High Likelihood Of Recurrence Research Articles

Comparison of prognosis between oncocytic thyroid carcinoma and follicular thyroid carcinoma: a population-based propensity score matching analysis.

Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20mm or more than 40mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.

TMEM17 Promotes Tumor Progression in Glioblastoma by Activating the PI3K/AKT Pathway.

Glioblastoma (GBM) is a highly aggressive and fast-growing brain tumor, characterized by rapid progression, a very poor prognosis, and a high likelihood of recurrence. Thus, effective new therapeutic targets are urgently needed. Transmembrane proteins (TMEMs) have pro-cancer effects on multiple cancer types, but the mechanisms underlying the effects of TMEM17, particularly its role in GBM, remain unclear. We conducted bioinformatics analyses and immunohistochemistry to evaluate the role of TMEM17 in a variety of cancer types. Functional assays were conducted included the Cell Counting Kit-8 assay, annexin V-FITC/PI double staining, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing assay, transwell invasion assay, and dual luciferase assay. We found that TMEM17 is associated with a poor prognosis in GBM. Prognostic analyses confirmed that high TMEM17 expression predicted poorer survival, establishing its significance as an independent prognostic factor. Functional assays demonstrated that silencing TMEM17 in GBM cell lines inhibited proliferation and invasion, and induced apoptosis, underscoring its role in tumor aggressiveness. From a mechanistic perspective, we discovered that the Ying Yang 1 (YY1) transcription factor can bind to the promoter of TMEM17, regulating its upregulation. Regarding downstream mechanisms, knocking down TMEM17 inhibited the phosphoinositide 3-kinase/AKT pathway. These findings suggest that TMEM17 plays a significant role in GBM and may be a potential therapeutic target for this cancer. These data prove that TMEM17 plays a key role in the regulation of GBM and has great potential as a clinical therapeutic target for GBM.

Effect of Vitamin D and Skeletal Muscle Mass on Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Exploring the uncharted: adenoid cystic carcinoma nestled in temporal bone

BackgroundAdenoid cystic carcinoma is an uncommon malignancy primarily arising from salivary glands. An extremely rare site for adenoid cystic carcinoma is the skull base. We report a case of adenoid cystic carcinoma of skull base who presented with common complaints of pain and right ear discharge. The discussion is made with emphasis on imaging evaluation simulating infective etiology with adjacent skull base osteomyelitis. Careful observation of the imaging findings and further evaluation of the patient revealed the neoplastic nature of the lesion with the final diagnosis being adenoid cystic carcinoma.Case presentationA 40-year-old female presented to our department with complaints of pain and right ear discharge since 6 months with progressive, extensive facial swelling and facial nerve palsy. The patient had undergone modified radical mastoidectomy thrice, but the details were not available. On imaging, there was a heterogenous extensive lesion extending from scalp till upper cervical region with extensive destruction of skull base and intra-cranial extension. The possibilities of temporal bone squamous cell carcinoma and extensive skull base osteomyelitis were considered. Further the biopsy of the lesion revealed adenoid cystic carcinoma.ConclusionsExtensive lesions of the skull base can be of infective, neoplastic and inflammatory etiology. Distinguishing between these conditions is crucial, as they have similar imaging characteristics but require different management approaches. The presence of a lesion that displaces or destroys fascial planes, accompanied by solid mass-like enhancement, indicates a higher probability of a neoplastic origin rather than an infectious etiology. With squamous cell carcinoma being the most common neoplasm, adenoid cystic carcinoma of the skull base also needs to be understood due to its propensity for perineural spread and a high likelihood of recurrence.

A Big Prospect for Hydrogel Nano-System in Glioma.

Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms.

Nasosinusal Teratocarcinosarcoma: Case Report and Literature Review

Sinonasal cancers are the most common malignant tumors of the anterior skull base. Teratocarcinosarcomas are extremely unusual malignat tumors involving nasosinusal area, they are characterized by their poor prognosis and high likelihood of recurrence and potentiel intracranial extension. Because of its histological heterogeneity, the diagnosis is very difficult and therefore requires a sufficient sample to avoid erroneous diagnoses. The most commonly used treatment option is radical surgery resection followed by radiotherapy +/- chemotherapy. We report herein the case of 44-year-old woman, presented with sinonasal teratocarcinosarcoma revealed by nasal obstruction and intermittent epistaxis. The diagnosis was confirmed by a histopathological study of surgical specimen. Pre-treatment workup was negative for metastasis disease. She has received adjuvant radiotherapy and chemotherapy after radical endoscopic sinonasal surgery. A follow-up examination at 2 years showed no evidence of recurrence.

