Survival Outcomes with Regorafenib and/or Trifluridine/Tipiracil Sequencing to Rechallenge with Third-Line Regimens in Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Subgroup Comparison from the ReTrITA Study.

Background: There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use.

Longitudinal Assessment of FT3 to FT4 Conversion Ratio in Predicting the Efficacy of First-Line Pembrolizumab-Based Therapy in Advanced Non-Small Cell Lung Cancer: A Propensity-Score Matching Analysis of Data from the National Drug Monitoring Agency.

Baseline thyroid function, as measured by the fT3 to fT4 ratio, has been shown to influence the prognosis of advanced cancer patients receiving active treatments. Although immune checkpoint blockade can alter the balance of thyroid hormones, this interaction has not been thoroughly investigated. The present research sought to determine whether changes in the fT3/fT4 ratio could affect the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) who were undergoing pembrolizumab-based therapies.

Postmortem biochemistry of GFAP, NSE and S100B in cerebrospinal fluid and in vitreous humor for estimation of postmortem interval: a pilot study.

Postmortem interval (PMI) is a challenging issue in forensic practice. Although postmortem biomarkers of traumatic brain injury (TBI) are recognised as an emerging resource for PMI estimation, their role remains controversial. This study aims to evaluate postmortem concentrations of three TBI biomarkers (GFAP, NSE and S100B) in two matrices (cerebrospinal fluid and vitreous humor), in order to find out if these markers could be adopted in PMI estimation.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population.

Background: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes.

Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia).

Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study.

Background: The TOPAZ-1 phase III trial reported a survival benefit with the anti-programmed cell death ligand 1 (anti-PD-L1) durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).

Objective: The present study investigated for the first time the impact on survival of adding durvalumab to cisplatin/gemcitabine compared with cisplatin/gemcitabine in a real-world setting.

Patients And Methods: The analyzed population included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab in combination with cisplatin/gemcitabine or with cisplatin/gemcitabine alone.

Efficacy of Regorafenib and Trifluridine/Tipiracil According to Extended RAS Evaluation in Advanced Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Analysis.

Background: There are few molecular markers driving treatment selection in later lines of treatment for advanced colorectal cancer patients. The vast majority of patients who progress after first- and second-line therapy undergo chemotherapy regardless of molecular data.

Objective: We aimed to assess the prognostic and predictive effects of specific RAS mutations on overall survival of patients receiving regorafenib (rego), trifluridine/tipiracil (TFD/TPI), or both.

Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652-3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer.

Purpose: The multi-kinase inhibitor (mKi) regorafenib has demonstrated efficacy in chemorefractory patients with metastatic colorectal cancer (mCRC). However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice.

Experimental Design: Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemorefractory patients with mCRC treated with regorafenib in a phase II clinical trial (PROSPECT-R n = 40; NCT03010722) and in a multicentric validation cohort (n = 241).

Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab.

Background: The results reported in the TOPAZ-1 phase III trial led to the approval of the combination of cisplatin and gemcitabine with durvalumab as the new first-line standard of care for patients with locally advanced or metastatic cholangiocarcinoma.

Objective: We performed a clustering analysis to classify patients into different groups based on their mutation profile, correlating the results of the analysis with clinical outcomes.

Methods: We selected 51 patients with cholangiocarcinoma who were treated with the combination of chemotherapy and durvalumab and who were screened using the next-generation sequencing-based FoundationOne gene panel.

Herpes zoster after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in actively treated cancer patients: a prospective study.

Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible.

Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis.

: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially.

Changes in Peripheral Immune Cells after the Third Dose of SARS-CoV-2 mRNA-BNT162b2 Vaccine and Disease Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Prospective Analysis of the Vax-on-Third-Profile Study.

Background: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients.

Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.

Background: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes.

Methods: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible.

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study.

Background: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles.

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study.

(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population.

Dynamic changes in peripheral lymphocytes and antibody response following a third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients.

The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response.

Femicide and forensic pathology: Proposal for a shared medico-legal methodology.

In a previous work, authors have proposed a medico-legal definition of femicide as the murder due to the failure to recognize the right of self-determination of women. The aim of this paper was to apply the proposed definition to a cohort of cases to characterise femicides and female homicides and assess whether femicides can be considered a distinct entity or not. A comparison between female and male homicides was performed to assess common and distinctive features.

Real-Life Experience of the Prognostic Significance of the Primary Tumor Location on the Timing of Colorectal Liver Metastases: A Retrospective Analysis.

Background Numerous research studies have looked into how the primary tumor location (PTL) affects patients' prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM). Material and methods From 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM.

Peripheral lymphocyte subset counts predict antibody response after SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients: Results from the Vax-On-Profile study.

Background: The adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine.

Methods: Absolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping.

Immune-related Thyroid Dysfunction (irTD) in Non-small Cell Lung Cancer (NSCLC) Correlates With Response and Survival.

Background: There is no clear information on the proportion of patients who need therapy for immune-related thyroid dysfunction (irTD) or who need to delay, omit, or discontinue immunotherapy. Furthermore, it is not well known whether irTD correlates with better outcomes or not.

Patients And Methods: We conducted a retrospective study in patients with metastatic non-small cell lung cancer (NSCLC) treated with anti-PD1 or anti-PD-L1.