BMC Cancer最新文献

Introduction: It is unclear whether patients with breast cancer (BC) who undergo mastectomy experience delays in adjuvant treatment when bilateral surgery is performed. This study was conducted with the objective of addressing this knowledge gap.

Methods: Stage 0-III BC patients who underwent mastectomy (including conventional mastectomy, nipple-sparing mastectomy [NSM], and skin-sparing mastectomy [SSM]) at a Swiss university hospital between 01/2013 and 12/2023 were identified from a prospectively maintained database. Multivariable Cox proportional hazards regression models were used to detect predictors of time to adjuvant treatment.

Results: A total of 394 patients were included, 308 (78.2%) of whom underwent unilateral mastectomy (UM) and 86 (21.8%) of whom underwent bilateral mastectomy (BM). Compared with patients who underwent UM, those who underwent BM were younger (median age [years] 49 vs. 60), more likely to carry a pathogenic germline BRCA variant (28.7% vs. 2.6%), presented with bilateral breast cancer (14.9% vs. 0%), and underwent neoadjuvant chemotherapy (34.5% vs. 12.4%). Patients who underwent BM were more likely to receive NSM or SSM (81.4% vs. 52.9%) and to develop wound healing disorders (20.7% vs. 11.4%). On univariable analysis, no differences in time to any adjuvant treatment were observed between BMs and UMs (median [days] 34 vs. 33; p = 0.444). Multivariable analysis suggested that bilateral mastectomy was associated with a shorter time to adjuvant chemotherapy (HR 2.54, 95% CI 1.15-5.58). Short-term postoperative complications were associated with prolonged time to any adjuvant treatment (HR 0.50, 95% CI 0.36-0.71) and time to adjuvant chemotherapy (HR 0.37, 95% CI 0.17-0.79).

Conclusion: Undergoing BM did not result in a delay in time to adjuvant treatment in comparison to UM.

Background: Treatment of paediatric acute myeloid leukaemia (AML) is challenging in low- and middle-income countries (LMICs) due to resource constraints with subsequent poorer outcome. This study evaluated treatment outcomes and the determinants of survival in paediatric AML patients in Uganda.

Methods: This retrospective cohort study reviewed data from children with AML treated at three centres in Uganda between January 2016 and December 2022. Treatment comprised induction with daunorubicin and cytarabine and consolidation with high-dose cytarabine. Patients with acute promyelocytic leukaemia were treated on protocols adapted from Children's Oncology Group AAML 1331. All patients received supportive care. The data were analysed using SPSS Version 20.

Results: One-hundred and fifty-nine children with AML were included with a median age at diagnosis of 9.0 years (IQR: 3.0-12.0). Of the 149 patients who initiated therapy, 69 (46.3%) achieved complete remission after the first induction therapy (CR1), and 81 (54.4%) achieved complete remission (CR) overall. Treatment-related mortality occurred in 50 (31.4%) of the patients, with an early death rate of 27.7% (n = 44). Among the 81 patients who achieved CR, 37 (45.7%) relapsed, of whom 27 (73.0%) subsequently died. The one-, three-, and five-year OS were 39.0%, 25.1%, and 16.7%, respectively. The corresponding EFS were 37.0%, 22.9%, and 15.2%, respectively. Median OS and EFS were 7.4 months (95% CI: 4.3-10.6) and 6.9 months (95% CI: 4.4-9.6), respectively. Factors significantly associated with poor OS included poor nutritional status (p = 0.026), delayed neutrophil recovery following induction (p = 0.030), failure to achieve CR1 (p = 0.031), and failure to complete treatment (p < 0.001).

Conclusions: Survival rates among children with AML in this study were low. Several clinical and biological prognostic factors influenced survival outcomes in this resource-limited setting. Improving outcomes will require improving supportive care or adopting resource-adapted treatment protocols that address the supportive care challenges in such a resource-limited setting.

Background: The identification of predictive biomarkers for nasopharyngeal carcinoma (NPC) treatment response is critical to improving clinical outcomes. Our previous studies demonstrated that the long non-coding RNA (lncRNA) LINC-PINT enhances the radiosensitivity of NPC cells. However, the clinical relevance of functional polymorphisms in LINC-PINT remains unclear.

Methods: A total of 199 Chinese NPC patients who received concurrent platinum-based chemoradiotherapy were enrolled. The association between the LINC-PINT rs1059698 polymorphism and short-term treatment efficacy (assessed 3 months post-treatment) was evaluated using multivariate logistic regression. LINC-PINT expression in NPC tissues was quantified by real-time polymerase chain reaction (PCR). A luciferase reporter assay was performed to assess the effect of rs1059698 on miR-646 binding. Eight machines were further employed learning algorithms to construct predictive models for treatment efficacy.

