Advanced Tumor Stage Research Articles

Tumor growth and vascular redistribution contributes to the dosimetric preferential effect of microbeam radiotherapy: a Monte Carlo study

The radiobiological mechanisms behind the favorable response of tissues to microbeam radiation therapy (MRT) are not fully described yet. Among other factors, the differential action to tumor and normal tissue vasculature is considered to contribute to MRT efficacy. This computational study evaluates the relevance of tumor growth stage and associated vascular redistribution to this effect. A multiscale approach was employed with two simulation softwares: TOPAS and CompuCell3D. Segmentation images of the angioarchitecture of a non-bearing tumor mouse brain were used. The tumor vasculature at different tumor growth stages was obtained by simulating the tumor proliferation and spatial vascular redistribution. The radiation-induced damage to vascular cells and consequent change in oxygen perfusion were simulated for normal and tumor tissues. The multiscale model showed that oxygen perfusion to tissues and vessels decreased as a function of the tumor proliferation stage, and with the decrease in uniformity of the vasculature spatial distribution in the tumor tissue. This led to an increase in the fraction of hypoxic (up to 60%) and necrotic (10%) tumor cells at advanced tumor stages, whereas normal tissues remained normoxic. These results showed that tumor stage and spatial vascular distribution contribute to the preferential effect of MRT in tumors.

Oncological outcomes of organ-sparing cystectomy versus standard radical cystectomy in male patients diagnosed with bladder cancer.

To compare the oncological outcomes between standard radical cystectomy (SRC) and organ-sparing cystectomy (OSC) in male patients diagnosed with bladder cancer. Patients with stage Ta-T3 bladder cancer who underwent OSC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The association between preoperative factors and the implementation of OSC was analyzed using logistic regression. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Patients' overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Subgroup analyses based on the T stage were also conducted. A total of 7264 patients were included, with 96.8% (7033 patients) receiving SRC and 3.2% (231 patients) receiving OSC. Patients with higher T stages and high-grade tumors were less likely to undergo OSC. After PSM, OSC was associated with significantly worse OS and CSS than SRC. Subgroup analysis revealed that OSC did not lead to worse OS and CSS in non-muscle invasive bladder cancer and T2 stage patients, but it resulted in significantly worse outcomes in T3 stage patients. Our study indicates that OSC is associated with poorer oncological outcomes compared to SRC, particularly in patients with advanced-stage tumors. These findings suggest the need for stringent selection criteria for OSC in bladder cancer patients. Given the negative impact on prognosis, stage T3 should potentially be considered a contraindication for OSC. Further evidence is required to confirm these assertions.

Homologous recombination deficiency score is an independent prognostic factor in esophageal squamous cell carcinoma.

Homologous recombination deficiency (HRD) represents an impairment in the homologous recombination repair (HRR) pathway, crucial for repairing DNA double-strand breaks and contributing to genomic instability in cancer. The HRD score may be a more reliable biomarker than HRR-related gene mutations for identifying patients sensitive to poly(ADP-ribose) polymerase inhibitors. Despite its relevance in various cancers, the HRD score remains underexplored in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed HRD scores in 96 ESCC patients, examining correlations with clinical characteristics and survival outcomes, and validated our findings using the TCGA dataset. Genomic sequencing utilized a custom superHRD next-generation sequencing panel, and HRD scores were calculated from 54,000 single-nucleotide polymorphisms using Kruskal-Wallis rank-sum tests and two cut-off points for analysis. Higher HRD scores correlated with advanced tumor stages, recurrence, and mutations in TP53 and ABCB1, while APC mutations were linked to lower HRD scores. Patients with high HRD scores had significantly shorter disease-free survival (p = 0.013) and a trend toward shorter overall survival (OS) (p = 0.005), particularly those not receiving adjuvant therapy. Conversely, HRD-high patients undergoing adjuvant therapy showed a trend toward longer OS (p = 0.015). Multivariate analysis identified HRD as an independent prognostic factor (hazard ratio = 2.814 for recurrence, p = 0.015). Validation with the TCGA dataset supported these findings. This study highlights the associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, suggesting HRD as a potential prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies, warranting further investigation to validate the therapeutic implications of HRD scores in ESCC.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed and Cox regression analysis was performed to identify risk factors. The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion. EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain.

Dynamic Anthropometrics in Pancreatic Cancer: Associations Between Body Composition Changes During Neoadjuvant Therapy and Survival Outcomes After Resection.

Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown. A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses. The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p=0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p=0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p=0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage. Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy.

Analysis of Swallowing Functional Preservation by Surgical Versus CRT After Induction Chemotherapy for Oropharyngeal Cancer

Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group.

Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma

Although the initial research focused on glycolysis, mitochondrial oxidative phosphorylation has become a major target of cancer cells. Cytochrome C oxidase assembly factor 6 (COA6) is a conserved assembly factor necessary for complex IV biogenesis. Nevertheless, the clinical predictive value of COA6, especially its correlation with immune cell infiltration in lung adenocarcinoma (LUAD), has not yet been elucidated. COA6 exhibited higher expression levels in LUAD cells and tumor tissues compared to normal tissues. Additionally, heightened COA6 expression was associated with reduced overall survival (OS) and advanced tumor stage. Apart from its role in mitochondrial respiratory processes, COA6 may be involved in the process of antigen binding, immunoglobulin receptor binding. Interestingly, we observed a positive correlation between COA6 expression and tumor mutational burden (TMB), as well as a significant association with decreased immune cell infiltration. COA6 was linked to resistance against gemcitabine and etoposide. We verified that COA6 was highly expressed in LUAD experimentally and cell proliferation was inhibited after COA6 knockdown. Thus, we conclude that the expression of COA6 was correlated with reduced immune cell infiltration. Additionally, COA6 functioned as a biomarker for drug sensitivity and the prognosis of lung adenocarcinoma.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer.

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

Promise and challenges of traditional Chinese medicine, specifically Calculus bovis, in liver cancer treatment

Liver cancer, one of the most common malignancies worldwide, ranks sixth in incidence and third in mortality. Liver cancer treatment options are diverse, including surgical resection, liver transplantation, percutaneous ablation, transarterial chemoembolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and traditional Chinese medicine (TCM). A multidisciplinary team (MDT) is essential to customize treatment plans based on tumor staging, liver function, and performance status (PS), ensuring individualized patient care. Treatment decisions require a MDT to tailor strategies based on tumor staging, liver function, and PS, ensuring personalized care. The approval of new first-line and second-line drugs and the establishment of standard treatments based on immune checkpoint inhibitors have significantly expanded treatment options for advanced liver cancer, improving overall prognosis. However, many patients do not respond effectively to these treatments and ultimately succumb to the disease. Modern oncology treatments, while extending patient survival, often come with severe side effects, resistance, and damage to the body, negatively impacting quality of life. Huang et al 's study published at World Journal of Gastroenterology rigorously validates the anticancer properties of Calculus bovis , enhancing our understanding of TCM and contributing to new liver cancer treatment strategies. For over 5000 years, TCM has been used in East Asian countries like China to treat various diseases, including liver conditions. Analysis of real-world clinical data suggests that for patients with advanced-stage tumors lacking effective treatments, integrated TCM therapies could provide significant breakthroughs.

Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer

BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Treatment regimens for laryngeal and hypopharyngeal squamous cell carcinoma: a "real life" multicenter study of 2307 patients.

This retrospective multicenter study aimed to evaluate surgical versus conservative treatment in patients with hypopharyngeal and laryngeal cancer under real world conditions. This study included 2307 patients diagnosed with hypopharyngeal or laryngeal squamous cell carcinoma (SCC) in five German tertiary head and neck centers between 01/2004 and 12/2014. Overall, 783 patients with advanced SCC consecutively underwent laryng(opharyng)ectomy (L(P)E). Patient chart data regarding age, sex, tumor location, TNM status, grading, indication for L(P)E, treatment modalities, R status, postoperative complications, and hospitalization time were analyzed. Patients with lacking data and incomplete staging and those who refused treatment or did not comply with the recommended treatment were excluded from survival analysis. A slight but significant increase was observed in L(P)E, referring to an increasing rate of tumor recurrence. While T1/2N0M0 laryngeal and hypopharyngeal cancer patients showed comparable overall survival (OS) for surgical and conservative treatment, surgery showed significantly better OS in lymph node-positive individuals and locally advanced tumor stages. Tumor recurrence occurred in more than one-third of the cases. In particular, in early glottic cancer recurrence, L(P)E represents a curative and safe treatment option, whereas in supraglottic and hypopharyngeal cancer, L(P)E was associated with reduced survival rates. Notably, 36% of patients with supraglottic cancer and 59% of patients with hypopharyngeal cancer recurrence could only be treated with palliative care. Comparable survival rates were demonstrated for cT1/2N0M0 laryngeal and hypopharyngeal SCC compared with primary chemo-/radiotherapy and larynx-preserving surgery. Better OS was achieved after surgery in nodal-positive patients and in those with locally advanced disease. Tumor recurrence should be anticipated in up to 39% of cases. Glottic cancer recurrence can be successfully and safely treated with L(P)E, whereas OS is reduced in hypopharyngeal cancer and possibly in supraglottic cancer.

