Clinical Medicine Insights-Oncology最新文献

Background: Combination therapy using an immune checkpoint inhibitor (ICI) and a tyrosine kinase inhibitor (TKI) is the standard first-line treatment for metastatic renal cell carcinoma (RCC). Oral TKIs enhance patient autonomy but require strict adherence and persistence.

Methods: We analyzed adults with metastatic RCC at Chao Comprehensive Cancer Center, receiving at least 2 TKI prescriptions between April 29, 2019, and August 29, 2022, assessing adherence via Medication Possession Ratio (MPR) and Proportion of Days Covered (PDC).

Results: A total of 66 individuals and 849 prescriptions were identified. The mean duration of TKI treatment was 237 days, with a median of 201 days. The mean persistence was 303 days, whereas the median was 233 days. Over 180 days, the median MPR was 83%, whereas the median PDC was 72%. The median variable PDC was 86%, while the median variable MPR was 105%. Asian patients experienced the longest average TKI therapy duration at 319 days, while Hispanic patients had the shortest at 223 days.

Conclusions: We observed a significantly longer median duration of oral TKI therapy (201 days) than the reported national average (< 100 days). This analysis of real-world data reveals that lengthier treatment durations for TKI + ICI combinations are feasible.

Background: Accumulating evidence suggests that the use of antibiotics (ATBs) is harmful to the survival of patients with non-small-cell lung cancer (NSCLC). However, the association between the prophylactic use of these agents during surgery and patient survival has been less well studied.

Methods: Data concerning the use of ATBs, including the cumulative defined daily dose (cDDD) and type, in stage I to III NSCLC patients were collected. The patients were subsequently divided into low or high-cDDD subgroups and ⩽2 or ⩾3 ATB-type subgroups. Differences in clinical variables, overall survival (OS), and disease-free survival (DFS) among these groups were assessed. Furthermore, differences in survival among specific ATB types (β-lactams and fluoroquinolones) were also tested. Finally, the risk factors for OS were determined using the Cox proportional hazards model.

Results: A total of 324 patients were included. Low cDDD was more common in patients with advanced T stages, whereas ⩽2 types of ATBs were common in female patients and those with adenocarcinoma, N₀ disease and stage I disease. No significant difference was found in OS among the low- or high-cDDD subgroups; however, a significant difference in OS was found between the ⩽2 and ⩾3 ATB. Similarly, patients with or without β-lactams displayed no difference in OS, whereas those with or without fluoroquinolones did. No differences were found in DFS between the subgroups. Multiple types of ATBs, rather than cDDD, were found to be risk factors for OS; however, they were not validated as independent risk factors.

Conclusions: This study, for the first time, explored the prognostic value of ATB use during surgery in NSCLC patients and revealed that multiple types of ATBs may be associated with OS in patients with stage I to III disease. Notably, patients treated with fluoroquinolones may have inferior outcomes than those without ATB use. However, multiple types of ATBs were not validated as independent risk factors for OS. These results suggest that the use of ATBs during surgery in early-stage NSCLC is generally safe; however, caution should be taken when selecting ATB types. Multiple ATB types should be avoided, and some specific ATB types, such as fluoroquinolones, should not be administered. Nonetheless, owing to the limited sample sizes, future studies are needed to validate our results.

Background: The incidence of testicular tumors during the COVID-19 pandemic has raised questions about the potential impact of viral infection on tumor development. This study aimed to explore the relationship between COVID-19 and testicular tumors through a retrospective analysis of 32 cases diagnosed before and during the pandemic.

Methods: A total of 32 testicular tumors were analyzed, with distribution based on the year of diagnosis. Immunohistochemical studies were conducted to assess SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) expression in tumor cells.

Results: The highest frequency of tumor diagnoses was observed in 2021 (19.4%), with a notable increase in diagnoses in 2022 compared with pre-pandemic years. No significant correlation was found between COVID-19 infection and tumor types (P = .476). The distribution of seminoma and mixed germ cell tumors (MGCT) was similar in both periods. Strong SARS-CoV-2 antibody positivity was found in 11 cases, with expression primarily in Leydig cells and some in Sertoli and plasma cells. The difference in SARS-CoV-2 expression between periods was statistically significant (P = 0013). The ACE2 expression was observed in all tumor groups, but statistical analysis was not significant.

Conclusion: The presence of SARS-CoV-2 nucleoprotein in the tumor microenvironment, particularly during the pandemic, suggests an indirect role of the virus in the development of testicular tumors. Although SARS-CoV-2 does not exhibit direct oncogenic effects, its presence could influence tumorigenesis through mechanisms like inflammation and oxidative stress. The ACE2 expression further supports the hypothesis that the virus may trigger adaptive changes in tumor cells. The SARS-CoV-2 could act as a co-factor in tumor progression, especially in individuals predisposed to testicular tumors.

Background: Skin involvement is one of the many clinical manifestations of lung cancer patients. However, there are fewer in-depth studies exploring the causal relationship between skin rashes and lung cancer subtypes, and the causal relationship is unknown. This study aims to explore the potential causal relationship between rash development and lung cancer diagnosis.