Results: NPC patients with a complete response (CR) showed significantly higher LINC-PINT expression than those with partial response (PR) or progressive disease (PD) (P < 0.05). The rs1059698 CC genotype was significantly associated with an improved treatment response (CR vs. PR + PD, OR = 0.189, 95% CI: 0.042-0.860, P = 0.031). Individuals carrying the CC genotype also exhibited approximately 1.5-fold higher LINC-PINT expression compared to AA genotype carriers (P < 0.001). Functional analysis showed that the A-to-C substitution at rs1059698 disrupted miR-646 binding to LINC-PINT. Additionally, the Gradient Boosting Machine (GBM) model incorporating rs1059698 and clinical variables achieved moderate predictive accuracy (AUC = 0.765 in training and 0.641 in validation).

Conclusions: Our findings suggest that the rs1059698 polymorphism were associated with NPC treatment response possibly by influencing the expression of LINC-PINT or altering miRNA-lncRNA interaction. LINC-PINT rs1059698 may serve as a predictive biomarker for chemoradiotherapy efficacy in NPC.

Introduction: Ovarian cancer significantly contributes to cancer-related deaths among women. Resistance to anchorage-dependent cell death (anoikis) plays a vital role in facilitating metastasis and worsening patient prognosis. Recent developments in the field of cancer biology have underscored the importance of long noncoding RNAs (lncRNAs) as crucial regulatory entities. However, their functions in the context of anoikis, particularly in ovarian cancer patients, remain inadequately understood.

Materials and methods: We conducted a comprehensive analysis of transcriptome data obtained from public databases, with a focus on screening lncRNAs associated with anoikis-related genes. A novel prognostic model that integrates risk scores to evaluate the predictive efficacy for patient outcomes was developed. We subsequently assessed the expression levels and functional role of the lncRNA BMPR1B-DT in ovarian cancer tissues through various techniques, including Western blot analysis, quantitative real-time polymerase chain reaction (qRT‒PCR), cell counting kit-8 (CCK‒8) assays, and flow cytometry.

Results: Our research demonstrates that the anoikis-related lncRNA prognostic model has significant clinical value in predicting the survival outcomes of ovarian cancer patients. Additionally, our study revealed that expression of the lncRNA BMPR1B-DT is upregulated in ovarian cancer tissues and cell lines. Moreover, we revealed that BMPR1B-DT promotes anoikis and inhibits proliferation under suspension culture conditions in ovarian cancer cells.

Conclusion: Our results suggest that BMPR1B-DT expression is critical in the process of anoikis in ovarian cancer patients. These insights underscore the necessity for further investigations aimed at translating these findings into clinical applications to improve diagnostic and therapeutic approaches for ovarian cancer patients.

Background: Identifying significantly mutated genes in tumors aids in understanding disease etiology and survival and may aid in the discovery of new drug targets. We aimed to detect and characterize mutated genes from a large, well-characterized group of colorectal cancers.

Methods: In tumor and paired normal samples from 6,111 colorectal patients, we sequenced 199 genes identified from whole exome sequencing of over 1,100 tumors. Analyses focused on non-silent mutations. We classified significantly mutated genes after stratification by hypermutation status, and estimated associations of mutated genes/pathways with disease-specific (DS)-survival using Cox regression, adjusting for age, sex, mutation burden, hypermutation status, and study while accounting for multiple comparisons (n = 4,874).

Results: We identified 57 genes that were significantly mutated in colorectal cancer, including 9 that were not previously reported. Among individual genes, only BRAF p.V600E mutations were significantly associated with poorer survival after correction for multiple testing (HR 1.96, P = 2.07 × 10^- 10), with a more pronounced association among those with non-hypermutated tumors (HR 2.24, P = 1.79 × 10^- 12). We also observed statistically significant associations with survival for four mutated pathways: TP53/ATM (HR 1.24, P = 7.96 × 10^- 4), RTK/RAS (HR 1.33, P = 3.81 × 10^- 6), TGF-beta (HR 1.25, P = 1.85 × 10^- 3), and WNT (HR 0.81, P = 2.52 × 10^- 03).

Conclusions: We identified 9 significantly mutated genes, some of which are known drug targets. Among individual genes, only the BRAF p.V600E mutation was significantly associated with DS-survival, suggesting a limited survival impact from mutations driving colorectal cancer development.

Introduction: It is crucial to identify effective molecular markers for early endometrial cancer (EC) detection and therapeutic targets for late-stage EC. However, the role of E26 transformation-specific homologous factor (EHF) in EC remains poorly characterized.

Materials and methods: Public databases were utilized to investigate the molecular features of EHF and its significance in the pathogenesis of EC. Analyses including single - gene correlation, functional enrichment, and immune infiltration were conducted. We used lentiviral-mediated EHF silencing in HEC-1B cells to examine EHF's impact on cell cycle, immigration, invasion, and proliferation.

