Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival.

BACKGROUND: Breast cancers exhibit considerable heterogeneity in their biology, immunology, and prognosis. Currently, no validated, serum protein-based tools are available to evaluate the prognosis of patients with early breast cancer. METHODS: The study population consisted of 521 early-stage breast cancer patients with a median follow-up of 8.9 years. Additionally, 61 patients with breast fibroadenoma or atypical ductal hyperplasia were included as controls. We used a proximity extension assay to measure the preoperative serum levels of 92 proteins associated with inflammatory and immune response processes. The invasive cancers were randomly split into discovery (n = 413) and validation (n = 108) cohorts for the statistical analyses. RESULTS: Using LASSO regression, we identified a nine-protein signature (CCL8, CCL23, CCL28, CSCL10, S100A12, IL10, IL10RB, STAMPB2, and TNFß) that predicted various survival endpoints more accurately than traditional prognostic factors. In the time-dependent analyses, the prognostic power of the model remained rather stable over time. We also developed and validated a 17-protein model with the potential to differentiate benign breast lesions from malignant lesions (Wilcoxon p < 2.2*10- 16; AUC 0.94). CONCLUSIONS: Inflammation and immunity-related serum proteins have the potential to rise above the classical prognostic factors of early-stage breast cancer. They may also help to distinguish benign from malignant breast lesions.

p53 as a Potential Actionable Target in Myxofibrosarcoma: A Molecular and Pathologic Review of a Single-Institute Series.

Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by high-local recurrence rate, poorly understood molecular pathogenesis, lack of specific prognostic markers, and effective targeted therapies. To gain further insights into the disease, we analyzed a well-defined group of 133 primary MFS cases. Immunohistochemical (IHC) staining for p53, MET, RET, and RB was performed. Twenty-five cases were analyzed by targeted resequencing of known cancer driver hotspot mutations, whereas 66 and 64 MFSs were examined for the presence of genetic variants in TP53 and MET gene, respectively. All clinical, histologic, immunostaining, and genetic variables were analyzed for their impact on 5-years overall survival (OS) and 5-years event-free survival (EFS). In our series, no grade I tumors relapsed and high grade are related to a positive MET immunostaining (P = .034). Both local recurrence (P = .038) and distal metastases (P = .016) correlated to the presence of "single nucleotide variant (SNV) plus copy number variation (CNV)" in TP53. Multivariate analysis revealed that age (>60 years), metastasis at presentation, and positive IHC-p53 signal are risk factors for a poor OS (P = .003, P = .000, and P = .002), whereas age (>60 years), synchronous metastasis, and tumor size (>10 cm) predict an unfavorable 5-years EFS (P = .011, P = .000, and P = .023). Considering the smaller series (n = 66) that underwent molecular screening, the presence of "SNV+CNV" in TP53 represents a risk factor for a worse 5-years EFS (hazard ratio, 2.5; P = .017). The present series confirms that TP53 is frequently altered in MFS (86.4% of cases), appearing to play an important role in MFS tumorigenesis and being a potentially drugable target. A positive p53 immunostainings is related to a poor diagnosis, and it is the presence of a single nucleotide genetic alterations in TP53 that is essential in conferring MFS an aggressive phenotype, thus supporting the use of molecular profiling in MFS to better define the role of p53 as a prognostic factor.

Effect of body mass index on the prognosis of children and adolescents with high-grade mature B-cell non-Hodgkin lymphoma.

BACKGROUND: Little progress has been made in determining the prognostic factors for children and adolescents with high-grade mature B-cell non-Hodgkin lymphoma (HG B-NHL). Based on the important role of body mass index (BMI) in cancer, this study explored the effect of BMI on the prognosis of patients with HG B-NHL. METHODS: Patients aged <18 years with newly diagnosed HG B-NHL were enrolled. Patients were divided into normal, overweight, obese, and emaciated BMI groups according to the growth criteria for children and adolescents. RESULTS: In total, 435 patients were enrolled in this study. There were 329 (75.6%), 46 (10.6%), 13 (3.0%), and 47 (10.8%) patients stratified into the normal, overweight, obese, and emaciated BMI groups, respectively. The event-free survival and overall survival rates of the entire cohort were 89.3% and 92.4%, respectively. The 5-year event-free survival rate for the patients with obese BMI was worse than those with overweight BMI (76.2% vs. 95.6%, p = .04). The 5-year overall survival rate for the patients with emaciated BMI was worse than those with normal (84.5% vs. 93.1%, p = .04) or overweight BMI (84.5% vs. 97.7%, p = .03). Cox multivariate analysis showed that obese or emaciated BMI at diagnosis was associated with an increased risk of death (p = 0.04; HR, 2.26) and was identified as an independent adverse prognostic factor in pediatric HG B-NHL. CONCLUSION: Obese or emaciated BMI at diagnosis is associated with poor prognosis in pediatric HG B-NHL and can be used for risk stratification.