Low Cubilin/Myeloperoxidase ratio as a promising biomarker for prognosis of high-grade T1 bladder cancer

PurposeT1 bladder cancer is known for its high progression and recurrence rates. Identifying aggressive tumours at the non-muscle-invasive stage is crucial to allow early interventions and subsequently increase patient survival. This study aimed to investigate the potential of the cubilin/myeloperoxidase (CUBN/MPO) ratio as a high-grade T1 bladder cancer biomarker.MethodsUrine samples were collected from 30 patients who underwent transurethral resection of the tumour with high-grade T1 bladder cancer (June 2015 to December 2019) before surgery. The urinary proteome was analysed using high-resolution mass spectrometry and the CUBN/MPO ratio was calculated. The primary outcome was the recurrence during the follow-up (around 31.5 months after resection). Univariate Cox regression and Kaplan–Meier curves were used for data analysis.ResultsPatients with a low CUBN/MPO ratio exhibited upregulated MPO and/or downregulated CUBN. This group of patients had a higher incidence of disease recurrence and progression. Low CUBN/MPO ratio was significantly associated with a higher likelihood of recurrence, progression, and death. It is worth noting that this study was exploratory and conducted on a small sample size, so further research is needed to validate these findings in larger cohorts.ConclusionThis study highlights the potential of the CUBN/MPO ratio as a prognostic biomarker for high-grade T1 bladder cancer.

Surgical margins and outcomes for eyelid melanoma: a systematic review and meta-analysis.

No randomized trials exist to inform the peripheral surgical margins or depth of wide excision for eyelid melanoma. We performed a meta-analysis examining surgical margins and Breslow depth for eyelid melanomas. A systematic review was performed in August 2022 using PubMed, Cochrane, and Medline databases (1/1/1990 to 8/1/2022). Inclusion criteria included studies reporting surgical treatment of primary cutaneous melanomas of the eyelid with reported surgical margins. Ten articles were included. The studies were examined by surgical margin size (group 1: ≤ 0.5cm; group 2 > 0.5cm and ≤ 1.5cm) and Breslow depth (group 1: ≤ 1mm; group 2: > 1mm). The odds ratio (OR) for local recurrence was 2.55 [95% CI 0.36-18.12], p = 0.18; regional metastasis was 0.70 [95% CI 0.00-23671.71], p = 0.48; and distant metastasis was 2.47 [95% CI 0.00-1687.43], p = 0.66. When examining by Breslow depth, the OR for local recurrence was 0.53 [95% CI 0.14-1.94], p = 0.34; regional metastasis was 0.14 [0.00-176.12], p = 0.54; and the OR for distant metastasis was 0.24 [95% CI 0.01-8.73], p = 0.46. There was a trend toward higher likelihood of recurrence and metastasis in the ≤ 0.5cm group. Similarly, there is a trend toward higher likelihood of recurrence and metastasis with Breslow depth > 1mm. A surgical margin of at least 0.5cm and achievement of negative margins via permanent sections or MMS are likely needed to prevent adverse outcomes. En face sectioning may be a superior method of histological processing for eyelid melanoma.

Multiple Serial Casting for Recurrent Clubfoot in Arthrogryposis Corrects Deformity With Diminishing Returns.

