Higher American Joint Committee Research Articles

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation.

Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

Maintenance chemotherapy for esophageal squamous cell carcinoma after standard concurrent chemoradiotherapy: a national propensity score matching cohort study.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive cancer, and its standard treatment is concurrent chemoradiotherapy (CCRT). Maintenance chemotherapy is often used to help prevent cancer recurrence, but its efficacy for patients with ESCC receiving CCRT remains unclear. We conducted a large head-to-head propensity score matching cohort study to estimate the effects of maintenance chemotherapy on overall survival and cancer-specific survival in patients with ESCC receiving standard CCRT. After propensity score matching (PSM), we recruited 2724 patients with ESCC (2177 in the maintenance chemotherapy group and 547 in the non-maintenance chemotherapy group). The adjusted hazard ratios (95% confidence intervals) of all-cause mortality and cancer-specific mortality for the maintenance chemotherapy group were 1.15 (1.06-1.26, P = 0.0014) and 1.08 (0.88-1.29, P = 0.1320), respectively, compared with the non-maintenance chemotherapy group. We also found that older age, relatively lower body mass index (BMI), higher American Joint Committee on Cancer clinical stage, and poor response to CCRT as measured using the Response Evaluation Criteria in Solid Tumors were poor independent predictors of all-cause mortality and cancer-specific mortality. Our findings indicated that maintenance chemotherapy may not improve the survival of patients with ESCC who have received CCRT. Additionally, we identified several key prognostic factors for patients with ESCC receiving CCRT, including relatively low BMI and poor response to CCRT. Further research is needed to understand the benefits and risks of maintenance chemotherapy in similar patient populations in order to identify new therapies that could improve treatment responses.

SBRT vs. Y90: HCC Treatment Outcomes and Costs.

Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.

Outcomes of Squamous Cell Carcinoma of the Lip Treated With Mohs Micrographic Surgery: A Retrospective Cohort Study.

Cutaneous squamous cell carcinomas (cSCCs) of the lip have been reported to be at higher risk for poorer post-treatment outcomes. To examine outcomes of patients with SCC of the lip treated with Mohs micrographic surgery (MMS) and identify factors for recurrence. This retrospective review of a single tertiary referral center's Mohs case logs from 2010 to 2019 identified cases of lip SCC. Clinicopathologic characteristics and outcomes (local recurrence [LR], metastasis, and disease-specific death) were reviewed. One hundred ninety cases of SCC of the lip were identified and demonstrated that MMS offered a disease-free survival of 96.8% over an average follow-up period of 42 months. Younger age (61 vs 74 years p = .006), increased MMS stages ( p = .009), and higher American Joint Committee on Cancer and Brigham and Women's Hospital T stages were risk factors for LR. Immunosuppression, large tumor size, mucosal lip involvement, aggressive histology, and perineural invasion were not associated with LR. The results of this study show that SCC of the lip behaved similarly to cSCC outside the lip area, and that both primary and recurrent lesions can be treated effectively with MMS.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

Integrated analysis of single-cell and bulk transcriptome identifies a signature based on NK cell marker genes to predict prognosis and therapeutic response in clear cell renal cell carcinoma.

