Wspolczesna Onkologia-Contemporary Oncology最新文献

Introduction: The HABER study aimed to evaluate real-world treatment patterns for hormone receptor-positive, HER-2-negative (HR+/HER-2-) advanced breast cancer (ABC) in Poland, focusing on adherence to local and international guidelines.

Material and methods: This retrospective, non-interventional analysis included 440 patients treated between September 2020 and August 2021 across 17 clinical sites. The trial was registered with ClinicalTrials.gov, NCT05478590.

Results: Most patients were postmenopausal (76.7%) with a mean age of 62.7 years, and nearly two-thirds had comorbidities. Almost half of the patients (48.6%) were diagnosed with de novo ABC. CDK4/6 inhibitor-based therapies were the predominant first-line treatment (74.1%), aligning with guideline recommendations. These therapies were more frequently combined with aromatase inhibitors (64.7%) than with fulvestrant (35.3%). The mean age ± standard deviation of patients treated with endocrine therapy (71.8 ±11.6 years) was higher than the age at which they received CDK4/6 inhibitors with endocrine therapy (61.3 ±11.7 years) or chemotherapy (62.0 ±13.2 years), p < 0.0001. Patients treated with CDK4/6 inhibitor-based therapy had more often the Eastern Cooperative Oncology Group performance status of 0-1 (90.8%) than those receiving endocrine therapy (48.1%) or chemotherapy (56.7%). Chemotherapy was used primarily for rapid disease progression or life-threatening visceral crises. CDK4/6 inhibitors remained the preferred treatment across all metastatic sites.

Conclusions: Treatment choice was influenced by patient demographics, performance status, and time from early breast cancer to relapse. The observed treatment patterns of first-line treatment of HR+/HER- ABC are highly aligned with current national and international guidelines.

Head and neck cancer (HNC) cases are increasing globally, with resistance to immunotherapies such as nivolumab posing a significant challenge. This systematic review examines the mechanisms of nivolumab resistance in HNC, with a focus on intrinsic tumor factors, the immunosuppressive tumor microenvironment (TME), and immune checkpoint dysregulation. Intrinsic mechanisms, such as mutations that impair antigen presentation and MYC amplification, reshape the TME to promote immune evasion. The tumor microenvironment, enriched with immunosuppressive cells such as tumor-associated macrophages and myeloid-derived suppressor cells, further compromises nivolumab's effectiveness. Moreover, cancer cells exploit immune checkpoints, including programmed death-ligand 1 (PD-L1), T-cell immunoglobulin and mucin domain-3, and LAG-3, to evade immune surveillance. Identifying predictive biomarkers, such as MYC amplification and PD-L1 expression, is essential for developing personalized treatments. This review underscores the complex nature of nivolumab resistance and the urgent need for comprehensive therapeutic strategies to improve outcomes in HNC patients.

Introduction: Retinoblastoma is a malignant, intraocular tumor which deve-lops within the first three years of life and has a variable prognosis. Aberrant expression of eukaryotic initiation factors (eIFs) has been reported in a variety of tumor entities, but there is a lack of data regarding eIF expression in retinoblastoma.

Material and methods: We analyzed the expression of eIF4a and eIF4e in 30 retinoblastomas and samples of other ocular diseases via immunohisto-chemistry. Via western blot, we determined the expression of eIF4a and eIF4e in the two retinoblastoma cell lines WERI-Rb1 and Y79. Furthermore, we evaluated the influence of the eIF inhibitor 4EGI-1 on the cell viabi-lity of both cancer cell lines.

Results: In this study, we observed increased expression of eIF4a and eIF4e in retinoblastoma samples compared to other ocular diseases. We also found that both proteins are expressed in the retinoblastoma cell lines WERI-Rb1 and Y79 and that their expression is independent of treatment with the eIF inhibitor 4EGI-1. However, inhibition of eIF function via 4EGI-1 reduced the cell viability of both cell lines in a dose- and time-dependent manner.

Conclusion: We provide evidence that eIF4a and eIF4e are overexpressed in retinoblastoma and that their inhibition might represent a therapeutic target for the therapy of retinoblastoma.

Introduction: The discovery of anti-cancer drugs from natural plants represents a large interest around the world. Ferulic acid (FA) is a natural phenolic acid has antitumor activity. Doxorubicin (DOX) is a potent chemotherapeutic agent used in the treatment of breast cancer, but its clinical uses are limited due to its toxic effects. This study aimed to evaluate the antitumour effect of FA and its nanosuspension (FA-NS) alone and in combination with DOX in Ehrlich solid tumour (EST)-bearing mice.

Material and methods: Thirty-five female mice were divided into 7 groups: control, EST, FA, FA-NS, DOX, FA + DOX, and FA-NS + DOX. Proliferation, autophagy, apoptosis, angiogenesis, oxidative stress, and total antioxidant capacity (TAC) were investigated.

