Prognostic Factor For Disease-specific Survival Research Articles

The prognostic analysis and a machine-learning based disease-specific survival state model in pulmonary large-cell neuroendocrine carcinomas.

Pulmonary large-cell neuroendocrine carcinoma (PLCNEC) is a rare and highly malignant lung cancer. Due to the paucity of data from clinical studies, its clinical characteristics and treatment remain controversial. The present study explored factors influencing the prognosis and survival outcomes of patients with PLCNEC and developed a dependable prognostic model using machine learning. The clinical data of PLCNEC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. A total of 2,897 PLCNEC patients were enrolled and univariate and multivariate Cox regression analyses were performed to explore independent prognostic factors for disease-specific survival (DSS). Ten machine learning algorithms were utilized to predict the 2-year survival. The clinicopathological data collected from The First Affiliated Hospital of Sun Yat-sen University between 2010 and 2022 were used to test the trained machine. Sex [hazard ratio (HR) 1.168, 95% confidence interval (CI): 1.063-1.284], age (HR 1.262, 95% CI: 1.144-1.391), surgery (HR 0.481, 95% CI: 0.413-0.559), chemotherapy (HR 0.450, 95% CI: 0.404-0.501), bone metastasis (HR 1.284, 95% CI: 1.124-1.466), brain metastasis (HR 1.167, 95% CI: 1.023-1.331), liver metastasis (HR 1.223, 95% CI: 1.069-1.399), American Joint Committee on Cancer-Node (AJCC-N), and tumor stage were independent prognostic factors. The gradient boosting decision tree (GBDT) performed better than other models, with an F1-score of 0.791 and an area under the curve of 0.831. Male, age ≥65 years, distant metastasis to the bone, liver, and brain are associated with a worse prognosis in PLCNEC patients, while surgery and chemotherapy are associated with improved prognosis. GBDT showed promising performance in predicting 2-year survival, which can serve as a valuable reference for clinical diagnosis and treatment of PLCNEC.

Survival outcome and prognostic factors of remnant gastric cancer: a propensity score-matched analysis.

Studies on survival and prognostic factors in individuals with remnant gastric cancer (RGC) after gastric cancer (GC) are rare. It is debatable whether prognosis of RGC after GC is worse than that of only primary GC (OPGC). The objective of this study is to compare the survival outcomes between post-GC RGC and OPGC undergoing surgical resection and to identify the prognostic factors of disease-specific survival (DSS) for RGC. We retrospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database among patients who underwent GC surgery in 1988-2020. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier (KM) survival analysis was performed to compare their overall survival (OS) and DSS. Multivariable Cox analyses were performed to identify the independent prognostic factors of DSS for post-GC RGC by estimating hazard ratios (HRs) with 95% confidence intervals (CIs). There were 76 patients with RGC and 32,763 patients with OPGC included and analyzed. After balancing the baseline characteristics by PSM, no significant difference existed between OPGC and RGC groups in both OS (P=0.65) and DSS (P=0.28). Fixed-time analyses also showed no difference between the two groups for the 5-year (60.0%, RGC vs. 53.3%, OPGC, P=0.38) and 10-year DSS (56.7%, RGC vs. 48.3%, OPGC, P=0.34). Multivariable analysis revealed that area of lower income ($75,000+ vs. <$55,000, HR =0.21, 95% CI: 0.05-0.89, P=0.03), cardiac tumor [middle vs. cardia, HR =0.16, 95% CI: 0.03-0.77, P=0.02; distal vs. cardia, HR =0.10, 95% CI: 0.02-0.58, P=0.01; not otherwise specified (NOS) vs. cardia, HR =0.11, 95% CI: 0.03-0.51, P=0.004], deeper invasion (T3-4 vs. Tis-2, HR =5.19, 95% CI: 1.21-22.15, P=0.03), higher grade (G3 vs. G1-2, HR =7.35, 95% CI: 1.41-38.48, P=0.02) and not receiving chemotherapy (yes vs. no/unknown, HR =0.16, 95% CI: 0.04-0.60, P=0.007) were independent risk factors for postsurgical DSS in patients with post-GC RGC. The prognosis of post-GC RGC was comparable to that of OPGC following surgical resection. The independent prognostic factors for RGC are similar to those established for OPGC. Our findings suggest that RGC following first GC might be the same entity to OPGC and curative resection should be considered in selected patients.

Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.

Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated. COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis. No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival. Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.

Prognostic value of radiological T category using conventional MRI in patients with oral tongue cancer: comparison with pathological T category

PurposeThis study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis.MethodsThis retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared.ResultsThe T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20).ConclusionThe T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.

Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Prognostic capacity of PIV (pan-immune-inflammation value) in patients with head and neck squamous cell carcinoma

IntroductionThe pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils × monocytes × platelets)/lymphocytes, has been proposed as a prognostic biomarker in different tumour models. The aim of this study is to analyse the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma (HNSCC). Patients and methodsRetrospective study of 1187 patients with HNSCC treated at our centre between 2000−2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. ResultsPIV value was significantly associated with toxic consumption (0.001), tumour location (0.0001), tumour extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category I: PIV < 136.3 (n = 118, 9.9%), category II: PIV 136.3–451.1 (n = 594, 50.0%), category III: PIV 451.1−1,141.2 (n = 357, 30.1%), and category IV: PIV > 1141.2 (n = 118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumour extension, or location of the primary tumour. The PIV category was and independent prognostic factor of disease-specific survival in a multivariable study. ConclusionsPIV is a prognostic biomarker in patients with HNSCC.

TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma.

Treatment resistance and relapse are common problems in head and neck squamous cell carcinoma (HNSCC). Except for p16, no clinically accepted prognostic biomarkers are available for HNSCC. New biomarkers predictive of recurrence and survival are crucial for optimal treatment planning and patient outcome. High translocator protein (TSPO) levels have been associated with poor survival in cancer, but the role of TSPO has not been extensively evaluated in HNSCC. TSPO expression was determined in a large population-based tissue microarray cohort including 611 patients with HNSCC and evaluated for survival in several clinicopathological subgroups. A TCGA HNSCC cohort was used to further analyze the role of TSPO in HNSCC. TSPO expression was downregulated in more aggressive tumors. Low TSPO expression associated with worse 5-year survival and was an independent prognostic factor for disease-specific survival. Subgroup analyses showed that low TSPO expression associated with worse survival particularly in p16-positive oropharyngeal cancer. In silico analyses supported the prognostic role of TSPO. Cellular respiration had the highest significance in pathway analyses for genes expressed positively with TSPO. Decreased TSPO expression associates with poor prognosis in HNSCC. TSPO is a prognostic biomarker in HNSCC to potentially guide treatment stratification especially in p16-positive oropharyngeal cancer.

Capacidad pronóstica del PIV (pan-immune-inflammation value) en pacientes con carcinoma escamoso de cabeza y cuello

IntroductionThe pan-immune-inflammation value (PIV), an index that results from the following ratio: (neutrophils×monocytes×platelets) / lymphocytes, has been proposed as a prognostic biomarker in different tumor models. The aim of this study is to analyze the prognostic capacity of PIV in patients with head and neck squamous cell carcinoma. Patients and methodsRetrospective study of 1,187 patients with head and neck squamous cell carcinoma treated at our center between 2000-2017. PIV value was obtained from an analysis performed within 3 weeks prior to the start of treatment. ResultsPIV value was significantly associated with toxic consumption (0.001), tumor location (0.0001), tumor extension (0.0001), and histological grade (0.016). Four categories were defined based on PIV value using a recursive partitioning analysis: category i: PIV<136.3 (n=118, 9.9%), category ii: PIV 136.3-451.1 (n=594, 50.0%), category iii: PIV 451.1-1,141.2 (n=357, 30.1%), and category iv: PIV>1,141.2 (n=118, 9.9%). A significant and ordered decrease in disease-specific survival was observed as the PIV category increased. This decrease in survival was independent of the type of treatment, tumor extension, or location of the primary tumor. The PIV category was an independent prognostic factor of disease-specific survival in a multivariable study. ConclusionsPIV is a prognostic biomarker in patients with head and neck squamous cell carcinoma.

Epidemiology and survival outcomes of patients with orbital region non-cutaneous squamous cell carcinoma: a population-based analysis.

