Early-stage Tumors Research Articles

Methylation changes and INS-IGF2 expression predict progression in early-stage Wilms tumor.

Wilms tumor, the most common pediatric kidney cancer, accounts for 5% of childhood cancers and is classified by stage and histological subtype. Despite high survival rates (80-85%), approximately 15% of patients experience relapse, reducing survival to around 50%. Epigenetic changes, particularly DNA methylation, play a critical role in Wilms tumor pathogenesis. This study investigates the prognostic potential of DNA methylation in stage I and II patients with favorable histology, aiming to identify early relapse biomarkers. Genome-wide methylation was assessed using methylation microarrays in tumor tissues from relapsed patients (n = 9) and those with complete responses (n = 9), alongside normal tissues (n = 3 each). Differentially methylated probes and regions were analyzed, with additional ROC and survival analyses. Real-time PCR was used to measure IGF2 and INS-IGF2 gene expression. The analysis revealed hypomethylation in intergenic regions in remission patients, identifying 14 differentially methylated positions as potential biomarkers. Increased INS-IGF2 expression was associated with relapse, suggesting its role in disease progression. While the study concentrated on stages I and II patients, where relapse rates are lower, this focus inherently led to a smaller sample size. Despite this, the findings provide valuable insights into the potential role of DNA methylation markers for monitoring disease progression and guiding personalized treatment in Wilms tumor patients.

Nanoparticle-Assisted Cancer Imaging and Targeted Drug Delivery for Early-Stage Tumor Detection and Combined Diagnosis-Therapy Systems for Improved Cancer Management

Nanoparticle-assisted imaging and targeted drug delivery represent a transformative approach in cancer diagnostics and therapeutics, particularly for early-stage tumor detection and integrated diagnosis- therapy systems. This review explores recent advancements in nanoparticle technology for magnetic resonance imaging (MRI), computed tomography (CT), optical imaging, and ultrasound, emphasizing the efficacy of nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs), gold and bismuth nanoparticles, and quantum dots as contrast agents. Nanoparticles offer unique advantages, including enhanced permeability and retention (EPR) effects, ligand-receptor targeting, and microenvironment-responsive drug release, which improve localization and accumulation in tumor tissues. Additionally, dual-function theranostic systems utilizing nanoparticles enable simultaneous diagnostic imaging and therapy, allowing real-time monitoring of therapeutic efficacy and minimizing off-target effects. The integration of nanoparticles for both diagnostic and therapeutic purposes holds significant promise for precision oncology, providing a more personalized, minimally invasive, and effective cancer management strategy. This review also discusses current limitations, including issues of biocompatibility, toxicity, and regulatory challenges, while proposing future directions to overcome these barriers. By presenting a comprehensive analysis of nanoparticle platforms in oncology, this paper aims to underscore their potential in revolutionizing cancer diagnosis and therapy, ultimately contributing to improved patient outcomes and advancing the field of nanomedicine.

Tumor Size as a Predictive Indicator for Lymph Node Metastasis in Papillary Thyroid Carcinoma: An Inverted L-Shaped Curve Analysis Based on the SEER Database.