Serum Exosomal MiR-874 as a Potential Biomarker for Nonsmall Cell Lung Cancer Diagnosis and Prognosis

AbstractLung cancer, primarily nonsmall cell lung cancer (NSCLC), is a leading cause of cancer-related fatalities globally. Due to late detection, the 5-year survival rate for NSCLC remains low. Therefore, the current research aimed to assess the diagnostic and prognostic value of serum exosomal miR-874 levels in NSCLC patients. This study involved 161 NSCLC patients and 80 control subjects. Blood samples were collected from all participants, and serum exosomal MiR-874 levels were quantified using quantitative reverse transcription-polymerase chain reaction. The study revealed a significant decrease in MiR-874 levels among NSCLC patients compared to controls. The receiver operating characteristic analysis demonstrated the diagnostic value of serum exosomal MiR-874 in effectively distinguishing NSCLC patients from controls.Furthermore, associations were observed between serum exosomal MiR-874 expression and adverse clinical factors such as young age, male sex, smoking, high tumor grade, squamous cell carcinoma histopathology, advanced tumor stage, and lymphatic involvement. Patients with high levels of MiR-874 had significantly longer overall and disease-free survival compared to those with lower levels. The study demonstrates that levels of serum exosomal miR-874 are considerably lower in NSCLC patients, indicating its potential as a diagnostic biomarker. The study's findings suggest that the expression of MiR-874 may predict the prognosis of NSCLC patients based on clinical features.

The Prognostic Impact of Tumor Size and BRAF Mutational Status in Middle Eastern Differentiated Thyroid Cancer.

Tumor size at diagnosis has been widely used as a major mortality risk factor in risk stratification of DTC. The current study was designed to analyze whether tumor size at diagnosis is a major prognostic factor in Middle Eastern DTC. We conducted a comparative study of the relationship between tumor size at diagnosis and event free survival (EFS) with respect to BRAF status in 1709 consecutive patients treated surgically for DTC. Patients were divided into four groups according to the size of tumor and BRAF mutation status: Group 1 (≤4 cm without BRAF mutation), Group 2 (≤4 cm with BRAF mutation), Group 3 (>4 cm without BRAF mutation) and Group 4 (>4 cm with BRAF mutation). Predictors of EFS were compared using the Log-rank test and Cox proportional hazards models. Tumor size >4cm was associated with adverse clinico-pathologic characteristics, such as older age, male gender, bilateral tumors, extrathyroidal extension, lymphovascular invasion, advanced tumor stage and persistent/recurrent disease. Tumor size was also inversely associated with BRAF mutation. Both tumor size (> 4cm) and BRAF mutation were associated with EFS on univariate analysis. On subgroup analysis, larger tumor size was an independent predictor of EFS (Group 3 vs. Group 1), irrespective of BRAF mutation status. Also, within the BRAF mutant tumors, larger tumor size was still an independent predictor of EFS (Group 4 vs. Group 2). Tumor size is an independent predictor of EFS in Middle Eastern DTC patients, regardless of BRAF mutational status.

Hypermethylation of the sodium channel beta subunit gene promoter is associated with colorectal cancer

AimsTo better understand the role of sodium channel beta subunit (SCNN1B) in the initiation and progression of colorectal cancer (CRC) and to identify potential biomarkers for the early detection and prognosis of CRC.MethodsA total of 74 pairs of CRC tissues and their adjacent normal tissues were collected between October 2016 and November 2017. The methylation levels of the SCNN1B promoter region in CRC tissues and their adjacent normal tissues were investigated by pyrosequencing. The expression of both SCNN1B mRNA and protein were detected by RT‒qPCR and immunohistochemistry, respectively.ResultsThe results showed that the methylation levels of the SCNN1B promoter region were significantly higher in CRC tissues than in adjacent normal tissues. The expression levels of SCNN1B mRNA and protein were significantly lower in the CRC tissues than in their adjacent normal tissues. Moreover, Pearson’s correlation analysis showed that the methylation levels of the SCNN1B promoter were negatively correlated with the SCNN1B mRNA levels in CRC tissues. In addition, the high methylation levels and low mRNA expression of SCNN1B showed a significant association with advanced tumour stage, increased risk of lymph node metastasis and poor prognosis of CRC patients.ConclusionThis study suggested that the decreased expression of SCNN1B due to its promoter hypermethylation may play an important role in the progression and prognosis of CRC, and the methylation levels of the SCNN1B promoter may serve as an effective molecular marker for predicting the progression and prognosis of CRC.

