Oncology Letters最新文献

[This corrects the article DOI: 10.3892/ol.2021.13018.].

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by bone marrow infiltration and the presence of monoclonal proteins in the blood and urine. However, despite the advances that have been made in terms of its treatment, relapsed/refractory MM (RRMM) remains a significant challenge. Chimeric antigen receptor (CAR)-T cell therapy, which involves the engineering of T-cells to express CARs targeting specific antigens on tumor cells, has emerged as a promising therapeutic approach for RRMM. The present case report presents a patient with RRMM with liver extramedullary disease (EMD) who achieved stringent complete remission following CAR-T cell therapy. This case report highlights the efficacy of CAR-T cell therapy in treating RRMM, also discussing the patient's clinical course, treatment outcomes and side effects, and moreover, a review of the literature that focuses on the treatment of EMD using CAR-T cell therapy.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited targeted treatment options, making the identification of reliable prognostic markers crucial for improving patient outcomes. The present study aimed to assess the predictive ability of pre-chemotherapy and pre-surgery inflammatory status on the prognosis of patients with TNBC undergoing neoadjuvant therapy. A total of 422 patients with TNBC who received neoadjuvant chemotherapy at the Inner Mongolia People's Hospital between January 2017 and December 2022 were selected for analysis. Fasting venous blood samples were collected 1 day prior to chemotherapy and 1 day prior to surgery to assess and calculate inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI). The optimal cut-off values of the inflammatory markers were determined using receiver operating characteristic curves. Survival analysis was used to evaluate the differences in survival and significant prognostic factors. Propensity score matching (PSM) analysis was performed to further asses the prognostic value of the relevant factors. Survival analysis indicated that patients with high pre-chemotherapy and pre-surgery NLR, PLR, SII and SIRI scores exhibited shorter overall survival (OS) rates compared with those with low scores (all P<0.05). Multivariate analysis revealed that tumor-node-metastasis stage, pathological complete response and pre-surgery SII were independent prognostic factors for OS. Following PSM, the area under the curve for SII was 0.642 and patients with high SII scores exhibited shorter OS rates than those with low scores (χ²=8.452; P=0.004). Therefore, these results indicated that both pre-chemotherapy and pre-surgery inflammatory statuses are associated with the OS of patients with TNBC undergoing neoadjuvant chemotherapy, notably pre-surgery SII.

Despite advancements in immunotherapy, particularly regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 blockades, the clinical outcomes in non-small cell lung cancer (NSCLC) remain variable with limited predictive biomarkers currently available. The present study investigated respiratory microbiota diversity as a potential biomarker to predict the efficacy of PD-1 blockades in patients with advanced NSCLC. A retrospective analysis was conducted on 60 patients treated with PD-1 blockades from May 2019 to May 2023. Clinical data were collected and respiratory microbiota from deep induced sputum specimens were analyzed using 16S rRNA gene sequencing. An index of respiratory microbiota α diversity was applied and exploratory analysis was performed accordingly. The objective response rate (ORR) and disease control rate among the 60 patients receiving PD-1 blockades was 23.3% (95% CI, 13.4-36.0%) and 58.3% (95% CI, 44.9-70.9%), respectively. Analysis of prognostic data of patients with advanced NSCLC receiving PD-1 blockades monotherapy demonstrated a median progression-free survival of 3.4 months (95% CI, 2.54-4.26) and a median overall survival (OS) of 12.3 months (95% CI, 6.29-18.31). Patients were stratified into high and low α diversity groups based on the Shannon diversity index of respiratory microbiota. The ORR was increased in the high diversity group (26.7%) compared with that of the low diversity group (20.0%), although the difference was not statistically significant (P=0.542). Notably, the high diversity group demonstrated a longer median PFS (3.9 vs. 2.8 months; P=0.017) and median OS (16.8 vs. 6.8 months; P=0.016) compared with that of the low diversity group. These findings suggested that PD-1 blockades demonstrate promising therapeutic activity for patients with previously treated advanced NSCLC in clinical practice. Respiratory microbiota α diversity might serve as a potential biomarker to predict the efficacy of PD-1 blockades monotherapy in patients with advanced NSCLC in the future. Therefore, further prospective studies are warranted to validate these findings and to explore the underlying mechanisms by which respiratory microbiota might modulate the immune response to cancer therapy.

