upper teeth and to correct the lower arch spee curve using third-class elastics. Eventually, on the same tads, a double cantilever was applied to control the overbite and intrusion during incisors' retraction. The Biga system is an easy biomechanical strategy that ensures the three-dimensional control of treatment mechanics in class II patients.

Background: Pelvic lymphnode dissection (PLND) is an integral part of surgical treatment for localized intermediate and high-risk prostate cancer. The most common complication of PLND is lymphocele formation. In the majority of cases the development of lymphoceles is clinically asymptomatic but in case of symptomatic/infected lymphocele an active treatment is required. The aim of this article is to analyse the current evidence on the treatment of symptomatic/infected lymphocele trough robotic approach. Materials and Methods: The search was applied to PubMed, EMBASE, and Cochrane databases with following terms: “lymphocele”, “symptomatic”, “infected”, “robot-assisted AND radical prostatectomy”, “robot-assisted”, “treatment”. Results: The search identified three series focusing on the treatment by robot-assisted approach of symptomatic and/or infected lymphocele. The main and most frequent reason for performing the robotic treatment was an infected lymphocele, the median time from robot-assisted radical prostatectomy and PLND to robotic treatment of lymphocele was 118 days (range 30-240). Robot-assisted treatment was successful in all reports. Conclusions: The drainage of lymphocele with the robot-assisted approach appeared safe, feasible, and with satisfactory outcomes for the definitive treatment of symptomatic/infected lymphocele.

Abstract BACKGROUND In the phase 2 REGOMA trial, regorafenib improved overall survival, as compared to lomustine, for glioblastoma (GBM) patients at first progression after chemoradiation. Here, we present the results of a real-life multicentre study that analysed response to treatments, tolerability, and outcome of GBM patients treated with regorafenib at first tumour progression. PATIENTS AND METHODS Regorafenib was given following an escalation dose protocol (1st cycle: 80 mg/day for 2 weeks, then 120 mg/day for one week; 2nd cycle: 120 mg/day for 2 weeks, then 160 mg/day for one week; 160 mg/day from the 3rd cycle). Progression-free survival (PFS) and overall survival (OS) were defined as time from regorafenib initiation and disease progression or death. RESULTS From January 2020 to January 2022, 66 GBM patients were included. Median age was 60.0 years. MGMTp methylation was found in 30 patients (45.5%). Median dose was 120 mg/day 21q28 day, which was lower than that used in REGOMA trial (149 mg). Median PFS (mPFS) was 2.7 months and median OS (mOS) 7.1 months. RANO response to regorafenib was partial response (PR) in 10 (15.1%), stable disease in 14 (21.2%), and progressive disease in 42 (63.7%) patients. Forty-six (69.7%) patients presented adverse events of any grade, and 21 (31.8%) grade III-IV toxicity. Two patients only (3.0%) interrupted regorafenib due to toxicity. In a multivariable analysis, factors associated with disease progression were higher age (p = 0.035) and absence of MGMTp methylation (p = 0.024). CONCLUSION In our study, mPFS and mOS were similar to those of the 59 patients enrolled in the regorafenib arm of REGOMA trial (2.7 vs 2.0 months; 7.1 vs 7.4 months, respectively). However, we observed a higher rate of PRs (15% versus 3.0%). Moreover, we had a lower incidence of discontinuations due to toxicity, maybe because of the lower dose intensity.

Summary: The optimal first line management of patients with symptomatic chronic lower extremity peripheral artery disease (PAD) includes secondary prevention of cardiovascular risk factors, pharmacological treatment, and supervised exercise therapy (SET). SET programs have shown to be effective in improving walking performance, functional performance, and quality of life. However, despite a large body of evidence, and despite national and international guidelines recommending SET as first line therapy, SET remains largely underused in patients with chronic PAD. This position paper aims to describe how SET is perceived, its accessibility and structure through Europe. An anonymous web-based survey was used. It comprised 21 questions developed in conjunction with an angiologist and a clinical exercise physiologist specialist in vascular rehabilitation. We had 131 responders from 17 countries. For patients with PAD, SET programs exist only in 59% of European countries. SET reimbursement is available in 41% of countries. SET programs showed to be heterogeneous across countries. Thirty-four percent of the SET programs are PAD-dedicated, while 23% are part of a cardiac rehabilitation program. In addition, among existing SET programs, 65% are dedicated to symptomatic patients with PAD only, 9% to both asymptomatic and symptomatic, 8% to post-revascularized patients only, and 1% to asymptomatic patients with PAD only. Finally, 17% reported not knowing which patients are eligible for enrolment in a SET program. Duration, frequency, and modality of SET also varied from country to country. Overall, these data indicate that a large variability of SET availability and characteristics exists across Europe. Therefore, there is an urgent need to provide detailed guidance to deliver optimal exercise therapeutic care in patients with PAD.