Radiology and Oncology最新文献

Background: Radiotherapy is a cornerstone of treatment for various cancers, but often causes collateral damage to surrounding healthy tissue, including skeletal muscle. Ionizing radiation leads to oxidative stress and inflammation, which impairs the regenerative capacity of muscle tissue. Irradiation reduces the number and functionality of satellite cells and disrupts the tightly regulated processes of myogenesis and tissue remodelling. In addition, irradiation alters the muscle microenvironment by promoting fibrosis and vascular damage, which further impedes effective regeneration. Cytokine signalling pathways are also dysregulated following irradiation, contributing to impaired activation and differentiation of satellite cells.

Conclusions: There is evidence that factors such as melatonin and growth factors can improve muscle regeneration. Understanding the molecular and cellular mechanisms underlying the impairment of muscle regeneration after radiotherapy is crucial for the development of targeted strategies to mitigate side effects and improve patients' quality of life. Overall, the preservation and restoration of muscle function in irradiated tissue remains a critical challenge that requires multidisciplinary approaches.

Background: Treatment of malignant mesothelioma (MM) still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue may reduce responsiveness to cisplatin-based chemotherapy. Hypoxia-inducible factors (HIF) play an important role in regulation of cellular adaptation to hypoxia. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in the HIF1A gene coding for the regulatory alpha subunit (HIF-1A) and their role in the response to chemotherapy in patients with MM.

Patients and methods: Our retrospective genetic association study included 234 patients with MM, who were treated with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine at the Institute of Oncology Ljubljana between January 2001 and September 2018. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were genotyped using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used a TaqMan assay for independent confirmation of rs11549465 genotyping results. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression.

Results: In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was significantly worse compared to homozygotes with the CC genotype, but only after adjustment for weight loss and CRP (RO_adj = 0.37; 95% CI = 0.14-0.97; P_adj = 0.044). HIF1A rs11549467 and rs2057482 were not associated with response to chemotherapy (all P > 0.05). None of the investigated SNPs were associated with progression-free survival or overall survival (all P > 0.05).

Conclusions: Among the investigated HIF1A SNPs, only rs11549465 has showed association with a worse response to chemotherapy after the adjustment for clinical parameters. The findings of this study have improved our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.

Background: Uveal melanoma (UM) patients with liver metastases often undergo hepatic artery infusion therapy (HAIC). Due to diffuse metastatic spread in the liver, patients often develop hepatomegaly and secondary, portal hypertension which may lead to splenomegaly. This study aimed to compare spleen volumetry and the change of spleen volume (SV) for the evaluation of HAIC treatment response.

Patients and methods: In this study, 179 UM patients (mean age 64.8 ± 11.0y, 53% female) with liver metastases undergoing HAIC were included. Treatment response was analyzed by RECIST 1.1 and SV on CT imaging before and after first HAIC. The correlation of change in spleen and liver volume was analyzed with Spearman test. Overall survival (OS) was calculated as the time from the first HAIC to patient death using Kaplan-Meier test and multivariate analysis was performed for RECIST 1.1 and SV.

Results: In the study population, OS was 13.8 months (95% CI 10.6-14.7 months). Change in SV before and after first HAIC was +4% (interquartile range [IQR] -4.0%-12.0%, p = 0.49) and showed a weak correlation with OS (r = -0.11, p = 0.18). UM patients with progressive disease (PD) according to RECIST 1.1 showed an increase in SV compared to patients with stable disease (SD) (p = 0.04). Compared to RECIST 1.1, SV was not significant prognostic factor that can identify a change in OS.

Conclusions: In uveal melanoma patients with liver metastases undergoing HAIC, neither the change of SV nor splenomegaly could be identified as prognostic factors for OS.

Background: First evaluation of the performance of MR cytometry incorporating transcytolemmal water exchange in predicting immunohistochemical factor status and molecular subtypes of breast cancer.

Patients and methods: We prospectively enrolled 90 breast cancer patients in the study. For each participant, pulsed gradient spin-echo (PGSE) with diffusion time of 70 ms and oscillating gradient spin-echo (OGSE) diffusion-weighted imaging of 25 Hz and 50 Hz were performed on a 3T MRI scanner. Time-dependent apparent diffusion coefficients (ADC) and microstructural parameters including cell diameter d , intracellular volume fraction v_in , water exchange rate constant k_in , and apparent extracellular diffusivity D_ex were calculated. Single- and multi-variable logistic regression analyses were performed to evaluate their performance in identifying immunohistochemistry (IHC) factor status and molecular subtypes. The area under the receiver operating characteristic curve (AUC) was computed.

