Five-year Survival Research Articles

Clinical analysis of endoscopic transnasal resection of skull base chondrosarcoma

Objective:To explore the surgical techniques and clinical outcomes of endoscopic transnasal approaches in the treatment of skull base chondrosarcomas. Methods:Data from patients diagnosed with skull base chondrosarcomas and treated via endoscopic transnasal surgery at the Department of Otorhinolaryngology and Head and Neck Surgery, Xuanwu Hospital, Capital Medical University, from 2013 to 2022 were collected. This retrospective study analyzed the patients' clinical presentations, histopathological grading, involved sites and extents, and complications following the endoscopic transnasal surgery. Disease-free survival rates were calculated using the Kaplan-Meier method. Results:Complete data from 31 patients showed that the primary tumor site was in the petroclival region in 27 cases（87%）, and the anterior skull base in 4 cases（13%）. Pathological grades were Grade Ⅰ（12 cases）, Grade Ⅱ（16 cases）, and Grade Ⅲ（3 cases）. Total resection was achieved in 25 cases, with residual disease post-surgery in 6 cases. The average follow-up duration was 35.7 months（ranging from 6 to 120 months）. Among those who achieved complete resection, recurrence occurred in 5 cases（5/25）, with a five-year disease-free survival rate of 80%. Postoperative complications included transient abducens nerve palsy in 6 patients and cerebrospinal fluid rhinorrhea in 4 patients. There were no cases of death or permanent cranial nerve palsy. Total resection rate（P=0.001） and involvement of the cerebellopontine angle and jugular foramen（P=0.037） were identified as independent risk factors for residual disease and recurrence of chondrosarcoma. Conclusion:The endoscopic transnasal approach is a safe and feasible treatment option for skull base chondrosarcomas.

Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of less than 10% making it one of the most fatal cancers. A lack of early measures of prognosis, challenges in molecular targeted therapy, ineffective adjuvant chemotherapy, and strong resistance to chemotherapy cumulatively make pancreatic cancer challenging to manage. The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer. Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC. Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer. This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Regulation of Tumor Growth and Invasion in Oral Squamous Cell Carcinoma by the Tumor Microenvironment Through the Enhancement of IGFBP-3 Expression.

Accumulated evidence indicates that interactions among various stromal cells within the tumor microenvironment (TME) significantly influence cancer progression. Oral cancers not diagnosed at early stages are associated with low five-year survival rates, highlighting the need for substantial improvements in patient outcomes. Understanding the interactions between cancer cells and the tumor microenvironment is crucial for identifying methods and developing treatment strategies that more effectively inhibit tumor progression and metastasis. This study investigated the roles of cancer-associated fibroblasts (CAFs) and THP-1 monocytes in tumor growth and invasion, observing changes in cancer biological characteristics through interactions with stromal cells. HSC2 oral squamous cell carcinoma (OSCC) cells were co-cultured with normal fibroblasts (NF), cancer-associated fibroblasts (CAF), or THP-1 cells. Changes in cancer cell invasion were investigated using Matrigel-coated transwell assays, collagen-based dermal equivalent assays, and in vivo mouse studies. HSC2 cells co-cultured with CAFs or THP-1 exhibited increased invasion compared to those co-cultured with normal fibroblasts (NF) in the dermal equivalent. In a mouse gingival xenograft model, cancer cells co-implanted with CAFs or THP-1 showed significantly increased tumor growth compared to those co-implanted with NF. Micro-CT (μCT) analysis revealed significant alveolar bone resorption around the mandible in tumors grown with CAFs or THP-1 cells. Conditioned media (CM) from CAFs or THP-1 significantly increased HSC2 invasion and migration, an effect that was inhibited by the protein secretion inhibitor Brefeldin (BFA). Furthermore, QuantSeq 3' mRNA sequencing indicated increased expression of IGFBP3, closely associated with cancer invasion, in HSC2 cells co-cultured with CAFs or THP-1. These findings suggest that cancer cells enhance their invasive characteristics through close interactions with the surrounding stromal cells.