Papillary thyroid carcinoma (PTC) frequently metastasises to lymph nodes, with lymph node metastasis (LNM) occurring with high frequency in small, early-stage tumors. The present study examines the inverse l-shaped relationship between tumor size and the likelihood of LNM in patients diagnosed with PTC. We performed a detailed retrospective cohort analysis of 48,021 cases of papillary thyroid cancer using data from the Epidemiology, and End Results (SEER) database from 1992 to 2019. Our study used various analytical methods, including logistic regression, spline curve fitting, and variable interaction assessment, to clarify the association between tumor size and LNM rates. We rigorously controlled for potential confounders such as patient age, sex, ethnicity, tumor size, extrathyroidal extension (ETE), histopathological characteristics and distant metastases. In addition, we thoroughly investigated and quantitatively assessed the relationship between adjusted tumor size measurements and the likelihood of LNM development. The median tumor size among the 48,021 patients diagnosed with PTC was 1.3 cm. Among these patients, 12,365 (25.75%) had LNM, with a median tumor size of 1.9 cm in this group. A comparative analysis shows a significant difference in tumor sizes between PTC patients who were LNM-positive and those who were LNM-negative. The relationship between tumor size and the likelihood of LNM exhibits a distinct nonlinear pattern. Specifically, below a diameter threshold of 1.978 cm, the probability of LNM significantly increases with larger tumor sizes (odds ratio [OR] = 2.363, 95% confidence Interval [CI]: 2.214-2.523). Once this threshold is surpassed, the effect of tumor size on LNM incidence levels off (OR = 1.031, 95% CI: 1.003-1.061). The results of this study confirm that tumor size significantly determines the likelihood of LNM in patients with PTC. We found an inverse l-shaped relationship between tumor size and the probability of LNM. As the tumor size increased below 1.978 cm, the likelihood of LNM increased, but not with tumor size above that threshold. These findings provide new insights into the complex relationship between tumor size and LNM in PTC.

Novel submucosal injection material comprising fully synthetic and self-assembling peptide solution in endoscopic submucosal dissection: A pilot study

Endoscopic submucosal dissection (ESD) requires an injection solution to create a submucosal cushion for safe endoscopic resection. This study evaluated the safety and feasibility of a new injection solution (PuraLift) in ESD for early-stage gastrointestinal tumors. This prospective, single-arm, single-center pilot study included eleven patients with gastrointestinal neoplasms of the stomach (n=5) or colorectum (n=6) who underwent ESD. All patients underwent outpatient follow-up at week 4 to confirm the presence or absence of adverse events. All underwent protocol treatment and post-treatment follow-up. None of the adverse events were judged to have a cause-and-effect relationship with the study. Questionnaires to the operators who performed the protocol treatment and assistants who performed submucosal injections were evaluated in comparison to saline, and maintenance of mucosal lifting was long, comparable, and short (9/2/0). En bloc and R0 resections were achieved in all patients without intraprocedural adverse events. The median size of the specimens was 40 (range, 20–70) mm. The median excision time was 52 (range, 22–130) min. The median volume of PuraLift was 32 (range, 22–130) mL. No postoperative bleeding or delayed perforation was observed in any patient. The novel injectable material, PuraLift, can potentially ensure safe and feasible in ESD.

Abstract PR013: Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers

Abstract Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide, and early detection is critical for successful treatment and improved survival rates. However, precancerous and early-stage CRC present significant diagnostic challenges due to the small size of lesions and the very low expression of tumor-specific biomarkers in the bloodstream. Current genomics-based diagnostic methods struggle to detect these lesions, making it imperative to develop more sensitive and specific approaches. Circulating extracellular vesicles (EVs) are emerging as a promising solution for early-stage CRC detection, since EVs are produced by tumor cells as well as the tumor microenviroment and host immune cells. Thus, EVs may offer the means to detect and monitor small early-stage tumors through both direct detection of tumor- associated biomarkers as well through tumor specific host response and tumor microenvironment biomarkers. Methods: To identify novel early-stage CRC specific biomarkers, we performed proteomics analysis on EVs purified from patient plasma using size exclusion chromatography and a proprietary buffer system that enhances EV and corona protein recovery. TrueDiscovery™ Data-independent acquisition (DIA) mass spectrometry (MS) analysis was conducted on 24 pre- cancer/stage 0 and 25 stage 1 CRC patients and 75 normal patient plasma samples. An in-house developed machine learning pipeline was used to identify differentially expressed proteins and model candidate multiplexes to identify those with extremely high diagnostic accuracy (> 0.99). Results: An average of ∼2,500 proteins were identified per sample and included in bioinformatics analysis. Comparative analysis between control patient EVs and either pre- cancerous/Stage 0, or Stage 1 colon cancer EVs using an in-house Machine Learning pipeline identified 336 and 493 differentially expressed proteins for each group (FDR adjusted p-value < 0.001). Of these, the best 17 pre/stage 0 proteins and 53 stage 1 proteins were trained and tested using Support Vector Machine to assess all potential 3-plexes in order to identify those with mean diagnostic accuracy > 99%. This yielded 5 3-plexes in precancer/stage 0 and 34 3-plexes in stage 1 with near perfect diagnostic accuracy. These plexes are currently being assessed in single analyte and multiplex immunoassays with the goal of translating candidate 3-plexes to the clinical. Conclusions: Key biomarkers from CRC patient EVs indicate the potential to detect and diagnose early-stage and low tumor burden cancers using our methods. Interestingly, the most accurate 3-plexes consist of proteins from immune, inflammatory and metabolic processes, suggesting that for the detection of early stage cancer it may be critical to include both tumor and host specific biomarkers. Citation Format: Poorva Mudgal, Cheryl Bandoski, Zachary Opheim, Martin Mehnert, Valesca Anschau, Issa Isaac, Alan Ezrin, Todd Hembrough. Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR013.

