Clinical Medicine Insights-Oncology最新文献

Background: S-1, an oral chemotherapy combining tegafur, gimeracil, and oteracil, has shown efficacy comparable with docetaxel for advanced non-small cell lung cancer (NSCLC) in clinical trials. However, its real-world effectiveness and safety remain underexplored.

Methods: This retrospective cohort study was conducted at 2 tertiary referral centers: National Cheng Kung University Hospital (NCKUH) from July 1, 2012 to July 1, 2023 (last follow-up in October 31, 2023) and Linkou Chang Gung Memorial Hospital (CGMH) from February 1, 2020 to January 31, 2023 (last follow-up in August 31, 2023). The study included 132 NSCLC patients receiving S-1 monotherapy (77 from CGMH and 55 from NCKUH). After excluding 31 patients with less than 2 weeks of treatment, 101 patients were analyzed.

Results: The objective response rate (ORR) was 7.9%, and the disease control rate (DCR) was 44%. Median progression-free survival (PFS) and overall survival (OS) were 2.6 and 6.0 months, respectively. First-line or second-line S-1 therapy significantly improved DCR (61.1% vs 33.8%, P = .008) and PFS (4.2 vs 2.3 months, P < .001) compared with third-line or later use. Cox regression analysis confirmed earlier-line S-1 treatment (⩽ 2) as an independent predictor for PFS (hazard ratio: 2.01, 95% confidence interval: 1.15-3.51, P = .014). Severe adverse events (grade ⩾ 3) occurred in 7.9% of cases.

Conclusions: S-1 monotherapy demonstrated comparable effectiveness and manageable toxicity in real-world settings, with significantly better outcomes when used as first-line or second-line treatment in NSCLC.

Background: Hepatocellular carcinoma (HCC) is associated with poor prognosis and high mortality. Notchless homolog 1 (NLE1) is an important WD40 protein. Although several studies have shown that NLE1 is dysregulated in cancer, the function in hepatocarcinogenesis remains unclear.

Methods: We screened for dysregulated WD40 proteins in HCC using data from the GSE5364 and GSE19665 datasets. A risk prediction model associated with WD40 proteins was constructed based on the TCGA database and validated with independent datasets (ICGC, GSE116174, and GSE14520). The significance of NLE1 was assessed using a genome-wide CRISPR screen and multiomics data from TCGA, CPTAC, multiple GEO datasets, and the single-cell dataset GSE166635. We further evaluated NLE1 expression in patient tissue microarrays. Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic relevance of NLE1. Logistic regression was performed to analyse the associations between NLE1 expression and the clinical features of patients with HCC. Drug sensitivity to NLE1 was evaluated using organoid assays. Proliferation assays (CCK-8 and colony formation assays) were used to assess the effect of NLE1 on HCC cell growth.

Results: We developed a risk prediction model based on WD40 proteins, which revealed significant differences in tumour immune cell infiltration between the high-risk and low-risk groups. In addition, high NLE1 expression was strongly associated with poor prognosis in HCC patients. Through organoid response characterization, we also found a significant correlation between NLE1 expression and sensitivity to the small molecules 17-AAG, AZD7762, and JQ1. Finally, enrichment analysis and proliferation assays confirmed that elevated NLE1 expression promotes HCC cell proliferation.

Conclusion: NLE1 is an independent diagnostic and prognostic biomarker that promotes the proliferation of HCC.

Background: Ovarian cancer (OC) is a significant health problem often diagnosed at an advanced stage due to the lack of early symptoms and effective screening methods. This study aimed to explore the role of CYB5R4 gene methylation as a potential biomarker for ovarian cancer.

Methods: DNA isolation was performed in the blood samples of 387 ovarian cancer patients, 50 individuals with benign ovarian diseases, and 100 healthy controls. The CYB5R4 gene methylation status was evaluated using the Methyl-Specific Restriction Enzymes (MSREs) technique and methylation levels were compared between the groups.

