Cancers

Introduction: Several studies have described how the restrictive measures due to COVID-19 have delayed melanoma diagnoses, resulting in an increased rate of more severe cases. Summarizing the sparse results in this context might help to understand the real impact of the COVID-19 pandemic on melanoma. We conducted a systematic review and meta-analysis to investigate how the clinical and prognostic factors of new melanoma diagnoses changed after COVID-19. Methods: A literature search in MEDLINE, EMBASE, and Scopus was conducted in September 2023. We included studies published in peer-reviewed journals reporting histopathological data on new diagnoses of cutaneous melanoma in adult patients during and/or after the lockdown compared to those diagnosed before the COVID-19 pandemic. A meta-analysis was conducted utilizing a random effects model. The between-study heterogeneity was assessed via Higgins’s I2 statistic. Publication bias was assessed using the Begg and Egger test. This study adhered to the updated PRISMA guidelines. The primary outcome was a comparison of melanoma thickness between the pre-COVID-19 and post-lockdown periods. The secondary outcomes were evaluations of the histopathological subtype, stage, and presence of ulceration and mitosis in melanomas diagnosed in these two pandemic phases. Results: The study included 45 articles. We found a significantly higher proportion of all factors indicating worse prognosis in the post-lockdown period compared to the pre-COVID-19 phase, including high thickness (SOR = 1.14, 95%CI 1.08–1.20 for 1–2 mm; SOR = 1.62, 95%CI 1.08–2.40, for >2 mm), the presence of ulcerations (SOR = 1.35, 95%CI 1.18–1.54), nodular subtype (SOR = 1.19, 95%CI 1.07–1.32), the presence of mitosis (SOR = 1.57, 95% CI 1.17–2.11), and stage III (SOR = 1.39, 95%CI 1.19–1.52) and IV (SOR = 1.44, 95%CI 1.26–1.63). Limitations include the limited studies’ geographical distribution and moderate heterogeneity affecting meta-analysis estimates. Conclusions: Our meta-analysis provided evidence of more advanced melanomas diagnosed in the post-COVID-19 pandemic period, emphasizing the importance of creating and updating pandemic preparedness plans to limit the impact of any future events on oncological care.

Background/Objectives: Clinical use of poly(ADP-ribose) polymerase inhibitors (PARPis) against metastatic high-grade serous ovarian carcinoma (HGSOC) is limited to cases with deficient a homologous recombination (HR). Our objective was to determine whether the impairment of the fractalkine receptor (CX3CR1) could sensitize HR-proficient cases to PARPis. Methods: The efficacy of a dual drug combination, including AZD8797, an inhibitor of CX3CR1, and several PARPis was examined using cell lines and xenograft models. Results: The effectiveness of PARPis and AZD8797 drug combinations ranged from additive to strongly synergistic. Olaparib was synergistic with AZD8797 in OVCAR-4, Caov-3, and OHSAHO. Niraparib and AZD8797 produced synergy in OVCAR-4 and ES2. Rucaparib and AZD8797 were strongly synergistic in Caov-3 and OVSAHO. Veliparib was strongly synergistic with AZD8797 in OVCAR-4 and Caov-3. Notably, a combination of veliparib and AZD8797 produced a strong synergistic effect in a xenograft model. Conclusions: While the exact mechanisms determining the nature of the PARPis and AZD8797 interaction remain to be uncovered, our data indicate that, in a subset of models, selected PARPis strongly synergize with the inhibition of CX3CR1, suggesting a potential therapeutic opportunity.

Background/Objectives: Metabolic and bariatric surgery (MBS) is known to reduce cancer risk. However, the association between specific bariatric procedures and cancer incidence is not well-studied. This study examined the association between four different MBS procedures and cancer incidence. Methods: Bariatric surgery registry data were linked with statewide cancer registry data from 1979 to 2018. The study included 27,092 adult subjects (aged ≥ 18 years old at surgery) who underwent MBS (BMI ≥ 30 kg/m2 at surgery) from 1979 to 2017. Cancer records were linked to MBS patient records, resulting in 1547 cancer cases. Cox proportional hazards regression was used to examine the association between MBS procedure types and cancer incidence. Results: Of all patients, 75% underwent Roux-en-Y gastric bypass (RYGB), 9% adjustable gastric banding (AGB), 10% sleeve gastrectomy (SG), and 6% duodenal switch (BPD-DS). The overall cancer incidence during the follow-up period was 6.4% for RYGB, 4.6% for AGB, 1.6% for SG, and 5.9% for BPD-DS. The mean follow-up duration from surgery to cancer incidence or censoring was 167 months (standard deviation = 121 months). Compared to RYGB, patients who underwent AGB (Hazard Ratio [HR] = 1.26, p = 0.03) and BPD-DS (HR = 1.91, p < 0.01) had a significantly higher hazard of developing cancer, while SG (HR = 1.17, p = 0.33) showed no significant difference. Conclusions: These findings suggest that AGB and BPD-DS may be associated with higher cancer risks compared to RYGB. Additional large population studies are needed to better understand the long-term cancer risks and mechanisms associated with different MBS types.