Abstract IA007: Modulating cfDNA biology to enhance liquid biopsies

Abstract Liquid biopsies could transform cancer care but require higher sensitivity to detect early-stage tumors and minimal residual disease (MRD) and to enable tumor molecular profiling and therapy response monitoring for most patients. In this talk, I will focus on the significant biological bottlenecks upstream of cell-free DNA (cfDNA) testing. I will posit that in many circumstances, insufficient circulating tumor DNA (ctDNA) drawn in a blood tube cannot be overcome by assay technology alone, and that in vivo modulation of cfDNA biology may also be required to enhance liquid biopsies. Inspired by widespread use of diagnostic drugs in other areas of medicine, we sought to create the first “priming agents” for liquid biopsies that could be administered before a blood draw to recover more ctDNA. I will describe two such approaches—a monoclonal antibody against double-stranded DNA and a liposome nanoparticle—that briefly attenuate cfDNA clearance by shielding it from nuclease digestion and cellular uptake. These enabled >10x more ctDNA to be collected when administered within 1-2 hours of a blood draw in mice. This improved the analytical limit of detection for ctDNA testing by >10-fold, provided more complete representation of the tumor genome in each blood sample, and increased the sensitivity for detection of small tumors from <10% to >75% in mice. Envisioning a future where liquid biopsies are optionally enhanced with priming, I will also explore a unique potential pairing with our tumor-informed, whole-genome, mutation enrichment sequencing MRD test called MAESTRO, and how it stands to enable routine ctDNA detection below 1 part per million. Citation Format: Viktor Adalsteinsson. Modulating cfDNA biology to enhance liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA007.

Late Local Recurrence of Carcinoma <i>in situ </i>- Only Bladder Cancer

Late recurrence (LR) of bladder cancer after radical cystectomy (RC) is rare, and few studies have been conducted. We report a case of local LR of bladder cancer 10.3 years after RC. The pathology at RC was almost carcinoma <i>in situ</i> (CIS) only. The patient underwent metastasectomy, and treatment with an immune checkpoint inhibitor (ICI) achieved a complete response (CR). A 61-year-old woman was referred to our hospital for macrohematuria and bladder irritability in June 2012. She underwent RC along with pelvic lymph node dissection and ileal conduit creation. The pathologic findings were CIS, G2>G3, pT1, pN0. She visited our hospital with complaints of lower abdominal discomfort in November 2022, and recurrence was found on the pelvic floor by abdominal computed tomography. Metastasectomy confirmed metastasis of urothelial carcinoma. As salvage therapy, systemic chemotherapy with a platinum agent and an ICI were administered, leading to CR. Long-term follow-up should be considered for patients with bladder cancer, even for early-stage CIS-only tumors. Metastasectomy could be the primary option for LR of bladder cancer after RC.

