Sodium levels and immunotherapy efficacy in mRCC patients with bone metastases: sub analysis of Meet-Uro 15 study.

Background: Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy.

Materials And Methods: This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond.

Long-term responders to nivolumab in previously treated advanced renal cell carcinoma: a sub-analysis of meet-URO15 study.

Background: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment.

Materials And Methods: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres.

Navigating resistance to ALK inhibitors in the lorlatinib era: a comprehensive perspective on NSCLC.

Introduction: The emergence of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC) has revolutionized targeted therapy. This dynamic landscape, featuring novel ALK inhibitors and combination therapies, necessitates a profound understanding of resistance mechanisms for effective treatment strategies. Recognizing two primary categories - on-target and off-target resistance - underscores the need for comprehensive assessment.

Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: analysis of the Meet-URO 15 study.

Background: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed.

An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53 mutations or copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.

Sodium Levels and Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Nivolumab.

Importance: Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs).

Objective: To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy.

Design, Setting, And Participants: In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study.

An Italian multicenter retrospective real-life analysis of patients with brain metastases from renal cell carcinoma: the BMRCC study.

Background: The treatment of patients with brain-spread renal cell carcinoma (RCC) is an unmet clinical need, although more recent therapeutic strategies have significantly improved RCC patients' life expectancy. Our multicenter, retrospective, observational study investigated a real-world cohort of patients with brain metastases (BM) from RCC (BMRCC).

Patients And Methods: A total of 226 patients with histological diagnosis of RCC and radiological evidence of BM from 22 Italian institutions were enrolled.

Immune-related gigantomastia: a case study.

PD-1/PDL-1 inhibitors have revolutionized cancer treatment, especially in lung cancer. Despite their efficacy, a new spectrum of side effects, called immune-related adverse events, may occur and their management could be difficult. Gigantomastia, a rare condition characterized by excessive growth of the breasts, has been associated with some drugs, but no correlation with immunotherapy has ever been reported.

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study.

Background: Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era.

Methods: We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups.

Overcoming Resistance to Checkpoint Inhibitors: Natural Killer Cells in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatments over the last 10 years, with even increasing indications in many neoplasms. Non-small cell lung cancer (NSCLC) is considered highly immunogenic, and ICIs have found a wide set of applications in this area, in both early and advanced lines of treatment, significantly changing the prognosis of these patients. Unfortunately, not all patients can benefit from the treatment, and resistance to ICIs can develop at any time.

An Olive Oil Mill Wastewater Extract Improves Chemotherapeutic Activity Against Breast Cancer Cells While Protecting From Cardiotoxicity.

Cardiovascular toxicity in cancer patients receiving chemotherapy remains one of the most undesirable side effects, limiting the choice of the most efficient therapeutic regimen, including combinations of different anticancer agents. Anthracyclines (doxorubicin) and antimetabolites (5-fluorouracil (5-FU), capecitabine) are among the most known agents used in breast cancer and other neoplasms and are associated with cardiotoxic effects. Extra-virgin olive oil (EVOO) is rich in polyphenols endowed with antioxidant cardioprotective activities.

Two Novel Ceramide-Like Molecules and miR-5100 Levels as Biomarkers Improve Prediction of Prostate Cancer in Gray-Zone PSA.

Reliable liquid biopsy-based tools able to accurately discriminate prostate cancer (PCa) from benign prostatic hyperplasia (BPH), when PSA is within the "gray zone" (PSA 4-10), are still urgent. We analyzed plasma samples from a cohort of 102 consecutively recruited patients with PSA levels between 4 and 16 ng/ml, using the SANIST-Cloud Ion Mobility Metabolomic Mass Spectrometry platform, combined with the analysis of a panel of circulating microRNAs (miR). By coupling CIMS ion mobility technology with SANIST, we were able to reveal three new structures among the most differentially expressed metabolites in PCa vs.

TIMP1 and TIMP2 Downregulate TGFβ Induced Decidual-like Phenotype in Natural Killer Cells.

Natural Killer (NK) cells have been found to be anergic, exhausted and pro-angiogenic in cancers. NK cell from healthy donors, exposed to TGFβ, acquire the CD56CD9CD49a decidual-like-phenotype, together with decreased levels of NKG2D activation marker, increased levels of TIM-3 exhaustion marker, similar to cancer-associated NK cells. Tissue inhibitors of metalloproteases (TIMPs) exert dual roles in cancer.

Second-line treatment in renal cell carcinoma: clinical experience and decision making.

Unlabelled: Currently, conventional treatments for metastatic RCC (mRCC) include immune-based combination regimens and/or targeted therapies, the latter mainly acting on angiogenesis, a key element of the process of tumor growth and spread. Although these agents proved able to improve patients' outcomes, drug resistance and disease progression are still experienced by a substantial number of VEGFR-TKIs-treated mRCC patients. Following the inhibition of the VEGF/VEGFRs axis, two strategies have emerged: either specifically targeting resistance pathways, at the same time continuing to inhibit angiogenesis, or using a completely different approach aimed at re-activating the immune system through the use of inhibitors of specific negative immune checkpoints.

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study).

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need.

Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab.

Correction to: Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis.

While typesetting the article the Table 3 column/row entries are interchanged. Please find below the updated Table.

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis.

Background: Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy.

Objective: To describe the outcome of cabozantinib in patients previously treated with immunotherapy.

The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review.

Carcinomas of unknown primary (CUP) account for 3-5% of all malignancy and, despite a reduction in incidence, the overall survival has not improved over the last decade. Chemotherapy regimens have not provided encouraging results. New diagnostic technologies, such as next generation sequencing (NGS), could represent a chance to identify potentially targetable genomic alterations in order to personalize treatment of CUP and provide insights into tumor biology.

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors.

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib.

The effect of a treatment delay on outcome in metastatic renal cell carcinoma.

Objectives: To investigate if a first-line treatment delay (TD) can negatively affect the outcomes of patients affected by metastatic renal cancer.

Patients And Methods: Patients with a diagnosis of metastatic renal cancer who were ineligible for active surveillance were included in the sample. A TD was defined as the time from the diagnosis of metastatic disease to the start of first-line therapy with tyrosine kinase inhibitors.

The outcome to axitinib or everolimus after sunitinib in metastatic renal cell carcinoma.

We aimed to investigate the different outcomes in patients with metastatic renal cell carcinoma treated with second-line axitinib or everolimus after sunitinib. Patients treated in 16 oncological centres in Italy were included, and those receiving axitinib or everolimus from January 2013 onwards were analysed for outcomes. Descriptive statistical tests were used to highlight differences between groups.

Safety and Efficacy of Cabozantinib in Metastatic Renal-Cell Carcinoma: Real-World Data From an Italian Managed Access Program.

Background: The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment with at least one previous antiangiogenic inhibitor. The aim of this analysis was to evaluate the safety and activity of cabozantinib in an unselected population.

Methods: Data were collected across 24 Italian centers.