(1) Background: Advanced-stage lung cancer poses significant management challenges. The goal of this study was to identify crucial clinical and PET radiomics features that enable prognostic stratification for predicting outcomes. (2) Methods: PET radiomics features of the primary lung lesions were extracted from 99 patients with stage IVB NSCLC, and the robustness of these PET radiomics features was evaluated against uncertainties stemming from extraction parameters and contour variation. We trained three survival risk models (clinical, radiomics, and a composite) through a penalized Cox model framework. We also created a Balanced Random Forest classification predictive model, using the selected features, to predict 1-year survival. (3) Results: We identified 367 common PET radiomics features that exhibited robustness to perturbations introduced by contour variation and extraction parameters. Our findings indicated that both the radiomics and the composite model outperformed the clinical model in stratifying the risk for survival with statistical significance. In predicting 1-year survival, the radiomics model and the composite model also achieved better predicting accuracies compared to the clinical model. (4) Conclusions: Robust PET radiomics analysis successfully facilitated the stratification of patient risk for survival outcomes and predicted 1-year survival in stage IVB NSCLC.

Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” to lncRNA H19 and “alanine, aspartate and glutamate metabolism” to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.

Epigenetic dysregulation is a hallmark of many human malignancies, with DNA methylation being a primary mechanism influencing gene expression and maintaining genomic stability. Genome-wide hypomethylation, characteristic of many cancers, is partly attributed to the demethylation of repetitive elements, including LINE-1, a prevalent non-LTR retrotransposon. The methylation status of LINE-1 is closely associated with overall genomic methylation levels in tumors. cfDNA comprises extracellular DNA fragments found in bodily fluids such as plasma, serum, and urine, offering a dynamic snapshot of the genetic and epigenetic landscape of tumors. This real-time sampling provides a minimally invasive avenue for cancer diagnostics, prognostics, and monitoring. The methylation status of LINE-1 in cfDNA has emerged as a promising biomarker, with several studies highlighting its potential in diagnosing and predicting outcomes in cancer patients. Recent research also suggests that cfDNA-based LINE-1 methylation analysis could serve as a valuable tool in evaluating the efficacy of cancer therapies, including immunotherapy. The growing clinical significance of cfDNA calls for a closer examination of its components, particularly repetitive elements like LINE-1. Despite their importance, the role of LINE-1 elements in cfDNA has not been thoroughly gauged. We aim to address this gap by reviewing the current literature on LINE-1 cfDNA assays, focusing on their potential applications in diagnostics and disease monitoring.

Late-stage epithelial ovarian cancer (EOC) involves the widespread dissemination of malignant disease throughout the peritoneal cavity, often accompanied by ascites. EOC metastasis relies on the formation of multicellular aggregates, called spheroids. Given that Liver Kinase B1 (LKB1) is required for EOC spheroid viability and LKB1 loss in EOC cells decreases tumor burden in mice, we investigated whether the LKB1 complex controls the invasive properties of human EOC spheroids. LKB1 signalling was antagonized through the CRISPR/Cas9 genetic knockout of LKB1 and/or the RNAi-dependent targeting of STE20-related kinase adaptor protein (STRAD, an LKB1 activator). EOC spheroids expressing nuclear GFP (green) or mKate2 (red) constructs were embedded in Matrigel for real-time live-cell invasion monitoring. Migration and invasion were also assessed in spheroid culture using Transwell chambers, spheroid reattachment, and mesothelial clearance assays. The loss of LKB1 and STRAD signalling decreased cell invasion through Matrigel and Transwell membranes, as well as mesothelial cell clearance. In the absence of LKB1, zymographic assays identified a loss of matrix metalloproteinase (MMP) activity, whereas spheroid reattachment assays found that coating plates with fibronectin restored their invasive potential. A three-dimensional EOC organoid model demonstrated that organoid area was greatly reduced by LKB1 loss. Overall, our data indicated that LKB1 and STRAD facilitated EOC metastasis by promoting MMP activity and fibronectin expression. Given that LKB1 and STRAD are crucial for EOC metastasis, targeting LKB1 and/or STRAD could disrupt the dissemination of EOC, making inhibitors of the LKB1 pathway an alternative therapeutic strategy for EOC patients.

Background: Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. Methods: This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. Results: The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson’s correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p < 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. Conclusions: The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma.

Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV–HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV–HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV–HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population.

Introduction: Women with late-stage metastatic breast cancer are at an increased risk of pain and distress from symptoms and often struggle with associated emotional and financial burden of their disease. Palliative care is known to alleviate symptom burden in patients with end-stage, terminal diseases but is often underutilized in both inpatient and outpatient settings. The current study aims to investigate the prevalence of palliative care consultation on inpatients with metastatic breast cancer and examine the association between palliative care consultation and length of hospital stay and total hospital charges. Methods: Patients diagnosed with metastatic breast cancer between 1998–2017 were abstracted from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Database (NIS). The primary outcome was the presence of a palliative care consultation (PCC) during the inpatient stay. Secondary outcomes were hospital length of stay and total hospital charges. Multivariable logistic regression was used to examine factors associated with the presence of a PCC. The relationship between PCC and hospital length of stay and total hospital charges were investigated using linear regression. Results: 513,509 cases of metastatic breast cancer were identified, 5.7% had a documented in-hospital palliative care encounter. Of those who received PCC, total hospital charges were about USD 5452 less than those who did not receive consultation. Women who received PCC had higher odds of a longer hospital stay. Predictors of PCC were older age, non-White race, and residing in a lower-income ZIP code. Conclusions: Palliative care remains to be an underutilized resource among patients with end-stage metastatic breast cancer.