Results: The multi-variable regression models generated from MR cytometry-derived metrics provided higher AUC compared to those from time-dependent ADC metrics, i.e. 0.744 vs. 0.645 for estrogen receptor (ER), 0.727 vs. 0.688 for progesterone receptor (PR), 0.734 vs.0.623 for HER2, and 0.679 vs. 0.633 for Ki67, 0.751 vs. 0.644 for Triple-Negative Breast Cancer (TNBC), 0.819 vs. 0.765 for HER2-enriched, 0.730 vs. 0.659 for Luminal A, 0.633 vs. 0.633 for Luminal B. MR cytometry with transcytolemmal water exchange (JOINT and EXCHANGE) outperformed the original one with the impermeable model (IMPULSED) in predicting PR (0.727 vs. 0.705), HER2 (0.734 vs. 0.689), Ki67 (0.679 vs. 0.646), TNBC (0.751 vs. 0.748) and HER2-enriched (0.819 vs. 0.739), Luminal A (0.730 vs. 0.666), Luminal B (0.633 vs. 0.630).

Conclusions: MR cytometry outperformed conventional ADC measurements in clinical breast cancer subtyping. Incorporating transcytolemmal water exchange further enhanced classification accuracy.

Background: Preoperative neoadjuvant chemoradiation (NACR) benefits disease control in most locally advanced rectal cancer (LARC) patients. However, effective biomarkers predicting response to NACR are still not accessible. This study aimed to find potential biomarkers to assess therapy response and susceptibility to LARC.

Materials and methods: Differentially expressed genes (DEGs) between NACR-sensitive and resistant patients were screened using GEO database. STRING and Cytoscape were utilized to construct PPI networks and identify hub genes. Based on CIBERSORT, TCGA, GTEx, GSEA and ROC curves, the connections between hub genes and specific signaling pathways, immune cell infiltration, prognosis value and miRNA-transcription factor (TF)-target network were investigated. Human Protein Atlas (HPA) database was used to visualize hub gene expression in clinical samples.

Results: We identified 2619 up- and 2466 down-regulated genes between NACR-sensitive and resistant patients. The up-regulated DEGs were searched for highly expressed genes in the NACR-resistant, TCGA and GTEx-related datasets compared to the NACR-sensitive group, yielding six hub genes (RRM2, HNRNPL, EZH2, METTL1, NHP2L1 and ASF1B). ROC curves demonstrated the predictive utility of the six genes in NACR sensitivity. Immune infiltration research revealed no significant relationship between NACR sensitivity and immune cell infiltration extent. The miRNA-TF-target network of hub genes was established. Finally, HPA database results showed that six genes were expressed at variable levels in rectal cancer patients.

Conclusions: This study identified six hub genes (RRM2, HNRNPL, EZH2, METTL1, NHP2L1 and ASF1B) up-regulated in LARC and valuable for predicting patient susceptibility and response to NACR.

Background: Background. Pancreatic adenocarcinoma (PAAD) is a malignancy with a very poor prognosis. The clinical significance of cuproptosis in PAAD combining single cell data with The Cancer Genome Atlas (TCGA) data is unclear.

Materials and methods: In this study, we first identified gene modules associated with cuproptosis by performing single-cell analysis and weighted co-expression network analysis (WCGNA). According to TCGA data, Cox regression and LASSO regression analysis were used to establish prognostic models, and PAAD patients were divided into high-risk and low-risk groups according to cuproptosis-related risk score. Then 7 algorithms were used to evaluate cancer immune microenvironment, followed by the mutation analysis. The expression levels and prognostic significance of the 8 model genes were analysed using single-gene analysis, Kaplan-Meier survival plots, and quantitative PCR (qPCR) validation. Finally, the biological function of CEP55 in PAAD was verified by in vitro experiments.

Results: We identified cuproptosis-related genes (CRG) in PAAD by performing single-cell analysis and WCGNA, and constructed a cuproptosis-related prognostic model of PAAD by comprehensive bioinformatics analyses. Based on cuproptosis-related risk score, there were significant differences in survival time between two groups. We further constructed a cuproptosis-related risk score-based nomogram to accurately assess PAAD patient prognosis. Immune infiltration analysis revealed that PAAD samples with higher cuproptosis-related scores exhibited significantly lower immune infiltration levels, which may mechanistically underlie their poorer clinical outcomes. Furthermore, the high-risk group had a higher mutation rate of the same mutated gene, which means that they are more likely to benefit from immunotherapy. Finally, we identified that CEP55 was significantly overexpressed in PAAD and correlated with poor patient prognosis. In vitro knockdown of CEP55 effectively suppressed proliferation and invasion capabilities in pancreatic cancer cell lines.