Arthrogryposis multiplex congenita (AMC) consists of more than 400 conditions involving severe joint contractures of at least two or more body regions. Management of clubfoot in patients with AMC is notoriously challenging, with a higher likelihood of recurrence than idiopathic clubfoot, which can be treated using the Ponseti technique to avoid or delay more invasive procedures. The purpose of this study is to determine the utility of multiple serial casting as a treatment of clubfoot in AMC using Pirani scores as an objective measure of deformity. Pirani scores were retrospectively collected from 17 AMC patients with a total of 30 clubfeet and two years follow-up from initiation of treatment. Patients with a minimum of three casting series were included. Pre-treatment and post-treatment deformity scores were examined across casting series using analysis of variance (ANOVA) statistical analysis. The first series pre-treatment Pirani score improved from 4.80±1.54 to 1.68±1.48 (p<0.001). The second series improved from 4.23±1.03 to 2.72±0.916 (p<0.001). The third series had the smallest improvement from 3.87±1.07 to 2.82±1.02 (p<0.001). Change in Pirani scores showed a significant decrease from the first series to the second (p=0.001) and third (p<0.001). In addition, the number of casting days was found to significantly affect the change in scores during the third series (p=0.038). The Ponseti technique can improve clubfoot in AMC as measured by the Pirani score. Data shows that early intervention yields better results, with a diminished yet effective ability to elicit change over time.

The prognostic significance of lncRNA FGD5-AS1 in various malignancies: a meta-analysis.

Cancer is widely recognized as a prominent contributor to global mortality due to factors such as delayed diagnosis, unfavorable prognosis, and high likelihood of recurrence. FGD5 transcription factor G antisense RNA 1(FGD5-AS1), a newly identified long non-coding RNA, has emerged as a promising prognostic biomarker, for malignancy prognosis. This meta-analysis aimed to assess the prognostic significance of FGD5-AS1 in various carcinomas. A systematic search was performed through five electronic databases to identify studies that investigating the role of FGD5-AS1 expression as a prognostic factor in carcinomas. The value of FGD5-AS1 in malignancies was estimated by odds ratios (ORs) and hazard ratios (HRs) with a corresponding 95% confidence intervals (CIs). Furthermore, the GEPIA database was used to further supplement our results. This analysis included 12 studies with 642 cases covering eight cancer types. High FGD5-AS1 expression exhibited a significant correlation with poor overall survival(OS) (HR = 2.04, 95%CI [1.72, 2.42], P < 0.00001), advanced tumor stage (OR = 3.47, 95%CI [2.34, 5.14], P < 0.00001), lymph node metastasis(LNM) (OR = 1.79, 95% CI [1.20,2.67], P = 0.004), and larger tumor size (OR= 5.25, 95%CI [2.68, 10.30], P < 0.00001). Furthermore, the FGD5-AS1 expression was notably upregulated in six types of malignancies as verified using the GEPIA online gene analysis tool. The findings of this meta-analysis indicated that high FGD5-AS1 expression was significantly associated with poor prognosis in diverse cancer types, suggesting that FGD5-AS1 may be a promising biomarker for predicting cancer prognosis. https://www.york.ac.uk/inst/crd, identifier CRD42024552582.

Daily Life Management Guidelines for Diabetic Foot Patients

Diabetic foot ulcers are a significant complication of diabetes, often leading to hospitalization and, in severe cases, lower limb amputation, causing substantial medical costs and reduced quality of life. Approximately 15% of diabetic patients develop foot ulcers, with 15% of these cases progressing to amputation, highlighting the critical need for foot care in diabetes management. These ulcers have a high mortality rate and a high likelihood of recurrence, highlighting the need for both blood sugar control and foot care. In South Korea, around 2.9% of diabetic patients over the age of 20 were diagnosed with diabetic foot ulcers in 2011, affecting approximately 100,000 individuals. Globally, about one-third of diabetic patients will experience foot ulcers in their lifetime, with a high recurrence rate. Diabetic foot ulcers are prone to infections, potentially leading to amputation or even death, emphasizing the importance of prevention and proper treatment. Educating patients with diabetic foot ulcer about foot care can significantly enhance their knowledge and performance in caring for their feet, including the use of moisturizers. Providing specific and practical foot care instructions is crucial to improve self-foot care practices and to minimize the risk of complications.

