BMC Cancer最新文献

Background: Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC).

Methods: This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part.

Results: The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m²)/cisplatin (75 mg/m²) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m²)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m²)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2-7.5 months), overall survival (29.7 months vs. 16.1-21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months).

Conclusions: The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin.

Trial registration: The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017.

Background: Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to late-stage diagnoses resulting from nonspecific early symptoms and the absence of early diagnostic biomarkers. MicroRNAs (miRNAs) play a crucial role in regulating diverse biological processes, and their abnormal expression is observed in various diseases, including cancer. Cancer stem cells (CSCs) are thought to act as a driving force in PDAC spread and recurrence. In pursuing the goal of unravelling the complexities of PDAC and its underlying molecular mechanisms, our study aimed to identify PDAC-associated miRNAs and relate them to disease progression, focusing on their involvement in various PDAC stages in patients and in reliable in vitro models, including pancreatic CSC (PaCSC) models.

Methods: The miRNA profiling datasets of serum and solid biopsies of PDAC patients deposited in GEO DataSets were analyzed by REML-based meta-analysis. The panel was then investigated by Real Time PCR in serum and solid biopsies of 37 PDAC patients enrolled in the study, as well as on BxPC-3 and AsPC-1 PDAC cell lines. We extended our focus towards a possible role of PDAC-associated miRNAs in the CSC phenotype, by inducing CSC-enriched pancreatospheres from BxPC-3 and AsPC-1 PDAC cell lines and performed differential miRNA expression analysis between PaCSCs and monolayer-grown PDAC cell lines.

Results: Meta-analysis showed differentially expressed miRNAs in blood samples and cancerous tissues of PDAC patients, allowing the identification of a panel of 9 PDAC-associated miRNAs. The results emerging from our patients fully confirmed the meta-analysis for the majority of miRNAs under investigation. In vitro tasks confirmed the aberrant expression of the panel of PDAC-associated miRNAs, with a dramatic dysregulation in PaCSC models. Notably, PaCSCs have shown significant overexpression of miR-4486, miR-216a-5p, and miR-216b-5p compared to PDAC cell lines, suggesting the recruitment of such miRNAs in stemness-related molecular mechanisms. Globally, our results showed a dual behaviour of miR-216a-5p and miR-216b-5p in PDAC while miR-4486, miR-361-3p, miR-125a-5p, miR-320d expression changes during the disease suggest they could promote PDAC initiation and progression.

Conclusions: This study contributed to an enhanced comprehension of the role of miRNAs in the development and progression of PDAC, shedding new light on the miRNA landscape in PDAC and its intricate interplay with CSCs, and providing specific insights useful in the development of miRNA-based diagnostic biomarkers and therapeutic targets.

Background: The HER-2 status of breast cancer (BC) has been classified as negative or positive for a long time. Given the efficacy of novel anti-HER2-targeted antibody drug conjugates (ADCs) in HER2-low BC, a distinct subgroup of HER2-low tumors has emerged within BC. The biology and prognostic impact of HER2-low expression are not yet well defined, and inconsistent results were reported. This study aims to evaluate the impact of low HER-2 status on the response to neoadjuvant chemotherapy (NACT) and disease- free survival (DFS) rates.

Methods: We retrospectively analyzed BC patients treated with NACT from 2017 to 2023 in two cancer centers. HER2-negative patients were included. HER-2 low status was defined by IHC + 1 or + 2/ISH non-amplified, and HER2-zero was defined by IHC 0. Pathological complete response (pCR) rates and DFS between HER2-low and HER2-zero populations were compared.

Results: 170 patients were identified. 122 (72%) of these patients were HER2- zero BC, whereas 48 (28%) were HER2-low BC. Overall, pCR was achieved in 35 (20.5%) patients. Of these, pCR was observed in 30 patients (44.6%) from the HER2- zero group, compared to 5 patients (10.4%) from the HER2-low group (p = 0.046), but significance was lost in multivariate analysis. Among the hormone receptor (HR) positive subtype, pCR was achieved 19.8% of HER2-zero tumors and 7.5% of HER2-low tumors (p = 0.08). For HR-negative subtype 34.1% HER2-zero tumors had pCR and 25% of the HER2-low tumors had pCR (p = 0.614). There was no association between DFS and HER2-low status.

Conclusions: Our study indicates that HER2-low status had no impact on pCR or DFS.

