Disease-specific Survival Research Articles

Endoscopic submucosal dissection for superficial esophageal cancer in the remnant esophagus after esophagectomy.

Treatment of esophageal cancer in the remnant esophagus after esophagectomy is highly invasive, therefore, early detection and minimally invasive treatment are considered necessary. Consequently, we aimed to clarify the safety and efficacy of endoscopic submucosal dissection (ESD) for residual esophageal cancer compared to that for esophageal cancer in a normal cervical esophagus. This study involved 47 patients with 59 residual esophageal cancers and 92 patients with 107 cervical esophageal cancers in normal esophagus who underwent ESD between January 2008 and December 2023. Their clinicopathological findings and long-term outcomes were retrospectively collected and evaluated. The median tumor diameter was 13mm, and the median procedure time was 31minutes in remnant esophagus group, with no significant difference between the two groups. No serious complications such as perforation, massive intraoperative bleeding, and pneumonia were observed in the remnant group, except for one case of postoperative bleeding. The rates of complete resection and disease specific survival were not significantly different between two groups, with complete resection rate of 86.4% and 5-year disease-specific survival rate of 95.7% in the remnant esophagus group. No local recurrence was observed during the median observation period of 43months in the remnant esophagus group. ESD for superficial cancer of the remnant esophagus showed a high complete resection rate without serious complications and good local-regional control with no evidence of local recurrence. This indicates that ESD is a safe and useful treatment for superficial cancer of the remnant esophagus.

Impact of the FIGO2023 staging system on endometrial cancer in Japan: differences between next-generation sequencing and simplified surrogate marker analysis.

The International Federation of Gynecology and Obstetrics (FIGO) revised the staging system of endometrial cancer in 2023. In this study, we aimed to determine stage transitions and prognosis of endometrial cancer using FIGO2008, FIGO2023 without molecular classification (FIGO2023), and FIGO2023 with molecular classification (FIGO2023m). Eighty-three patients diagnosed with endometrial cancer who underwent surgery and next-generation sequencing (NGS) molecular profiling as part of the Project HOPE cohort study were enrolled. Each case was staged according to the FIGO2008 and FIGO2023 criteria, and we evaluated changes in stage and disease-specific survival (DSS). Molecular classification based on NGS was performed to evaluate FIGO2023m, and the concordance rate with immunohistochemical marker analysis was assessed. Transitioning from FIGO2008 to FIGO2023 resulted in the restaging of 18 cases. Conversely, transitioning from FIGO2008 to FIGO2023m led to the restaging of 15 cases. The concordance rate between FIGO2023 and FIGO2023m staging was 96.4%. With FIGO2023m, the 5-year DSS was 97.6% for stage I (95% confidence interval [CI] 83.9-99.7), 83.3% for stage II (95% CI 56.8-94.3), 100% for stage III (95% CI NA), and 25.0% for stage IV (95% CI 0.9-66.5). Discrepancies in disease staging due to discordance between simplified surrogate marker analysis and NGS evaluation occurred in two cases. The revision of the staging system from FIGO2008 to FIGO2023 and FIGO2023m resulted in the restaging of several cases, with significant changes between stages I and II.

Pan-cancer exploration of PNO1: A prospective prognostic biomarker with ties to immune infiltration

