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Non-small cell lung cancer (NSCLC) constitutes the majority of the lung cancer population and the prognosis is poor. In recent years, immunotherapy has become the standard of care for advanced NSCLC patients as numerous trials demonstrated that immune checkpoint inhibitors (ICI) are more efficacious than conventional chemotherapy. However, only a minority of NSCLC patients benefit from this treatment. Therefore, there is an unmet need for biomarkers that could accurately predict response to immunotherapy. Liquid biopsy allows repeated sampling of blood-based biomarkers in a non-invasive manner for the dynamic monitoring of treatment response. In this review, we summarize the efforts and progress made in the identification of circulating biomarkers that predict immunotherapy benefit for NSCLC patients. We also discuss the challenges with future implementation of circulating biomarkers into clinical practice. [ABSTRACT FROM AUTHOR]

Real-world outcomes of chemo-antiangiogenesis versus chemo-immunotherapy combinations in EGFR-mutant advanced non-small cell lung cancer patients after failure of EGFR-TKI therapy. Chemotherapy Plus Immunotherapy Versus Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone in EGFR-Mutant NSCLC After Progression on Osimertinib. Keywords: EGFR mutation; lung cancer; immunotherapy; non-small cell lung cancer EN EGFR mutation lung cancer immunotherapy non-small cell lung cancer 117 120 4 03/08/23 20230201 NES 230201 1. [Extracted from the article]

Aim: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population. Methods: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated. Results: Two hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively). Conclusion: In our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC). Materials and methods: Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment (“baseline”), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses. Results: The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS. Conclusions: This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform. [ABSTRACT FROM AUTHOR]

Background: Afatinib is an oral irreversible epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) indicated in first-line treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). Dose dependent side effects can limit drug exposure, which may impact on extracranial and central nervous system (CNS) disease control.Methods: We performed a retrospective study of 125 patients diagnosed with advanced EGFRm+ NSCLC treated with first-line afatinib at a tertiary Asian cancer center, exploring clinicopathological factors that may influence survival outcomes. Median progression free survival (PFS) was estimated using the Kaplan-Meier method. Comparison of PFS between subgroups of patients was done using log-rank tests and Cox proportional hazards models.Results: Out of 125 patients, 62 (49.6%) started on 40 mg once daily (OD) afatinib, 61 (48.8%) on 30 mg OD and 1 (0.8%) on 20 mg OD. After median follow-up of 13.8 months from afatinib initiation, the observed response rate was 70.4% and median PFS 11.9 months (95% CI 10.3-19.3). 42 (33.6%) patients had baseline brain metastases (BM) and PFS of those who started on 40 mg OD (n = 17) vs. 30 mg OD (n = 25) was 13.3 months vs. 5.3 months (HR 0.39, 95% CI 0.15-0.99). BM+ patients who started on 40 mg had similar PFS to patients with no BM (13.3 months vs. 15.0 months; HR 0.79, 95% CI 0.34-1.80).Conclusion: In patients with advanced EGFRm+ NSCLC with BM+, initiating patients on afatinib 40 mg OD was associated with improved PFS compared to 30 mg OD, underscoring the potential importance of dose intensity in control of CNS disease. [ABSTRACT FROM AUTHOR]

A 34-year-old woman presented to our outpatient clinic with swelling and erythema over the site of her childhood Bacillus Calmette-Guérin (BCG) vaccination scar, 7 days after receiving her first dose of the BNT162b2 (Pfizer-BioNTech) messenger ribonucleic acid (mRNA) vaccine against SARS-CoV-2 on the ipsilateral arm (Figure 1A). However, BCG scar flares after vaccination with current mRNA vaccines against SARS-CoV-2 appear to be benign, as in the cases presented here, and should not alarm physicians, limit vaccinations, nor be a reason for vaccine hesitancy. Reactivation of the BCG scar has been described with influenza vaccination, childhood Kawasaki disease and viral infections; [2],[3] hence it is possible that non-mRNA-based SARS-CoV-2 vaccines could lead to similar reactions. [Extracted from the article]

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Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies in non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain-null (NSG) mice and established humanized mouse NPC-patient-derived xenograft (NPC-PDX) model successfully. Epstein–Barr virus was detected in the NPC in both NSG and humanized mice as revealed by Epstein–Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) and immunohistochemical (IHC) staining. In the NPC-bearing humanized mice, the percentage of tumor-infiltrating CD8+ cytotoxic T cells was lowered, and the T cells expressed higher levels of various inhibitory receptors, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) than those in blood. The mice were then treated with nivolumab and ipilimumab, and the anti-tumor efficacy of combination immunotherapy was examined. In line with paired clinical data, the NPC-PDX did not respond to the treatment in terms of tumor burden, whilst an immunomodulatory response was elicited in the humanized mice. From our results, human proinflammatory cytokines, such as interferon-gamma (IFN-γ) and interleukin-6 (IL-6) were significantly upregulated in plasma. After treatment, there was a decrease in CD4/CD8 ratio in the NPC-PDX, which also simulated the modulation of intratumoral CD4/CD8 profile from the corresponding donor. In addition, tumor-infiltrating T cells were re-activated and secreted more IFN-γ towards ex vivo stimulation, suggesting that other factors, including soluble mediators and metabolic milieu in tumor microenvironment may counteract the effect of ICB treatment and contribute to the tumor progression in the mice. Taken together, we have established and characterized a novel humanized mouse NPC-PDX model, which plausibly serves as a robust platform to test for the efficacy of immunotherapy and may predict clinical outcomes in NPC patients. [ABSTRACT FROM AUTHOR]

Background Immune checkpoint inhibitors (ICI) appear particularly promising for head and neck cancers, as evidenced by recent clinical trials. Despite durable antitumor responses in a subset of advanced cancer patients, most head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal cancer (NPC) are intrinsically resistant to immunotherapy. Here, we aim to reveal immune infiltrative landscape of HNSCC and NPC and further to identify predictive biomarkers for selection of patients to receive ICI-based treatments. Methods A measure of mRNA deregulation in tumor microenvironment, termed as tumor matrisome index (TMI), was assessed using RNA-seq and microarray-acquired expression datasets. Receiver operating characteristic (ROC) curves and survival data were analyzed to evaluate the diagnostic and prognostic value of TMI, respectively. Parallel analyses of signatures predictive of immunotherapy response, including innate PD-1 resistance signature (IPRES), were performed using Gene set variation analysis (GSVA). Machine learning-based deconvolution algorithm (i.e. CIBERSORT) was applied to all datasets to reveal specific immune cell types associated with TMIhigh tumors. Results TMI achieved a mean AUC value of 0.903 and 0.991 in differentiating normal tissues from NPC and HNSC, respectively. Integrative genomic analyses reveal that TMI is closely associated with IPRES signatures and CIBERSORT-estimated relative abundance of specific immune cell populations. Of clinically targetable immune checkpoints, OX-40L emerged as a promising target for anti-tumor immunity in TMIhigh NPC tumors. Conclusion TMI signatures are integral components of protumoral extracellular matrix. The developed metrics to measure the extent of such matrisomal abnormalities may represent a novel predictive biomarker for cancer immunotherapy. [ABSTRACT FROM AUTHOR]