GATA6-AS1 suppresses epithelial–mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a hypoxic microenvironment, a high rate of heterogeneity as well as a high likelihood of recurrence. Mounting evidence has affirmed that long non-coding RNAs (lncRNAs) participate in the carcinogenesis of PDAC cells. In this study, we revealed significantly decreased expression of GATA6-AS1 in PDAC based on the GEO dataset and our cohorts, and showed that low GATA6-AS1 expression was linked to unfavorable clinicopathologic characteristics as well as a poor prognosis. Gain- and loss-of-function studies demonstrated that GATA6-AS1 suppressed the proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT) process of PDAC cells under hypoxia. In vivo data confirm the suppressive roles of GATA6-AS1/SNAI1 in tumor growth and lung metastasis of PDAC. Mechanistically, hypoxia-driven E26 transformation-specific sequence-1 (ETS1), as an upstream modulatory mechanism, was essential for the downregulation of GATA6-AS1 in PDAC cells. GATA6-AS1 inhibited the expression of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) eraser, and repressed SNAI1 mRNA stability in an m6A-dependent manner. Our data suggested that GATA6-AS1 can inhibit PDAC cell proliferation, invasion, migration, EMT process and metastasis under hypoxia, and disrupting the GATA6-AS1/FTO/SNAI1 axis might be a viable therapeutic approach for refractory hypoxic pancreatic cancers.

Coexpression network analysis identified MT3 as a hub gene that promotes the chemoresistance of oral cancer by regulating the expression of YAP1

BackgroundOral cancer is considered one of the most malignant types of tumors and is known for its high likelihood of recurrence and metastasis. During clinical treatment, patients with oral cancer often develop resistance to chemotherapy, making the treatment process challenging. The purpose of this study was to investigate the genes related to chemotherapy resistance and their mechanisms in oral cancer patients.MethodsThe “limma” package was used to identify the differentially expressed genes between tumor and normal tissues from TCGA dataset. Subsequently, the “WGCNA” package was utilized to discover genes associated with chemoresistance. Cisplatin-resistant oral cancer cell lines were obtained through exposure to gradually increasing doses of cisplatin. SiRNA was used to knock down the MT3 and YAP1 genes to validate their functions. Finally, the therapeutic efficacy of combining a YAP1 inhibitor with cisplatin was confirmed by inoculating an oral cancer cell line in mice.ResultsIn our study, we analyzed 43 OSCC samples and identified 724 different genes using the weighted gene coexpression network analysis (WGCNA) method. Among these genes, MT3 stood out as strongly associated with chemotherapy resistance. Patients with high MT3 expression had worse prognoses, and MT3 levels were elevated in drug-resistant patients. Knocking down MT3 reversed tumor cell chemoresistance. We also observed that MT3 increased the expression of YAP1, potentially contributing to chemotherapy resistance by inducing tumor stemness through YAP1. In animal models, using YAP1 inhibitors improved the effectiveness of cisplatin in treating chemoresistant oral cancer.ConclusionsMT3 is related to chemotherapy resistance, which may be caused by its promotion of YAP1 expression and induction of tumor cell stemness. Inhibiting the activity of MT3 and YAP1 is helpful for increasing chemotherapy sensitivity.

Development of Automated Risk Stratification for Sporadic Odontogenic Keratocyst Whole Slide Images with an Attention-Based Image Sequence Analyzer

(1) Background: The categorization of recurrent and non-recurrent odontogenic keratocyst is complex and challenging for both clinicians and pathologists. What sets this cyst apart is its aggressive nature and high likelihood of recurrence. Despite identifying various predictive clinical/radiological/histopathological parameters, clinicians still face difficulties in therapeutic management due to its inherent aggressive nature. This research aims to build a pipeline system that accurately detects recurring and non-recurring OKC. (2) Objective: To automate the risk stratification of OKCs as recurring or non-recurring based on whole slide images (WSIs) using an attention-based image sequence analyzer (ABISA). (3) Materials and methods: The presented architecture combines transformer-based self-attention mechanisms with sequential modeling using LSTM (long short-term memory) to predict the class label. This architecture leverages self-attention to capture spatial dependencies in image patches and LSTM to capture sequential dependencies across patches or frames, making it suitable for this image analysis. These two powerful combinations were integrated and applied on a custom dataset of 48 labeled WSIs (508 tiled images) generated from the highest zoom level WSI. (4) Results: The proposed ABISA algorithm attained 0.98, 1.0, and 0.98 testing accuracy, recall, and area under the curve, respectively, whereas VGG16, VGG19, and Inception V3, standard vision transformer attained testing accuracies of 0.80, 0.73, 0.82, 0.91, respectively. ABISA used 58% fewer trainable parameters than the standard vision transformer. (5) Conclusions: The proposed novel ABISA algorithm was integrated into a risk stratification pipeline to automate the detection of recurring OKC significantly faster, thus allowing the pathologist to define risk stratification faster.

