Histologic Transformation in Cancer: The Path for Clinical Translation.

Unlabelled: Lineage plasticity, a critical hallmark of cancer progression, enables tumor cells to evade inhibition of primary oncogenic pathways through histologic transformation. This adaptive process, driven by stemness-associated features and epigenetic reprogramming, poses significant challenges in treatment. Using non-small cell lung cancer and prostate cancer as models, we examine the utility of tissue and liquid biopsies in detecting histologic transformations and tailoring treatments to specific subtypes, which has profound clinical implications, potentially improving outcomes in patients with advanced, therapy-resistant disease.

Leveraging sequences missing from the human genome to diagnose cancer.

Background: Cancer diagnosis using cell-free DNA (cfDNA) has the potential to improve treatment and survival but has several technical limitations.

Methods: In this study, we developed a prediction model based on neomers, DNA sequences 13-17 nucleotides in length that are predominantly absent from the genomes of healthy individuals and are created by tumor-associated mutations.

Results: We show that neomer-based classifiers can accurately detect cancer, including early stages, and distinguish subtypes and features.

Molecular Landscape and Therapeutic Strategies of Lung Cancer Lineage Plasticity.

Histologic transformation from lung adenocarcinoma (LUAD) to SCLC or lung squamous cell carcinoma (LUSC) represents distinct but converging processes of cellular plasticity. Cellular plasticity, the ability to switch phenotypes between distinct developmental lineages, is critical in embryogenesis, tissue repair, and homeostasis. Tumor cells exploit these mechanisms to adapt to external pressures, such as therapeutic interventions, resulting in phenotypic transitions that drive therapeutic resistance and poor prognosis.

Breaking Through: Immunotherapy Innovations in Pleural Mesothelioma.

The prognosis of pleural mesothelioma (PM) is poor and conventional chemotherapy regimens have shown limited antitumor activity. Recent use of immune checkpoint inhibitors (ICIs) has shown promise, with CheckMate-743 trial establishing nivolumab plus ipilimumab as first line treatment in unresectable PM. Nevertheless, real-world applicability as well as differential benefit of immunotherapy according to histologic are areas of active debate.

Robotic-Assisted Thoracoscopic Surgery Versus Video-Assisted Thoracoscopic Surgery: Which Is the Preferred Approach for Early-Stage NSCLC?

Lung cancer is the leading cause of cancer-related mortality among both men and women worldwide, underscoring the need for an effective treatment strategy. For early-stage non-small cell lung cancer [NSCLC], surgical resection is the standard treatment. Robotic-assisted thoracic surgery [RATS] and video-assisted thoracic surgery [VATS] are better than open thoracotomy because they are less invasive.

Quantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-type Non-Small Cell Lung Cancer.

Purpose: Antibody-drug conjugates (ADC) are a promising approach for the management of patients with non-small cell lung cancer (NSCLC). However, only a small subset of patients derive benefit from these therapies.

Experimental Design: We used quantitative immunofluorescence assays to measure the levels of four ADC target proteins (HER2, TROP2, HER3, and EGFR) in three NSCLC tissue microarray cohorts stratified according to EGFR mutation [EGFR mutated (n = 83), EGFR wild-type (n = 128), and EGFR unknown (n = 232)].

Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy.

Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo).

Occult checkpoint inhibitor myocarditis during adjuvant nivolumab plus ipilimumab: a smoldering but severe toxicity.

Checkpoint inhibitor myocarditis is a rare but life-threatening toxicity of immunotherapy, occasionally manifesting as persistent troponin elevation. Dual checkpoint blockade with ipilimumab and nivolumab has been found to induce immune-related myocarditis in patients with metastatic melanoma. We herein report a case of smoldering immune-related myocarditis in a 54-year-old male after a single infusion of nivolumab plus ipilimumab as adjuvant treatment for completely resected stage IV melanoma.

Quantitative Measurement of HER2 Expression in Non-Small Cell Lung Cancer With a High-Sensitivity Assay.

Recently, low human epidermal growth factor receptor 2 (HER2) protein expression has been proposed as a predictive biomarker for response to the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. HER2 expression in non-small cell lung cancer (NSCLC) patients has never been carefully measured, and little is known about the frequency of cases with unamplified but detectable levels of the protein. Although some HER2-targeted therapies have been studied in NSCLC patients, they have been restricted to those with genomic ERBB2 gene alterations, which only represent relatively rare cases of NSCLC.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study.

Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC.

Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone.

Biological and therapeutic implications of the cancer-related germline mutation landscape in lung cancer.

Although smoking is the primary cause of lung cancer, only about 15% of lifelong smokers develop the disease. Moreover, a substantial proportion of lung cancer cases occur in never-smokers, highlighting the potential role of inherited genetic factors in the cause of lung cancer. Lung cancer is significantly more common among those with a positive family history, especially for early-onset disease.

Predictive capacity of immune-related adverse events and cytokine profiling in neoadjuvant immune checkpoint inhibitor trials for head and neck squamous cell carcinoma.

Objectives: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

Methods: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin).

Spatially Informed Gene Signatures for Response to Immunotherapy in Melanoma.

Purpose: We aim to improve the prediction of response or resistance to immunotherapies in patients with melanoma. This goal is based on the hypothesis that current gene signatures predicting immunotherapy outcomes show only modest accuracy due to the lack of spatial information about cellular functions and molecular processes within tumors and their microenvironment.

Experimental Design: We collected gene expression data spatially from three cellular compartments defined by CD68+ macrophages, CD45+ leukocytes, and S100B+ tumor cells in 55 immunotherapy-treated melanoma specimens using Digital Spatial Profiling-Whole Transcriptome Atlas.

Efficacy and Safety of Tinzaparin Thromboprophylaxis in Lung Cancer Patients with High Thromboembolic Risk: A Prospective, Observational, Single-Center Cohort Study.

Background: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk.

Methods: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.

Utilizing nullomers in cell-free RNA for early cancer detection.

Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome.

A new prognostic model in chemotherapy-treated patients with recurrent or metastatic head and neck cancer: An analysis of ECOG-ACRIN E1305.

Introduction: For patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) periodic reassessment of prognostic factors provides valuable information that can aid in patient stratification.

Patients And Methods: This post hoc analysis included all patients with R/M HNSCC enrolled in the ECOG-ACRIN E1305 phase III clinical trial who received first-line treatment with platinum-containing chemotherapy doublet with or without bevacizumab. Overall survival (OS) was estimated using the Kaplan-Meier method.

Molecular interactions of antibodies with PD-1/PD-L1 proteins.

To compare the protein-protein interactions of antibodies targeting PD-1 and its ligand (PD-L1) with their targets in an attempt to explain the antibodies' binding affinity. The structural features of complexes between pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab and PD-1/PD-L1 are described, with the use of software and based on crystallographic data. Pembrolizumab has more structural features, including the number and type of the bonds and total binding surface area, which could rationalize its different clinical behavior compared with nivolumab.

Eligibility for screening with low-dose CT in a real-world cohort of patients with lung cancer in Greece: A brief report.

Introduction: NELSON and NLST prompted the implementation of lung cancer screening programs in the United States followed by several European countries. This study aimed to assess the sensitivity of different screening criteria among patients with lung cancer in Greece and investigate reasons for ineligibility.

Methods: We performed a retrospective analysis on patients with lung cancer referred to the largest referral center in Athens, Greece, between June 2014 and May 2023.

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better.

Background: Stimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma.

Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck.

Background: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

Methods: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy.

Takotsubo Cardiomyopathy in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Summary of Included Cases.

Background: There are emerging reports of Takotsubo syndrome (TTS) in cancer patients treated with immune checkpoint inhibitors (ICIs); however, the association of the two remains uncertain.

Methods: A systematic literature review was performed in the PubMed database and web sources (Google Scholar) according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Case reports/series or studies including cancer patients treated with ICIs and presenting with TTS were considered.

Digital Spatial Profiling Links Beta-2-microglobulin Expression with Immune Checkpoint Blockade Outcomes in Head and Neck Squamous Cell Carcinoma.

Unlabelled: Programmed cell death protein-1 (PD-1)-targeted immunotherapy is approved for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Although its efficacy correlates with PD-L1 expression, response is limited even among positive cases. We employed digital spatial profiling (DSP) to discover potential biomarkers of immunotherapy outcomes in HNSCC.