Mammography In Breast Cancer Screening – Current Knowledge, Challenges, The Impact of Artificial Intelligence, And Effectiveness With A Focus On Poland

Mammography is a critical tool in breast cancer screening and secondary prevention, enabling early detection and significantly reducing breast cancer mortality. This literature review assesses the effectiveness of mammography in identifying early-stage tumors, discussing its advantages, limitations, and specific challenges. Additionally, advancements in imaging techniques, such as 3D tomosynthesis, are examined, especially for their enhanced sensitivity in women with dense breast tissue, which reduces structural overlap and improves diagnostic precision. The integration of artificial intelligence (AI) in mammographic image analysis opens new opportunities, supporting radiologists by automating the detection and classification of potential lesions, thereby increasing screening efficiency and reducing false-positive rates. However, effective implementation of AI requires seamless integration with clinical systems and ongoing research to refine algorithms for diverse clinical needs. Furthermore, legal frameworks are essential to delineate responsibility in AI-supported diagnostics. This review emphasizes the status of breast cancer screening in Poland, where participation rates remain low despite the availability of free screenings. This highlights the need for improved public awareness and accessibility, especially in underserved areas. Overall, the findings underscore the fundamental role of mammography in breast cancer detection, with AI and other technological advancements significantly enhancing diagnostic accuracy while identifying areas for further improvement.

TMIC-30. FOREBRAIN TO HINDBRAIN INVASION IN GLIOBLASTOMA IS DIRECTED BY ANATOMICALLY DISTINCT REACTIVE ASTROCYTES

Abstract Initial detection of glioblastoma (GBM) often reveals a large mass in the forebrain; however, the hazard for many patients lies in extensive invasion that can extend far from the primary tumor. New evidence suggests that end-stage GBM coincides with malignant infiltration of the pons and brainstem. Mechanisms that direct tumor cells from initial positions within the forebrain to terminal positions in the brainstem are largely unknown. Our analysis indicates that spatially defined, reactive astrocytes instruct GBM cells to either proliferate or invade. During development, astrocytes help establish directional gradients and boundaries that mediate proper routing of migrating neural cells and extending axons. We posit that onco-reactive astrocytes re-engage these guidance programs to direct tumor cells to the brainstem. To test this hypothesis, we exposed a series of human GBM models to media conditioned by cortical, midbrain, or brainstem reactive astrocytes. When treated with cortical conditioned media, tumor cells were driven into a state of hyper-proliferation, which mirrored early-stage forebrain tumor generation. In contrast, midbrain and brainstem conditioned medias suppressed proliferation and enhanced the rate of tumor cell migration. RNA sequencing corroborated these functional data, identifying cell division programs augmented in GBM cells exposed to cortical astrocyte conditioned media. This contrasted with axon development and guidance programs enriched in GBM cells exposed to midbrain and especially brainstem conditioned medias. Finally, mRNA and protein analysis identified region-specific engagement with the Eph-ephrin guidance system patterned along a forebrain to hindbrain trajectory. These data support a new hypothesis that GBM tumors recapitulate a form of neurodevelopment, invading specific anatomic regions based on cues generated by resident reactive astrocytes.

Meta-analysis reveals an inverse relationship between Alzheimer’s disease and cancer

Recent reports have suggested an inverse relationship between Alzheimer's disease (AD) and cancer, although the underlying mechanism remains unclear. We performed an epidemiological meta-analysis to assess cancer likelihood in AD patients and vice versa and explored the role of APOE in tumor immunity across 33 The Cancer Genome Atlas (TCGA) cancer types. Our analysis revealed that people with AD are epidemiologically less likely to develop cancer than individuals without AD (RR: 0.53), and cancer patients are less likely to develop AD than non-cancer patients (RR: 0.61). Notably, APOE expression was positively associated with anti-tumor immune signatures and prevalent in early-stage tumors. This research reveals that AD patients are less likely to develop cancer and vice versa, pinpoints APOE gene as a risk factor for AD with anti-tumor activity, and provides new insight into the epidemiologically observed inverse relationship between both diseases.