Exosomes: Toward a potential application in bladder cancer diagnosis and treatment

AbstractBladder cancer (BC) is a prevalent malignant tumor of the urinary system, known for its rapid progression and high likelihood of recurrence. Despite ongoing efforts, clinical diagnosis and treatment of BC remain limited. As such, there is an urgent need to investigate potential mechanisms underlying this disease. Exosomes, which contain a variety of bioactive molecules such as nucleic acids, proteins, and lipids, are regarded as extracellular messengers because they are implicated in facilitating intercellular communication in various diseases and are pivotal in tumor advancement, serving as a promising avenue for such researches. Nevertheless, the heterogeneous nature of BC necessitates further exploration of the potential involvement of exosomes in disease progression. This review comprehensively outlines the biological attributes of exosomes and their critical roles in tumorigenesis, while also discussing their potential applications in regulating the progression of BC involving clinical diagnosis, prognostication and treatment.

Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma.

Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches. To obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single-cell RNA sequencing and T-cell/B-cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour-infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence insitu hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma. Promoting natural killer (NK) cell and CD8_GZMK T-cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2-like activity of tumour-associated macrophages (TAMs) could be an effective approach. Antigen-presenting cancer-associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen-presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro. Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.

Patterns of Locoregional Pancreatic Cancer Recurrence after Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes

Neoadjuvant treatment for patients with localized pancreatic adenocarcinoma (PDAC) has improved survival duration. As survival increases, local disease control becomes even more important. We sought to understand the patterns of locoregional recurrence following total neoadjuvant therapy (TNT) and determine the impact of treatment volumes on recurrence. Patients with PDAC managed with neoadjuvant chemotherapy and chemoradiation (TNT) followed by surgery who developed an isolated locoregional or simultaneously locoregional and distant recurrence were identified. Locoregional recurrences were individually contoured utilizing commercially available software. When available, original neoadjuvant dose distributions were registered to the scans on which the locoregional recurrences were contoured. Recurrences where then classified as in-field (> 95% of prescription dose), marginal (50-95% of prescription dose), or out of field (< 50% of prescription dose). Target volumes were created using four commonly utilized PDAC contouring guidelines to characterize the relationship of the local recurrence to the RT dose distribution. Of 474 patients treated with TNT and surgery, 80 (17%) patients developed a locoregional recurrence with or without distant recurrence, visible on diagnostic imaging. Of the 80 patients, 56 (70%) had tumors in the pancreatic head; 46 (57.5%) were borderline resectable, 23 (28.8%) locally advanced, and 11 (13.6%) resectable. The most common initial neoadjuvant therapies were FOLFIRINOX (57.5%) and gemcitabine/nab-paclitaxel (18.8%). Chemoradiation included concurrent gemcitabine (47.5%) or 5-fluorouracil (26.3%). RT dose distributions were available for 38 patients; 22 (57.9%) had in-field failures, 9 (23.7%) marginal failures, and 7 (18.4%) out of field failures. Each published contouring atlas covered a relatively low percentage of recurrences, which are summarized in Table 1. Regions at particularly high likelihood of recurrence that were under covered on existing atlases included: aortic-diaphragmic junction, retro-pancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery (SMA). We present the largest series (to our knowledge) of mapped locoregional recurrences for patients being treated with TNT in PDAC. These recurrences differ substantially from established atlases and highlight anatomical regions of highest priority for RT coverage. A novel visual contouring volume highlighting these regions will be presented which will strive to advance the use of RT in the TNT setting.