Background: Physical activity is thought to be a key component in reducing postoperative complications following major abdominal surgery. The available literature on exercise interventions following radical cystectomy in patients with bladder cancer is scarce but suggests that physical activity and exercise might improve physical function and health-related quality of life, thus calling for further investigation. The CanMoRe-trial is a single-blinded randomised controlled trial (Clinicals Trials NCT03998579 25/06/2019), aimed at evaluating the impact of an exercise intervention in primary care following robot-assisted radical cystectomy. This study seeks to explore patients' experiences of the exercise intervention in the CanMoRe-trial to gain a better understanding of facilitating aspects and potential barriers.

Methods: A qualitative study was conducted involving 20 patients from the intervention group of the CanMoRe-trial who were interviewed individually between October 2020 and March 2023 using a semi-structured interview guide. The interviews were recorded and transcribed verbatim and reflexive thematic analysis was used to analyse the data.

Results: Four main themes were identified: Having to adapt to new circumstances, describing the challenges regarding physical activity patients face after discharge. Optimising conditions for rehabilitation, describing how practical conditions affect patients' ability to exercise. Motivated to get back to normal, describing patients´ desire to get back to normal life and factors influencing motivation. Importance of a supportive environment, describing the impact of social support, support from physiotherapists, and how the environment where exercise takes place impacts patients' ability to exercise.

Conclusion: This study found that patients participating in the CanMoRe-trial are positive towards physical exercise in PC following radical RARC. They are motivated to get back to normal life but face major challenges when arriving home following surgery, which affect their ability to perform physical activity and engage in exercise. Conditions need to be optimised to support patients' ability to engage in exercise by providing an accessible PC location to perform exercise in. A supportive environment is also needed, including guidance from healthcare professionals regarding which type of exercise, intensity and amount of exercise that should be performed, enabling patients gradually to develop self-efficacy regarding exercise and focusing on goals related to patients' normal lives before surgery.

Background: There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate.

Methods: We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021.

Results: The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69-0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61-0.82; P < 0.001) of the combination therapy were significantly prolonged. Finally, 168 EGFR-mutated BM advanced LAC patients in the real world were verified, and the median iPFS of the combination therapy (n = 88 and EGFR-TKIs alone (n = 80) were 16.0 and 9.0 months, respectively, (P < 0.001). The median OS was 29.0 and 27.0 months, respectively, with no dramatic difference (P = 0.188).

Conclusions: Research on EGFR-mutant LAC brain metastasis has turned towards exploring optimal treatment strategies for this condition. Our meta-analysis and real-world data analysis consistently demonstrate that combination therapy offers a substantial improvement in patient survival compared to EGFR-TKI monotherapy. Notably, among patients undergoing salvage radiotherapy (RT), our subgroup analysis reveals that those initially treated with third-generation TKIs experience more significant benefits than those treated with first- or second-generation TKIs.

Background and objectives: Lung cancer is one of the prevailing malignancies worldwide. Surgical interventions hold an important position in the treatment framework for lung cancer. Pleural metastasis is often assumed to be a surgical contraindication, but not all instances of pleural metastasis can be accurately identified before surgery. The question of how to address pleural metastasis detected intraoperatively is still undecided.

Methods: This retrospective study included 187 lung cancer patients who underwent surgery from 2005 to 2017 in whom pleural metastasis was discovered incidentally during the operation. Data on demographic, surgical, pathological, postoperative treatment, and survival information were collected for further analysis.

Results: For patients with intraoperatively detected pleural metastasis, two independent protective prognostic factors were receiving primary tumor resection (compared to only receiving pleural nodule biopsy, HR = 0.079, p = 0.022) and receiving postoperative adjuvant chemotherapy (HR = 0.081, p < 0.001). Simultaneously, performing systematic lymph node dissection during primary tumor resection was found to be detrimental to long-term prognosis (HR = 2.375, p = 0.044). However, the resection of pleural metastatic lesions did not significantly impact patient prognosis.

Conclusion: Our study supports the implementation of major tumor resection in patients with pleural metastasis detected intraoperatively but not lymph node dissection or the resection of pleural metastatic lesions. Postoperative chemotherapy is also necessary.

Background: Patients with cancer (PwC) who undergo specific treatments reported greater fatigue and reduced functional capacity as predominant outcomes, compromising their QoL during and following the treatment. Prehabilitation intervention, provided after diagnosis and before treatments, is to optimize the physiological reserve and address modifiable risk factors before surgery or chemotherapy to improve post-treatment results. The primary aim of this study is to obtain a common line of efficacy compared with prehabilitation treatment; the secondary endpoint is to assess the methodological quality of the studies eligible in the review.