Non-cutaneous squamous cell carcinoma (ncSCC) of the orbital region is very rare. Thus, its epidemiological characteristics and prognosis are poorly understood. The aim of the study was to assess the epidemiological characteristics and survival outcomes of ncSCC of the orbital region. Incidence and demographic data on ncSCC of the orbital region were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and analyzed. The chi-square test was used to calculate the differences between groups. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for disease-specific survival (DSS) and overall survival (OS). The overall incidence of ncSCC in the orbital region from 1975 to 2019 was 0.68/1,000,000, and the incidence showed an increasing trend during this period. A total of 1,265 patients with ncSCC of the orbital region (mean age, 65.3 years) were identified in the SEER database. Of these, 65.1% were aged ≥60 years, 87.4% were White, and 73.5% were male. The conjunctiva (74.5%) was the most common primary site, followed by the orbit (12.1%), lacrimal apparatus (10.8%), and overlapping lesion of the eye and adnexa (2.7%). Multivariate Cox regression analysis revealed that age, primary site, SEER summary stage, and surgery were independent prognostic factors for DSS, whereas age, sex, marital status, primary site, SEER summary stage, and surgery were independent prognostic factors for OS. The incidence of ncSCC in the orbital region has increased over the past 40 years. It usually affects White people, men, and people aged ≥60 years, and its most common site is the conjunctiva. Orbital SCC has worse survival outcomes than SCC of other sites in the orbital region. Surgery is the independent protective treatment for ncSCC of the orbital region.

Five- and 10-year survival in extramammary Paget's disease: A focus on wide local excision.

This study aimed to analyze extramammary Paget's disease (EMPD)-specific survival, overall survival, and recurrence rate (RR) in patients with EMPD in South Korea, with a focus on wide local excision. We retrospectively reviewed the medical records of patients with EMPD from 1993 to 2020 at Kyungpook National University Hospital. We determined the survival and RRs after wide local excision. A total of 95 patients (66 males and 29 females; mean age 67.4 years) were included. The 5-year disease-specific survival and overall survival were 91.8% and 79.3%, respectively, whereas the 10-year rates were 81.6% and 64.7%, respectively. No significant sex differences were observed. Seventy-five patients (78.9%) underwent wide local excision. Mucosal involvement and lymphadenopathy were identified as the significant prognostic factors of disease-specific survival in multivariate analysis. The RR was 14.7% in patients who underwent wide local excision: seven local, two regional, and two distant metastases, with a mean recurrence-free interval of 42.3 months. Based on the survival and RRs obtained, surgical treatment of EMPD with wide local excision provides fair curative resection. Wide local excision can be a feasible treatment option for extramammary Paget's disease.

Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder

BackgroundWith the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer.MethodsThe expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically.ResultsIn UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle.ConclusionsLow expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Jumonji domain-containing protein RIOX2 is overexpressed and associated with worse survival outcomes in prostate cancers.

Histone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown. Transcriptomic profiles of Jumanji domain-containing protein genes were assessed using multiple public expression datasets generated from RNA-seq and cDNA microarray assays. RIOX2 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Gene expression profiles were analyzed using the bioinformatics software R package. Western blot assay examined androgen stimulation on RIOX2 protein expression in LNCaP cells. Among 35 Jumanji domain-containing protein genes, 12 genes were significantly upregulated in prostate cancers compared to benign compartments. COX regression analysis identified that the ribosomal oxygenase 2 (RIOX2) gene was the only one significantly associated with disease-specific survival outcomes in prostate cancer patients. RIOX2 upregulation was confirmed at the protein levels using immunohistochemical assays on prostate cancer tissue sections. Meanwhile, RIOX2 upregulation was associated with clinicopathological features, including late-stage diseases, adverse Gleason scores, TP53 gene mutation, and disease-free status. In castration-resistant prostate cancers (CRPC), RIOX2 expression was positively correlated with AR signaling index but negatively correlated with the neuroendocrinal progression index. However, androgen treatment had no significant stimulatory effect on RIOX2 expression, indicating a parallel but not a causative effect of androgen signaling on RIOX2 gene expression. Further analysis discovered that RIOX2 expression was tightly correlated with its promoter hypomethylation and MYC gene expression, consistent with the notion that RIOX2 was a c-Myc target gene. The Jumanji domain-containing protein RIOX2 was significantly overexpressed in prostate cancer, possibly due to c-Myc upregulation. RIOX2 upregulation was identified as an independent prognostic factor for disease-specific survival.

