14 research outputs found
Post nephrectomy management of localized renal cell carcinoma. From risk stratification to therapeutic evidence in an evolving clinical scenario
No full textStandard treatment for localized non-metastatic renal cell carcinoma (RCC) is radical or partial nephrectomy. However, after radical surgery, patients with stage II-III have a substantial risk of relapse (around 35%). To date a unique standardized classification for the risk of disease recurrence still lack. Moreover, in the last years great attention has been focused in developing systemic therapies with the aim of improving the disease-free survival (DFS) of high-risk patients, with negative results from adjuvant VEGFR-TKIs. Therefore, there is still a need for developing effective treatments for radically resected RCC patients who are at intermediate/high risk of relapse. Recently, interesting results came from immune-checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway, with a significant benefit in terms of disease-free survival from adjuvant pembrolizumab. However, the con-flicting results of diverse clinical trials investigating different ICI-based regimens in the adjuvant setting, together with the still immature data on the overall survival advantage of immunotherapy, requires careful consider-ations. Furthermore, several questions remain unanswered, primarily regarding the selection of patients who could benefit the most from immunotherapy. In this review, we have summarized the main clinical trials investigating adjuvant therapy in RCC, with a particular focus on immunotherapy. Moreover, we have analyzed the crucial issue of patients' stratification according to the risk of disease recurrence, and we have described the possible future prospective and novel agents under evaluation for perioperative and adjuvant therapies
Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel-Lindau syndrome-related kidney cancers
No full textHereditary and sporadic renal cell carcinomas (RCCs) are often associated with Von Hippel-Lindau (VHL)-gene inactivation. Patients with VHL disease have an increased risk of RCC, leading to bilateral nephrectomy and dialysis. In patients with advanced RCC, no standard second-lines are available after progression to immune checkpoint inhibitors (ICIs), and new agents are required to manage progression. HIFs have emerged as a promising target for metastatic RCC patients who have progressed to ICI-based combinations, as well as for those with RCC and VHL syndrome where the goal is to delay surgery and/or and preserve kidney function and avoid dialysis. This review describes the available evidence supporting the use of the small-molecule HIF-2 alpha inhibitor, belzutifan (MK-6482), as well as other new anti-HIF molecules that have demonstrated significant efficacy in VHL disease-related RCCs as well as for sporadic RCC that has progressed after the use of ICI-based combinations
Theranostics revolution in prostate cancer: Basics, clinical applications, open issues and future perspectives
No full textIn the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment
Highlights from the 2024 ASCO Genitourinary Symposium: focus on urothelial and prostate cancer
No full textThe 2024 ASCO Genitourinary Cancer Symposium, this year celebrating the 20th anniversary, delved into key advancements in urothelial carcinoma (UC) and prostate cancer (PC). For UC, insights emerged from adjuvant pembrolizumab for muscle-invasive urothelial carcinoma, and from the efficacy of the EV-302 study of enfortumab vedotin +pembrolizumab in the metastatic setting. In PC, adjuvant therapy with high-dose radiotherapy schedules plus long-t erm ADT was explored. In metastatic castration-resistant PC, highlights included a novel combo (cabozantinib+atezolizumab) for poor prognosis patients; confirmed benefits of ARSI+PARPi in BRCA-mutated patients; and safety considerations for ARSI treatments. The symposium continued its role as an indispensable platform for shaping specialized oncological care
Theranostics revolution in prostate cancer: Basics, clinical applications, open issues and future perspectives
No full textIn the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment
«Every part full of these involvements». The Intimate and the Global in «Emergency» (2022) by Daisy Hildyard
No full textIl presente articolo si propone di analizzare il romanzo Emergency (2022) di Daisy Hildyard per mostrare come il testo esplori la complessa rete di interconnessioni messa a nudo dal cambiamento climatico e dalla recente pandemia. Verrà esaminato come l\u27autrice utilizzi modalità tradizionali (p.es. il genere pastoral) per rivisitarne ed espanderne la portata in un’epoca nella quale locale e globale coesistono.This article endeavours to analyse how Daisy Hildyard’s novel Emergency (2022) explores the complex and often ambivalent enmeshing of life on Earth, bared by climate change and the recent pandemic. It will also be shown how the author uses traditional modes (i.e. the pastoral) to revisit and expand its scope in a time when the global and the local are always encroaching on each other
New approaches to prototype 3D vascular-like structures by additive layer manufacturing
No full textIn this paper preliminary results are summarized on the use of a combined Additive Layer Manufacturing