Methods: From the Genome-wide Association Studies (GWAS) database, we sourced comprehensive data on skin rash, lung cancer, and gene expression Quantitative Trait Loci (eQTL). Drawing from this, we conducted a comprehensive analysis that integrated Mendelian Randomization (MR), protein-protein network analysis, and enrichment analysis to explore the causal relationship and potential mechanisms between rash and lung cancer.

Results: This study reveals an increased risk of rash in small and squamous cell lung cancer patients, with odds ratios of 1.08 and 1.26, respectively. However, no causal link between rash and lung cancer was found. Genetic analysis identified 3 genes positively associated with both conditions and 6 negatively associated, suggesting complex genetic interactions. Sensitivity analysis did not indicate heterogeneity or pleiotropy.

Conclusions: Our study shows that squamous cell lung cancer patients are more likely to get skin rashes. But the rash is not directly linked to lung cancer. Future research should explore rashes as a therapeutic target and prognostic indicator.

Background: This study systematically assesses the efficacy of immunotherapy as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) and bone metastases who lack driver gene mutations. This analysis draws on data from randomized controlled trials to support individualized treatment strategies.

Methods: Randomized controlled trials published up to October 1, 2024, were retrieved from PubMed, EMBASE, the Cochrane Library, and the Web of Science. Statistical analyses were conducted using RevMan 5.4 and STATA 17.0, with the results presented in forest plots. Progression-free survival (PFS) and overall survival (OS) were analyzed using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024604768).

Results: Meta-analysis demonstrated a significant improvement in OS and PFS for patients with bone metastases receiving immunotherapy (OS: HR: 0.81, 95% CI: 0.71-0.92; PFS: HR: 0.78, 95% CI: 0.62-0.98). Although the survival benefit of immunotherapy was lower in patients with bone metastases than in those without, it was superior to chemotherapy.

Conclusions: Among patients with driver gene-negative NSCLC and bone metastases, immunotherapy significantly improved OS and PFS, thus supporting its role as an effective first-line treatment. Further large-scale trials are recommended to enhance treatment precision and validate these findings.

Background: The DNA methylation statuses of PAX1 and ZNF582 show great promise as biomarkers for the detection of oral squamous cell carcinoma (OSCC). This study aims to investigate the distribution of PAX1 or ZNF582 methylation in the exfoliated oral epithelial cells (OECs) of OSCC.

Methods: Methylation data from 528 tumors and 50 adjacent nontumor tissues were acquired from The Cancer Genome Atlas and analyzed using UALCAN database. Sixty-one OSCC cases from Peking University School and Hospital of Stomatology were included in this study and the exfoliated OECs collected by oral swabs were collected from the cancerous lesion (CL), adjacent normal (AN), and contralateral normal (CN) sites. The methylation levels of these 2 genes in different sites were evaluated.

Results: PAX1 and ZNF582 were both hypermethylated in OSCC compared with nontumor sites but showed different methylation patterns within the oral environment. Generally, a CL-centric methylation pattern of PAX1 where methylation levels decrease gradually from CL through AN to CN was observed, suggesting a field cancerization effect. ZNF582 methylation levels are significantly higher at lesion sites compared with normal sites, but no significant difference is observed between AN and CN. Coexistence of ZNF582 methylation in CL and AN or CN sites was also observed in some patients with OSCC. Furthermore, ZNF582 methylation was more sensitive among patients with OSCC.

Conclusions: DNA methylation detection of PAX1 and ZNF582 in the exfoliated OECs is helpful for OSCC diagnosis. Hypermethylated PAX1 and ZNF582 show different methylation patterns in the oral cavity of patients with OSCC.

Serine hydroxymethyltransferase 2 (SHMT2) is a crucial mitochondrial enzyme in 1-carbon (1C) metabolism. It catalyzes the conversion of serine to glycine, generating 1C units essential for purine and pyrimidine synthesis, thereby supporting DNA replication and repair. Abnormally high expression is associated with malignant progression and treatment tolerance in various cancers. This review systematically summarizes the functions of SHMT2 in different types of cancer, underscoring on its roles in metabolism, immune microenvironment, and key signaling pathways (PI3K/AKT/mTOR, JAK-STAT, etc.) and outlines its epigenetic regulation and posttranslational modification mechanisms. Compared with the existing research, we focused on the latest regulatory mechanisms of SHMT2 and its potential in cancer treatment, such as the development and application of small-molecule inhibitors (SHIN2 and AGF347).

Background: Computed tomography with bone scans (CT-B) has been widely used for staging metastatic hormone-sensitive prostate cancer (mHSPC), but whole-body magnetic resonance imaging (WB-MRI) is increasingly adopted. This study compares WB-MRI and CT-B in detecting metastatic sites, disease classification (CHAARTED and LATITUDE), and treatment outcomes in mHSPC.