Survival Outcomes and Disparities in Surgery Refusal for Papillary Thyroid Cancer.

Surgery is the cornerstone of treatment for papillary thyroid cancer (PTC), yet some patients refuse surgery, which may impact their survival outcomes. Understanding factors associated with surgery refusal could inform interventions to improve acceptance of recommended care. This retrospective cohort study evaluated the impact of surgery refusal on overall survival (OS) and identified associated demographic and clinical factors using data on patients with PTC from the National Cancer Database from 2004 to 2019. OS was analyzed using the Kaplan-Meier method, with survival curves compared using the log-rank test. Patient characteristics were analyzed using Pearson Chi-square tests or Wilcoxon Rank Sum tests. Of the 201,051 patients with PTC who were advised to undergo surgery, 200,656 (99.8%) underwent surgery, while 395 (0.2%) refused. Patients who refused surgery were older (mean age 55.2 years vs. 48.7 years), more often male (27.8% vs. 22.8%), and represented higher proportions of Black, Asian, Hispanic, lower-income, uninsured, and non-privately insured patients (p<0.001). OS rates were significantly lower in patients who refused surgery, with one-year and five-year survival rates of 87% and 34%, respectively, compared to 96% and 56% for those who underwent surgery. Surgery refusal in patients with PTC was associated with poorer OS outcomes and was more frequent among older adults, socioeconomically disadvantaged populations, and racial and ethnic minorities. Interventions addressing patient concerns and barriers to surgery are critical to improving treatment acceptance and survival among these groups.

Real-world data on the clinical features, therapy patterns, and outcomes of older adults with diffuse large B-cell lymphoma in Latin America: A study from the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL)

IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, predominantly afflicting older adults. There remains a notable absence of data regarding DLBCL in older adults in Latin America. Materials and MethodsWe conducted a retrospective analysis of 608 newly diagnosed Latin American patients with DLBCL aged ≥65 years. ResultsThe median age at diagnosis was 74 years (range: 65–96 years), 51 % were female, 36 % had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 65 % had advanced disease. The most common regimens used were standard-dose R-CHOP (n = 420, 69 %), R-CVP (n = 77, 12 %), R-mini-CHOP (n = 74, 12 %), and CHOP/CVP (n = 30, 5 %). With a median follow-up of 60 months (95 % confidence interval [CI]: 38.7–75.2 months), the five-year overall survival (OS) rate was 50 % (95 % CI, 43–58). An ECOG PS ≥2 (hazard ratio [HR] 1.93; 95 % CI 1.51–2.46; p < 0.01), advanced clinical stage (HR 1.46; 95 % CI 1.12–1.91; p < 0.01), increased serum lactic dehydrogenase level (HR 1.48; 95 % CI 1.16–1.87; p < 0.01), and albumin level < 3.5 mg/dL (HR 1.64; 95 % CI 1.29–2.10; p < 0.01) were associated with an inferior OS. Using anthracyclines (HR 0.50; 95 % CI 0.38–0.66; p < 0.01) and using rituximab (HR 0.51; 95 % CI 0.36–0.73; p < 0.01) were independently associated with a superior OS. DiscussionIn a large cohort of Latin American older patients with DLBCL, therapy and outcome patterns are similar to those reported internationally. The lack of standardized geriatric assessments in Latin America represents an essential area for research to better stratify older patients with DLBCL deemed to be at higher risk for toxicity.

Surgical treatment and outcomes in aortic valve endocarditis and perivalvular abscesses.

Patients with aortic root abscesses experience increased morbidity and mortality compared to those without abscess in aortic valve infective endocarditis. The superior intervention for patients with aortic root abscess is not determined. This research investigates the degree to which increased morbidity and mortality of aortic root abscess, and to describe perioperative characteristics and outcomes of root operations versus root-sparing repairs of aortic root abscess. All patients who underwent surgical treatment of active aortic valve endocarditis between 2011 and 2022 at a single institution were reviewed, yielding 218 patients, of whom 64 had perivalvular abscess. Patients were treated with either simple (root-sparing) or complex (root replacement) techniques. Patients with abscess demonstrated significantly higher rates of previous cardiac surgery, redo endocarditis surgery, aortocavitary fistula, heart block, and prosthetic valve endocarditis. One quarter of abscesses were not detected on preoperative imaging. Presence of abscess was a significant predictor of operative mortality. Prosthetic valve endocarditis was a significant predictor of complex repair in patients with abscess. Five-year survival was similar between simple and complex repair groups in patients with abscess. Aortic root abscess confers significant morbidity and mortality, and measures should be taken to ensure early detection and treatment of this condition.