Optimal Treatment Strategies for Early-Stage Primary Mediastinal Germ Cell Tumors

Data on optimal therapy for patients with primary mediastinal germ cell tumors consist overwhelmingly of single-institution studies with small sample sizes. The objective of this study is to assess the association of survival outcomes with surgery vs non-operative management for patients with early-stage primary mediastinal germ cell tumors. Overall survival of all patients with seminomas and non-seminomatous primary germ cell tumors in the mediastinum who received 1) chemotherapy, or 2) surgery with or without chemotherapy (referred to as 'surgery' for simplicity) for early-stage disease from 2004-2015 in the National Cancer Database was assessed using Kaplan-Meier analysis, propensity score-matched analysis, and multivariable Cox proportional hazards analysis. Among patients with seminomas, chemotherapy alone was used in 120 (80.5%) patients and surgery was used in 29 (19.5%) patients. There was no significant difference in 5-year survival between surgery and chemotherapy in unadjusted and propensity score-matched analysis. Among patients with non-seminomatous tumors, chemotherapy alone was used in 91 (46.7%) patients and surgery was used in 104 (53.3%) patients. Surgery was associated with improved 5-year survival when compared to chemotherapy in unadjusted, and multivariable-adjusted, and propensity score-matched analysis. In this national analysis, multimodality treatment involving surgery was associated with improved survival when compared to chemotherapy alone for early-stage primary mediastinal non-seminomatous germ cell tumors. For seminomas of the mediastinum, chemotherapy was associated with similar long-term outcomes when compared to multimodality treatment involving surgery.

Postoperative Outcome And Complications Among Peritoneal Carcinomatosis Patients

Introduction: Peritoneal carcinomatosis is a recurrence pattern in gastric cancer, commonly complicating the postoperative course, especially in high-risk individuals. These complications adversely affect quality of life, increase mortality, and have immediate postoperative clinical implications. Surgery is the best treatment for early-stage tumors, despite its associated risks, including mortality. Aim: To evaluate the impact of postoperative complications on the clinical outcomes of patients undergoing peritoneal cancer surgery. Methods: This cross-sectional observational study was conducted at the National Institute of Cancer Research and Hospital, Dhaka, Bangladesh, over twenty-one months from July 2017 to March 2019. Forty-two patients were selected based on inclusion and exclusion criteria and diagnosed clinically, radiologically, and histopathologically. Data were collected using a structured case record form and analyzed using SPSS-22. Results: The mean age of participants was 66.19 ± 10.38 years, with 33.3% aged 56-65 years. The cohort included 64.3% males and 35.7% females, with 52.4%, 40.5%, and 7.1% having a BMI of 18.5-24.9 kg/m², 25- 30 kg/m², and >30 kg/m², respectively. Smoking and betel leaf use were common (61.9% and 83.3%, respectively), with 69% from the middle class. Tumors primarily involved the proximal and distal stomach, with a mean size of 6.20 ± 1.86 cm, predominantly Type 3 and Type 4, and stages T4a and N2. No metastasis was observed. Total and lower radical gastrectomies were performed, with complications occurring in 9.5% (chest infection) and 14.3% (wound infection), while 76.2% had no complications. Conclusion: Complications can serve as indicators of postoperative clinical outcomes. The findings highlight the need for systemic changes in healthcare to reduce postoperative morbidity and mortality, thereby decreasing hospital stays.