MOAI: a multi-outcome interaction identification approach reveals an interaction between vaspin and carcinoembryonic antigen on colorectal cancer prognosis.

Identifying and characterizing the interaction between risk factors for multiple outcomes (multi-outcome interaction) has been one of the greatest challenges faced by complex multifactorial diseases. However, the existing approaches have several limitations in identifying the multi-outcome interaction. To address this issue, we proposed a multi-outcome interaction identification approach called MOAI. MOAI was motivated by the limitations of estimating the interaction simultaneously occurring in multi-outcomes and by the success of Pareto set filter operator for identifying multi-outcome interaction. MOAI permits the identification for the interaction of multiple outcomes and is applicable in population-based study designs. Our experimental results exhibited that the existing approaches are not effectively used to identify the multi-outcome interaction, whereas MOAI obviously exhibited superior performance in identifying multi-outcome interaction. We applied MOAI to identify the interaction between risk factors for colorectal cancer (CRC) in both metastases and mortality prognostic outcomes. An interaction between vaspin and carcinoembryonic antigen (CEA) was found, and the interaction indicated that patients with CRC characterized by higher vaspin (≥30%) and CEA (≥5) levels could simultaneously increase both metastases and mortality risk. The immunostaining evidence revealed that determined multi-outcome interaction could effectively identify the difference between non-metastases/survived and metastases/deceased patients, which offers multi-prognostic outcome risk estimation for CRC. To our knowledge, this is the first report of a multi-outcome interaction associated with a complex multifactorial disease. MOAI is freely available at https://sites.google.com/view/moaitool/home.

Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

BACKGROUND: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. PATIENTS AND METHODS: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. RESULTS: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. CONCLUSION: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

BACKGROUND: Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. METHODS: This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). CONCLUSIONS: One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery : A Retrospective Cohort Study.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Preoperative Prediction of Long-Term Survival After Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

Survival outcomes and treatment experience of 124 patients with primary central nervous system lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare malignancy of the central nervous system with high invasiveness. There is little consensus on the treatment of PCNSL. This study retrospectively studied data from PCNSL patients in a single center to summarize treatment experience and explore prognostic factors. METHODS: Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: In multivariate analysis, cerebrospinal fluid lactic acid dehydrogenase (CSF LDH; p = 0.005 and p = 0.002), neutrophil to lymphocyte ratio (NLR; p = 0.014 and p = 0.038), and completion of four cycles of induction therapy (p < 0.001and p < 0.001) were significant and independent predictors of overall survival (OS) and progression-free survival (PFS), respectively. CONCLUSION: On the basis of this study, we propose that PCNSL patients should receive early induction therapy with sufficient cycles. Subsequent consolidation therapy can prevent relapses and improve survival. In patients with PCNSL, the independent prognostic factors for OS and PFS were CSF LDH level, NLR, and full cycles of induction therapy.

Recent treatment and prognosis in 643 patients with extramammary Paget's disease.

Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.

Low serum apolipoprotein A1 level predicts poor prognosis of patients with diffuse large B-cell lymphoma in the real world: a retrospective study.