N6-methyladenosine RNA modification in head and neck squamous cell carcinoma (HNSCC): current status and future insights.

N6-methyladenosine (m6A) plays a pivotal role in regulating epitranscriptomic mechanisms and is closely linked to the normal functioning of diverse classes of RNAs, both coding as well as noncoding. Recent research highlights the role of m6A RNA methylation in the onset and progression of several cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC ranks as the seventh most common cancer globally, with a five-year patient survival rate of just 50%. Elevated m6A RNA methylation levels and deregulated expression of various m6A modifiers, i.e. writers, readers, and erasers, have been reported across nearly all HNSCC subtypes. Numerous studies have demonstrated that m6A modifications significantly impact key hallmarks of HNSCC, such as proliferation, apoptosis, migration, and invasion. Furthermore, m6A impacts epithelial-mesenchymal transition (EMT), drug resistance, and aerobic glycolysis, and disrupts the tumor microenvironment. Additionally, transcripts regulated by m6A in HNSCC present themselves as potential diagnostic and prognostic biomarkers. This review attempts to comprehensively summarize the role of m6A RNA methylation and its modifiers in regulating various facets of HNSCC pathogenesis.

Identification and interaction mechanism of novel small molecule antagonists targeting CC chemokine receptor 1/3/5 for treatment of non-small cell lung cancer.

Non-Small Cell Lung Cancer (NSCLC) was one of the most prevalent forms of lung cancer. Due to its ease of invasion and migration, the five-year survival rate was relatively low. Therefore, new strategies for NSCLC treatment were needed. CC chemokine receptor 1/3/5 (CCR1/CCR3/CCR5), a member of the G-protein coupled receptor family, could promote the migration and invasion of NSCLC cells by binding to related chemokines. Consequently, targeting CCR1, CCR3 and CCR5 might prevent the progression of the disease. So far, no compound had been reported as a common antagonist for CCR1, CCR3, and CCR5. In this research, we utilized virtual screening and structural optimization to obtain compound 5, which effectively inhibited the migration and invasion of NSCLC cells. Meanwhile, Western Blot and Enzyme linked immunosorbent assay (ELISA) manifested that compound 5 suppressed migration and invasion of NSCLC cells by suppressing the nuclear factor κB (NF-κB) and the consequently decreased Matrix Metalloproteinase-9(MMP-9) secretion. Moreover, drug affinity responsive target stability (DARTS) experiment and molecular simulations confirmed that compound 5 was capable of binding with CCR1/CCR3/CCR5, and Van der Waals forces were instrumental in the binding process. Ile91, Tyr113, Gln284, and Ser184(CCR1-ligand5), Ile189, Met213, and Leu209(CCR3-ligand5), Phe109, Gln194, and Thr195(CCR5-ligand5) had Van der Waals interactions with ligand 5. Dynamic cross-correlation matrix (DCCM) and free energy landscape (FEL) showed that compound 5 could stably bind to CCR1/CCR3/CCR5 to change conformation of the protein and the tendency of residue movements, leading to a persistent inhibitory effect. This study aimed to provide assistance in the rational design of common antagonists for CCR1, CCR3, and CCR5.

Early Outcomes for Management of Atrioventricular Septal Defect-Tetralogy of Fallot in the Last Decade: A Congenital Heart Surgeons' Society Study.