Accumulating evidence has highlighted the effects of natural killer (NK) cells on shaping anti-tumor immunity. This study aimed to construct an NK cell marker gene signature (NKMS) to predict prognosis and therapeutic response of clear cell renal cell carcinoma (ccRCC) patients. Publicly available single-cell and bulk RNA profiles with matched clinical information of ccRCC patients were collected from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), ArrayExpress, and International Cancer Genome Consortium (ICGC) databases. A novel NKMS was constructed, and its prognostic value, associated immunogenomic features and predictive capability to immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies were evaluated in ccRCC patients. We identified 52 NK cell marker genes by single-cell RNA-sequencing (scRNA-seq) analysis in GSE152938 and GSE159115. After least absolute shrinkage and selection operator (LASSO) and Cox regression, the most prognostic 7 genes (CLEC2B, PLAC8, CD7, SH3BGRL3, CALM1, KLRF1, and JAK1) composed NKMS using bulk transcriptome from TCGA. Survival and time-dependent receiver operating characteristic (ROC) analysis exhibited exceptional predictive capability of the signature in the training set and two independent validation cohorts (E-MTAB-1980 and RECA-EU cohorts). The seven-gene signature was able to identify patients within high Fuhrman grade (G3-G4) and American Joint Committee on Cancer (AJCC) stage (III-IV). Multivariate analysis confirmed the independent prognostic value of the signature, and a nomogram was built for clinical utility. The high-risk group was characterized by a higher tumor mutation burden (TMB) and greater infiltration of immunocytes, particularly CD8+ T cells, regulatory T (Treg) cells and follicular helper T (Tfh) cells, in parallel with higher expression of genes negatively regulating anti-tumor immunity. Moreover, high-risk tumors exhibited higher richness and diversity of T-cell receptor (TCR) repertoire. In two therapy cohorts of ccRCC patients (PMID32472114 and E-MTAB-3267), we demonstrated that high-risk group showed greater sensitivity to ICIs, whereas the low-risk group was more likely to benefit from anti-angiogenic therapy. We identified a novel signature that can be utilized as an independent predictive biomarker and a tool for selecting the individualized treatment for ccRCC patients.

Analysis of Aldehyde Dehydrogenase 2 as a Prognostic Marker Associated with Immune Cell infiltration and Chemotherapy Efficacy in Head and Neck Squamous Cell Carcinoma.

Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.

Prognostic value of preoperative enhanced computed tomography as a quantitative imaging biomarker in pancreatic cancer.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with high mortality and short survival time. Computed tomography (CT) plays an important role in the diagnosis, staging and treatment of pancreatic tumour. Pancreatic cancer generally shows a low enhancement pattern compared with normal pancreatic tissue.AIMTo analyse whether preoperative enhanced CT could be used to predict postoperative overall survival in patients with PDAC.METHODSSixty-seven patients with PDAC undergoing pancreatic resection were enrolled retrospectively. All patients underwent preoperative unenhanced and enhanced CT examination, the CT values of which were measured. The ratio of the preoperative CT value increase from the nonenhancement phase to the portal venous phase between pancreatic tumour and normal pancreatic tissue was calculated. The cut-off value of ratios was obtained by the receiver operating characteristic (ROC) curve of the tumour relative enhancement ratio (TRER), according to which patients were divided into low- and high-enhancement groups. Univariate and multivariate analyses were performed using Cox regression based on TRER grouping. Finally, the correlation between TRER and clinicopathological characteristics was analysed.RESULTSThe area under the curve of the ROC curve was 0.768 (P < 0.05), and the cut-off value of the ROC curve was calculated as 0.7. TRER ≤ 0.7 was defined as the low-enhancement group, and TRER > 0.7 was defined as the high-enhancement group. According to the TRER grouping, the Kaplan-Meier survival curve analysis results showed that the median survival (10.0 mo) with TRER ≤ 0.7 was significantly shorter than that (22.0 mo) with TRER > 0.7 (P < 0.05). In the univariate and multivariate analyses, the prognosis of patients with TRER ≤ 0.7 was significantly worse than that of patients with TRER > 0.7 (P < 0.05). Our results demonstrated that patients in the low TRER group were more likely to have higher American Joint Committee on Cancer stage, tumour stage and lymph node stage (all P < 0.05), and TRER was significantly negatively correlated with tumour size (P < 0.05). CONCLUSIONTRER ≤ 0.7 in patients with PDAC may represent a tumour with higher clinical stage and result in a shorter overall survival.

Advancing head and neck cancer following the coronavirus disease 2019 pandemic.

Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown. This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people. A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017). Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.

Head and Neck Acinic Cell Carcinoma: A New Grading System Proposal and Diagnostic Utility of NR4A3 Immunohistochemistry.