Results: Our results showed that FA alone or in combination with DOX decreased tumour weight, proliferation, and angiogenesis by downregulating AKT and vascular endothelial growth factor receptor 2 levels, with marked elevation in autophagy and apoptosis indicated by upregulating Beclin-1, LC3-II, and caspase-3 levels. In addition, reduction of oxidative stress was indicated by decreased malondialdehyde and elevated TAC levels. Interestingly, the combination treatment mitigates DOX-induced different toxicities through the reduction of high levels of troponin-1, creatine kinase-MB, alanine transaminase, aspartate transaminase, urea, and creatinine.

Conclusions: The combination of FA with DOX has the ability not only to promote the antitumour activity of DOX but also to ameliorate the side effects of DOX with more significant results when the FA was formulated by the nanotechnology.

Introduction: Immune checkpoint inhibitors (ICIs) are a therapeutic option for recurrent/metastatic cervical cancer (r/mCC) following platinum-based chemotherapy. However, real-world data on their effectiveness and safety remain limited, particularly in Eastern Europe. This study evaluates the real-world outcomes of ICI monotherapy in pretreated patients with r/mCC.

Material and methods: This multicentre retrospective study included 39 patients with r/mCC who received ICI monotherapy (cemiplimab or pembrolizumab) after disease progression on platinum-based chemotherapy in 5 reference centres in Poland. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The secondary endpoint was treatment safety. Kaplan-Meier estimates were used for survival analysis, and Cox proportional hazards models assessed prognostic factors, with p < 0.05 considered statistically significant.

Results: After a median follow-up of 8.8 months, the median PFS was 5.7 months (95% confidence interval [CI] 4.9-6.4), and the median OS was 10.9 months (95% CI: 7.3-14.5). The objective response rate was 23% (n = 9), while the DCR was 64% (n = 25). Immune checkpoint inhibitors were generally well tolerated, with thyroid dysfunction, anaemia, and hepatic toxicity being the most common adverse events (AEs). The discontinuation of treatment due to AEs occurred in only 5% of the patients (n = 2). Immune-related adverse events (irAEs), particularly endocrine toxicities, were associated with significantly prolonged PFS (HR 0.2, 95% CI: 0.09-0.6, p = 0.001; HR 0.2, 95% CI: 0.06-0.6, p = 0.004, for the occurrence of irAEs and endocrine toxicities, respectively).

Conclusions: Immune checkpoint inhibitor monotherapy demonstrated modest efficacy in pretreated patients with r/mCC, with a manageable safety profile and irAEs of predictive significance for PFS.

Colorectal cancer (CRC) is the fourth most common cancer worldwide and a leading cause of cancer-related mortality. Despite improvements in cancer prevention, early diagnosis, and therapeutic options, metastatic CRC (mCRC) remains a major challenge, with a significantly lower 5-year survival rate compared to localized CRC. The heterogeneity of CRC, both localized and metastatic, necessitates a thorough molecular characterization to guide treatment strategies. A significant aspect of CRC progression involves the tumor microenvironment, particularly tumor-associated macrophages (TAMs), which are abundant and exhibit high plasticity. Tumor-associated macrophages, especially those polarized into the M2 phenotype, support various aspects of tumor progression, including angiogenesis, metastasis, and immune evasion. The PD-1/PD-L1 immune checkpoint axis, overexpres-sed in M2 TAMs, contributes to immune suppression, facilitating tumor growth. While some studies suggest that TAMs may have a positive role in CRC prognosis, others associate TAM infiltration with poor outcomes, particularly in metastatic disease. The relationship between TAMs and the PD-1/PD-L1 axis in CRC is still not fully understood, though emerging data highlight their potential to shape the immune resistance environment. Further research is needed to clarify the role of TAMs and the PD-1/PD-L1 network in CRC progression and to develop more effective immunotherapies targeting these pathways. This review systematically explores the current literature on TAMs and their interaction with the PD-1/PD-L1 axis in CRC, emphasizing the need for continued investigation to improve patient outcomes.

Introduction: The purposes of this study were to clarify whether non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutation have a higher incidence of cancer-associated venous and arterial thrombosis/thromboses (CATs) than EGFR-negative patients, and whether patients who develop CATs have a significantly poorer survival.

Material and methods: The relationship between EGFR mutation and the development of CATs was evaluated retrospectively in 1,891 patients with NSCLC, including 381 who were EGFR-positive. Propensity matching and logistic regression analysis were performed.

Results: Among 1,891 patients with NSCLC, 37 patients (2.0%) developed CATs. After propensity matching, the incidence of CATs was 3.9% in EGFR-positive patients and 0.9% in EGFR-negative patients (p = 0.011). Therefore, the risk of developing CATs was higher in EGFR-positive than EGFR-negative patients. In EGFR-positive patients, the most common time to develop CATs was at the time of lung cancer diagnosis, but there were some patients who developed CATs during second-line treatment or later when EGFR-tyrosine kinase inhibitors were no longer effective. In advanced EGFR-positive patients, there was no significant difference in overall survival depending on the presence or absence of CATs, but the development of CATs impaired the long survival expected in EGFR-positive patients.