We sought to determine the management and early outcomes of complete atrioventricular septal defect-tetralogy of Fallot (AVSD-TOF) for a contemporary multicenter cohort. Of 739 participants in the Congenital Heart Surgeons' Society AVSD cohort (January 2012-May 2021), 40 had AVSD-TOF. We first compared survival differences for patients with AVSD-TOF versus those with isolated AVSD using propensity matching. Secondly, for patients with AVSD-TOF, we compared staged (n = 16) versus primary (n = 24) repair by assessing the following: patient characteristics, progression of atrioventricular valve (AVV) regurgitation, and time-related reoperation and survival. Five-year survival was similar between matched AVSD-TOF and isolated AVSD groups (80% vs 81%, P = .9). Compared with primary repair patients, staged patients had smaller pulmonary valve annulus Z-score measured at first presentation (-2.2 vs -2.9, P = .006). All staged patients (12 Blalock-Thomas-Taussig shunts, 3 right-ventricular-outflow-tract stents, 1 ductal stent) survived to complete repair. Freedom from AVSD-related reoperation five years post-AVSD-TOF repair was 57% after staged versus 90% after primary repair (P < .05) and left AVV reoperations were the most frequent reintervention. Survival five years after AVSD-TOF repair was 80% (63% after staged vs 90% after primary repair; P = .08). Patients undergoing AVSD-TOF repair have similar survival compared with matched isolated AVSD patients. Although approximately half of AVSD-TOF patients had initial palliation and all survived to complete repair, staged repair patients had lower survival and a higher reintervention rate compared with primary repair patients. The decision to pursue staged versus primary repair for future babies with AVSD-TOF remains challenging and should be chosen based on individual circumstances.

Predictive Value of Preoperative Morphology Parameters in Patients Undergoing On-Pump and Off-Pump Coronary Artery Bypass Surgery.

Coronary heart disease is the most common cause of death worldwide. It is responsible for almost a third of deaths in patients over the age of 35. Various biomarkers are currently being studied in detail for their value in predicting postoperative mortality in patients undergoing CABG. The aim of this study is to analyze the predictive value of certain blood morphological parameters in CABG and off-pump coronary artery bypass grafting (OPCAB). A total of 520 patients who underwent surgery in two consecutive years and underwent CABG (404) or OPCAB (116) were included in this retrospective study. Gender, age, comorbidities, five-year survival rate, detailed information on hospitalization, surgery, intensive care unit parameters and preoperative blood samples from the cubital vein were recorded. Inverse propensity treatment weighting was applied to adjust for confounding factors at baseline. No differences were found between OPCAB and CABG as an isolated comparison. In the standardized population, patients with abnormal lymphocyte counts had an increased risk of death at one-year and five-year follow-up. In the standardized population, abnormal red blood cell distribution width (RDW-SD), neutrocyte-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were associated with increased mortality in each period analyzed. Abnormal PLR, RDW-SD and NLR are associated with increased early and late mortality in patients undergoing CABG and OPCAB. Abnormal lymphocytes are only associated with increased late mortality.

The PLCG2 Inhibits Tumor Progression and Mediates Angiogenesis by VEGF Signaling Pathway in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents the most prevalent form of renal cell carcinoma. The management of early-stage ccRCC has a better prognosis, while patients with metastatic ccRCC have a lower five-year survival rate. Angiogenesis serves as the fundamental process underlying tumor metastasis. Therefore, it is crucial to discover new targets for angiogenesis to improve patient survival rates. The Cancer Genome Atlas database, International Cancer Genome Consortium database, Clinical Proteomic Tumor Analysis Consortium database, and a gene set of the vascular endothelial growth factor (VEGF) signaling pathway were utilized to identify differentially expressed genes. Western blot (WB), quantitative real-time polymerase chain reaction, and immunohistochemistry were employed to validate the downregulation of phospholipase C gamma 2 (PLCG2) in ccRCC tissues and cells. Cell Counting Kit-8 (CCK-8) assays, transwell assays, tube formation assays, and oil-red staining were performed to elucidate the biological functions of PLCG2 in tumor cells. Gene set enrichment analysis was applied to explore the downstream pathway. Subcutaneous tumor models and live small animal fluorescent imaging assay were utilized for in vivo investigation of the roles played by PLCG2. Our study has identified a novel biomarker, PLCG2, for ccRCC. PLCG2 is a central gene in regulating angiogenesis in ccRCC, as validated by bioinformatics analysis. The findings revealed a diminished expression of PLCG2 in both ccRCC tissues and cells. Further experiments in vivo and in vitro have demonstrated the significant roles of PLCG2 in tumor proliferation, invasion, migration, and lipid accumulation. Results of tube formation assays and WB support the role of PLCG2 in regulating VEGFA expression and angiogenesis. Our results show that PLCG2 functions as a potential biomarker and an independent prognostic indicator for ccRCC. PLCG2 may modulate angiogenesis by influencing the expression of VEGFA. Therefore, targeting PLCG2 could potentially lead to drug discovery and improved cancer treatment strategies.