Conclusions: In this study, a novel prognostic model of PAAD was constructed to evaluate the prognosis and immune microenvironment of PAAD patients, and CEP55 was identified as a central gene of PAAD. In vitro studies verified the biological function of CEP55, providing a new potential target for the treatment of PAAD.

Background: This study investigated the clinical utility of ultrasound in diagnosing sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL), focusing on muscle mass, strength, and physical fitness.

Patients and methods: A prospective analysis was conducted on 167 patients with DLBCL (88 with sarcopenia and 79 without). Muscle thickness (MT), cross-sectional area (CSA), and subcutaneous fat thickness (SFT) were measured using ultrasound at various anatomical sites. Diagnostic efficacy of muscle indices for sarcopenia was assessed using receiver operating characteristic (ROC) curves.

Results: Patients with sarcopenia exhibited significant reductions in MT and CSA across multiple muscle groups, including biceps brachii (BB), vastus intermedius (VI), and rectus femoris (RF) (all p ≤ 0.001). ROC analysis identified RF-CSA as the most effective indicator of sarcopenia, with an area under the curve (AUC) of 0.87, a sensitivity of 86%, and a specificity of 83% at a critical value of 7.08 cm². Multivariate analysis revealed that reduced MT and CSA significantly increased the risk of sarcopenia after adjusting for age, gender, and physical performance.

Conclusions: Ultrasound was a cost-effective and accessible diagnostic tool for identifying sarcopenia in DLBCL patients. Early detection through ultrasound can guide timely interventions and improve clinical outcomes.

Background: Immunohistochemical staining for p16 is used to differentiate precancerous cervical lesions in tissue samples, but the interpretation of patchy p16 expression remains challenging. We performed human papillomavirus (HPV) genotyping and evaluated immunohistochemical expression of HPV E4 protein - a marker for transient infections, stem cell transcription factor NANOG, and transcription factor SOX11 to detect possible high-grade squamous lesions in atypical p16 patchy squamous epithelium.

Materials and methods: We analyzed 24 cervical tissue samples with atypical squamous epithelium and patchy p16 expression along with the following controls: 11 cases of atypical squamous epithelium with null p16 expression, 9 condylomas, 12 cases of cervical intraepithelial neoplasia (CIN) grade 1, 11 cases of CIN2, and 9 cases of CIN3. In addition, HPV genotyping of tissue and related cervical smears from up to two years prior to biopsy was performed. Immunohistochemical staining for Ki67, HPV E4, NANOG, and SOX11 was performed and compared with follow-up data.

Results: High-risk HPV infection was detected in 6/24 cases with patchy p16 expression and HPV E4 was expressed in 1/24 cases with patchy p16, weak NANOG expression was found in 11/24 cases with patchy p16 expression while no SOX11 expression was observed. During 10 months of follow-up, additional CIN1 and two CIN3 were identified, and another CIN1 and CIN3 after 5 and 6 years, accordingly.

Conclusions: Our study showed that atypical squamous epithelium with patchy p16 expression poses a risk for highgrade precancerous lesions, harbouring high-risk HPV infection. Novel markers may hold diagnostic value in other specific contexts.

Background: The Lightning^® software, was added to the Gamma Knife's Leksell GammaPlan^® as a fully automated inverse planner, differently from the prior software, Wizard^®. In this paper we compare their treatment planning capacity and quality.

Materials and methods: Thirty-eight cases were compared under four different planning techniques. First, manual forward planning aided by the Wizard^® optimization tool. Second, inverse planning with Wizard^®. The third and fourth plans used Lightning^® with and without consideration for organs at risk (OAR). They were analysed for: planning time, number of shots, coverage, selectivity, gradient index, bean-on time, and OAR dose. Comparison based on pathology was added due to their idiosyncrasies. For quality comparison, dose-volume histograms (DVH) were compared to plans developed under our treatment standards. Tumor's volume and time to plan were correlated with Pearson's coefficient.

Results: Lightning^® had better coverage (8%) and gradient index (15%) but had 12% decrease in selectivity. Planning and delivery times had a reduction of 57% and 5% respectively, despite having three times the number of shots. Only Lightning^® with protection of OAR met the dose constrains in all plans. DVH showed similar plan qualities.

Conclusions: Lightning^® allowed the planner to explore different optimization parameters to achieve a plan that suits the clinical problem at hand. It took less time to calculate shots placement, OAR protection and the ideal isodose line than the Wizard^®. This can be useful to plan multiple and complex targets at a faster time, increase the patient's tolerance and, may have a radiobiological advantage by impacting intra-fraction repair.