Genetic signatures of and expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy.

Background: Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damage exerted by platinum agents. Alteration in this repair mechanism may affect patients' survival.

An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy-EDEN trial GOIRC 04-2016.

Background: As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment.

Methods: EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B).

Predictive and prognostic factors in patients with anaplastic lymphoma kinase rearranged early-stage lung adenocarcinoma.

Objectives: This study aimed to evaluate the predictive and prognostic factors in clinical stage I, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients.

Methods: A multicentric, retrospective, case-control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy.

Efficacy and Safety of Chemotherapy after Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.

There are currently few data about the safety and effectiveness of chemotherapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed from prior immunotherapy. Data from patients with consecutive stage IIIB-IV, ECOG performance status (PS) 0-2, non-small-cell lung cancer (NSCLC) treated with combination or single-agent chemotherapy following progression on an earlier immunotherapy regimen were retrospectively gathered. Recorded were baseline attributes, outcome metrics, and toxicities.

Pembrolizumab-associated anti-MDA5 dermatomyositis in a patient with lung cancer: a first case report.

We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed.

Purpose: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers.

Methods: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs).

Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression.

Background: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients.

Methods: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease.

Using peripheral immune-inflammatory blood markers in tumors treated with immune checkpoint inhibitors: An INVIDIa-2 study sub-analysis.

The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of <3.

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration.

Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020.

Combi-TED: a new trial testing Tedopi with docetaxel or nivolumab in metastatic non-small-cell lung cancer progressing after first line.

Despite the positive results obtained by first-line chemoimmunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), only a few second-line options are available after disease progression. Combi-TED is a phase II international study that will assess the efficacy of Tedopi, a cancer vaccine, combined with either docetaxel or nivolumab and compared with docetaxel monotherapy in patients with metastatic NSCLC after chemoimmunotherapy. The study, currently in the recruitment phase, will assess 1-year overall survival (primary end point), patient's progression-free survival and overall response rate, as well as the correlation of efficacy with several tumor or blood biomarkers.

SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry.

Background: COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2.

Methods: OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death.

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

Purpose: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice.

Methods: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.

Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in -associated retinitis pigmentosa.

Severe, early-onset photoreceptor (PR) degeneration associated with mutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models of ablation are determined by the hypomorphic expression or the loss of the paralog . Here, we find that loss of and reduced expression/loss of led to RPE inflammation even before eye-opening.

Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification.

For many years the standard of care for small cell lung cancer (SCLC) has remained unchanged. Despite decades of active research, current treatment options are limited and the prognosis of patients with extended disease (ED) SCLC remains poor. The introduction of immune checkpoint inhibitors (ICIs) represents an exception and the only recent approval for ED-SCLC.

KRAS G12 isoforms exert influence over up-front treatments: A retrospective, multicenter, Italian analysis of the impact of first-line immune checkpoint inhibitors in an NSCLC real-life population.

Background: KRAS is commonly mutated in non-small cell lung cancer (NSCLC); however, the prognostic and predictive impact of each G12 substitution has not been fully elucidated. The approval of specific G12C inhibitors has modified the idea of KRAS "undruggability", and although the first-line standard consists of immune checkpoint inhibitors (ICIs) with or without chemotherapy, as suggested at ASCO 2022, the outcome in KRAS-mutated population is still controversial.

Methods: We retrospectively described the clinical and pathological characteristics of a homogeneous G12 mutated cohort of 219 patients treated in four Italian oncologic units.

Gender Matters. Sex-related Differences in Immunotherapy Outcome in Patients with Non-small Cell Lung Cancer.

Background: Emerging evidence identified sex as a variable regulating immune system functions and modulating response to immunotherapy in cancer patients.

Objective: This retrospective study analysed sex-related differences in immunotherapy outcomes in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).

Methods: e retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single-agent nivolumab and pembrolizumab at Medical Oncology Unit, Careggi University Hospital, Florence (Italy), between April 2014 to August 2019.

Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic horizons of various cancers. However, immune-related adverse events have been reported, including interstitial lung diseases. Our aim was to describe the clinical and radiological features and survival of a multicentre cohort of patients who developed ICI-related lung toxicity.

Vaccination against SARS-CoV-2 protects from morbidity, mortality and sequelae from COVID19 in patients with cancer.

Background: Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.

Methods: Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.

Results: 2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.