Conclusions: EGFR-positive patients are currently treated with tyrosine kinase inhibitors and are expected to have a certain long-term prognosis. However, there is concern that overall survival might be shortened if CATs develop. Therefore, the possibility of developing CATs in EGFR-positive NSCLC patients must be addressed.

Introduction: Thymic epithelial tumours (TET) are a rare, histologically varied group of malignancies, classified by the World Health Organization into 5 subtypes ranging from indolent to aggressive forms. Formalin-fixed paraffin-embedded (FFPE) tissues represent the conventional approach for preserving TET tissues in pathology archives, ensuring long-term stability. Advancements in molecular techniques have significantly improved the molecular analysis in TET. Their efficacy is dependent upon the extraction of high-quality DNA from FFPE samples. The formalin-fixed paraffin-embedded preservation method and extended storage duration, however, pose challenges for molecular analysis because of DNA crosslinking, fragmentation, and reduced recovery efficiency and purity.

Material and methods: This investigation evaluated the performance of 3 commercial DNA extraction kits: the QIAamp® DNA FFPE Tissue Kit, the GeneJET® FFPE DNA Purification Kit, and the MasterPure™ Complete DNA and RNA Purification Kit, across 20 FFPE and 3 fresh TET samples, representing various sexes, ages, histological subtypes, and preservation conditions. The evaluation of DNA yield, purity, and compatibility for subsequent applications was conducted for each method.

Results: The QIAamp kit produced the most substantial and reliable DNA yields of 1785.5 ng (Qubit) and 3280 ng (NanoDrop), along with a high level of purity. The DNA has been determined to be appropriate for polymerase chain reaction, Sanger sequencing, and whole genome sequencing regarding its quality and quantity.

Conclusions: The QIAamp kit demonstrates superior performance compared to the others, providing high- quality DNA that is suitable for all molecular applications across all TET subtypes and sample conditions.

Introduction: This study investigated the impact of alterations in six key genes (HMGB1, ROS1, IL6, FGFR1, FGFR2, and TLR4) on survival outcomes in patients with esophageal squamous cell carcinoma (ESCC). These genes are implicated in signaling pathways such as RTK-Ras, PI3K-Akt, TLR, and SHP2.

Materials and methods: Genomic data from five datasets were merged to identify 437 ESCC patients, categorized into altered (n = 66, 15%) and unaltered (n = 371, 85%) groups. Gene expression was analyzed using the GSE53624 dataset, and survival outcomes were assessed with Kaplan-Meier curves and log-rank tests. Hazard ratios (HR) were derived to quantify risk.

Results: The altered group exhibited a significantly higher tumor mutational burden (TMB) and mutation count than the unaltered group (p < 1E-7). While disease-free survival analysis of 76 patients showed no significant difference, overall survival (OS) analysis of 288 patients demonstrated significantly worse survival in the altered group [median OS (95% CI): 18.63 months (18.17-28.13) vs. 40.93 months (28.42 - not reached); HR = 2.16 (1.33-3.52)]. Additionally, higher HMGB1 expression was significantly associated with poorer survival (p < 0.008). Expression-treatment response correlation using the GSE45670 dataset showed that HMGB1 expression in the pathological complete remission group was significantly higher than in the normal epithelium group, p = 0.016.

Conclusions: This study highlights that genomic alterations in these six genes are associated with poorer OS in ESCC, despite higher TMB potentially increasing tumor neo-antigens. These findings underscore the need for further research to explore their prognostic and therapeutic potential.

Introduction: Perirectal spacers reduce the radiotherapy (RT) dose delivered to the rectum, but their impact on treatment toxicity remains debated. We conducted a systematic review and meta-analysis to synthesise emerging data (PROSPERO: CRD42024506380).

Material and methods: MEDLINE, Embase, Scopus, and Google Scholar were searched through 2024/08/18 for prospective randomised (RCT) and non-randomised trials evaluating the clinical outcomes of perirectal spacing in prostate cancer (PCa) patients. Random effects generalised linear mixed models were used to pool odds ratios (OR) for rectal adverse events (AEs) from RCTs. Non-randomised trials were summarised qualitatively. The risk of bias was assessed using the RoB2 and ROBINS-I tools.

Results: Three RCTs (n = 645) were identified. The rates of grade ≥ 2 (G ≥ 2) rectal AEs in control groups were low, ranging 4.2-13.8% for early AEs and 0-1.4% for late AEs. Perirectal spacers were associated with decreased incidence of early G ≥ 2 rectal AEs (OR: 0.43; 95% CI: 0.19-0.96), but not of late G ≥ 2 rectal AEs (OR: 0.26; 95% CI: 0.02-2.91). Assuming a comparator risk of 7.1% and 1%, this corresponded to a number needed to treat of 26 patients to avoid one early AE, and 135 pa- tients to avoid one late G ≥ 2 AE, respectively. Randomised clinical trial were at moderate risk of bias due to concerns regarding the concealment of allocation.

Conclusions: There is evidence that perirectal spacers result in a small decrease in acute rectal toxicity. However, modern RT for clinically localised PCa is generally well-tolerated, and severe AEs are rare. Greater scrutiny of the risks and benefits associated with perirectal spacers is necessary.