Investigation of the effect and prediction factors of bevacizumab on immunoregulation in glioblastoma

Glioblastoma (GB) is one of the most common and malignant tumours that originates in the brain. It has a high likelihood of recurrence and a poor survival rate. Professor Toshihide Tanaka, Chief Medical Officer, Jikei University School of Medicine, conducts translational research based on clinical samples of glioblastoma tumours obtained from brain tumour surgery procedures as well as animal studies. He heads up a multidisciplinary team focused on the design and selection of personalised treatments for hypervascular malignant gliomas. In their current project, the researchers are investigating the use of Bevacizumab (Bev), a monoclonal antibody that targets vascular endothelial growth factor (VEGF). VEGF enhances tumour growth by changing the surrounding environment to one more favourable for tumour growth. The effect of Bev on cancers is transient and the mechanisms of resistance to Bev are yet to be investigated in detail. The researchers are therefore seeking to discover predictive biomarkers of microenvironment-targeted therapy for GB. In order to investigate the effect and prediction factors of Bev on immunoregulation in GB, Tanaka and the team perform in situ observations using histological techniques including immunohistochemistry using tumour tissues from patients who have undergone surgical resection. The researchers have been able to demonstrate a decrease in microvascular density and an improvement in the tumour microenvironment after treatment with Bev.

A novel coiled-coil domain containing-related gene signature for predicting prognosis and treatment effect of breast cancer.

Breast cancer (BRCA) is a prevalent tumor worldwide. The association between the coiled-coil domain-containing (CCDC) protein family and different tumors has been established. However, the prognostic significance of this protein family in breast cancer remains uncertain. Gene expression and clinical data were obtained from the TCGA, METABRIC, and GEO databases. Prognosis genes were identified using univariate Cox and LASSO Cox regression, leading to the establishment of a prognostic signature. Subsequently, the risk model was conducted based on survival and clinical feature analyses, and a nomogram for prognosis prediction was developed. Furthermore, analyses of biological function, immune characteristics, and drug sensitivity were performed. Finally, single-cell sequencing data were utilized to uncover the expression patterns of genes in the risk model. Five genes were identified and utilized for risk modeling. The model demonstrated excellent prognostic value as indicated by ROC and Kaplan-Meier analysis. The high-risk group exhibited shorter survival time and higher likelihood of recurrence. Functional annotation indicated a correlation between the risk score and immune pathways. Conversely, the low-risk group displayed a greater enrichment in immune pathways and exhibited more active immune microenvironment characteristics. Additionally, drug sensitivity analysis using both public and our sequencing data revealed that the risk model possessed a broad range of predictive values. We have developed a gene signature and have verified that patients with low-risk are more likely to have better prognosis and respond positively to therapy. This finding offers a valuable point of reference for BRCA individualized treatment.

First seizure from sleep: Clinical features and prognosis.

Patients with a first-ever unprovoked seizure commonly have subsequent seizures and identifying predictors of recurrence has important management implications. Both prior brain insult and epileptiform abnormalities on electroencephalography (EEG) are established predictors of seizure recurrence. Some studies suggest that a first-ever seizure from sleep has a higher likelihood of recurrence. However, with relatively small numbers and inconsistent definitions, more data are required. Prospective cohort study of adults with first-ever unprovoked seizure seen by a hospital-based first seizure service between 2000 and 2015. Clinical features and outcomes of first-ever seizure from sleep and while awake were compared. First-ever unprovoked seizure occurred during sleep in 298 of 1312 patients (23%), in whom the 1-year cumulative risk of recurrence was 56.9% (95% confidence interval [CI] 51.3-62.6) compared to 44.2% (95% CI 41.1-47.3, p < .0001) for patients with first-ever seizure while awake. First-ever seizure from sleep was an independent predictor of seizure recurrence, with a hazard ratio [HR] of 1.44 (95% CI 1.23-1.69), similar to epileptiform abnormalities on EEG (HR 1.48, 95% CI 1.24-1.76) and remote symptomatic etiology (HR 1.47, 95% CI 1.27-1.71). HR for recurrence in patients without either epileptiform abnormalities or remote symptomatic etiology was 1.97 (95% CI 1.60-2.44) for a sleep seizure compared to an awake seizure. For first seizure from sleep, 76% of second seizures also arose from sleep (p < .0001), with 65% of third seizures (p < .0001) also from sleep. Seizures from sleep were less likely to be associated with injury other than orolingual trauma, both with the presenting seizure (9.4% vs 30.6%, p < .0001) and first recurrence (7.5% vs 16.3%, p = .001). First-ever unprovoked seizures from sleep are more likely to recur, independent of other risk factors, with recurrences also usually from sleep, and with a lower risk of seizure-related injury. These findings may inform treatment decisions and counseling after first-ever seizure.