Technology in Cancer Research & Treatment最新文献

ObjectivesThis retrospective study presents an integrative transcriptomic approach for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by developing an immune response predictive score (IORPS) derived from tumor microenvironment (TME) transcriptomic profiles.MethodsA total of 30 R/M HNSCC patients treated with pembrolizumab or nivolumab, with available immune TME profiling data, were analyzed. IORPS was constructed based on the cumulative weighting of differentially expressed gene (DEG) expression levels. The predictive performance of conventional biomarkers, individual DEGs, and IORPS was evaluated for immunotherapy response and prognostic outcomes. The clinical relevance of IORPS was further validated using two external cohorts from the GEO database (CLB-IHN: GSE159067 and GHPS: GSE159141).ResultsBy comparing immune tumor microenvironment (TME) profiles between good and poor responders, GZMH, IFNG, and FASLG were identified as key DEGs with significantly higher expression in favorable immunotherapy responders. The IORPS, derived from transcriptomic profiling, demonstrated robust predictive accuracy for both immunotherapy response and survival outcomes in patients with R/M HNSCC.ConclusionCompared with the variable predictive performance of current biomarkers such as TPS and CPS, IORPS provides improved accuracy and reliability in identifying and stratifying patients most likely to benefit from immune checkpoint blockade therapy.

IntroductionCommercial automatic planning modules are currently limited to single, conventional disease types, which severely restricts their utility when dealing with unconventional plans. Given that such unconventional plans are actually the norm in most hospitals, there is an urgent need for an automatic planning algorithm that can be applied to a wide range of clinical situations. To address this issue, we developed an algorithm capable of automatically cropping target areas and setting optimization conditions for multiple diseases, known as the Auto Crop and Optimization Setup Algorithm (ACOSA). This paper presents the principles of ACOSA and conducts a preliminary comparative evaluation of its performance against existing solutions.MethodsThe development of ACOSA utilized the Eclipse Script Application Programming Interface (ESAPI) scripting language provided by Eclipse. Based on the input prescriptions, the algorithm simulates the operations of a physicist, automatically crops the target areas, and sets appropriate optimization parameters. Retrospectively, 20 cases of glioma and head and neck cancers were selected. Without considering organ-at-risk dose limits, dose calculations were performed using both ACOSA and Eclipse's built-in AutoCrop, and a dosimetric comparison was conducted.ResultsIn terms of target volume homogeneity index (HI) and D98, the AutoCrop group demonstrated slight superiority over the ACOSA group. However, the ACOSA group exhibited superior performance in conformity index (CI), gradient index (GI), D2, and particularly in parameters reflecting the rate of low-dose fall-off outside the target volume, including Ratio20, Ratio30, and Ratio40, when compared to the AutoCrop group.ConclusionsACOSA can be reliably applied in clinical settings and demonstrates superiority over the AutoCrop module of the Eclipse planning system.

IntroductionIdentifying therapeutic targets and early screening biomarkers is essential for improving the prognosis of lung cancer. CCT3 has been linked to tumor progression; however, its role in lung cancer proliferation and invasion, as well as its diagnostic significance remain poorly understood.MethodsCCT3 expression and its clinical correlations in lung cancer were analyzed utilizing data from the TCGA and GEO databases. The impact of CCT3 on cell proliferation, migration, and invasion was evaluated through CCK-8, colony formation, and Transwell assays. Western blotting was employed to assess the regulation of the PI3 K/AKT pathway and markers associate with epithelial-mesenchymal transition (EMT). Serum CCT3 levels in 714 participants were measured via ELISA, with diagnostic efficacy analyzed using receiver operating characteristic (ROC) curve analysis.ResultsCCT3 was over-expressed in lung cancer tissues, which was correlated with the stage of non-small lung cancer (NSCLC). CCT3 promotes cell proliferation, migration, and invasion by activating the PI3 K/AKT pathway and modulating EMT. In vivo, CCT3 knockdown significantly suppressed tumor growth in xenograft models. Elevated serum levels of CCT3 have been observed in patients with lung cancer, exhibiting high diagnostic efficacy for distinguishing NSCLC from benign nodules (AUC=0.873) and enhancing performance for small cell lung cancer when combined with proGRP.ConclusionCCT3 facilitates the progression of lung cancer through the PI3 K/AKT-EMT axis, positioning it as a potential therapeutic target and biomarker.

Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. No validated prognostic score has been established to guide clinical decisions in the extensive stage (ES). This narrative review critically examines the evolution of prognostic models in SCLC. We aim to highlight current gaps and propose directions for the development of clinically actionable tools. We conducted a comprehensive review of the literature on SCLC prognostic models, focusing on historical context, model design, variables used, validation methods, and real-world applicability. Comparative strengths and limitations were analysed across different model types. We analysed early scoring systems, modern nomograms, inflammation-based and nutritional scores, as well as integrative models. Historical tools are often limited to disease stage, performance status, basic laboratory values, most lack external validation, are retrospective, or were developed on chemotherapy-only cohorts. Recent models incorporate broader clinical data and, in some cases, nomograms or web-based calculators. Yet, few have undergone external validation or demonstrated utility in diverse clinical settings. The absence of dynamic, personalized models prevents integration into contemporary practice. Although numerous prognostic tools have been proposed, a reliable, validated tool is still lacking. Future prognostic models must move beyond static clinical parameters. Incorporating molecular biomarkers, real-world data, and machine learning could enable the development of validated, adaptive tools with true clinical relevance. Collaborative, prospective efforts will be critical to achieve this goal.

IntroductionBlood perfusion insufficiency and hypoxia are the main causes of drug resistance to chemotherapy in breast cancer. Increasing blood perfusion can improve drug delivery. This study aimed to investigate the effects of ultrasound-stimulated microbubbles (USMBs) on hemoperfusion in invasive breast cancer (IBC).MethodsIn this prospective clinical trial, 36 patients diagnosed with IBC were enrolled sequentially. The treatment group (n = 18, enrolled from June 2022 to April 2025) were treated with SonoVue^® microbubbles (MBs) stimulated by ultrasound, with a mechanical index (MI) of 0.2-0.3: 1 mL of SonoVue^® MBs was injected at 3.5-min intervals three times for a USMB treatment lasting 10 min. The control group (n = 18, enrolled from May to November 2025) received identical MB injections without ultrasound stimulation. Contrast-enhanced ultrasound (CEUS) was used to evaluate the changes in blood perfusion.ResultsIn the treatment group, in comparison with the pre-treatment findings, the tumor perfusion area expanded (P < .001) and the time to peak (TTP) increased (P < .05) after USMB treatment. For regions exhibiting low enhancement inside the lesion on CEUS before USMB treatment, the area under the curve (AUC) (P < .001) and mean transit time (MTT) (P < .05) both increased following therapy. In the control group, none of the parameters showed statistically significant differences after the MB injections.ConclusionUSMB treatment can improve blood perfusion in IBC, especially by enhancing the AUC and MTT in hypoperfused regions. These findings highlight the potential of USMB treatment as a noninvasive technique to enhance intratumoral drug delivery, although further validation of this approach is required.Clinical trial registration number: NCT06158217.

