Chinese clinical oncology最新文献

Background: Central nervous system (CNS) tumours, especially glioma, are a complex disease and many challenges are encountered in their treatment. Artificial intelligence (AI) has made a colossal impact in many walks of life at a low cost. However, this avenue still needs to be explored in healthcare settings, demanding investment of resources towards growth in this area. We aim to develop machine learning (ML) algorithms to facilitate the accurate diagnosis and precise mapping of the brain tumour.

Methods: We queried the data from 2019 to 2022 and brain magnetic resonance imaging (MRI) of glioma patients were extracted. Images that had both T1-contrast and T2-fluid-attenuated inversion recovery (T2-FLAIR) volume sequences available were included. MRI images were annotated by a team supervised by a neuroradiologist. The extracted MRIs thus obtained were then fed to the preprocessing pipeline to extract brains using SynthStrip. They were further fed to the deep learning-based semantic segmentation pipelines using UNet-based architecture with convolutional neural network (CNN) at its backbone. Subsequently, the algorithm was tested to assess the efficacy in the pixel-wise diagnosis of tumours.

Results: In total, 69 samples of low-grade glioma (LGG) were used out of which 62 were used for fine-tuning a pre-trained model trained on brain tumor segmentation (BraTS) 2020 and 7 were used for testing. For the evaluation of the model, the Dice coefficient was used as the metric. The average Dice coefficient on the 7 test samples was 0.94.

Conclusions: With the advent of technology, AI continues to modify our lifestyles. It is critical to adapt this technology in healthcare with the aim of improving the provision of patient care. We present our preliminary data for the use of ML algorithms in the diagnosis and segmentation of glioma. The promising result with comparable accuracy highlights the importance of early adaptation of this nascent technology.

Background: The low level of median survival rate after complete therapy (i.e., surgery and concomitant chemotherapy and radiotherapy) in high-grade glioma (HGG) patients reflects the needs for a better understanding about HGG pathogenesis, including the role of epigenetic in glioma. MicroRNA (miRNA), a small chain non-coding RNA, has been increasingly utilized in the management of other oncology cases and might possess an immense potential in HGG. The expression of miRNA-10b and miRNA-21 (i.e., two miRNAs that are frequently studied due to its involvement in glioma) are higher in HGG patients and their role in regulatory mechanism of glioma has been established. However, the influence of those miRNAs in toxicity, recurrence, and overall survival of HGG patients is still unclear. We aim to assess the predictive value of plasma miRNA-10b and miRNA-21 in the chemotherapy toxicity, recurrence, and overall survival of HGG patients.

Methods: This is an observational analytic study using hospital-based mixed cohort approach. The study is conducted in RSUP Dr. Sardjito, Yogyakarta, from January 2021 to December 2024. We prospectively assess the plasma miRNA level from HGG patients who met the inclusive and exclusive criteria. The consecutive sampling is used until the sample size is met. Statistical analysis will be conducted for temozolomide toxicity using Spearman's rank correlation, for recurrence using logistical regression, and for overall survival test.

Results: In this ongoing study, we plan to collect samples from 155 HGG patients. As of April 2024, we managed to collect 96 samples (median age of 49 years and 55% of male patients). Most of the patients were diagnosed with World Health Organization (WHO) grade IV tumors (69.3%), with the most common diagnosis was glioblastoma (62%). Most of the patients had unmethylated O6-methylguanine-DNA methyltransferase (MGMT) and wild-type isocitrate dehydrogenase (IDH) status (62% and 57%, respectively). There was no difference in miRNA-21 expression based on MGMT status (methylated or unmethylated), nor IDH status (wild type or mutant), with P=0.39 and P=0.25, respectively. Moreover, we found no significant difference in miRNA-10b expression in both MGMT status and both IDH status (P=0.19 and P=0.09). As for the data regarding toxicity, recurrence, and overall survival was still on the process of data collection.