Results: High EHF expression was linked to a more dismal prognosis of EC. The degree of tumor invasion, histologic type and stage, and clinical stage were significantly associated with EHF overexpression. Functional enrichment research conclusively indicated that EHF was closely linked to various activities, including the cell cycle, metabolic pathways, and interleukin 17 signaling pathway. The expression of EHF exhibited a negative connection with the presence of dendritic cells, natural killer (NK) cells, CD4 + type 1 T-helper cells, and the varying infiltration levels of other immune cells. In vitro study revealed increased EHF levels in endothelial cell tissues and cell lines. Analyses of functional components showed that EHF greatly enhances EC cell migration and development.

Conclusion: Elevated EHF expression in EC patients correlated with diminished immune cell infiltration and a worse outcome. Decreasing EHF levels also affected the invasion and proliferation of EC cells. These findings highlight EHF as a putative prognostic and diagnostic biomarker for EC.

Background: Enzalutamide at standard doses (160 mg/day) is effective in advanced prostate cancer (PCa) but is associated with considerable adverse events (AEs) and high financial costs. Preliminary reports suggest that low/intermediate doses (≤80 mg/day) retain efficacy while reducing toxicity. This study evaluates the efficacy and safety of low/intermediate dose vs standard-dose enzalutamide in a real-world cohort.

Methods: This retrospective observational study included 140 assessable patients treated with enzalutamide for metastatic castration resistant (80%) or sensitive (20%) PCa. Patients were categorized by cumulative average daily dose relative to the standard dose (160 mg/day): low (≤50%, n = 11), intermediate (>50% and ≤80%, n = 16), and high (>80%, n = 113). The primary endpoint was the 12-month progression-free survival (PFS) by restricted mean time. Secondary endpoints included PSA response (decline ≥50% at 3 months), overall survival (OS) at 36 months and worsening of AEs of interest (fatigue, neurological disorders, hypertension).

Results: There were no significant differences in PFS at 12 months on high vs intermediate dose (10.4 vs 11.4 mo, p= 0.09) and high vs low dose (10.4 vs 9.2 mo, p = 0.37), nor was there on PSA response (70% vs 75% vs 60% on high, intermediate, low doses, respectively). Intermediate or low doses showed no evidence of adverse effects on OS at 36 months. The rate of fatigue worsening on high vs intermediate vs low dose was 61.1%, 63.0% and 27.3% (p = 0.03 for high vs low).

Conclusions: Low/intermediate doses of enzalutamide show comparable efficacy than high dose while improving tolerability, indicating the need for further search of its optimal dose. Moreover, our findings prompt a study of the optimal dose in advanced disease and in the prevention/interception setting in patients with low/intermediate risk PCa under active surveillance.

Background: Accurate diagnosis of oral mucositis (OM) is essential for effective management and plays a critical role in ensuring reliable outcomes in clinical trials evaluating OM-prevention and treatment strategies. Currently, no evidence-based guidelines specify which clinical profession should be primarily responsible for OM assessments in patients undergoing high-dose chemotherapy. In most Scandinavian countries, nurses perform daily OM assessments, while dentists specialized in orofacial medicine (considered the gold standard) conduct supplementary evaluations several times per week. However, the concordance between nurses' assessments and those conducted by dentists specialized in orofacial medicine remains unclear. Therefore, this study aimed to evaluate the interrater reliability in of OM assessments between these two professions.

Methods: This study utilized data from a randomized, blinded, multicenter, parallel-group, phase 3 trial conducted at five university hospitals in Sweden and Norway. A total of 127 patients aged 18 years or older, diagnosed with multiple myeloma or lymphoma, and scheduled to receive high-dose conditioning chemotherapy in preparation for hematopoietic stem cell transplantation, were included. The primary objective was to evaluate the interrater reliability of OM assessments across all severity grades using the World Health Organization (WHO) oral toxicity scale (grades 0-4). The secondary objective was to evaluate the interrater reliability of OM assessments across all severity grades at each individual study site.

Results: Overall interrater reliability between nurses and dentists specialized in orofacial was found to be fair for OM of any grade (κ = 0.211, p < 0.001). However, agreement levels at individual study sites ranged from no agreement to fair agreement.

Conclusion: The interrater reliability in the assessment of oral mucositis between dentists specialized in orofacial medicine and nurses ranged from no-, to fair agreement. This highlights the need for targeted interventions to improve nurses' assessment skills or to integrate a specialized dentist as a permanent member of the multidisciplinary team in oncology and hematology settings. Trial registration This study is based on data from a previously registered clinical trial (ClinicalTrials.gov; Identifier: NCT03203733, Registered on November 20, 2020).