Chromosomal abnormalities are common characteristics of neuroblastoma, and have been associated with treatment, relapse and survival risk factors. The processes governing the incidence or advancement of chromosomal copy number abnormalities remain unclear, despite progress in understanding their prognostic implications. The present study aimed to provide a comprehensive understanding of genetic alterations, clinical implications, and the association between copy number aberrations (CNAs) and clinical parameters. Single nucleotide polymorphism (SNP) array analysis was performed on a set of 45 neuroblastoma samples to examine chromosomal CNAs and SNPs. Logistic regression analysis was performed to identify SNPs associated with adverse drug reactions (ADRs). In the present study, numerous CNAs were observed in 92% of neuroblastoma tumors, while CNAs were found in 15% of ganglioneuroblastoma tumors. The segmental alterations were mainly observed in stage 3 or 4 neuroblastoma cases that had tumor sizes >10 cm. The present study concentrated on analyzing entire chromosome modifications and revealed that, in contrast to gain, loss of heterozygosity (LOH) mostly occurred during stages 3 and 4 of neuroblastoma. Only stage 3 and 4 neuroblastomas with tumor sizes >10 cm were found to exhibit loss of the Y chromosome, which was associated with similar clinical characteristics as segmental alterations. LOH of the whole chromosome might be a subgroup of whole chromosome alterations, and could be a novel prognosis and treatment marker. Using a regression model, 13 SNPs were identified to be strongly associated with ADRs following chemotherapy for neuroblastoma. Although validation studies in independent cohorts are required, the present findings support the use of CNAs and SNPs for predicting neuroblastoma treatment outcomes.

Sintilimab, a fully human immunoglobulin G4 monoclonal antibody targeting the programmed cell death receptor 1 (PD-1) pathway, has emerged as significant in cancer immunotherapy, demonstrating promising antitumor effects in various malignancies. The present review summarizes the current clinical data, highlighting the role of sintilimab in treating various types of cancer, including non-small cell lung cancer, liver cancer, gastric cancer and neuroendocrine tumors. The review also explores the mechanism of action of sintilimab, its structural and pharmacokinetic properties and its safety profile, which includes a comprehensive analysis of immune-related adverse events. Notably, the high binding affinity of sintilimab to PD-1 and its fully humanized nature contribute to its potent immunotherapeutic effects and favorable safety profile. Clinical trials have shown that sintilimab, either used as a monotherapy or in combination with chemotherapeutic agents, can significantly extend progression-free and overall survival in patients with advanced cancers. Furthermore, the economic implications and accessibility of sintilimab, particularly in resource-limited settings, are discussed. The current review reports on the innovative potential of sintilimab in shaping future cancer treatment strategies and emphasizes the need for personalized therapy based on individual patient biomarkers. The study reveals that sintilimab is not only a viable alternative to existing PD-1 inhibitors, but also a promising candidate for further research and development in immuno-oncology.

Venetoclax, an orally administered B-cell lymphoma 2 inhibitor, requires dose adjustments when coadministered with cytochrome P450 inhibitors in patients with acute myeloid leukemia (AML). The present study retrospectively analyzed data on progression-free survival (PFS), overall survival (OS) and drug-related adverse events in patients with AML who received adjusted low-dose venetoclax with antifungal agents, compared with those receiving conventional chemotherapy regimens (I3A7, LDAC, and I2A5), at a single hospital. In total, 45 patients with AML who were treated between January 2015 and December 2021 were retrospectively included. A significantly longer median OS time was observed in the group receiving idarubicin [12 mg/m² intravenous (IV) on days 1-3] and cytarabine (100 mg/m² continuous IV infusion on days 1-7) (I3A7 group) (median not reached) compared with that in the venetoclax group [10.7 months; 95% confidence interval (CI), 6.3-20.8], the low-dose cytarabine (LDAC) group (4.7 months; 95% CI, 0.8-18.7) and the group receiving idarubicin (12 mg/m² IV on days 1-2) with cytarabine (100 mg/m² continuous IV infusion on days 1-5) (I2A5 group) (2.3 months; 95% CI, 0.5-2.3). Similarly, the median PFS time was significantly longer in the I3A7 group (29.0 months; 95% CI, 1.1-29.0) compared with that in the venetoclax (8.0 months; 95% CI, 0.8-10.8), LDAC (2.1 months; 95% CI, 0.1-6.4) and I2A5 (0.9 months; 95% CI, 0.1-4.7) groups. Grade 3 or higher adverse hematological events were common across all treatment groups. Cardiovascular events and grade 3 or higher tumor lysis syndrome occurred only in the venetoclax group (14 and 7%, respectively). In conclusion, low-dose venetoclax combined with antifungal agents appears to be less effective than standard treatment but superior to both LDAC and the I2A5 treatment regimens. Venetoclax also demonstrates a relatively low infection risk. However, careful monitoring for cardiovascular events and tumor lysis syndrome during venetoclax administration is crucial, particularly in patients with relevant medical histories.