Acinic cell carcinoma (AciCC) is traditionally considered as a low-grade salivary gland carcinoma. However, a subset demonstrates high-grade features with a higher mortality rate and distant metastasis. In this large retrospective study of 117 cases, we aimed to establish a histologic grading scheme for AciCC. Adverse independent prognostic factors identified on the multivariate analysis included older age, tumor necrosis, nuclear anaplasia, lymphovascular invasion, absence of tumor-associated lymphoid stroma, and high American Joint Committee on Cancer (AJCC) pT and pN stages. A 3-tiered grading scheme using 4 pathologic parameters (mitotic index, necrosis, tumor border, and fibrosis at the frankly invasive front) was subsequently applied. Compared with low/intermediate-grade, high-grade AciCC defined as a mitotic index ≥5/10 HPFs and/or necrosis was an independently adverse prognostic factor. The 5-year overall survival was 50% in high-grade AciCCs, and 100% in low-grade or intermediate-grade AciCCs. Compared with low-grade or intermediate-grade AciCC, high-grade tumors were associated with older age, larger tumor size, focal rather than diffuse zymogen granules, solid architecture, infiltrative tumor border, fibrosis at the frankly invasive front, lymphovascular invasion, perineural invasion, positive margin, high pT, and pN stages. NR4A3 was a highly sensitive and specific immunohistochemical stain for diagnosing AciCC with a sensitivity and specificity of 96% and 93%, respectively. In conclusion, although we proposed a 2-tiered grading system for AciCC with high-grade tumors defined by a mitotic count ≥5/10 HPFs and/or necrosis, more studies are needed to assess the prognostic value of intermediate grade. NR4A3 immunohistochemical stain is a useful diagnostic marker for AciCC.

Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas

Cutaneous melanoma can be lethal even if detected at an early stage. Epigenetic profiling may facilitate the identification of aggressive primary melanomas with unfavorable outcomes. We performed clustering of whole-genome methylation data to identify subclasses that were then assessed for survival, clinical features, methylation patterns, and biological pathways. Among 89 cutaneous primary invasive melanomas, we identified three methylation subclasses exhibiting low methylation, intermediate methylation, or hypermethylation of CpG islands, known as the CpG island methylator phenotype (CIMP). CIMP melanomas occurred as early as tumor stage 1b and, compared with low-methylation melanomas, were associated with age at diagnosis ≥65 years, lentigo maligna melanoma histologic subtype, presence of ulceration, higher American Joint Committee on Cancer stage and tumor stage, and lower tumor-infiltrating lymphocyte grade (all P < 0.05). Patients with CIMP melanomas had worse melanoma-specific survival (hazard ratio= 11.84; confidence interval= 4.65‒30.20) than those with low-methylation melanomas, adjusted for age, sex, American Joint Committee on Cancer stage, and tumor-infiltrating lymphocyte grade. Genes hypermethylated in CIMP compared with those in low-methylation melanomas included PTEN, VDR, PD-L1, TET2, and gene sets related to development/differentiation, the extracellular matrix, and immunity. CIMP melanomas exhibited hypermethylation of genes important in melanoma progression and tumor immunity, and although present in some early melanomas, CIMP was associated with worse survival independent of known prognostic factors.

Influence of positive margins on tumour recurrence and overall survival after gastrectomy for gastric cancer.

Incidence of positive surgical margins after curative gastrectomy ranges from 1% to 20%. It has been suggested that positive surgical margin is an adverse prognosis factor, with a higher local recurrence and worse overall survival (OS). However, the management of these patients remains unclear. A total of 267 patients who underwent gastrectomy with curative intent between January 2010 and December 2018 in our centre were enrolled in this study. Post-operative histological analysis revealed positive resection margins in 18 patients (8%). Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. Patients with positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, whole stomach involved and poorly differentiated tumours. Local recurrence was described in 50% of cases with positive margins. The multivariate analysis demonstrated that the TNM stage was the only independent prognostic factor associated with recurrence. OS for positive margins at 1, 3 and 5 years was 75%, 57% and 26%, respectively. The median survival in patients with positive margins was 38.33 versus 81.17 months for R0 patients (p=0.027). Multivariate analysis showed that age (hazard ratio [HR] 1.041, 95% confidence interval [CI] 1.02-1.07, sex (HR 2.00, 95% CI 1.22-3.30) and TNM stage (p < 0.001) were independent factors of OS. Positive resection margin was an indication of advanced and more aggressive disease rather than an independent prognosis factor for OS or recurrence in gastric cancer.