Long-term relative survival of patients with gastric cancer from a large-scale cohort: a period-analysis

BackgroundGastric cancer poses a significant global health challenge. We aim to use period analysis to assess the changes in gastric cancer treatment at our center over the past 15 years. This study reflects the current state of gastric cancer treatment at our center and provides valuable data to support clinical advancements.MethodWe used period analysis to evaluate the survival status of 3915 patients with gastric cancer at Nanfang Hospital, Southern Medical University, over a 15-year period spaning from 2008 to 2022. The 5-year relative survival rates were analyzed.ResultOur findings indicate that the 5-year relative survival rate at our center from 2018 to 2022 is 71.4%. From 2018 to 2022, the 5-year relative survival rates for patients aged < 40, 40–54, 55–69, and ≥ 70 reached 67.5%, 73.5%, 72.0%, and 67.1%, respectively. For stage IV patients, the 5-year relative survival rate reached 29% in 2018–2022. For stage I-III patients, the 5-year relative survival rate reached 89.7% in 2018–2022. The five-year relative survival rate for patients who underwent laparoscopic surgery at our center rose from 50.3% in 2008–2012 to 71.4% in 2018–2022. Overall, there has been a notable increase in the 5-year relative survival rates, regardless of age, gender, region, or tumor stage.ConclusionPeriod analysis over the past 15 years shows significant improvement in the 5-year survival rate for gastric cancer at our center. This progress is due to standardized surgical techniques, perioperative management, and immunotherapy, providing robust data for evaluating the efficacy of recent treatments.

Rurality and pediatric cancer survival in the United States: An analysis of SEER data from 2000 to 2021

BackgroundCancer is the leading cause of death by disease among children in the United States. Residing in rural areas may impact cancer outcomes as rural areas tend to have fewer available healthcare resources. Few population-based studies have investigated rural/urban disparities in pediatric cancer outcomes. The objective of this study was to examine rural/urban differences in (1) five-year relative survival and (2) cancer-specific survival among children in the United States. MethodsThe study is a population-based longitudinal study using data from the Surveillance, Epidemiology, and End Results (SEER) 17 registries database (2000–2021). We included data for individuals aged 0–19 with a first primary malignant cancer diagnosed from 2000 to 2016. Rurality was measured by Rural-Urban Continuum Codes (RUCCs). Five-year relative survival rates, Kaplan-Meier curves, and Cox regression analysis were used to determine the differences in pediatric cancer survivorship between rural and urban areas. ResultsBoth five-year relative survival rates and log-rank tests of survival probabilities over time by rurality showed no statistically significant difference between individuals living in urban versus rural counties. However, after adjusting for age, sex, race/ethnicity, cancer type, median household income, and region, children diagnosed in rural counties had a 9 % higher risk of death compared to children diagnosed in urban counties (95 % CI 1.02–1.17), with the highest increased risk observed for children with retinoblastoma (aHR: 6.12, 95 % CI 2.01–18.59). A higher increased risk of death was observed for children living in the most rural counties (aHR: 1.18, 95 % CI 1.07–1.32). ConclusionIn this study, residing in rural areas was associated with an increased risk of death from pediatric cancer, especially for children residing in rural areas not adjacent to urban areas. Our findings warrant further investigation to determine the rural/urban disparities in pediatric cancer outcomes and to develop interventions to deliver high-quality cancer care to rural children.