MYEOV overexpression induced by demethylation of its promoter contributes to pancreatic cancer progression via activation of the folate cycle/c-Myc/mTORC1 pathway

BackgroundWhile molecular targeted drugs and other therapies are being developed for many tumors, pancreatic cancer is still considered to be the malignant tumor with the worst prognosis. We started this study to identify prognostic genes and therapeutic targets of pancreatic cancer.MethodsTo comprehensively identify prognostic genes in pancreatic cancer, we investigated the correlation between gene expression and cancer-specific prognosis using transcriptome and clinical information datasets from The Cancer Genome Atlas (TCGA). In addition, we examined the effects of the suppression of candidate prognostic genes in pancreatic cancer cell lines.ResultWe found that patients with high expression levels of MYEOV, a primate-specific gene with unknown function, had significantly shorter disease-specific survival times than those with low expression levels. Cox proportional hazards analysis revealed that high expression of MYEOV was significantly associated with poor survival and was an independent prognostic factor for disease-specific survival in pancreatic cancer patients. Analysis of multiple cancer samples revealed that the MYEOV promoter region is methylated in noncancer tissues but is demethylated in tumors, causing MYEOV overexpression in tumors. Notably, the knockdown of MYEOV suppressed the expression of MTHFD2 and other folate metabolism-related enzyme genes required for the synthesis of amino acids and nucleic acids and also restored the expression of c-Myc and mTORC1 repressors.ConclusionThere is a significant correlation between elevated MYEOV expression and poor disease-specific survival in pancreatic cancer patients. MYEOV enhances the activation of several oncogenic pathways, resulting in the induction of pancreatic cancer cell proliferation. Overall, MYEOV acts as an oncogene in pancreatic cancer. Furthermore, MYEOV may be a prognostic biomarker and serve as an ‘actionable’ therapeutic target for pancreatic cancers.

Prognostic Nomogram and Competing Risk Analysis of Death for Primary Thyroid Lymphoma: A Long-term Survival Study of 1638 Patients.

A total of 1638 PTL patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. We have identified through Cox analysis that age in years, diffuse large B-cell lymphoma (DLBCL) pathology, lymph node dissection, radiation, and chemotherapy were independent prognostic factors for disease-specific survival (DSS). Based on these findings, we built a nomogram for predicting 5- and 10-year DSS and analyzed the overall survival (OS) by calculating cumulative incidence of death. The overall cumulative incidences of the 5- and 10-year PTL-specific cumulative death probabilities were 14.0% (95% CI: 12.3%-15.9%) and 16.3% (95% CI: 14.4%-18.4%), respectively, while the 5- and 10-year cumulative death probabilities from other causes were 12.4% (95% CI: 10.6%-12.3%) and 24.7% (95% CI: 22.1%-27.4%). Results from the competing risk hazards regression analysis revealed that older age and Ann Arbor grading were associated with a greater probability of death from other causes and death from PTL. Radioactive therapy by external beam radiation was associated with death from other causes only. DLBCL histology, lymph node dissection, and chemotherapy were correlated with death from PTL. Cumulative incidence curves demonstrated that the pathological type of lymphoma is the factor determining the likelihood of dying from PTL versus other causes. Patients' age, Ann Arbor stage, pathological type of lymphoma, and the use of specific therapy regimen should all be taken into consideration when devising individualized treatment strategies for PTL. Decision models based on our findings may help clinicians make better decisions by taking into account the competing risk of death from causes other than PTL.

Prognostic Value of a Modified Albumin-Bilirubin Score Designed for Patients with Esophageal Squamous Cell Carcinoma After Radical Resection.