The partner of NOB1 homolog (PNO1) is an RNA-binding protein that participates in ribosome biogenesis and protein modification. The functions of this molecule are largely unknown in cancers, particularly breast cancer. We employed bioinformatics methods to probe the putative oncogenic functions of PNO1 based on expression profiles and clinical data from the cancer genome atlas (TCGA), genotype-tissue expression project (GTEx), human protein atlas (HPA), cancer cell line encyclopedia (CCLE), UALCAN, drug sensitivity in cancer (GDSC) and UCSC XENA databases. Our analyses revealed that PNO1 was overexpressed in 31 malignancies, which excluded kidney chromophobe (KICH) and acute myeloid leukemia (LAML). Prognostic assessments have demonstrated that high PNO1 expression was significantly correlated with poor overall and disease-specific survival in various cancers. The promoter methylation level of PNO1 is significantly decreased in breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), prostate adenocarcinoma (PRAD), thyroid carcinoma (THCA) and uterine corpus endometrial carcinoma (UCEC). Furthermore, inhibition of PNO1 decreased the viability, migration and invasion of breast cancer cells, and these results were confirmed by mouse xenograft models of breast cancer. In addition, we discovered that tumor microenvironment (TME), immune infiltration, and chemotherapy sensitivity were influenced by PNO1 expression. Concordantly, our analyses revealed a significant positive correlation between PNO1 and programmed cell death ligand 1 (PD-L1) expression across breast carcinoma samples. In conclusion, these findings indicate that PNO1 could act as a promising prognostic biomarker and adjunct diagnostic indicator, because it affects tumor growth and invasion. Our study offers valuable new perspectives on the oncogenic role of PNO1 in various types of cancers.

UBR1 is a prognostic biomarker and therapeutic target associated with immune cell infiltration in gastric cancer.

Ubiquitination is a targeted protein modification process mediated by intracellular molecules. UBR1 encodes a protein that binds to unstable N-terminal residues of substrate proteins and contributes to the formation of substrate-linked polyubiquitin chains. However, the function and cellular pathways of UBR1 in tumors have received inadequate attention. This study aimed to investigate the potential of UBR1 as a prognostic biomarker and immunotherapy target for stomach adenocarcinoma (STAD) as well as its biological function and molecular mechanism in relation to the disease. Differential expression and pan-cancer gene set enrichment analysis (GSEA) were conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx) datasets. The Human Protein Atlas (HPA) database was utilized to identify UBR1-enriched pathways in AGS cells and to compare immunohistochemical differences between cancerous and adjacent non-cancerous tissues in gastric cancer. Quantitative Polymerase Chain Reaction (QPCR) and Western blot (WB) analyses were employed to validate these findings in both cancerous and adjacent non-cancerous tissues of gastric cancer. UBR1 expression in GES-1 and four gastric cancer cell lines was assessed using QPCR and WB. Kaplan-Meier curves, univariate and multivariate Cox regression analyses, and receiver operating characteristic (ROC) curve analyses were performed to evaluate the prognostic and diagnostic roles of UBR1. Additionally, the correlation between UBR1 expression and clinical parameters was analyzed using TCGA and GEO databases. UBR1 mutation data were obtained from the cBioPortal database. The mutation landscape, mutation-associated genes, protein structure, tumor mutation burden (TMB), and microsatellite instability (MSI) correlations were analyzed and illustrated. The biological functions of UBR1 were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The correlation between UBR1 and immune infiltration was assessed using TIMER and EPIC computational methods. Protein expression levels of UBR1 in gastric cancer cell lines were determined by immunohistochemistry (IHC) and WB analysis. Quantitative real-time PCR (qRT-PCR) was employed to analyze mRNA expression. Immunoprecipitation (IP) assays were conducted to detect protein-protein interactions between UBR1 and PDL1, while cellular immunofluorescence was used to observe the co-localization of these proteins. Cell proliferation was evaluated using CCK8 and colony formation assays. Cell migration was assessed using Transwell and wound healing assays. Finally, apoptosis was analyzed using flow cytometry, and WB was used to detect changes in apoptotic proteins and NF-κB P65 pathway proteins. UBR1 was upregulated in 28 cancer types, including STAD, and its overexpression was validated in gastric cancer cell lines and tissues. UBR1 expression was associated with advanced pathological characteristics. High UBR1 expression was linked to poor prognostic outcomes, including overall survival (OS), progression-free interval (PFI), disease-specific survival (DSS), as well as responses to surgery, chemotherapy, and HER2 expression. UBR1 expression showed significant correlations with clinical parameters such as age, gender, TNM stage, pathological stage, tumor resection, and anti-reflux therapy. Amplifications and deletions were the most frequent genetic alterations associated with UBR1. According to KEGG and GSEA analyses, UBR1 was significantly associated with several cancer pathways, oxidative phosphorylation, and the TNF-NFκB pathway. UBR1 also exhibited a significant correlation with immune cell infiltration and immunotherapy, including a direct interaction with PDL1. Knockdown of UBR1 inhibited the proliferation, migration, and invasion of STAD cells and promoted apoptosis. UBR1 is overexpressed in STAD, promoting its progression and positively correlating with immune cell infiltration and immunotherapeutic responses. Therefore, UBR1 could be a promising biomarker for the prognosis and immunotherapy of STAD.