Tumour budding and CD8+ T cells: ‘attackers’ and ‘defenders’ in rectal cancer with and without neoadjuvant chemoradiotherapy

Tumour budding ('attacker') and CD8+ T cells ('defender') are recognised as important parameters for risk stratification in colon cancers and, combined, may have an even stronger clinical impact. Here, we determine the value of tumour budding and CD8+ in rectal cancer patients treated with/without neoadjuvant therapy. Using digital scans of all tumour slides/case, we analysed CD8+ T cell counts in two patient cohorts: 45 neoadjuvantly treated and 47 primarily surgically treated (totalling n=543 slides) after double-staining of the surgical resection specimen for pan-cytokeratin and CD8+ . Tumour buds in hot-spots were manually counted (area=0.785mm2 ) and CD8+ T cell counts were analysed separately both in tumour budding hot-spots and the densest CD8+ regions throughout the tumour. In neoadjuvantly treated patients, only tumour budding and not CD8+ T cells was associated with tumour features, including more advanced ypT (P=0.0062), venous invasion (P=0.002), lymphatic invasion (P=0.0003) and perineural invasion (P=0.0017), as well as higher American Joint Committee on Cancer (AJCC) tumour regression score (P=0.0035), indicating less tumour response. Overall survival was also worse in patients with high-grade budding in univariate analysis only. In contrast, all three variables, namely tumour budding (P=0.0347), CD8+ T cells in budding hot-spots (P=0.0382) and CD8+ T cells in the densest areas (P=0.0117) were also associated with worse (budding) and better (CD8) survival time in the multivariate setting. In rectal cancer, tumour budding has clinical relevance in both primarily surgically treated patients and in those with neoadjuvantly treated patients, where it characterises highly aggressive residual disease. CD8+ T cell counts appear not to have prognostic relevance in the neoadjuvant context.

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

BackgroundPrevious studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC. MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models. ResultsA total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage. ConclusionBCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.

Factors leading to the risk of stroke mortality: a cross-sectional study with lung cancer patient-based large sample.

To identify the risk factors for stroke mortality among lung cancer patients on the basis of the Surveillance, Epidemiology, and End Results (SEER) database. The clinical data of lung cancer patients diagnosed between 2004 and 2016 were collected in the SEER database. The stroke mortality of lung cancer patients was compared with the general population using standardized mortality ratios (SMRs). COX proportional hazard model was applied to analyze the risk factors for stroke mortality among lung cancer patients. Among 82 454 patients, 4821 (5.85%) died of stroke. The stroke mortality rate in lung cancer patients significantly increased compared with the general population [SMR: 1.73, 95% confidential interval (95% CI), 1.69–1.78]. Differences were pronounced between the patients with stroke death and those without regarding all the basic characteristics (P < 0.001). Multivariate COX analysis showed that the risk factors for stroke mortality among lung cancer patients included increasing age, males, the black, grade II–III, distant metastasis and higher American Joint Committee on Cancer (AJCC) TNM stage, whereas adenocarcinoma was found to be a protective factor compared with squamous cell carcinoma. Increasing age, males, the black, grade II–III, distant metastasis and higher TNM stage are associated with an increased risk of stroke mortality among lung cancer patients, but adenocarcinoma with a lowered risk.

A population-based study of the three major variants of papillary thyroid carcinoma.