Conclusions: MiRNA is a promising epigenetic modulator that might be utilized in HGG management. A better understanding on the role of miRNA in HGG patients might be able to improve clinical outcome.

Background: Diffuse intrinsic pontine glioma (DIPG), is an aggressive form of paediatric high-grade glioma (pHGG) that affects children below the age of 10 months. The survival period for a child suffering from DIPG has not changed in decades (approximately 10 months). This pattern is similar for most pHGG; even though the survival period is more extended, tumour recurrence and death are almost inevitable. This is primarily due to the presence of the blood-brain barrier (BBB), which blocks the entry of most therapeutics into the brain, and also due to tumour heterogeneity associated with central nervous system (CNS) tumours that blunt the efficacy of targeted therapy. The development of a meaningful cure for paediatric brain cancer hinges on discovering chemotherapy agents that (I) can cross the BBB; (II) accumulates explicitly in tumour tissues; and (III) can block pathways leading to the escape of cancer stem cells, promoting recurrence.

Methods: This project aims to develop therapeutics that can cross the BBB, a significant hindrance to delivering medicines across the brain, and specifically target cancer cells without affecting normal brain cells. We will accomplish this by attaching novel dyes possessing tumour specificity to various classes of chemotherapy agents. The compounds will be tested on patient-derived paediatric brain cancer cell lines and the most potent compounds will be progressed to an animal model of DIPG.

Results: Several drug-dye conjugates were designed and synthesized to target various aberrant pathways involved in disease initiation and progression of DIPG. These were tested first in patient-derived DIPG cell lines. Several of these drug-dye conjugates showed potent antiproliferative effect in various DIPG cell lines. One of these conjugates is currently undergoing maximum tolerated dose study in an animal model of DIPG.

Conclusions: The present work details an effort to develop BBB crossing tumour specific therapeutic agents for the treatment of DIPG. The work has resulted in several promising drug-dye conjugates showing antiproliferative activity in various patient-derived DIPG cell lines, enabling the progression of such conjugates into animal models of DIPG. Such studies will inform the utility of such drug-dye conjugates for application in difficult to treat pHGGs such as DIPG.

Background: Intracranial tumors constitute a significant burden on global morbidity and disability, posing a risk for the development of cachexia. Cancer cachexia is a multi-organ syndrome of systemic inflammation and negative energy balance which may lead to diminished treatment efficacy and reduced survival rates. The association between intracranial tumor features and incidence of cachexia remains unknown. The purpose of this study is to investigate the association between the characteristics of intracranial tumors and the incidence of cachexia in patients.

Methods: We conducted a retrospective cross-sectional study to observe hospitalized intracranial tumor patients at Dr. Cipto Mangunkusumo Hospital. This study described the prevalence and the percentage of baseline characteristics, the diagnosis of cachexia was based on Evans criteria. Kolmogorov-Smirnov for the normality test. Bivariate analysis was done using the Chi-square test for qualified categorical variables, the Fischer test for unqualified categorical variables, and the Mann-Whitney test for ordinal variables.

Results: Our study revealed of 36 subjects with intracranial tumor diagnosis, the incidence of cachexia was higher in secondary brain tumors compared to primary brain tumors [odds ratio (OR) 5.5; 95% confidence interval (CI): 1.28-23.69; P=0.02]. Cancer cachexia occurs through inflammation, autonomic, and neuroendocrine pathways, leading to increased energy expenditure and decreased energy intake. The burden of secondary brain tumor amplifies the overall metabolic demands and systemic inflammation thus contributing to cachexia progression, which is identified by significant weight loss in patients with secondary brain tumor groups compared to primary tumors (P=0.01). Patients with cachexia tend to experience malnutrition and fatigue (P=0.04), which may interfere with their survival rates and quality of life. The most common neurological deficit observed in our subjects is headache (72.2%), while patients presenting with clinical manifestations of extremity weakness were more likely to develop cachexia (OR 6.4; 95% CI: 1.23-35.44; P=0.04). There were no significant differences in age distribution, gender, and brain tumor location among the subject groups.