(ALM) and indirect replication methodology to reconstruct reticular-like, three-dimensional (3D) structures mimicking the 3D vascular network of the adult human thyroid gland. In a first step, we developed a fractal-like algorithm capable of modeling the native arterial distribution of the adult thyroid lobe, allowing for
vascular growth within its geometrical domain. Although some arbitrary simplifications were adopted, yet the
vascular density of the computational simulation showed good consistency with that of a native thyroid lobe. In
a second step, single vascular branches were prototyped based on the STL output of the algorithm and ALM
techniques, up to the achievement of a model having satisfactory geometrical/morphological accuracy. In a
third step, the problem of reproducing the vascular geometry with a biocompatible polymer was addressed, and different protocols of replication technology were evaluated. Limits and possible methodological solutions are discussed
Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A Phase 2 Study
No full textBackground and Objective: Combinations of VEGFR-TKIs plus ICI against PD1/PD-L1 are the standard first-line therapy for patients with mRCC, irrespective of the prognostic class. This study aims to investigate the feasibility and safety of withdrawing the VEGFR-TKI but continuing the anti- PD1/PD-L1 in patients who achieve response to their combination. Methods: This was a single-arm phase 2 trial in patients with treatment naïve mRCC with prior nephrectomy, without symptomatic/bulky disease and no liver metastases. Enrolled patients received axitinib+avelumab, after 36 weeks of therapy those who achieved tumor response interrupted axitinib and continued avelumab maintenance until disease progression. The primary endpoint was the rate of patients without progression eight weeks after the axitinib interruption. Secondary endpoints were the median value for progression free (mPFS) and overall survival (mOS) and the safety in the overall population. Key Findings and Limitations: 79 patients were enrolled and 75 evaluated for efficacy. A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after eight weeks and thus achieving the primary endpoint. The mPFS of the overall population was 24 months while the mOS was not reached. The ORR was 76% (12% CR, 64% PR), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of AEs of any grade was 59% and 3% for grade 3 or 4. This study was limited by the lack of the comparative arm. Conclusions and Clinical Implications: The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of response to the VEGFR-TKI+ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance led to decreased side effects and should be further investigated as a new strategy to delay tumor progression
Early primary tumor response in metastatic RCC patients treated with immune checkpoint inhibitors-based combinations
No full textBackground:
25-30% of renal cell carcinoma presents with metastases (mRCC) at diagnosis.
The activity of immune checkpoint inhibitor (ICI)-combinations on the primary tumor (PT) is debated.
Patients andMethods:
mRCC patients (pts) with PT who received first-line nivolumab plus ipilimumab (N/I) or pembrolizumab plus axitinib (P/A) were included. We investigated the early primary tumor response (EPTR) at the first radiological assessment.
Results:
73 pts were included. The median early reduction of the PT longest diameter was 12.4% with P/A versus 6.2% with N/I (p = 0.42). We evaluated if the type of EPTR could affect the metastases response. Among pts with PT stable disease (SD), 8.3% had metastatic disease progression (PD) with P/A and 34.8% with N/I. Early PT partial response (PR) was associated with no metastatic PD with both N/I and P/A. The 2 pts with PT PD had also metastatic PD to P/A. Of the 3 PT with PD to N/I, 1 had metastatic SD and 2 PD. In the overall population, of the 94.1% without PT progression (PR+SD), 47.5% had metastatic PR, 35.6% SD, 16.9% PD.
Conclusions:
ICIs-combinations achieved an early PT PR in about 10-20%, without any complete responses. Only a small percentage of PT had an early PD, mainly associated with metastatic PD. However, among those PT without an early progression, metastatic PR can be achieved in approximately 50% of cases
A combined Additive Layer Manufacturing / Indirect Replication method to prototype 3D vascular-like structures of soft tissue and endocrine organs
No full textWe describe an innovative methodology combining Additive Layer Manufacturing and indirect replication to reconstruct reticular-like, three-dimensional structures mimicking the vascular network of soft tissue and endocrine organs. Using a fractal-like algorithm capable of modeling the intraparenchymal vascular distribution of these viscera, single intraglandular branches of the human thyroid arteries were prototyped with synthetic resin, based on the algorithmic STL output and ALM techniques. Satisfactory dimensional accuracy was obtained for these models, which were used as masters to evaluate protocols for their indirect replication, through both single and double procedures. Additional studies were conducted using casts of the human kidney arteries, obtained by injection / corrosion of the isolated organ. Satisfactory 3D reproduction of the external morphology of the kidney vessels was achieved. We conclude that our approach has the potential to develop up to the reconstruction with biomaterials of an entire, intraparenchymal vascular tree of soft tissue and endocrine organs