ObjectiveTo explore the clinicopathological features and relative prognostic risks of the three major variants of papillary thyroid carcinoma (PTC).MethodsWe retrospectively analyzed the clinicopathological characteristics and prognoses of patients with the three major PTC variants, conventional papillary thyroid carcinoma (CPTC), follicular-variant papillary carcinoma (FVPTC), and tall-cell papillary thyroid carcinoma (TCPTC), based on data from the Surveillance, Epidemiology, and End Results database from 2005 to 2009.ResultsA total of 29,555 patients were enrolled. In terms of their demographic and clinicopathological characteristics, TCPTC had the highest prevalence of older patients, men, patients with locally advanced stage (T stage and N stage), and mortality, while FVPTC had the lowest prevalence in relation to these factors. The three variants differed significantly in terms of 5-year overall survival and 5-year disease-specific survival. Cox regression analysis identified male sex, age ≥45 years, and higher American Joint Committee on Cancer and TNM stage as independent factors predicting a poor prognosis in relation to both overall and disease-specific survival.ConclusionsCPTC, FVPTC, and TCPTC have different clinicopathological characteristics and prognoses, indicating the need for different treatment strategies for these three variants of PTC.

Exploration of the Immune-Related Signatures and Immune Infiltration Analysis in Melanoma.

In the present study, we aimed to investigate immune-related signatures and immune infiltration in melanoma. The transcriptome profiling and clinical data of melanoma were downloaded from The Cancer Genome Atlas database, and their matched normal samples were obtained from the Genotype-Tissue Expression database. After merging the genome expression data using Perl, the limma package was used for data normalization. We screened the differentially expressed genes (DEGs) and obtained immune signatures associated with melanoma by an immune-related signature list from the InnateDB database. Univariate Cox regression analysis was used to identify potential prognostic immune genes, and LASSO analysis was used to identify the hub genes. Next, based on the results of multivariate Cox regression analysis, we constructed a risk model for melanoma. We investigated the correlation between risk score and clinical characteristics and overall survival (OS) of patients. Based on the TIMER database, the association between selected immune signatures and immune cell distribution was evaluated. Next, the Wilcoxon rank-sum test was performed using CIBERSORT, which confirmed the differential distribution of immune-infiltrating cells between different risk groups. We obtained a list of 91 differentially expressed immune-related signatures. Functional enrichment analysis indicated that these immune-related DEGs participated in several areas of immune-related crosstalk, including cytokine-cytokine receptor interactions, JAK–STAT signaling pathway, chemokine signaling pathway, and Th17 cell differentiation pathway. A risk model was established based on multivariate Cox analysis results, and Kaplan-Meier analysis was performed. The Kruskal-Wallis test suggested that a high risk score indicated a poorer OS and correlated with higher American Joint Committee on Cancer-TNM (AJCC-TNM) stages and advanced pathological stages (P < 0.01). Furthermore, the association between hub immune signatures and immune cell distribution was evaluated in specific tumor samples. The Wilcoxon rank-sum test was used to estimate immune infiltration density in the two groups, and results showed that the high-risk group exhibited a lower infiltration density, and the dominant immune cells included M0 macrophages (P = 0.023) and activated mast cells (P = 0.005).

Epidemiology and Survival Outcomes for Eyelid Primary Malignant Melanoma: An Analysis of 1397 Cases in the SEER Database.