Sirtuin-1 (SIRT1) expression levels are upregulated in various types of cancer and are associated with adverse outcomes. However, there is limited research on SIRT1 expression in types of gynecological cancer. The present study primarily sought to investigate the expression characteristics of SIRT1 in non-endometrioid endometrial cancer (EC) using immunohistochemistry. The secondary endpoint was to evaluate the impact of SIRT1 expression levels on progression-free survival (PFS). The present study was a single-center, retrospective cohort study that included patients who underwent hysterectomy between June 2017 and December 2021 and had a postoperative histopathological diagnosis of non-endometrioid EC. The tissue slides were stained with a monoclonal antibody targeting the SIRT1 protein. The nuclear staining reaction of SIRT1 was considered to be positive in the presence of any percentage of nuclear staining. The cytoplasmic staining reaction of SIRT1 was assessed using the immune reactivity scoring (IRS) system, which was determined by multiplying the scores for the staining percentage and staining intensity. IRS values of 0 to 2 were considered as negative expression; 3 to 4 as low expression; 6 to 8 as moderate expression; and 9 to 12 as high expression. Cox proportional hazards regression models were used to identify factors influencing PFS. Data from a total of 43 patients who met the eligibility criteria were presented. Cytoplasmic staining with SIRT1 was detected in all samples (100%), whereas no nuclear staining was evident in any of the tissue samples. According to the IRS results, 20.9% of samples exhibited negative cytoplasmic expression, 14.0% exhibited low expression, 37.2% exhibited moderate expression and 27.9% exhibited high expression. The estimated 3-year PFS rate was 43.6%. Cox regression models demonstrated no independent factor influencing PFS. In conclusion, SIRT1 expression was found to be cytoplasmic in non-endometrioid EC. According to the IRS, ~80% of cases exhibited varying degrees of SIRT1 expression. However, SIRT1 expression levels had no significant impact on PFS.

Leiomyoma is a benign muscular abnormality that commonly occurs in the middle and distal third of the esophagus, leading to thickening of the esophageal wall and subsequent esophageal luminal narrowing. Notably, esophageal leiomyoma often does not show increased 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). The present study described a case of esophageal leiomyoma combined with adrenal adenoma. Results of the PET-computed tomography analysis revealed that FDG metabolism was increased in the lower segment of the esophagus and the left adrenal gland, with maximum standardized uptake values of 6.5 and 4.1, respectively. Therefore, initially, the patient was diagnosed with an esophageal malignant tumor with left adrenal metastasis. Open surgery was performed for complete removal of the lesions, and results of a routine pathological analysis revealed esophageal leiomyoma combined with adrenal cortical adenoma. The present study indicates that to avoid unnecessary surgeries, esophageal leiomyoma and adrenal cortical adenoma should be diagnosed through a comprehensive assessment with endoscopy, endoscopic ultrasound, computed tomography, magnetic resonance imaging and tissue sample pathology, not just PET.

The present study aimed to investigate the expression of ferroptosis genes in non-small cell lung cancer and their relationship with prognosis, and to analyze the relationship between ferroptosis genes and tumor immunity. To evaluate the expression levels of ferroptosis genes and their association with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), The Cancer Genome Atlas LUAD and LUSC data were downloaded, patient clinical information and ferroptosis gene expression profiles were extracted, and differential gene expression, survival and correlation analyses were performed using R. Using immune correlation analysis, the value of ferroptosis genes for immunotherapy was explored. The potential application of ferroptosis genes in immunotherapy was further validated by immunohistochemical staining. A number of ferroptosis-associated genes were differentially expressed in tumor tissues compared with in non-tumor tissues. CDGSH iron-sulfur domain-containing protein 1 (CISD1) was upregulated in both LUAD and LUSC tumor tissues, and was associated with tumor Tumor-Node-Metastasis stage. Notably, high levels of CISD1 in LUAD indicated a poor prognosis, and CISD1 was negatively correlated with CD4⁺ T cells based on the immune score. Furthermore, CISD1 may be involved in pathways such as cellular response to hypoxia, DNA repair, extracellular matrix-related genes, epithelial-mesenchymal transition markers, oxidative phosphorylation and PI3K-AKT-mTOR pathway. Immunohistochemical staining indicated that CISD1 was highly expressed in LUAD tissues, it was associated with a poor prognosis of patients with LUAD, and it was negatively associated with CD4 and CD20. In conclusion, the ferroptosis gene CISD1 may be associated with the prognosis of LUAD, and high levels of CISD1 could indicate a shorter survival time. Furthermore, CISD1 has potential applications in immunotherapy. These findings may provide novel theoretical insights into the treatment of LUAD.