Conclusions: Patients with secondary brain tumors and extremity weakness are more likely to develop cachexia. The severity of cachexia can help distinguish between primary and secondary brain tumors. Clinicians should pay attention to neurological deficits, particularly extremity weakness, as it can worsen cachexia.

Background: Glioblastoma (GBM) is an immunosuppressive, universally lethal cancer driven by GBM stem cells (GSCs). The interplay between GSCs and the immunosuppressive microglia plays crucial roles in promoting malignant growth of GBM, however, the molecular mechanisms underlying this crosstalk are incompletely understood.

Methods: We performed RNA sequencing to explore the mechanism by which periostin (POSTN) regulates GSCs and microglia. The biological function of POSTN in GBM development was confirmed in vitro and in vivo. Specifically, tumorsphere formation assay, proliferation analysis, migration assays, enzyme-linked immunosorbent assay, immunoblotting, and intracranial mouse model were performed.

Results: We identified POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/β-catenin/FOS like antigen 1 (FOSL1) pathway. In addition to its GSC intrinsic effects, POSTN is able to recruit microglia and upregulate cluster of differentiation 70 (CD70) expression through PI3K/AKT/nuclear factor-kappa B (NFκB) pathway in microglial cells, which in turn promotes the Treg development and functionality, and generates an immunosuppressive tumor microenvironment. Inhibition POSTN disrupts the GSC maintenance, inhibits recruitment of immunosuppressive microglial, reduces Treg development and function, and suppresses GBM growth, suggesting that targeting POSTN may effectively improve GBM treatment.

Conclusions: In conclusion, our study defined POSTN as a key regulator in mediating the molecular crosstalk between GSCs and immune-suppressive Microglia in the tumor microenvironment in GBM. POSTN activates the PI3K/AKT/β-catenin/FOSL1 pathway in an autocrine manner to promote GSC self-renewal and tumor growth. At the same time, POSTN recruits microglia in a paracrine manner and upregulates the expression of CD70 in microglia through the PI3K/AKT/NFκB pathway, thereby promoting the development and function of Treg and generating an immunosuppressive tumor microenvironment. Our findings indicate that targeting the POSTN gene may be a promising approach to ablating GSCs, breaking the immunosuppressive environment and overcoming treatment resistance in GBM.

Background: There remains controversy in the observed survival of gliomas worldwide, especially for glioblastoma (GBM). The 5-year survival rate ranged wildly, but comparable higher in several Asian countries, such as China showed almost 18% from CONCORD-3 data. Are there any special factors relating to long-term survivors (LTSs)?

Methods: We reviewed our single center real-world data for the last 20 years, of 536 GBM [World Health Organization (WHO) grade 4] patients revealed 5-year overall survival (OS) of 19.1%. We analyzed our GBM patients and searched for possible factors relating to LTSs. We collected tumor samples of 13 LTSs (OS >60 months) and 19 short-term survivors (OS <24 months), and performed whole exome sequencing and transcriptome sequencing.

Results: From treatment setting, besides surgical resection, post-operational adjutant treatment (radiotherapy plus chemotherapy) are the most important factor contributing to long-term survival. Whole exome sequencing analysis revealed a higher proportion of mutation signature 19 was associated with LTSs. Analysis of copy number variation (CNV) showed that the LTSs had higher copy number variants at the chromosomal level (P=0.049). At the arm level, the proportion of 19p amplification in the LTS was significantly higher than in the short-term survivors (P=0.001). And in The Cancer Genome Atlas (TCGA) GBM dataset, GBM patients with 19p amplification also had a better prognosis (log-rank P=0.04). Based on RNA sequencing (RNAseq) and differential expression analysis, the differentially expressed genes were enriched in hypoxia-related processes, apoptosis, and immune-related processes.