Association of Patient and Tumor Characteristics With Outcomes in Young Head and Neck Squamous Cell Carcinoma Patients.

We retrospectively studied young patients with head and neck squamous cell carcinoma (HNSCC) to identify factors associated with disease-specific survival (DSS). Patient and tumor characteristics of patients aged ≤45 who received treatments for non-metastatic HNSCC were collected to identify factors associated with DSS. Proportional hazards regression was applied separately for surgical and non-surgical patients. 230 patients were included. Surgical and non-surgical patients had similar DSS. Higher pathologic stages, positive margins, perineural invasion (PNI), extranodal extension and negative HPV status were associated with worse DSS for surgical patients and negative HPV status for non-surgical patients. In the multivariate analysis, pathologic stages, positive margins, and PNI were associated with worse DSS in surgical patients. Pathologic stages, positive margins, and PNI are independently associated with worse DSS in young surgical HNSCC patients. PNI is a uniquely strong prognostic factor for young patients.

Roles of naïve CD4+ T cells and their differentiated subtypes in lung adenocarcinoma and underlying potential regulatory pathways

BackgroundNaïve CD4+ T cells and their differentiated counterparts play a significant regulatory role in the tumor immune microenvironment, yet their effects on lung adenocarcinoma (LUAD) are not fully understood.MethodsWe utilized Mendelian randomization to assess the causal association between naïve CD4+ T cells and LUAD. Employing a modified single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm with The Cancer Genome Atlas (TCGA) database, we determined the infiltration levels of naïve CD4+ T cells and their differentiation subtypes and investigated their correlation with clinical characteristics. Potential regulatory pathways of T helper cells were identified through Mantel tests and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis.ResultsMendelian randomization analysis revealed an inhibitory effect of naïve CD4+ T cells on LUAD (false discovery rate < 0.05), which was corroborated by observational experiments using TCGA database. Specifically, T helper cell type 2 demonstrated a promotive effect on LUAD in terms of overall, disease-free, and progression-free survival (p < 0.05). Moreover, regulatory T cells exhibited a protective effect on LUAD in terms of disease-specific survival (p < 0.01). Concurrently, we explored the overall impact of naïve CD4+ T cell differentiation subtypes on LUAD, revealing upregulation in pathways such as neutrophil degranulation, MAPK family signaling pathways, and platelet activation, signaling, and aggregation.ConclusionNaïve CD4+ T cells and their differentiated counterparts play essential regulatory roles in the tumor immune microenvironment, demonstrating bidirectionality in their effects.Thus, elucidating the mechanisms and developing novel cell differentiation-inducing agents will benefit anti-cancer therapy.

Impact of Reclassification of Oncocytic and Follicular Thyroid Carcinoma by the 2022 WHO Classification.

