Clinical Medicine Insights-Oncology最新文献

In China, esophageal cancer (EC) is one of the most prevalent malignant tumors of the digestive system. EC has a high incidence and mortality rate, of which esophageal squamous cell carcinoma (ESCC) accounts for more than 90%. Due to a lack of effective prevention and treatment methods, the 5 year survival rate is less than 30%. In recent years, microecology has become a hot spot in cancer research, and dysbiosis may play an important role in the etiology of EC. Presently, research on the relationship between the microbiome and ESCC remains in its early stages. This narrative review examines the relationship between the oral and esophageal microbiota and ESCC. A better understanding of this relationship may facilitate early detection and the optimization of treatment strategies.

Cryoablation is gaining attention as a minimally invasive treatment option for prostate cancer (PCa), offering a balance between effective oncological control and preserving genitourinary functions and quality of life. Focal cryoablation is emerging as a viable option for patients with PCa, particularly those who prioritize functional outcomes such as erectile functions and urinary continence. Whole-gland cryoablation, on the contrary, may be more appropriate for intermediate- and high-risk PCa where complete ablation of the prostate is necessary to ensure oncological control. Despite promising results, there is considerable heterogeneity in the available data regarding the long-term oncological and functional outcomes of cryoablation techniques, making it premature to issue definitive treatment recommendations. Further studies, particularly randomized controlled trials, are needed to clarify the role of cryoablation in PCa treatment. This narrative review aims to present the most relevant and up-to-date evidence on both focal and whole-gland cryoablation in PCa, providing a comprehensive overview of their current clinical applications, outcomes, and future potential.

Background: Non-Hodgkin Lymphoma (NHL) is an increasingly prevalent hematological malignancy in Egypt, highlighting the need for a better understanding of its genetic risk factors. The TP53 and MDM4 genes play critical roles in cellular homeostasis and cancer development. This study aimed to assess the frequency of the TP53 (SNP rs1042522) Arg72Pro and MDM4 (SNP rs4245739) A > C polymorphisms as potential risk factors for NHL in adult Egyptian patients.

Methods: A case-control study was conducted involving 80 adult NHL patients and 100 control age- and sex-matched healthy controls. Genotyping for the TP53 (rs1042522) Arg72Pro and MDM4 (rs4245739) A > C polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: A significant association was found between the homozygous TP53 Pro/Pro genotype and increased susceptibility to NHL (47.5% in patients vs 4.0% in controls; P < .001), as well as a higher frequency of the mutant C allele among NHL cases (63.8% vs 28.0%; P < .001). In contrast, no significant association was observed between MDM4 polymorphisms and NHL risk. In addition, analysis of treatment outcomes revealed no statistically significant differences in overall survival or progression-free survival based on TP53 or MDM4 genotypes.

Conclusions: These findings suggest that the TP53 Arg72Pro polymorphism is a significant genetic marker for NHL susceptibility in the Egyptian population, while MDM4 polymorphisms do not appear to contribute to disease risk. Further studies are warranted to elucidate the genetic mechanisms underlying NHL and to explore their implications for risk stratification and therapeutic strategies.

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.