Conclusions: From our single-institution data, the factors relating to GBM LTSs should be both clinical management and genomic alternation which could be potential novel targets be applied to future clinical practice.

Background: Three-dimensional (3D) exoscope and navigation systems have recently become remarkably advanced in neurosurgery. Robotic navigation is being used in various facilities. Based on the created surgical plan, robotic navigation automatically determines the path to guide the instrument. It seamlessly integrates with continuous real-time navigation and robotic alignment functions to improve the efficiency of intraoperative workflow and support highly accurate positioning. We have achieved good results in surgeries utilizing robotic navigation at our institution, and we report on the results and prospects.

Methods: At our hospital, 15 patients underwent surgery using Stealth AutoguideTM (Medtronic) in conjunction with the StealthStation S8 (Medtronic). The mean age was 56.2 years; 10 were men, and five were women. We used the exoscopic systems with KINEVO 900 (Zeiss) or ORBEYE (Olympus).

Results: The cases comprised of 11 gliomas, two primary central nervous system lymphomas, one germ cell tumor, and one brain abscess. Seven biopsies (six burr holes, one craniotomy) and six fence posts were used for Stealth AutoguideTM, tubing in two cases. Biopsies were performed quickly and reliably. In the cases where fence posts were used, it was possible to position the post quickly on the target and place it accurately in the planned area to determine the extent of removal. In addition, using the 3D exoscope system allowed the surgeon to simultaneously view the operating field and navigation screen without moving the surgeon's line of sight, making the operation safer.

Conclusions: Surgery using robotic navigation was performed safely and efficiently, and highly accurate positioning was achieved regardless of the surgical technique. This system is expected to continue improving the accuracy, safety, and reproducibility of surgery and reducing the burden on the patient.

Background: Survival prognostication plays a key role in the decision-making process for the surgical treatment of patients with spinal metastases. In the past traditional scoring systems such as the modified Tokuhashi and Tomita scoring systems have been used extensively, however in recent years their accuracy has been called into question. This has led to the development of machine learning algorithms to predict survival. In this study, we aim to compare the accuracy of prognostic scoring systems in a surgically treated cohort of patients.

Methods: This is a retrospective review of 318 surgically treated spinal metastases patients between 2009 and 2021. The primary outcome measured was survival from the time of diagnosis. Predicted survival at 3 months, 6 months and 1 year based on the prognostic scoring system was compared to actual survival. Predictive values of each scoring system were measured via area under receiver operating characteristic curves (AUROC). The following scoring systems were compared, Modified Tokuhashi (MT), Tomita (T), Modified Bauer (MB), Van Den Linden (VDL), Oswestry (O), New England Spinal Metastases score (NESMS), Global Spine Study Tumor Group (GSTSG) and Skeletal Oncology Research Group (SORG) scoring systems.

Results: For predicting 3 months survival, the GSTSG 0.980 (0.949-1.0) and NESM 0.980 (0.949-1.0) had outstanding predictive value, while the SORG 0.837 (0.751-0.923) and O 0.837 (0.775-0.900) had excellent predictive value. While for 6 months survival, only the O 0.819 (0.758-0.880) had excellent predictive value and the GSTSG 0.791(0.725-0.857) had acceptable predictive value. For 1 year survival, the NESM 0.871 (0.822-0.919) had excellent predictive value and the O 0.722 (0.657-0.786) had acceptable predictive value. The MT, T and MB scores had an area under the curve (AUC) of <0.5 for 3-month, 6-month and 1-year survival.

Conclusions: Increasingly, traditional scoring systems such as the MT, T and MB scoring systems have become less predictive. While newer scoring systems such as the GSTSG, NESM and SORG have outstanding to excellent predictive value, there is no one survival scoring system that is able to accurately prognosticate survival at all 3 time points. A multidisciplinary, personalised approach to survival prognostication is needed.