Purpose There has not been a recent population-based study regarding the epidemiological trend and survival of eyelid primary malignant melanoma (PMM). Our study aims to evaluate the updated incidence trends and discuss the factors affecting the survival outcomes of eyelid PMM. Methods A total of 1397 eyelid PMM cases diagnosed between 1975 and 2016 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rates and annual percent changes (APC) were calculated. Kaplan-Meier and Cox proportional hazards regression models were used to calculate survival outcomes and identify potential prognostic factors. Results The overall age-adjusted incidence of eyelid PMM rose from 0.039 (95% confidence interval [CI], 0.012–0.088) in 1975 to 0.103 (95% CI, 0.070–0.143) per 100 000 population in 2016, with significant APC of 1.313% (p < 0.001). Male subjects showed a higher average age-adjusted incidence rate than female subjects (p < 0.001). Survival analyses showed that 5-year accumulative overall survival (OS) and disease-specific survival (DSS) for patients with eyelid PMM were 70.5% and 90.6%. Additionally, 10-year OS and DSS were 51.8% and 86.1%, respectively. Analyses of Kaplan-Meier survival curves with the log-rank test revealed that older age, White race, nodular melanoma, higher American Joint Committee on Cancer (AJCC) stage (II to IV), advanced stage, distant metastasis, and no-surgery treatment were associated with lower OS and DSS rates. Age, histology, AJCC stage, and stage at diagnosis were found to be independent predictors of OS and DSS in multivariate models. Conclusion The incidence of eyelid PMM increased with significant APC and male predominance. Age, histology, AJCC stage, and stage at diagnosis might be independent predictors of prognosis, emphasizing the importance of improved diagnosis of eyelid PMM.

GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in pancreatic cancer.

Background: General Transcription Factor II-I Repeat Domain-Containing Protein 1 (GTF2IRD1) is a member of the GTF21 gene family, which encodes a set of multifunctional transcription factors. However, the potential function of GTF2IRD1 in pancreatic cancer (PC) still remains unknown. Study on GTF2IRD1 might provide a new insight into the carcinogenesis and therapeutics of PC.Methods: In the current study, the clinical significance and potential biological of GTF2IRD1 were evaluated by bioinformatics analysis. The oncogenic role of GTF2IRD1 in PC was also determined using in vitro studies. Possible associations between GTF2IRD1 expression and tumor immunity were analyzed using ESTIMATE algorithm and single-sample Gene Set Enrichment Analysis (ssGSEA).Results: GTF2IRD1 expression was significantly up-regulated in tumor tissues, and positively associated with higher histologic grade, higher American Joint Committee on Cancer (AJCC) stage, and worse prognosis. Function enrichment analysis demonstrated that GTF2IRD1 may be involved in pancreatic adenocarcinoma pathway, TGF-β signaling pathway, and tumor-infiltrating lymphocyte (TIL) related biological functions, such as T-cell receptor signaling pathway, leukocyte transendothelial migration, resistin as a regulator of inflammation, and regulation of leukocyte-mediated cytotoxicity. Knockdown of GTF2IRD1 expression inhibited cancer cell proliferation, colony formation, and invasion in vitro. ESTIMATE algorithm and ssGSEA demonstrated that GTF2IRD1 expression negatively correlated with the infiltration and anti-tumor activity of TILs, especially for CD8+ T cells.Conclusion: The study demonstrates that GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in PC.

Prevalence of p16 expression in oropharyngeal squamous cell carcinoma in southern Brazil

Our aim was to evaluate the prevalence of human papillomavirus (HPV)-positive tumors in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) at a single center in southern Brazil and determine the short-term prognostic factors in this sample. Ninety-one consecutive patients with newly diagnosed primary OPSCC between January 2017 and December 2019 were retrospectively included. Demographic, clinical, pathologic, and survival data were collected. HPV status was determined by using p16 immunohistochemistry. The overall prevalence of HPV-positive (HPV+) OPSCC was 20.9%. Patients with HPV+ tumors presented a nodal metastasis as the first clinical sign (P=.02); reported less alcohol (P < .001) and tobacco use (P < .001); exhibited lower tumor stages (P < .001) and higher microscopic grades (P=.01); and had higher chances of having resectable tumors (P=.008). p16-negative status (P=.01); unresectable/inoperable tumors (P < .001); presence of nodal metastasis (P=.005); and higher American Joint Committee on Cancer (AJCC) stage (P=.002) were significantly associated with worse disease-specific survival. The prevalence of HPV+ OPSCC in southern Brazil is relatively low, and p16-positive status was associated with Better prognosis. Higher AJCC stage, nodal metastasis, and unresectability/inoperability were associated with the highest hazard ratios for death resulting from OPSCC.