Methods: The systematic review was conducted from September to February 2024, in accordance with PRISMA guidelines. Databases consulted were MEDLINE, Scopus, Web of science and CINAHL, RCTs related to Prehabilitation intervention on PwC were included. The methodological quality of the included studies was assessed through the RoB2 Cochrane tool and the PEDro scale. Meta-analysis was performed to estimate relative treatment effects among evaluated outcomes.

Results: Forty-two studies were included in the systematic review, 13 were included in the quantitative analysis. The results of the studies reporting reduced postoperative hospital stay, improved endurance, muscle strength, respiratory function, quality of life, and urinary incontinence. Critical analysis of the articles using the PEDro scale revealed 28 RCTs with a good rating, 9 with a fair rating, and 5 with a poor rating; in contrast, the Cochrane RoB2 tool revealed that all articles were at high risk of bias. Meta-analysis showed statistically significant values for 6MWT (38.53, 95%CI 33.03 - 44.04); HADS-depression (-0.71, 95%CI -0.93 -0.49) and HADS-anxiety (-0.49, 95%CI -0.76 -0.23).

Conclusions: Prehabilitation represents a specific intervention that aims to improve postoperative outcomes in fragile patients undergoing surgery, increasing their preoperative physiological reserve in anticipation of the stress they will face and facilitating the postoperative recovery of functional capacity. Prehabilitation is a good intervention to use, especially in terms of functional capacity and mental health, the latter being very impactful in terms of reduced levels of anxiety and depression. These data make it possible to justify supportive intervention by physical therapists aimed at improving and restoring health-related QoL especially in the short term.

Background: Cervical cancer is the most common cause of cancer-related mortality among women in Africa. Cervical cancer screening in women is associated with decreased incidence and mortality of cervical cancer. There is a dearth of recent data regarding the prevalence and associated factors of cervical cancer screening in sub-Saharan Africa. Therefore, this study is intended to determine the prevalence and associated factors impacting cervical cancer screening among women in four sub-Saharan African countries.

Methods: Data from the recent demographic and health surveys of four countries in sub-Saharan Africa conducted between 2022 and 2023. Multilevel mixed-effects logistic regression was used to determine the factors associated with the outcome variable. Variables with a p-value < 0.05 were declared statistically significant.

Results: The prevalence of cervical cancer screening among women of childbearing age in four sub-Saharan African countries was 8.90% (95% CI: 8.67%, 9.13%). At the individual level, being older, educated, non-breastfeeding, employed, wealthier, sexually active, using contraceptives, having media exposure, visiting healthcare facilities in the last 12 months, and residing in urban areas were associated with higher odds of cervical cancer screening. At the community level, being from communities with a high level of literacy and media exposure increases the odds of cervical cancer screening among women in sub-Saharan Africa.

Conclusion: The prevalence of cervical cancer screening among childbearing-age women was found to be low. To improve cervical cancer screening practices among women of childbearing age, it is therefore advised to support women's empowerment, mass media campaigns, and regular visits to healthcare facilities.

Background: Uveal melanoma (UM) is the most common primary intraocular tumour in adults, and approximately 50% of patients will develop metastasis. Epigenetic changes are a major factor in cancer progression. We aimed to determine whether methylation profiles could be altered using a DNA methyltransferase (DNMT) inhibitor in UM cell lines.

Methods: Four primary and metastatic UM cell lines were treated with azacytidine and analysed for cell proliferation, colony formation, and BAP1 protein expression. Genomic and cell-free (cf)DNA methylation were compared.

Results: In all cell lines, azacytidine treatment resulted in dose-dependent effects on proliferation, colony formation, and radiosensitivity. Methylation profiling revealed differences in methylation between cell lines according to BAP1 expression. Matched primary and metastatic cell lines showed very similar patterns. Alterations were seen in pathways known to be important in UM progression, such as PI3K/Akt and MAPK signaling, and in pathways involved in cancer progression, such as regulation of stemlike potential, cell motility, and invasion. These changes were maintained in genomic and cell-free DNA.

Conclusions: This data suggests that DNMT inhibitors cause changes in UM cells that are maintained in cfDNA. The results suggest that targeting methylation in UM treatment and monitoring response to treatment using cfDNA methylation could be a valuable tool.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC.

Methods: Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1's impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells.

Results: Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration.

Conclusions: GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.