IntroductionThis retrospective study aimed to investigate the correlation between TP53 identified via next-generation sequencing (NGS) and p53 expression in colorectal adenocarcinoma (CRC), as assessed by immunohistochemistry (IHC). Additionally, we characterized p53 IHC staining patterns and sought to determine the optimal threshold for p53 expression as a surrogate for TP53 mutation status.MethodsIn this retrospective cohort analysis, we included 294 archived surgically resected CRC specimens from patients who did not receive preoperative chemotherapy were analyzed. All data were collected from pathology database and electronic medical records. TP53 mutations were identified using NGS, and p53 expression was evaluated by IHC. The correlation between mutation status and IHC staining patterns was assessed, and sensitivity and specificity were calculated.ResultsThe TP53 mutation rate was 78.2%, comprising missense (68.4%), nonsense (12.4%), frameshift (11.0%), and splice-site (8.3%) mutations. Missense mutations were associated with nuclear p53 staining, while frameshift mutations mostly showed loss of expression. Nonsense and splice-site mutations exhibited diverse patterns, including loss of expression, nuclear staining with/without cytoplasmic staining, or cytoplasmic staining alone. Among cases with loss of p53 expression, the TP53 mutation rate was 88.9%. When the proportion of strong p53-positive cells exceeded 55%, the missense mutation-positivity rate increased significantly (P < 0.05). The sensitivity and specificity of p53 IHC in predicting TP53 mutations were 92.3% and 94.8%, respectively.ConclusionsCRC predominantly exhibited missense TP53 mutations. p53 IHC revealed diverse expression patterns, including overexpression, complete loss, cytoplasmic staining, and normal-type patterns. Strong p53 expression (>55%) correlated closely with TP53 missense mutations, supporting IHC as a reliable surrogate. However, cases showing loss of p53 expression should undergo gene sequencing to confirm mutation status.

IntroductionDespite the advent of anti-PD-1 immunotherapy as a promising treatment for HCC, there remains a significant gap in the comprehensive analysis of peripheral blood immunological markers that could predict treatment response. This study aims to identify peripheral blood immunological markers predictive of anti-PD-1 therapy response in HCC patients to improve clinical outcomes.MethodsWe retrospectively analyzed 69 HCC patients treated with anti-PD-1 therapy, divided into a training cohort (n = 30) and a validation cohort (n = 39). Clinical characteristics, hematological indices, cytokine levels, and serum PD-1 were assessed. Logistic regression and ROC curve analyses were performed to evaluate prognostic value, with bootstrap validation to assess model robustness. In addition, tumor samples from 6 patients underwent WES, and bioinformatic analyses were conducted to explore mutational profiles and their associations with immune infiltration as supportive mechanistic validation.ResultsThe IL-2/IL-10 ratio was significantly associated with tumor progression after adjustment for covariates (OR 2.918, 95% CI 1.191-7.150, p = 0.019) and achieved superior predictive performance (AUC 0.884, 95% CI 0.766-1.000) compared with conventional inflammation-based scores. Bootstrap validation confirmed model stability (corrected AUC ≈ 0.88), and external validation supported predictive value. Whole-exome sequencing revealed that mutations in genes such as FLT3, TET2, and IDH2 were commonly present in HCC. Immune infiltration analyses indicated that these mutations were associated with increased Treg and decreased Th1 infiltration, consistent with the clinical trend. Additional analyses of public transcriptomic datasets further supported these observations.ConclusionOur study reveals that a low IL-2/IL-10 ratio is significantly associated with adverse prognosis in HCC patients and may serve as a practical and biologically relevant biomarker for predicting the efficacy of anti-PD-1 therapy. Moreover, systematic evaluation of immune status could provide important guidance for predicting immunotherapy efficacy and supporting future clinical decision-making in HCC management.