Retrospective Evaluation of GEC-ESTRO Constraints for Definitive Radiochemotherapy with Brachytherapy and Correlation with Oncologic Outcome in Cervical Cancer: A Monocenter Study.

This study aims to evaluate patients with locally advanced cervical cancer who underwent definitive radiochemotherapy, including brachytherapy, at the University Hospital of Muenster (UKM), focusing on target volume coverage, oncologic outcome parameters, and organs at risk (OAR) toxicities. Results are compared with the Gyn GEC-ESTRO (GGE) recommendations. Of a cohort of 48 patients, treated between 2013 and 2023, the physical radiation treatment planning with application of CT and MRI and oncologic follow-up data was analyzed. Target volume structures, comprising the high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), Point A, and corresponding EQD2(α/β=10) doses were determined. Endpoints included local tumor control, overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Total OAR (D2cc) EQD2(α/β=3) doses were correlated with adverse events defined by CTCAE v5.0 and LENT-SOMA criteria. Median follow-up was 58.0 months (95% CI [27.6, 88.4]). FIGO stage I was present in 7 (15%) patients, II in 13 (27%), and III in 28 (58%) patients. A total of 38 (79%) patients showed a complete remission 3 months after treatment. The 5-year event-free rate was 67.4% (95% CI [49.3, 80.3]) for OS, 77.0% (95% CI [56.7, 88.6]) for RFS and 68.1% (95% CI [49.7, 80.9]) for PFS. Incomplete radiation treatment and advanced tumor stages led to worse outcomes. Meeting Point A GGE recommendations increased chances for complete remission and could decrease chances of an event occurring for OS, PFS, and RFS. Compliance with GGE recommendations lowered the chances of OAR toxicity occurring. MRI-based target volume definition for brachytherapy in cervical cancer may improve patients' OS, PFS, and RFS. Time-to-event endpoints are consistent with comparable studies, and adherence to current ESGO/ESTRO/ESP guidelines is endorsed.

Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study

Introduction Although relatively uncommon, osteoradionecrosis (ORN) remains a serious complication following radiotherapy. Various therapeutic approaches, including hyperbaric oxygen therapy (HBOT), are utilized in managing ORN. This study aims to evaluate the role of HBOT in ORN management and to identify predictive factors influencing the evolution of head and neck ORN after HBOT. Methods This retrospective study includes 46 patients who received HBOT for head and neck ORN between 2017 and 2020. The patients were divided into two groups: Group 1 (n=36) included those with regression or stabilization of ORN, while Group 2 (n=10) comprised patients with worsening lesions. We performed a statistical study in order to identify factors influencing ORN progression under treatment. Results ORN affected the mandible in 93.5% of patients, the maxilla in 2 cases, and the skull base in 4 cases. All patients received HBOT, with an average of 44.65 sessions. Pre-operative HBOT was administered in 17% of cases, and post-operative HBOT was given in 42% of cases. After at least 20 sessions, ORN regressed in 33% of cases, stabilized in 45%, and worsened in 22%. Analysis of factors influencing ORN progression on the univariate study revealed significant associations with high blood pressure (p=0.046), larger tumor size (p=0.004), advanced tumor stages (p=0.048), mean radiation dose (p=0.002), delays between dental care and radiotherapy (p=0.045), and the location of ORN within the mandible (p=0.049). Additionally, the number of HBOT sessions significantly affected ORN evolution, with more sessions correlating with better outcomes (p=0.001). In the multivariate analysis, variables such as the average interval between dental care and radiotherapy (p=0.043) as well as the number of HBOT sessions (p=0.040) emerged as significant influencers of ORN evolution. Conclusion Our study provides valuable insights into the management of ORN by identifying key predictors that influence the post-therapeutic evolution of head and neck ORN after HBOT.

Identification of PANoptosis Subtypes to Assess the Prognosis and Immune Microenvironment of Lung Adenocarcinoma Patients: A Bioinformatics Combined Machine Learning Study.

