Prognostic immunotherapy score (PIS) in patients with advanced urothelial carcinoma treated with pembrolizumab: real-world data and validation from ARON-2 dataset.

Recent years have seen the development and advent of novel combinatorial strategies based on immunotherapy, and immune checkpoint inhibitor (ICI) - based treatment has established itself as a mainstay in the treatment of metastatic urothelial carcinoma (UC). Herein, we aimed to validate the prognostic value of a previously developed score, the Prognostic Immunotherapy Score (PIS), including female sex, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) and liver metastases, in patients treated with pembrolizumab for advanced UC from the ARON-2 dataset. We retrospectively analyzed clinical data from Metastatic UC patients diagnosed at age ≥ 18 years.

Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG.

Background: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.

Patients And Methods: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses.

Biosimilars in osteoporosis treatment: focus on denosumab.

Introduction: Osteoporosis is a significant public health issue due to its associated morbidity, mortality, and economic burden. Despite available effective treatments, a treatment gap persists, characterized by delayed diagnosis, undertreatment, and poor adherence. Biosimilars, such as biosimilars for denosumab, offer an opportunity to improve treatment accessibility and affordability for osteoporosis and cancer-related bone loss.

Management of trastuzumab deruxtecan-related adverse events in breast cancer: Italian expert panel recommendations.

Trastuzumab deruxtecan (T-DXd) - antibody - drug conjugate targeting the human epidermal growth factor receptor 2 (HER2) - has demonstrated high efficacy in clinical studies, with high rates of durable responses and improved outcomes in HER2-positive and HER2-low metastatic breast cancer (mBC) patients. T-DXd has demonstrated a generally manageable safety profile across the DESTINY trials, but there is an emerging unmet need for additional real-world clinical practice information. Italian experts conducted a Delphi panel and several roundtables to develop recommendations for the prevention and practical management of T-DXd-related AEs and toxicities, including nausea and vomiting (N/V), neutropenia, anemia, cardiovascular events, interstitial lung disease/pneumonitis (ILD/P), and treatment safety.

TTF-1 Negativity Predicts Poor Outcomes in Advanced Non-Squamous NSCLC Also in the Immunotherapy Era: A Multicenter Cohort Study and Meta-Analysis.

Despite advances in immunotherapy, reliable biomarkers beyond PD-L1 expression are urgently needed to optimize treatment decisions in advanced non-squamous NSCLC. Thyroid Transcription Factor-1 (TTF-1), a biomarker associated with favorable prognosis in chemotherapy-treated patients, has unclear prognostic implications in the immunotherapy era. : We conducted a multicenter retrospective study involving 163 advanced non-squamous NSCLC patients treated with first-line immunotherapy or chemo-immunotherapy and an additional historical chemotherapy-only cohort (n = 37).

Geographical Differences in the Management and Outcomes of Patients With Advanced Urothelial Carcinoma Treated With Pembrolizumab After Progression on Platinum-Based Chemotherapy: Results From ARON-2 Study.

Purpose: Our investigation assessed the impact of geographical disparities in the treatment of patients with advanced urothelial cancer (aUC) included in the international, real-world ARON-2 trial.

Patients And Methods: The study population comprised 1,137 patients with aUC treated with pembrolizumab for relapsed or progressive disease after platinum-based chemotherapy (PBC) at 63 institutions in 19 countries. Patients were divided into three geographical areas: Europe (area 1: 791 patients), the United States (area 2: 156 patients), and Asia (area 3: 190 patients).

Impact of Molecular Androgen and Estrogen Response Scores on Outcomes Following Neoadjuvant Pembrolizumab in Muscle-Invasive Bladder Cancer.

Purpose: Androgen and estrogen influence bladder cancer pathogenesis, but their role in modulating treatment response, especially immunotherapy, remains unclear. This post hoc analysis of the PURE-01 trial evaluated the impact of androgen and estrogen signatures on outcomes in patients with muscle-invasive bladder carcinoma treated with neoadjuvant pembrolizumab followed by radical cystectomy.

Experimental Design: Pretreatment transurethral resection of bladder tumor samples from 102 PURE-01 patients was analyzed using the Decipher Bladder whole-transcriptome assay to classify genomic subtypes.

Real-World Outcomes and Molecular Profiling for Patients with Metastatic Castration-resistant Prostate Cancer with Lung Metastases: A Long-term Multicenter Experience.

Background And Objective: The prognostic impact of lung metastases (LuMs) in metastatic castration-resistant prostate cancer (mCRPC) remains poorly defined. Our aim was to evaluate the clinical and molecular characteristics of patients with mCRPC with LuMs and their outcomes.

Methods: This retrospective multicenter study included 930 patients with mCRPC across 13 centers in Italy.

Impact of Drug-Drug Interactions on Clinical Outcomes in Metastatic Melanoma Patients Treated With Combined BRAF/MEK Inhibitors: A Real-World Study.

The unique pharmacokinetics of BRAF and MEK inhibitors make patients vulnerable to drug-drug interactions (DDIs), which may compromise treatment efficacy in metastatic melanoma. This study evaluates the impact of DDIs on clinical outcomes in patients with metastatic melanoma treated with BRAF/MEK inhibitors. This multicenter, observational, retrospective study assessed DDIs using the Drug-PIN software.

Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors.

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies.

Process management method in head and neck cancer patient care.

Management of patients with head and neck cancer (HNC) is a complex process that involves extensive knowledge on (at least) the discipline of surgery, radiation oncology, medical oncology and molecular biology. It includes prevention, cancer treatment, follow up schedule and potential risk from treatment (radiation exposure). A major point is that perhaps now more than ever process management needs to be at the center of the HNC care.

Delphi consensus on the management of adverse events in patients with metastatic triple-negative breast cancer treated with sacituzumab govitecan.

Background: Metastatic triple-negative breast cancer (BC; mTNBC) is one of the most aggressive cancers, difficult to treat due to the absence of hormone target receptors. Sacituzumab govitecan (SG) is a new therapeutic approach that exploits the combination of an antibody directed against the Trop-2 antigen expressed in solid epithelial tumors and the active metabolite SN-38, to precisely target cancer cells. The development of consensus recommendations requires synthesizing expert opinions, especially when direct evidence is limited.

Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study.

Non-small cell lung cancer (NSCLC) patients without gene driver mutations receive anti-PD1 treatments either as monotherapy or in combination with chemotherapy based on PD-L1 expression in tumor tissue. Anti-PD1 antibodies target various immune system components, perturbing the balance between immune cells and soluble factors. In this study, we identified the immune signatures of NSCLC patients associated with different clinical outcomes through network analysis.

Early Detection of the Pathogenetic Variants of Homologous Recombination Repair Genes in Prostate Cancer: Critical Analysis and Experimental Design.

It has been shown that the pathogenic variants (PVs) of the DNA Damage Response (DDR) genes, whether of a germinal or somatic nature, represent a predictive biomarker of high sensitivity to treatment with inhibitors of the enzyme poly-ADP-ribose polymerase (PARP) in patients with hormone-resistant metastatic prostate cancer (HRPCa). Moreover, the detection of PVs of the Homologous Recombination Repair (HRR) genes in PCa patients can help to define the patient's prognosis and the choice of the therapeutic procedure. Among men with metastatic PCa, the frequency of PVs in HRR genes ranges from 11% to 33%, which is a significantly higher rate compared to non-metastatic PCa, where the incidence is between 5% and 10%.

Beyond the BRCA1/2 genes in ovarian cancer: the role of germline pathogenic variants in the ATM gene.

Background: Ovarian Cancer (OC) prevention and early-stage detection represents a challenge due to the lack of effective surveillance. The identification of high-risk women is crucial as it provides access to prophylactic oophorectomy and reduces disease burden. Next-Generation Sequencing approaches enable the investigation of several genes associated with monogenic hereditary cancer predisposition, including ovarian cancer.

Pain Assessment and Management in Oncological Practice: A Survey from the Italian Network of Supportive Care in Oncology.

Cancer pain is prevalent across all stages of the disease, significantly impacting patients' lives. Despite the availability of guidelines, its assessment and management remain suboptimal in many clinical settings. This study aimed to explore how healthcare professionals in Italy assess and manage cancer pain, identifying gaps and educational needs to improve adherence to best practices.

PARP inhibitor-based treatment in metastatic, castration-resistant prostate cancer (mCRPC): A systematic review and meta-analysis.

Background: We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.

Methods: Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR-), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored.

On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study.

Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non-small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum-based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell-free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z-averaged hydrodynamic diameter and polydispersity index.

The Protein Corona on Nanoparticles for Tumor Targeting in Prostate Cancer-A Review of the Literature and Experimental Trial Protocol.

The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches to the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a "protein corona" composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced.

Anti-PD1 therapies induce an early expansion of Ki67CD8 T cells in metastatic non-oncogene addicted NSCLC patients.

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

Diagnostic accuracy and inter-reader agreement of the nacVI-RADS for bladder cancer treated with neoadjuvant chemotherapy: a prospective validation study.

Objective: The primary aim was to determine the performance of neoadjuvant chemotherapy VI-RADS (nacVI-RADS) in predicting response to systemic therapy in patients with MIBC and to evaluate its inter-reader agreement.

Materials And Methods: Prospective study, including patients with non-metastatic muscle-invasive bladder cancer (MIBC) who underwent neoadjuvant chemotherapy before radical cystectomy (RC). Patients underwent pre- and post-treatment MRI.

Apalutamide in Metastatic Castration-sensitive Prostate Cancer: Results from the Multicenter Real-world ARON-3 Study.

Background And Objective: Apalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC.

Methods: We retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study.

Viral Hepatitis in Western Patients with Advanced Intrahepatic Cholangiocarcinoma: Retrospective Assessment of Prevalence, Prognostic and Predictive Significance.

Despite a biologically established causative role of viral hepatitis (VH), i.e. HBV and HCV infections, on intrahepatic cholangiocarcinoma (ICC), only few large Western cohorts exploring the association between VH and ICC development are available.

Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of and Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial.

Purpose: To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable / wild-type (wt) metastatic colorectal cancer (mCRC).

Patients And Methods: IMPROVE (ClinicalTrials.gov identifier: NCT04425239) was an open-label, multicenter, randomized phase II noncomparative trial.