MLN4924 Suppresses head and neck squamous cell carcinoma progression by inactivating the mTOR signaling pathway via the NEDD8/CUL4/TSC2 axis

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a five-year survival rate below 50 %. Standard treatments for HNSCC include surgery, radiotherapy, chemotherapy, and targeted therapies, but they still have significant limitations. Neddylation, a post-translational modification involving the attachment of NEDD8 (neural precursor cells expressed developmentally down-regulated 8) to proteins, is frequently dysregulated in HNSCC, thereby promoting tumor growth. MLN4924, also known as Pevonedistat, is a Neddylation inhibitor that has shown promise in suppressing HNSCC cell proliferation and invasion, establishing it as a potential therapeutic option. However, its precise molecular mechanism remains unclear. This study aims to investigate the mechanism of MLN4924 in HNSCC. This study examined the effects of MLN4924 on HNSCC and its associated molecular pathways. Bioinformatic analysis indicated that NEDD8, a critical component of the Neddylation pathway, is linked to poor prognosis and the mTOR (mammalian target of rapamycin) signaling pathway in HNSCC. MLN4924 significantly suppressed cell migration, invasion, and the epithelial-mesenchymal transition (EMT) pathway, and downregulated NEDD8 expression. Mechanistic studies demonstrated that MLN4924 inhibited the binding of NEDD8 to cullin4 (CUL4) and prevented the Neddylation of tuberous sclerosis complex 2 (TSC2), leading to the inactivation of the mTOR pathway. These findings were confirmed in vivo, where MLN4924 effectively inhibited tumor growth. Overall, MLN4924 disrupted Neddylation pathway and stabilized TSC2, thereby inactivating the mTOR pathway. The study provided a theoretical basis for the clinical potential of MLN4924 in improving treatment outcomes for HNSCC patients, offering a novel strategy for addressing this challenging disease.

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial. Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. Design: Retrospective cohort study. Settings: Comprehensive cancer center in New York. Patients: Patients with rectal adenocarcinoma diagnosed between January 2006 to December 2020. Interventions: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was utilized for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision Main Outcome Measures: Local regrowth rate, organ preservation rate, disease-free survival and overall survival. Results: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189) and complete (n = 395). Eighty-one (43%) patients in the near-complete group and 351 (89%) patients in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders, and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete response (68%). Overall survival at 5 years was similar between the three cohorts (complete 90%, near-complete 86%, and incomplete 85%). Limitations: Retrospective nature. Conclusion: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract.

Features of Lateral Pelvic Lymph Nodes Associated With Pathological Involvement After Total Neoadjuvant Therapy in Patients Undergoing Lateral Pelvic Lymph Node Dissection

BACKGROUND: There is a lack of consensus regarding treating involved lateral pelvic lymph nodes in rectal cancer. OBJECTIVE: This study aimed to evaluate the clinical and magnetic resonance imaging-based factors associated with pathological lateral pelvic lymph node metastasis in patients undergoing total neoadjuvant therapy and lateral pelvic lymph node dissection. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a single comprehensive cancer center. PATIENTS: A total of 107 patients with advanced low rectal cancer with pretreatment enlarged lateral pelvic lymph nodes (≥7 mm in long-axis) undergoing total neoadjuvant therapy with long-course chemoradiotherapy, followed by total mesorectal excision and lateral pelvic lymph node dissection, were enrolled. MAIN OUTCOME MEASURES: Pathological lateral pelvic lymph node metastasis and survival. RESULTS: Among 107 patients, 48 had a short-axis lateral node diameter &lt;7 mm at baseline, while 59 had ≥7 mm. The ≥7 mm group showed significantly higher rates of pathological lateral pelvic lymph node metastasis (44.1% vs. 2.1%; p &lt; 0.0001). In this group, pathological lateral pelvic lymph node metastasis was independently associated with pre-treatment malignant features and post-treatment short-axis diameter ≥4 mm. Five-year relapse-free survival was significantly lower in patients with post-treatment lateral node diameter ≥ 4 mm than those with &lt;4 mm (71.1% vs. 86.2%, p = 0.0364). Patients with pathological lateral pelvic lymph node metastasis had significantly lower overall survival, relapse-free survival, and local recurrence-free survival rates. LIMITATIONS: Selection bias exists in a retrospective analysis. CONCLUSIONS: Pathological lateral pelvic lymph node metastasis is rare in patients with pre-treatment short-axis diameter &lt;7 mm. In patients with pre-treatment short-axis diameter ≥7 mm, pre-treatment malignant features and post-treatment short-axis diameter are both associated with pathological lateral pelvic lymph node metastasis. These factors should be considered when deciding whether to proceed with lateral pelvic lymph node dissection after total neoadjuvant therapy. See Video Abstract.