The 2022 WHO Classification categorizes oncocytic (OTC) and follicular thyroid carcinoma (FTC) based on the degree of capsular and vascular invasion into minimally invasive (MI), encapsulated angioinvasive (EA) and widely invasive tumors (WI). While associations with clinical outcomes have been studied extensively in FTC, robust clinical data are lacking for OTC. We aimed to investigate the impact of the reclassification of OTC and FTC by the 2022 WHO Classification on clinical outcomes. All adult OTC and FTC patients treated at the Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. All tumors were extensively revised by two independent pathologists, facilitated by Palga: Dutch Pathology Databank. Kaplan-Meier curves were used to study the association of the 2004 and 2022 WHO Classification with overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and radioactive iodine (RAI) refractory disease. Fifty-two OTC and 89 FTC patients were included, of which 15 (28.8%) OTC and 34 (38.2%) FTC tumors were reclassified as EAOTC or EAFTC. The 2022 WHO Classification substantially improved risk stratification in both subtypes for DSS, compared with the 2004 edition. Ten-year DSS rates were 100% for MIOTC, 92.9% for EAOTC and 56.5% for WIOTC, compared to 100% (MIOTC) and 64.2% (WIOTC) following the 2004 WHO Classification. For FTC and RAI-refractory disease, similar trends were observed. Classification of OTC and FTC into three subcategories as defined by the 2022 WHO Classification substantially improves discrimination between low, intermediate and high risk patients, especially for DSS and RAI-refractory disease.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Disparities in pediatric parotid cancer treatment and presentation: A National study

ObjectivesAlthough parotid gland malignancies are uncommon, they nevertheless represent a cause of morbidity and mortality in the pediatric population. Few studies have sought to identify disparities related to their presentation, treatment, and survival. There is a need to understand these variations to improve care for historically underrepresented groups. Study designRetrospective Cohort Study. SettingSurveillance, Epidemiology, and End Results (SEER) Program Database. MethodsAnalysis of pediatric patients with parotid gland malignancies between 2000 and 2019. Race and ethnicity were classified as Non-Hispanic White, Non-Hispanic Black, Asian, and Hispanic for multivariable analysis. Outcomes included tumor size and stage at diagnosis, survival, and need for facial nerve sacrifice. Kaplan-Meier analysis was used to analyze survival. Multivariable logistic regression was conducted to identify predictors of outcomes. Results149 patients met the criteria for inclusion. Stratified by race/ethnicity, Non-Hispanic Black (Median 23 mm, IQR 15–33), Asian (30 mm, 14–32), and Hispanic (23 mm, 20–28) patients had larger tumors at presentation than Non-Hispanic White patients (18 mm, 12–25, p = 0.017). Disease-specific survival differed by time-to-treatment (log-rank, p = 0.01) and overall survival differed by income (p < 0.001). On multivariable analysis, Hispanic patients were more likely to experience facial nerve sacrifice (OR 3.71, 95%CI 1.25–11.6, p = 0.020), and Non-Hispanic Black (OR 3.37, 0.95–11.6, = 0.053) and Asian (OR 5.67, 1.46–22.2, p = 0.011) patients presented with larger tumors compared to Non-Hispanic White patients. ConclusionsVariations in presentation and treatment exist across race and ethnicity in pediatric parotid cancer. Identifying these disparities may help improve access and outcomes for underserved patient populations. Level of evidenceIII.

Immediate and delayed flap reconstruction have equivalent outcomes and associated costs following soft tissue sarcoma surgery.

Surgical treatment of soft tissue sarcoma (STS) involves wide resection of the tumor, which can necessitate soft tissue reconstruction with local or free tissue flaps. This retrospective study compares cost, surgical and oncologic outcomes between patients undergoing reconstruction with immediate versus delayed flap coverage following STS resection. Thirty-four patients who underwent planned flap reconstruction following resection of primary STS were identified retrospectively. Twenty-four (71%) received immediate reconstruction during the index surgery and 10 (29%) underwent planned delayed reconstruction. Preoperative patient-specific metrics, tumor characteristics, and surgical and patient outcomes were collected. Total hospital charges associated with every encounter during the perioperative period were obtained. Patient demographics, comorbidities, tumor metrics, and surgical characteristics were equivalent between groups. Postoperative wound complications, reoperations, readmissions, and disease-specific survival did not differ between cohorts. Costs associated with each reconstruction strategy were equivalent on bivariate and multivariate testing, when accounting for operating room time, hospital length of stay, and reoperation rate. Our study identifies no significant difference in patient outcome measures or cost between planned immediate and delayed flap reconstruction following STS resection. These results support the implementation of either treatment strategy in keeping with patient-centered, multidisciplinary care principles.