IntroductionCT-guided biopsy has good diagnostic accuracy, but adverse events such as pneumothorax are common. There are few reports on the safety and efficacy of CT-guided biopsy in the elderly.MethodsThis was a retrospective single-centre cohort study. Patients who underwent CT-guided lung biopsy between February 2017 and August 2024 were included. Patient background, disease background, examination status, and adverse events were ascertained. Elderly were defined as those aged 75 years and older. The primary outcome was the incidence of all adverse events, and the secondary outcomes were the incidence of pneumothorax and diagnostic accuracy. Categorical variables were compared by Chi-square test, and continuous variables by t-test. Multivariable analysis was performed by logistic regression analysis adjusted for age, sex, lung comorbidities, and radiological findings of target lesion.ResultsThere were significant differences between the two groups in ECOG-PS and the distance from the surface to pleura and target. In the primary outcome, any adverse events occurred in 207 patients (56.2%), with no significant difference between elderly (97/180, 53.9%) and non-elderly (110/188, 58.5%) patients (p = 0.401). Pneumothorax was the most common adverse event, occurring in 151 (41.0%) patients, with no significant difference between elderly (68/180, 37.8%) and non-elderly (83/188, 44.1%) (p = 0.244). On multivariate analysis, elderly (75years or older) was not clearly associated with the occurrence of all or severe adverse events, pneumothorax, and confirmed diagnosis. Location in the lower lung field and distant from the pleura were significantly associated with the incidence of all adverse event. In the secondary outcomes, emphysema or interstitial pneumonia, location in the lower lung field, and distant from the pleura were significantly associated with pneumothorax. There was no significant difference in the diagnostic accuracy disease between the elderly and non-elderly patients.ConclusionsThe incidence of adverse events and diagnostic accuracy of CT-guided biopsy are similar in elderly and non-elderly patients, and this method is useful even in elderly patients.Key pointThe safety and efficacy of CT-guided lung biopsy in elderly patients are equivalent to those in non-elderly patients.

IntroductionOsteosarcoma (OS) is a highly aggressive primary bone malignancy with poor prognosis. Histone modifications play crucial roles in tumor progression, but their systematic investigation in OS remains unexplored.MethodsThis study integrated single-cell RNA sequencing data and large-scale clinical information to systematically analyze the spatial heterogeneity of histone modifications in OS and their clinical significance. We employed Seurat for single-cell data analysis, CellChat for cell-cell communication network analysis, and LASSO Cox regression to construct a prognostic model. Additionally, we conducted functional enrichment analysis, immune characteristics analysis, and drug sensitivity prediction.ResultsWe identified five major cell types in the OS microenvironment and discovered significant differences in histone modification levels among different cell types, with osteosarcoma cells and endothelial cells exhibiting higher modification levels. Cell-cell communication network analysis revealed the importance of signaling pathways such as SPP1, CypA, MIF, IGFBP, and VEGF in OS. Based on nine histone modification-related genes, we constructed an efficient prognostic model (AUC values of 0.713, 0.845, and 0.888 for 1-, 3-, and 5-year predictions, respectively), which was validated in an external cohort (AUC = 0.808). Immune microenvironment analysis showed significantly higher proportions of CD8+ T cells and Treg cells in the low-risk group. Drug sensitivity analysis revealed that the low-risk group was more sensitive to Imatinib, Rapamycin, and Sunitinib, while the high-risk group was more sensitive to MAPK pathway inhibitors.ConclusionThis study systematically revealed the spatial heterogeneity of histone modifications in OS and their clinical significance for the first time, proposing an "epigenetic-immune" regulatory network hypothesis and developing a histone modification-based prognostic model. Our proposed "epigenetic-guided personalized medication strategy" provides new insights for precision treatment of OS, potentially significantly improving patient prognosis.

Colorectal cancer (CRC) remains a formidable global health challenge, with the majority of patients exhibiting microsatellite stable (MSS) and proficient mismatch repair (pMMR) tumors that are largely unresponsive to immune checkpoint inhibitors (ICIs). The management of MSS/pMMR CRC remains a clinical challenge due to the intrinsic resistance to ICIs. The innovative strategy of combining cetuximab, an EGFR-targeting monoclonal antibody with immunomodulatory properties, offers a promising strategy to enhance the immunotherapeutic response in MSS/pMMR CRC. This combination therapy is rooted in the complementary therapeutic mechanisms of cetuximab and ICIs, which may synergistically improve overall response rates and durability of response. Although some preclinical and clinical data have suggested additional promising results, there are still some challenges and questions that need to be addressed. Further large-scale, randomized, phase III clinical trials are required to confirm the efficacy and safety of this combination therapy. The ongoing clinical trials evaluating the safety and efficacy of cetuximab-ICI combinations are eagerly anticipated to pave the way for a new era in personalized immunotherapy for MSS/pMMR CRC.