PANoptosis, a novelty mechanism of cell death involving crosstalk between apoptosis, pyroptosis, and necroptosis, is strongly associated with tumor cell death and immunotherapy efficacy. However, its relevance in lung adenocarcinoma (LUAD) remains to be elucidated. In this study, we acquired 18 PANoptosis-related differentially expressed gene (PRDEG) of LUAD. Based on these genes, LUAD samples were identified with different sub-types by unsupervised clustering. Next, we compared the differences between the subtypes, including clinical features, immune microenvironment, and potentially sensitive drugs. Further-more, we used machine learning to identify hub prognostic PRDEGs, construct a risk score, and validate it on other external datasets. We incorporated the patient's clinical information and risk score into the proportional hazards model and lasso-cox models to find key prognostic features and constructed five prognostic models. The best model was identified via the area under the curve and validated on an external dataset. LUAD patients were divided into two clusters named C1 and C2, respectively. The C2 cluster exhibited shorter survival time, more advanced tumor stage, higher suppressive immune cell scores, such as dendritic cells, and higher expression of inhibitory immune checkpoints, such as LAG3 and CD86. TIMP1, CAV1, and CD69 were recognized as key prognostic factors, and risk scores predicted survival with significant differences in the external validation set. Risk score and N-stage were identified as critical prognostic features. The Coxph model outper-formed other machine learning clinical models. The 1-, 3-, and 5-year time-ROCs in the exter-nal validation set were 0.55, 0.59, and 0.60, respectively. We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of patients with LUAD as well as the tumor mi-croenvironment.

Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma.

Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin. Based on efficacy and safety data from global pivotal (randomized phase III) clinical studies, TTFields therapy (Optune Gio) is US Food and Drug Administration-approved for newly diagnosed (nd) and recurrent glioblastoma (GBM) and Conformité Européenne-marked for grade 4 glioma. Here we review data on the multimodal TTFields mechanism of action that includes disruption of cancer cell mitosis, inhibition of DNA replication and damage response, interference with cell motility, and enhancement of systemic antitumor immunity (adaptive immunity). We describe new data showing that TTFields therapy has efficacy in a broad range of patients, with a tolerable safety profile extending to high-risk subpopulations. New analyses of clinical study data also confirmed that overall and progression-free survival positively correlated with increased usage of the device and dose of TTFields at the tumor site. Additionally, pilot/early phase clinical studies evaluating TTFields therapy in ndGBM concomitant with immunotherapy as well as radiotherapy have shown promise, and new pivotal studies will explore TTFields therapy in these settings. Finally, we review recent and ongoing studies in patients in pediatric care, other central nervous system tumors and brain metastases, as well as other advanced-stage solid tumors (ie, lung, ovarian, pancreatic, gastric, and hepatic cancers), that highlight the broad potential of TTFields therapy as an adjuvant treatment in oncology.

Predictive value of prognostic nutritional index in patients undergoing gastrectomy for gastric cancer: A systematic review and meta-analysis.

The value of prognostic nutritional index (PNI) in gastrectomy remains controversial. This meta-analysis aimed to evaluate the predictive value of PNI in patients undergoing gastrectomy for malignancy. We retrieved studies from medical literature databases to analyze the endpoints of overall survival, cancer-specific survival, recurrence-free survival, and clinicopathologic features. The hazard ratio (HR) and 95% confidence interval (CI) were used to access the survival prognostic value of PNI in patients after gastrectomy. Odds ratio and mean difference were used to evaluate the relationship between the low PNI and clinicopathologic features. In total, we included 38 articles (39 trial comparisons) which contained 23,756 gastrectomy patients. The results showed that low PNI was associated with shorter overall survival (HR: 1.82, 95% CI 1.62-2.03), shorter cancer-specific survival (HR: 1.44, 95% CI 1.24-1.67), and shorter recurrence-free survival (HR: 2.52, 95% CI 1.41-4.47). Besides, patients with low PNI had a higher risk of postoperative complications compared with high PNI (HR: 1.65, 95% CI 1.30-2.09). And low PNI group was found to be related to older, lower BMI, larger tumor size, deeper tumor invasion, poorer differentiation, more advanced tumor stage, total gastrectomy, and the presence of lymph node metastasis, lymphatic invasion, and vessel invasion. PNI was significantly associated with survival and postoperative complications of gastric cancer patients undergoing gastrectomy. Therefore PNI has the potential to be a prognostic predictor for gastrectomy.