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The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor's tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody–drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments. [ABSTRACT FROM AUTHOR]

This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF. [ABSTRACT FROM AUTHOR]

The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts—24%) and MET exon 14 skipping mutation (11 pts—18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79–4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08–7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript. [ABSTRACT FROM AUTHOR]

The clinical status and prognosis of patients with human immunodeficiency virus (HIV) infection has dramatically changed in the recent years. Cardiovascular diseases can be related to combined antiretroviral therapy and to the aging of HIV-positive population, resulting in significant mortality and morbidity in those patients. It is crucial to understand whether the HIV-status affects the indications and outcomes of cardiac surgery. A literature search was conducted through electronic databases up to 15 May 2020 following PRISMA guidelines. Variables (i.e. patients characteristics) and endpoints (i.e. postoperative complications) were considered as defined in the original publications. All paper describing post-operative outcomes after cardiac surgery were included. Methodological quality of all included studies was assessed using the Newcastle-Ottawa Scale, the Cochrane Risk of Bias tool and the US Preventive Services Task Force grade. A total of eight studies were included in this systematic review; five studies discussed the outcomes of patients with HIV infection, while three studies compared results based on HIV status. All evidences derived from retrospective observational studies with high variability and poor-to-fair quality. Most patients underwent surgical myocardial revascularization. HIV status is not associated with differences in operative mortality (P = 0.32), postoperative mediastinitis (P = 0.30) or pulmonary infective complications (P = 0.67). Cardiac surgery can be considered safe in HIV-positive patients, and HIV status alone should not be considered as a contraindication for cardiac surgery and should not be considered a risk factor for postoperative mortality or perioperative complications. Further studies are required for patients with AIDS.

Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical–pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the PIK3CA (47%), FGFR (19%) and ERBB2 genes (12%), and to a lesser extent in other genes. Of the 61 patients with pathogenic mutations, 46 (75%) had at least one actionable mutation. Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. Median PFS for these patients was 3.8 months. The study results show that using the NGS test on cancer tissue of metastatic breast cancer could influence the therapeutic choices, considering the small sample size and limited follow-up. About 9% of the study population had their therapy modified based on the results of NGS. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. Methods: We further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. Results: After the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor b (TGF-b) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over-expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLCO<55) compared to controls; thesewere lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan (OGN) thatmight play a key role in the fibrogenic processes. Discussion: Our work showed that the analysis of FFPE samples was able to identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or involved in the immune landscape of lung cancer, thusmaking possible commonmechanisms between lung carcinogenesis and fibrosis progression, two pathological conditions at risk for each other in the real life. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal cancer is a rare gynecologic malignancy. While in a localized disease, concurrent chemoradiation grants local control and better overall survival, in a metastatic setting, the management options are very limited. Furthermore, recurrent cervical, vulvar, and vaginal carcinomas notoriously develop resistance to treatment, and consequently, their prognosis is still poor. Case Presentation: We herein present the case of a woman with a nodal relapse of vaginal carcinoma, effectively treated with third-line immunotherapy. We will also provide a review of the literature on the new therapeutic strategies for advanced vaginal carcinoma, with a focus on pembrolizumab immunotherapy. Conclusion: Pembrolizumab might represent a promising option for the management of vaginal and vulvar cancer, but data to support its use in this setting are still lacking. This case highlights the need for further investigation and trial designs for this rare disease. [ABSTRACT FROM AUTHOR]

Background: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. Results: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients' prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA−/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) still ranks as the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Despite the recent progress in the therapeutic algorithm of the advanced disease with the advent of immune checkpoint inhibitors (ICIs) and next-generation HER2-directed therapies, survival rates remain poor, with a median survival hardly exceeding 12 months. Furthermore, only 40% of patients remain eligible for second- and later-line treatments due to the aggressiveness of the disease and the rapid deterioration of performance status (PS). Thus, current research is focusing either on the identification of novel treatment options or the development of personalized strategies to optimize the continuum of care and ultimately improve patients' outcome. In this article, we provide an overview of the current treatment landscape for advanced GC with a particular emphasis on later-line treatments and outline novel perspectives on the horizon. [ABSTRACT FROM AUTHOR]

Since 2016, the progressive use of immune checkpoint inhibitors (ICIs) starting from second-line treatment has led to an improvement in overall survival in locally advanced and metastatic urothelial cancer (UC). Clinical trials are underway testing the role of ICIs since the first stages of the disease, alone or in combination with standard therapies. This review summarizes the current updated evidence regarding the role of ICIs in the different stages of UC, the ongoing clinical trials exploring the potential benefit of immunotherapy alone or in combination with standard-of-care therapies, as well as the promising association of ICIs with antibody-drug conjugates (ADCs). In the first-line setting, ICIs alone in platinum-unfit patients have shown unconvincing results; the ongoing EV-302 trial will probably suggest enfortumab vedotin plus pembrolizumab as a new effective option. The optimal duration of maintenance immunotherapy is still to be determined, finding a balance with the risk-benefit profile. The clinical benefit of ICIs as second-line treatment is limited to a subset of patients that cannot be definitively established yet. In the next 5 years, a lot of new ADCs will likely emerge for the treatment of UC. [ABSTRACT FROM AUTHOR]