Intelligence algorithm for the treatment of gastrointestinal diseases based on immune monitoring and neuroscience: A revolutionary tool for translational medicine

The research team has developed an information system based on clinical blood cell analysis and designed and implemented highly innovative algorithms. A neural network model was created based on these feature data of the blood cell population. Artificial intelligence algorithms can label susceptible populations for digestive tract cancer with an accuracy rate of over 80 %. A multi universe optimized BP neural network model was implemented based on TCGA data of common immune antigens in clinical laboratories. The working mechanism of this model is to assign values to the parameters of the BP neural network by using the process of searching for the best fitness in multiple universes. This model can predict the five-year survival rate of patients based on immunohistochemical data. Based on these data, an AI algorithm was used to develop a clinical prognostic model with an accuracy rate of over 99 %. The research team used single-cell sequencing data to locate cell subtypes in the features of immunohistochemical data, providing a biological basis for artificial intelligence models. The research team explored the potential biological mechanisms of cancer progression and occurrence based on gastrointestinal neuroendocrine products, and these algorithms have contributed to the prediction of cancer survival and incidence,team invented a simple and efficient algorithm.

Abstract B040: Investigating the impact of tumor EMT states on immune cell infiltration in breast cancer

Abstract Breast cancer is one of the most frequently diagnosed cancers and the second leading cause of women’s cancer death. Although the five-year survival rate for women in the United States with nonmetastatic invasive breast cancer is 90%, this rate drops to less than 30% for those with tumors that have metastasized to distant organs. Epithelial-to-Mesenchymal Transition (EMT) plays a critical role in tumor metastasis by enabling the loss of epithelial characteristics and the gain of mesenchymal traits, leading to increased cell motility, invasion, and resistance to therapy. Consequently, targeting the EMT process may prevent tumor cell migration and improve patient outcomes. Rather than being a binary switch from an epithelial to a mesenchymal state, cells undergoing EMT can assume a spectrum of intermediate states, some of which may reshape the tumor microenvironment by recruiting pro-tumor immunosuppressive cells, such as regulatory T cells, M2-like macrophages, and myeloid-derived suppressor cells. However, the impact of EMT on the immune composition of the tumor microenvironment and the causative mechanisms remain poorly understood. Using multi-omics approaches in a mouse model of triple-negative breast cancer, we assessed the interaction between tumor and immune cells in the tumor microenvironment driven by the EMT. A heterogeneous mouse breast cancer cell line (4T1) was used to isolate five distinct single-cell-derived clonal populations residing in distinct states within the EMT spectrum. These EMT clones, along with the parental 4T1 cell line, were orthotopically transplanted into the mammary fat pads of BALB/c mice. Primary tumors were subsequently harvested and dissociated for single-cell RNA-sequencing (scRNA-seq) and DNA methylation analysis. Lungs were histologically evaluated for metastases. Tumors derived from an intermediate EMT clone exhibited increased tumor growth kinetics and a higher incidence of metastasis compared to epithelial or mesenchymal clones. In scRNA-seq data, tumors derived from different EMT clones largely retained their original EMT states in vivo and recruited distinct immune cell profiles. DNA methylation analysis further revealed that these tumors displayed unique methylation patterns in EMT-related CpGs. This study introduced a model that captures the complexity of the tumor microenvironment across the EMT spectrum. This was accomplished through immunophenotyping using scRNA-seq and identifying unique epigenetic patterns through DNA methylation. Our findings highlight the potential for distinct immune cell populations to be recruited to tumors in different EMT states, thereby influencing survival and metastasis outcomes. Furthermore, our results open new opportunities for developing cancer combination treatment strategies that target specific tumor-immune cell interactions. Citation Format: Hanxu Lu, Meisam Bagheri, Todd Miller, Diwakar Pattabiraman, Brock Christensen. Investigating the impact of tumor EMT states on immune cell infiltration in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B040.