High expression of HM13 correlates with poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between HM13 expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. HM13 was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high HM13 expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. HM13 expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. HM13 was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.

Prognostic and immune infiltration implications of SIGLEC9 in SKCM

The occurrence and progression of skin cutaneous melanoma (SKCM) is strongly associated with immune cells infiltrating the tumor microenvironment (TME). This study examined the expression, prognosis, and immune relevance of SIGLEC9 in SKCM using multiple online databases. Analysis of the GEPIA2 and Ualcan databases revealed that SIGLEC9 is highly expressed in SKCM, and patients with high SIGLEC9 expression had improved overall survival (OS). Furthermore, the mutation rate of SIGLEC9 in SKCM patients was found to be 5.41%, the highest observed. The expression of SIGLEC9 was positively correlated with macrophages, neutrophils and B cells, CD8 + T cells, CD4 + T cells, and dendritic cells, according to TIMER. Based on TCGA-SKCM data, we verified that high SIGLEC9 expression is closely associated with a good prognosis for SKCM patients, including overall survival, progression-free interval, and disease-specific survival. This positive prognosis could be due to the infiltration of immune cells into the TME. Additionally, our analysis of single-cell transcriptome data revealed that SIGLEC9 not only played a role in the normal skin immune microenvironment, but is also highly expressed in immune cell subpopulations of SKCM patients, regulating the immune response to tumors. Our findings suggest that the close association between SIGLEC9 and SKCM prognosis is primarily mediated by its effect on the tumor immune microenvironment.

Expression of p16INK4a, FLOT2, and EGFR in oropharyngeal carcinoma, prognostic significance and correlation with clinicopathological characteristics.

Various factors can affect the survival of patients with oropharyngeal cancer. We assessed the expression of protein p16INK4a, Flotillin2, epidermal growth factor receptor, and other clinicopathological features and their prognostic value for this type of cancer. We gathered patient data on demographics, clinicopathological characteristics, treatment patterns, and outcomes. Histologically and by immunochemistry staining we determined expression of prognostic factors and molecular biomarkers. The primary endpoints were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Survival was assessed using the Kaplan-Meier method and Cox regression model analyses of potential prognostic parameters. After a median follow-up of 78 months, the median OS was 41 months, with an event recorded in 77.8% of patients. Median DFS was 22 months, 37 patients (51.4%) had disease relapse. The DSS survival rate was 58.3% with a median survival of 68 months. In regards to molecular biomarkers previously mentioned, there was no statistical significance for survival categories. After conducting a multivariate analysis of significant variables, we found that only recurrence, vascular invasion, and surgical intervention remained as factors with independent effects on both OS and DFS. Recurrence and the N stage were identified as independent prognostic factors for DSS. Our analysis underscores the complexity of factors that collectively influence survival following the diagnosis of OPSCC. Several factors were found to be statistically significant. These factors included the type of surgical procedure, disease relapse, vascular invasion, lymphatic invasion, perineural invasion, advanced T stage of the disease, N stage of the disease, and smoking status. The significance of these factors may vary across different types of survival. This analysis did not find any significant impact on survival from the growth factors tested, namely epidermal growth factor receptor, Flotillin2, and p16INK4a, in the applied regression models.

Tumor contour irregularity on preoperative CT predicts prognosis in renal cell carcinoma: a multi-institutional study

Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC). We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models. The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3cm or larger (all p<0.001). Multivariate analyses confirmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84-0.92) in the training set, 0.92 (95%CI: 0.88-0.98) in the internal validation set, and 0.86 (95%CI: 0.81-0.90) in the external test set, surpassing existing prognostic models. Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3cm or larger. This study was funded by grants from National Natural Science Foundation of China; Shanghai Municipal Health Commission; China National Key R&D Program and Science and Technology Commission of Shanghai Municipality.