Esophageal cancer: new developments in prevention and therapy

Esophageal carcinomas comprise 2 entities, squamous cell carcinoma and adenocarcinoma, which differ in pathogenesis and treatment. Elimination of inflammatory influences and risk factors, such as obesity and gastroesophageal reflux that contribute to a rising incidence of adenocarcinoma, is crucial for tumor prevention. In Germany, general endoscopic screening for upper GI tumors is not recommended, whereas endoscopic surveillance is applied in the presence of Barrett's metaplasia. In the future, better prediction models will be needed to identify patients at risk who will benefit from endoscopic surveillance. Precancerous lesions and early tumor stages can be removed endoscopically using modern resection methods. In recent years, therapeutic strategies for advanced esophageal tumors have undergone significant changes. In the multimodal treatment of locally advanced stages, radiochemotherapy remains to play a key role for squamous cell carcinoma, whereas new evidence highlights the importance of perioperative chemotherapy for the optimal management of adenocarcinoma. Systemic treatment options for both tumor entities have been significantly expanded due to the successful use of immune checkpoint inhibitors in adjuvant and palliative treatment regimen. Determination of PD-L1 and MSI status has therefore become decisive for the choice of therapy. In metastatic stages of adenocarcinoma, chemotherapy can now be supplemented by multiple antibodies directed against Her2, PD1, or claudin 18.2, and the antibody-drug conjugate trastuzumab deruxtecan has become a Her2-targeted option in second line treatment.

Recommendation for Clinical T Staging in Patients with Non-Small Cell Lung Cancer: Volumetric Measurement: A Retrospective Study from Turkey.

Currently, clinical T staging in non-small cell lung cancer (NSCLC) is based on the largest radiological diameter observed on computed tomography (CT). Under this system, tumors with varying shapes-such as spherical, amorphous, or spiculated tumors- can be assigned the same T stage even with different volumes. We aimed to propose a 3-dimensional (3D) volumetric staging system for NSCLC as an alternative to diameter-based T staging and to conduct comparative survival analyses between these methods. We retrospectively analyzed data from patients who underwent surgery for pT1-4N0M0 primary NSCLC between January 2018 and May 2022. Digital Imaging and Communications in Medicine data from patient CT scans were uploaded to 3D Slicer software for volumetric tumor measurement. Using the paired samples t-test or the Wilcoxon test, we compared the expected tumor volumes, calculated by tumor diameter, with the actual volumes measured by 3D Slicer. Receiver operating characteristic analysis was employed to determine the cut-off value for tumor volume. Kaplan-Meier analysis was utilized to assess overall survival, while the log-rank method was applied to compare survival differences between groups. The significance of changes in T stage was evaluated using the marginal homogeneity test. The study included 136 patients. Significant differences were observed between expected and actual tumor volumes (p=0.01), and associated changes in T stage were also significant (p=0.04). The survival analysis performed using tumor volume (p=0.009) yielded superior results compared to that based on diameter (p=0.04) in paients with early tumor stage. T-factor staging based on tumor volume could represent an alternative staging method for NSCLC.

Psychological Well-Being and Quality of Life in Laryngeal Cancer Patients across Tumor.

Background/Objectives: Laryngeal cancer significantly impacts patients' psychological well-being and quality of life (QoL). This study aims to evaluate the psychological impact and QoL in patients with laryngeal cancer, focusing on differences based on tumor stage and treatment. Methods: This longitudinal study included 75 patients diagnosed with laryngeal cancer. Participants were assessed at diagnosis and 3 months post-treatment using validated tools such as the Hospital Anxiety and Depression Scale (HADS) and the EORTC QLQ-H&N35 questionnaire. This study analyzed the impact of tumor stage, treatment type, and demographic factors on psychological well-being and QoL. Results: Patients with early-stage tumors (Stage I) reported significantly better psychological well-being and QoL compared to those with more advanced tumors (Stages III and IV) both before and after treatment. The non-significant p-values in advanced stages suggest a uniformity of severe distress and poor QoL among these patients. Treatment led to significant reductions in anxiety and depression in early-stage patients, while those with advanced-stage disease showed less improvement. Conclusions: The findings highlight the critical need for early psychological intervention, particularly in advanced-stage laryngeal cancer patients who continue to experience substantial psychological distress and poor QoL despite treatment. Integrating comprehensive psychological support into standard care is essential to improve overall outcomes for these patients.

Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis

Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.

Comparing Closure Techniques for Pharyngeal Mucosa After Total Laryngectomy: Manual Suture, Linear Stapler, and Thyroid Gland Flap-A Retrospective Analysis.