The application of statistical techniques in assessing the impact of medical interventions: A case study of diabetes management

Abstract. Esophageal cancer (EC) ranks seventh among all cancers in terms of frequency and is the sixth leading cause of cancer-related deaths worldwide. The 5-year relative survival rate for esophageal cancer stands at a dismal 21%, which is nearly the lowest among all cancers. In China alone, over 477,900 individuals are diagnosed with EC annually. Advances in whole-genome sequencing technologies have enabled researchers to identify numerous gene mutations across the entire gene sequence in EC patients. This paper aims to consolidate current knowledge on several key genes implicated in EC, as revealed by whole-genome sequencing of patient biopsies. By examining research papers published within the last decade, this study captures the main findings and elucidates the influence of mutations in SOX2, TP53, NOTCH1, SMAD4, and CDKN2A on the formation, progression, and prognosis of both esophageal adenocarcinomas and squamous cell carcinomas. The insights gained are expected to contribute positively to the overall comprehension of esophageal cancer.

Epidemiology, trends, and survival of ocular and orbital rhabdomyosarcoma: a nationwide study in the USA (1996-2018) : Ocular and orbital rhabdomyosarcoma in the USA.

Rhabdomyosarcoma (RMS) is a rare malignancy that affects both children and young adults. Therefore, the current incidence and mortality rates of ocular and orbital rhabdomyosarcoma (ORMS) need to be clarified. We aimed to explore the epidemiology, trends, and survival outcomes of ORMS in the United States population spanning over two decades, from 1996 to 2018. We retrospectively reviewed 92,633 patients with ocular and adnexal malignancies and identified 640 ORMS cases from the North American Association of National Cancer Registries. Demographics, tumor characteristics, treatment modalities, and survival outcomes were analyzed. Most ORMS cases (71.7%) were reported in children aged-0-9 years. The age-adjusted incidence of ORMS was 0.1 per million population (ppm), with males demonstrating a higher incidence (0.12 ppm) than females (0.09 ppm). Whites had the highest incidence rate (0.11 ppm). Embryonal ORMS is the most common histological subtype. The incidence trend over the 22-year study period revealed a decline in ORMS from 0.124 to 0.076, in contrast with the incidence of whole-body RMS, which showed an insignificant increase. The 5-year relative survival rates of patients with ORMS were 89.7%, whereas the 10-year relative survival rate was 87.2%. The 5-year relative survival trend for ORMS increased but was insignificant. ORMS primarily affects young children and males, with the embryonal subtype being the most common. Despite the declining incidence, survival rates have remained stable, underscoring the need for further research on the risk factors, diagnostics, and management strategies to improve patient outcomes. What is known Ocular and Orbital Rhabdomyosarcoma (ORMS) predominantly affects children, especially males, and is the most frequent primary tumor in the orbit during childhood. The embryonal subtype is the most common histological subtype of ORMS. What is new A significant decline in the incidence of ORMS was observed over the 22-yearstudy period, in contrast to the overall incidence of whole-body rhabdomyosarcoma. It has a characteristic bigeminal distribution with a peak at 3-4 and another at 6 years. Patients receiving combined treatment modalities showed improved survival rates, while those undergoing surgery alone had poorer outcomes. Despite advancements in treatment, there has been no significant increase in the 5-year relative survival trends for ORMS.