Endoscopic submucosal dissection for lesions developing in the irradiated area of head and neck cancer.

Effective treatment of lesions that develop in the irradiated area of head and neck squamous cell carcinoma is a major concern. This study aimed to clarify the efficacy and safety of endoscopic resection for such lesions. Among consecutive patients who underwent endoscopic resection for histologically proven head and neck squamous cell carcinoma between January 2014 and December 2021, those who received definitive radiotherapy/chemoradiotherapy before endoscopic resection were included in this single-center, retrospective study. Short- and long-term outcomes were evaluated. Among 422 patients who underwent endoscopic resection for 615 lesions, 43 patients with 57 lesions were eligible. All 57 lesions were treated with endoscopic submucosal dissection and en bloc resection was achieved in all lesions. Grade 3 of Common Toxicity Criteria for Adverse Events v5.0 occurred in eight (19%) patients (dysphagia, seven; stricture, three; aspiration pneumonia, two; and pharyngeal necrosis, one [some cases overlapped]), but no grade ≥4 events occurred. Enteral nutrition by gastrostomy was temporarily required in two patients owing to dysphagia and laryngeal necrosis. During the median follow-up of 40 (interquartile range, 29.5-61) months after endoscopic submucosal dissection for the lesions developed in the irradiated area, local recurrence and metachronous lesions developed in two (5%) and nine (21%) patients, respectively. However, total laryngectomies and tracheostomies were avoided in all patients. The 3-year overall and disease-specific survivals were 81% (95% confidence interval, 64%-91%) and 94% (95% confidence interval, 79%-99%), respectively. Favorable local control and safety of endoscopic submucosal dissection were demonstrated.

The Impact of Li-Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes, and Genetic Testing Recommendations.

Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous, occurring mostly in sporadic but also syndromic settings. The role of pathogenic germline variants (PGV) as LMS drivers and their impact on outcomes remains uncertain. We performed a comprehensive clinicopathologic and molecular analysis using a tumor-normal DNA next-generation sequencing assay (Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Cancer Targets) of germline-associated LMS compared with sporadic LMS. Among 285 LMS [120 soft-tissue LMS (STLMS) and 165 uterine LMS (ULMS)] with germline testing, 78 (27%, 43 STLMS and 35 ULMS) cases harbored PGV, with 35/78 (45%) of PGV carriers showing biallelic inactivation of the corresponding gene in the tumor (26 STLMS and nine ULMS). The most frequent germline predispositions were TP53 (Li-Fraumeni syndrome; 17 patients, 16 in STLMS) and RB1 (retinoblastoma; 13 patients, 11 in STLMS). Germline TP53 and somatic RB1 alterations often co-occurred in the tumor andvice versa. Other biallelically inactivated PGV were enriched in DNA damage repair-related genes: CHEK2, MSH2, MSH6, RAD51D, BRCA2, and FANCA. Monoallelic PGV were mostly in ULMS and associated with co-occurring TP53 and RB1 somatic alterations. Patients with STLMS with biallelic but not monoallelic PGV were significantly younger than patients with sporadic STLMS (median ages 38 vs. 52 vs. 58 years). No differences in disease-specific or progression-free survival were observed in germline-associated versus sporadic LMS regardless of biallelic status. Although patients with ULMS had a relatively low proportion of PGV, a high percentage of patients with STLMS with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations.

Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients

BACKGROUND Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.

Usefulness of pre- and post-treatment volumetric PET/CT parameters in predicting prognosis and evaluating recurrence for chemoradiotherapy-treated hypopharyngeal cancer.