Methods: This retrospective study included patients with mHSPC diagnosed between February 2017 and August 2023 at 2 UK NHS hospitals. Patients underwent baseline staging with either WB-MRI or CT-B. Data on demographics, disease extent, and treatment were analysed. Patients were stratified using CHAARTED and LATITUDE criteria. Survival outcomes were assessed using Kaplan-Meier and Cox regression analyses.

Results: Among 203 patients (120 WB-MRI, 83 CT-B), WB-MRI identified higher rates of bone-only disease (47% vs 22%, P < .001), high-volume (49% vs 22%, P < .001), high-risk (47% vs 18%, P < .001), and de novo metastatic disease (91% vs 65%, P < .001), but lower lymph node-only metastases (10% vs 26%, P = .003) and prior radical treatment (surgery: 2% vs 13%, P < .001; radiotherapy: 7% vs 25%, P < .001). CHAARTED (HR 4.922, 95% CI: 1.937-12.507, P < .0001) and LATITUDE (HR 4.807, 95% CI: 1.674-13.809, P = .003) classifications independently predicted overall survival, with significant volume/risk differences only observed in WB-MRI (P < .001 and P = .001, respectively).

Conclusions: Whole-body magnetic resonance imaging appears to enhance staging accuracy and risk stratification in mHSPC, potentially influencing treatment decisions. While limited by retrospective design, these findings suggest that WB-MRI may optimise management in mHSPC, warranting further prospective validation.

Background: The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, specifically the cysteine residue mutation KRAS (G12C), has garnered significant attention as a therapeutic target for solid cancer patients with KRAS mutations. Despite this interest, the efficacy and safety profiles of KRAS G12C inhibitors remain incompletely understood. In this study, we comprehensively evaluate the effectiveness and toxicity of relevant KRAS G12C inhibitors (Sotorasib, Adagrasib, Garsorasib, and Divarasib) in patients with colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), and pancreatic ductal adenocarcinomas (PDAC).

Methods: Our systematic review is guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We review the available clinical trials data on KRAS G12C inhibitors in KRAS G12C-mutated solid tumors. We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials from January 2020 until August 2023.

Results: A total of 17 eligible studies were included. KRAS G12C inhibitions with Sotorasib (41.2%) and Adagrasib (41.2%) each of them were reported in 7 studies. Divarasib was reported in 2 studies (11.8%) and Garsorasib was reported in 1 study (6.7%). Sotorasib showed a significant clinical benefit in terms of objective response rate (ORR) (7.1%-47%), progression-free survival (PFS) (4-6.8 months), and overall survival (OS) (4-24 months); it is more efficient in NSCLC patients with an OS of 2 years, PFS of 6.3 months, and an ORR of 41%. Adagrasib also showed significant clinical activity with an ORR (19%-53%), PFS (3.3-11.1 months), and OS (10.5-23.4 months), with more effectiveness in NSCLC patients with an OS of 23.4 months, PFS of 11.1 months, and an ORR of 53.3%. Adagrasib is more efficient with an ORR of 35.1%, PFS of 7.4 months, and an OS of 14 months in patients with PDAC, than Sotorasib which showed an ORR of 21%, PFS of 4 months, and an OS of 6.9 months. However, Adagrasib and Sotorasib are moderately efficient in CRC clinical trials.

Conclusion: This study confirms that patients treated with these KRAS G12C inhibitors, exclusively or combined with conventional therapies, achieve better treatment responses and modulate the progressions of these solid tumors.

Background: Detoxification enzymes of the glutathione S-transferase (GST) family are cytosolic phase II detoxification enzymes and play an important role in the normal functioning of the human antioxidant system. When the normal function of GST is disturbed or absent, there can be disturbances in cell metabolism, proliferation, and apoptosis. Deletions in the GSTM1 and GSTT1 genes have been observed in several different diseases as well as in the development of cancer. There is a need to analyze the relationship between glioma and GSTM1 and GSTT1 gene deletion to better understand the relationship between brain tumors and GST polymorphisms, which is crucial for adopting a multidisciplinary approach to prognosis and treatment of brain tumors.

Methods: In a cross-sectional clinical-laboratory study, gene deletions were examined in 34 patients with brain tumors originating from glial cells-gliomas and 88 healthy individuals. All participants were of Polish nationality and were not related.

Results: An increase in GSTM1 and GSTT1 gene deletions was observed in glioma patients compared with the control group. The greatest increase showing a marked rise of 10 times (11.8% vs 1.14%, P < .05) is in the null genotype of both genes (GSTM1-/GSTT1) [odds ratio [OR] = 0.86; 95% confidence interval [CI] = 0.09-0.802] but less in the genotype with deletion of 1 GST gene (GSTM1-/GSTT1+ and GSTM1+/GSTT1-). In addition, the findings indicated a decrease in the non-deletion genotype of both genes (GSTM1+/GSTT1+) in healthy individuals. This study showed a higher frequency of GST gene deletion in glioma patients in the studied population.

Conclusions: Based on the obtained findings, it can be said that the examination of the selected detoxification enzymes can be a useful marker in the diagnosis of glioblastoma.