Results: Ovarian cancer patients exhibited the highest mean methylation percentage (9.45%) and median (6.23%), followed by healthy controls with a mean of 9.14% and a median value of 4.47%. Statistical analysis showed significant differences in methylation levels (P = .041), suggesting that CYB5R4 methylation may be associated with ovarian cancer progression.

Conclusion: The CYB5R4 gene methylation may serve as a potential biomarker for ovarian cancer, particularly in distinguishing between malignant and benign conditions. Further research is needed to validate these findings and explore the clinical utility of CYB5R4 methylation in ovarian cancer management.

Objectives: Peripheral T-cell lymphomas (PTCLs) are rare, aggressive non-Hodgkin lymphomas with limited treatment options and poor prognosis, especially upon relapse. Both autologous and allogeneic stem cell transplants have been used, although allogeneic transplantation is preferred for resistant cases. This systematic review and meta-analysis aim to clarify the impact of allogeneic transplantation on survival and treatment outcomes in PTCL patients.

Methods: We systematically searched the electronic databases PubMed, Scopus, and Web of Science from each database's inception to September 2024. Following the PRISMA guidelines, we included adult patients with PTCL undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT). We used proportional meta-analysis by executing a random-effects model (DerSimonian-Laird), with data transformation via the Freeman-Tukey method. Heterogeneity was assessed through I² and prediction intervals. We evaluated the risk of bias with the Methodological Index for Non-Randomized Studies (MINORS) tool and assessed evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. All analyses were performed using the R software package.

Results: Our search retrieved 448 articles after first scanning and removing the duplicates. A total of 112 titles were eligible for full-text screening. Finally, 10 studies were included with a total of 1586 patients. The 1-year overall survival (OS) proportion of 63.4% (95% confidence interval [CI] = 56.6% to 70%) across 9 studies with 1555 observations and 1077 events. The 1-year progression-free survival (PFS) proportion of 56.1% (95% CI = 51.1% to 61.1%) across 7 studies, with 1224 observations and 711 events. The 1-year non-relapse mortality (NRM) proportion of 22.3% (95% CI = 15.4% to 29.9%) across 6 studies with 1379 observations and 243 events recorded.

Conclusions: This systemic review supports the use of allogeneic hematopoietic stem cell transplantation for patients with PTCL; however, further research is needed to confirm its various benefits and limitations as a possible innovation in the field.

Background: In this study, our goal was to elucidate the role for imatinib monotherapy for treatment of patients with localized gastrointestinal stromal tumors (GISTs) who are precluded from standard-of-care surgical resection due to their medical comorbidities or patient preference.

Methods: A single-center retrospective study was conducted on a consecutive cohort of adult patients with pathology-confirmed gastrointestinal stromal tumors. The cohort of interest (n = 11) was the subset of patients on imatinib therapy alone with no prior history of curative-intent surgical resection. We analyzed patient demographics, GIST disease characteristics, treatment type, and medical comorbidities at the time of diagnosis. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier univariate analysis.

Results: Eleven patients met our inclusion criteria. Median age was 77 years (range 65-82) and 7 patients (64%) were men. Eight cases were gastric primary, 2 cases were duodenal, and 1 was esophageal. Four cases had genomics available, 3 of which harbored KIT mutations. For all cases, the documented mitotic rate was less than 5 per 5 mm². Median tumor size was 38 mm (range 20-58 mm). The most common medical comorbidity precluding patients from surgery was cardiac disease. All patients received imatinib as their only treatment modality and median time on treatment was 16 months. Two patients had progression of disease through treatment. Treatment was generally well tolerated with no documented grade III or grade IV adverse events. With a median follow-up of 35 months, the 1-year PFS and OS were 90% and 100%. The 3-year PFS and OS were also 90% and 100%.

Conclusion: Patients tolerated imatinib monotherapy well and demonstrated robust survival data. Our research highlights a new potential application for imatinib in a patient population that has historically been precluded from standard-of-care therapy for their disease.

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.