To investigate the usefulness of pre- and post-treatment metabolic tumor volume (MTV) obtained from positron emission tomography (PET) in predicting prognosis and evaluating recurrence in patients with hypopharyngeal cancer (HPC). Forty-three consecutive HPC patients treated with chemoradiotherapy were retrospectively analyzed. Maximum standard uptake value (SUVmax) and MTV of tumor (T) and lymph node (N) were analyzed. On multivariate analysis using pre-treatment parameters, MTV-T (p = 0.049) and MTV-TN (p = 0.043) were significantly associated with local control (LC), and MTV-N (p = 0.049) was significantly associated with disease-specific survival (DSS). Post-treatment MTV-TN was also significantly associated with prognosis (p < 0.001 in LC; p = 0.002 in DSS) and recurrence (area under curve 0.95). Neither pre- nor post-treatment SUVmax was significantly associated with prognosis. Pre- and post-treatment MTV appears useful for predicting prognosis and evaluating recurrence.

The contribution of rural/urban residence to incidence and survival in thymoma and thymic carcinoma, a retrospective cohort study of the SEER 2000–2020 database

ObjectiveRural-urban healthcare disparities have been demonstrated throughout the United States, particularly in acquiring oncologic care. In this study, we aim to discern the role of rural-urban health disparities in thymic cancer incidence and uncover potential survival disparities. MethodsThe Surveillance, Epidemiology, and End Results (SEER) 17-State database was queried for all cases of thymoma (ICD-O-3/3 codes: 8580–8585) and thymic carcinoma (8586) located in the thymus (primary site code C37.9) diagnosed between 2000 and 2020. Residence was established using SEER Rural-Urban Continuum Codes. Incidence trend modeling for rural versus urban patients was completed using Joinpoint Regression Software. Chi-square, Kaplan-Meier with log-rank testing, and Cox proportional hazards was completed using SPSS, with significance set to p <0.05. ResultsJoinpoint analysis revealed a significant growth in incidence in the urban population compared to a stagnant incidence among the rural population. Disease specific survival was higher among urban patients on univariate modeling (p = 0.010), and confirmed on multivariate analysis, whereby rural living conferred an adjusted hazard ratio of 1.263 (95 % CI 1.045–1.527; p = 0.016) in comparison to urban patients. ConclusionsThese findings demonstrate differences between thymic cancer incidence and outcomes in patients living in urban versus rural environments and demonstrate an important disparity.

Pre-receptor regulation of 11-oxyandrogens differs between normal and cancerous endometrium and across endometrial cancer grades and molecular subtypes.

Endometrial cancer (EC) is a prevalent gynecological malignancy globally, with a rising incidence trend. While classic androgens have been implicated with EC risk, the role of their 11-oxygenated metabolites is poorly understood. Here, we studied 11-oxyandrogen formation from steroid precursors in EC for the first time. We performed in vitro studies on a panel of four EC cell lines of varying differentiation degree and molecular subtype and a control cell line of normal endometrium to assess 11-oxyandrogen formation from steroid precursors. We also characterized the transcriptomic effects of dihydrotestosterone (DHT) and 11-keto-DHT on Ishikawa and RL95-2. Key molecular players in 11-oxyandrogen metabolism and action were explored in endometrial tumors using public transcriptomic datasets. We discovered that within endometrial tumors, the formation of 11-oxyandrogens does not occur from classic androgen precursors. However, we observed distinct regulatory mechanisms at a pre-receptor level in normal endometrium compared to cancerous tissue, and between low- and high-grade tumors. Specifically, in vitro models of low-grade EC formed higher levels of bioactive 11-keto-testosterone from 11-oxyandrogen precursors compared to models of noncancerous endometrium and high-grade, TP53-mutated EC. Moreover, the potent androgen, DHT and its 11-keto homologue induced mild transcriptomic effects on androgen receptor (AR)-expressing EC model, Ishikawa. Finally, using public transcriptomic datasets, we found HSD11B2 and SRD5A2, coding for key enzymes in steroid metabolism, to be associated with better disease-specific survival, whereas higher intra-tumoral AR expression correlated with lower recurrence in TP53-wt tumors. The intra-tumoral metabolism of 11-oxyandrogen precursors is characteristic for low-grade EC of non-TP53-alt molecular subtypes. Our findings support further exploration of circulating 11-oxyandrogens as prognostic biomarkers in EC.