The albumin-bilirubin (ALBI) score was originally developed to assess the severity of liver dysfunction in patients with hepatocellular carcinoma and has subsequently been used as a prognostic marker for that disease. Here, we examined the value of the preoperative ALBI score as a prognostic marker for patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. We retrospectively analyzed data from 449 patients who underwent curative resection for ESCC. The ALBI score was calculated as (log10 serum bilirubin [μmol/l] × 0.66) + (serum albumin [g/l] × - 0.0852). Receiver operating characteristic curve analysis was used to define a preoperative modified ALBI (mALBI) score for patient stratification. Of the 449 ESCC patients, 232 and 217 were assigned to mALBI Grade 1 or Grade 2 groups based on preoperative ALBI scores of ≤ - 3.33 or > - 3.33, respectively. Preoperative mALBI grade was significantly associated with age, excessive alcohol consumption, squamous cell carcinoma antigen level, and clinical disease stage. The mALBI Grade 2 group had significantly shorter disease-specific and recurrence-free survival than the mALBI Grade 1 group. Multivariate analysis demonstrated that mALBI Grade 2 was an independent prognostic factor for disease-specific survival (hazard ratio 1.86, 95% confidence interval 1.18-2.93, P = 0.0074). In most subgroup analyses, mALBI Grade 2 was associated with a greater risk of disease-specific death. mALBI grade serves as a simple and useful prognostic marker for disease-specific survival in patients with ESCC after radical esophagectomy.

The preoperative G8 geriatric screening tool independently predicts survival in older patients with endometrial cancer: results of a retrospective single-institution cohort study

PurposeThe aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival.MethodsPreoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan–Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters.Results153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35–15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31–6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively).ConclusionsThis is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS).MethodsBetween 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines.ResultsDSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0–57.6 vs. 20.6 months, 95% CI 10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19–9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02–2.16], lymph node metastases N1–2 (HR 1.71, 95% CI 1.16–2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453).ConclusionsOur results indicate that the pancreatic stroma is associated with PDAC patients’ DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Disease-Specific Survival of AJCC 8th Stage II Gastric Cancer Patients After D2 Gastrectomy.

The association between the risk factors and long-term prognosis in patients with stage II gastric cancer after radical gastrectomy has been fully revealed. The purpose of this study was to investigate the independent risk factors for treatment failure in stage II gastric cancer. Demographic, clinical, and pathological information of 247 stage II gastric cancer patients who underwent radical D2 gastrectomy in our department between January 2011 and December 2014 were collected and retrospectively analyzed. The relationship between and long-term clinical outcomes of stage II gastric cancer was analyzed using t-tests, chi-square tests, receiver operating characteristic (ROC) analysis, time-dependent ROC analysis, K–M curves, and a Cox regression model. The median follow-up of 247 stage II gastric cancer patients was 5.49 years (range: 0.12–8.62 years). The Kaplan–Meier estimated 3-year and 5-year DSS rates of the study group were 92.7% (95% CI 89.4–95.9) and 88.7% (95% CI 84.7–92.7), respectively. Higher age (>70 vs. ≤70, log-rank p = 0.0406), nerve invasion (positive vs. negative, log-rank p = 0.0133), and non-distal gastrectomy (distal partial gastrectomy vs. other surgical methods, log-rank p = 0.00235) had worse prognoses compared to controls. Univariate and multivariate analyses of disease-specific survival showed that these three factors were independent prognostic factors for patients with stage II disease. The area under time-dependent ROC curve (AUC) is 0.748 of 5-year survival and c-index is 0.696 based on the three-marker model drawn for stage II patients. Subgroup analyses showed an interaction between tumor location and nerve invasion. The age, perineural invasion, and surgical approach are independent prognostic factors for disease-specific survival after radical gastrectomy. Tumor location may be an important confounding factor for outcomes by affecting surgical methods and the hazards of nerve invasion.

Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients.

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

A SEER analysis of survival and prognostic factors in merkel cell carcinoma of the head and neck region

While Merkel cell carcinoma (MCC) of the head and neck is highly malignant, it remains poorly characterized due to its rarity. The purpose of this study was to examine prognostic factors for overall survival (OS) and disease-specific survival (DSS) in patients with MCC of the head and neck region. The Surveillance, Epidemiology and End Results registry was reviewed for patients diagnosed between 1984 and 2016 with histologically confirmed, primary MCC of the head and neck region. A total of 2818 patients met the inclusion criteria, with a median age at diagnosis of 77 years. At five and 10 years, respectively, the OS was 42.4% and 25.1% and the DSS was 67.9% and 64.1%. Multivariate Cox analysis indicated that predictors of decreased DSS included age at diagnosis ≥75 years, white race, increasing tumor spread, lymph node involvement and either the lip or the scalp/neck as a primary site. When adjusting for the aforementioned factors, tumor depth was not found to be a prognostic factor for DSS. We anticipate these results will help clinicians to counsel patients regarding expectations and potential prognosis.