Objective: This study aimed to compare the clinical effectiveness of manual suture (group A), linear stapler (group B), and thyroid gland flap (group C) for pharyngeal mucosal closure after total laryngectomy (TL) in laryngeal cancer patients. Methods: The data of laryngeal cancer patients who underwent TL between January 1, 2017, and December 1, 2021, were analyzed. Patients were categorized into group A, group B, and group C based on the closure technique. Various parameters, including general data, hospitalization days, total cost, pharyngeal closure time, pharyngeal fistula, pre- and post-surgical calcium levels, and thyroid function indexes, were compared. Results: The study included 81 patients (mean age: 64.09 ± 9.20 years), the general data of the 3 groups of patients were comparable. Tumor stage and primary tumor location varied significantly among the groups (P = .002 and P < .001, respectively). Group A was more commonly used for advanced-stage tumors with widespread invasion. Group B was primarily used for early-stage tumors localized to the larynx. Group C was preferred for cases with mucosal defects or extensive hypopharyngeal invasion. Group B presented a significantly shorter operation time and slightly lower total cost (P = .006). Pharyngeal fistula incidence was 17.28% (14/81), with comparable rates among the groups [12.35% (10/50) in group A, 12.5% (2/16) in group B, and 13.3% (2/15) in group C]. No dysphagia complications were observed during the 2-to-5-year follow-up. Blood calcium levels and thyroid function indicators showed no significant differences before and after surgery among the 3 groups (P > .05). Conclusion: Thyroid gland flap is a safe option that can be used to repair mucosal defects and close the pharyngeal cavity after TL surgery, but in the absence of mucosal defects and widespread tumor invasion, linear staplers are the most time-efficient method.

Enhanced anti-tumor efficacy of electroporation (EP)-mediated DNA vaccine boosted by allogeneic lymphocytes in pre-established tumor models

BackgroundTumor-reactive T cells play a crucial role in anti-tumor responses, but T cells induced by DNA vaccination are time-consuming processes and exhibit limited anti-tumor efficacy. Therefore, we evaluated the anti-tumor effectiveness of reactive T cells elicited by electroporation (EP)-mediated DNA vaccine targeting epidermal growth factor receptor variant III (pEGFRvIII plasmid), in conjunction with adoptive cell therapy (ACT), involving the transfer of lymphocytes from a pEGFRvIII EP-vaccinated healthy donor.MethodsThe validation of the established pEGFRvIII plasmid and EGFRvIII-positive cell model was confirmed through immunofluorescence and western blot analysis. Flow cytometry and cytotoxicity assays were performed to evaluate the functionality of antigen-specific reactive T cells induced by EP-mediated pEGFRvIII vaccines, ACT, or their combination. The anti-tumor effectiveness of EP-mediated pEGFRvIII vaccines alone or combined with ACT was evaluated in the B16F10-EGFRvIII tumor model.ResultsEP-mediated pEGFRvIII vaccines elicited serum antibodies and a robust cellular immune response in both healthy and tumor-bearing mice. However, this response only marginally inhibited early-stage tumor growth in established tumor models. EP-mediated pEGFRvIII vaccination followed by adoptive transfer of lymphocytes from vaccinated healthy donors led to notable anti-tumor efficacy, attributed to the synergistic action of antigen-specific CD4+ Th1 cells supplemented by ACT and antigen-specific CD8+ T cells elicited by the EP-mediated DNA vaccination.ConclusionsOur preclinical studies results demonstrate an enhanced anti-tumor efficacy of EP-mediated DNA vaccination boosted with adoptively transferred, vaccinated healthy donor-derived allogeneic lymphocytes.

Predictive Significance of Combined Plasmatic Detection of BRAF Mutations and S100B Tumor Marker in Early-Stage Malignant Melanoma.

Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.

Stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system: a systematic review and meta-analysis.

To summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0. A total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size ≥4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node ≥ 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1. The migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions. CRD 42023451793.