BACKGROUND: Apolipoprotein A1 (ApoA1) is a member of the apolipoprotein family with diverse functions. It is associated with the pathogenesis and prognosis of several types of tumors. However, the role of serum apolipoprotein A1 (ApoA1) in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to elucidate its influence on clinical outcomes in patients with DLBCL. METHODS: We retrospectively analyzed a cohort of 1583 consecutive DLBCL patients admitted to the Fujian Medical University Union Hospital between January 2011 and December 2021. 949 newly diagnosed DLBCL patients who met the inclusion criteria were enrolled for statistical analysis. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value for serum ApoA1 levels for prognostic prediction among patients with DLBCL. The correlations between serum ApoA1 levels and clinical and laboratory parameters were analyzed. Prognostic significance was analyzed using univariate and multivariate Cox proportional hazards models. RESULTS: Newly diagnosed patients with DLBCL demonstrated low serum ApoA1 levels (< 0.925 g/L), had more B symptoms, higher levels of serum lactate dehydrogenase (LDH) (>upper limit of normal), poorer performance status (Eastern Cooperative Oncology Group score of 2-4), higher percentage of advanced stage and non-germinal center B-cell (non-GCB) subtype, more cases of > 1 extranodal site, higher International Prognostic Index (IPI) score (3-5), and higher incidence of relapse or refractory diseases compared with those with high serum ApoA1 levels (≥ 0.925 g/L). Low serum ApoA1 levels were an independent adverse prognostic factor for overall survival (OS) but not progression-free survival (PFS). CONCLUSIONS: Low serum ApoA1 levels were associated with poor treatment response and inferior survival in newly diagnosed patients with DLBCL.

A preliminary study of IgG4 expression and its prognostic significance in oral squamous cell carcinoma.

BACKGROUND: IgG4, which plays a pivotal role in the progression of phenotypically diverse tumors, serves as a prognostic marker because of its influence on cancer immunity. Nevertheless, the functions of IgG4 in tongue squamous cell carcinoma (TSCC) remained to be identified. METHODS: To evaluate the significance of IgG4 expression in TSCC, we performed immunohistochemical analysis of patients with TSCC (n = 50) to evaluate the correlation of IgG4 expression with patients' clinicopathological features and prognoses. RESULTS: Higher IgG4 expression detected in TSCC tissues was associated with the less advanced mode of invasion (Yamamoto-Kohama [YK] 1-3) (P = 0.031) and with well-differentiated TSCC (P = 0.077). Kaplan-Meier analyses revealed that the higher IgG4 expression group exhibited better prognosis indicated by overall survival (OS) (P = 0.04) and recurrence-free survival (RFS) (P = 0.016). Univariate analysis of OS indicated that IgG4 expression was associated with longer OS (P = 0.061), and multivariate analysis of RFS revealed that IgG4 expression served as an independent prognostic factor for longer RFS (P = 0.005). CONCLUSION: These results indicate that relatively higher IgG4 levels serve as a favorable prognostic factor for TSCC.

AP-2α gene deregulation is associated with renal cell carcinoma patient survival.

BACKGROUND: Renal cell carcinoma (RCC), one of the most fatal urologic tumors, accounts for approximately 3% of all adult cancers and exhibits a high metastatic index at diagnosis and a high rate of relapse. Radical or partial nephrectomy is a curative option for nonmetastatic RCCs. Targeted therapy has been shown to improve the survival of patients with metastatic RCCs. However, the underlying cellular and molecular events associated with RCC pathogenesis are not well known. METHODS: To investigate the clinical role of the transcription factor activator protein (AP)-2α in RCC, methylated CpG island recovery assays and microarray analysis were employed. COBRA and RT‒qPCR assays were performed to assess AP-2α expression in RCC. RESULTS: A negative correlation was noted between AP-2α mRNA expression levels and methylation status. Multivariate analyses showed that AP-2α mRNA was a major risk factor not only for overall and disease-free survival in RCC but also for disease-free survival in clear cell RCC. CONCLUSIONS: Our results indicated that AP-2α expression was deregulated in RCC and associated with overall patient survival and disease-free survival. Such findings suggest that AP-2α might play an important role in the pathogenesis of RCC.

Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study.

BACKGROUND: Endometrial cancer is the most common gynecological malignancy; however, there is no useful blood diagnostic biomarker. This study aimed to determine the utility of tissue factor pathway inhibitor 2 (TFPI2), a biomarker of ovarian cancer, as a diagnostic marker for endometrial cancer. METHODS: We examined serum TFPI2 levels in patients with endometrial cancer (n = 328) compared to those in healthy controls (n = 65) and evaluated the performance of serum TFPI2 levels as a diagnostic marker. We investigated the clinicopathological characteristics of patients with TFPI2-negative and TFPI2-positive endometrial cancer. Using immunohistochemistry (IHC), we examined TFPI2 expression in tumor tissues of 105 patients with type II endometrial carcinoma and evaluated the correlation between serum and tissue TFPI2 positivity. RESULTS: Patients with endometrial cancer had significantly higher serum TFPI2 levels than controls (196.7 pg/mL vs. 83.3 pg/mL; p < 0.001). The sensitivity and specificity were 54.3% and 95.4%, respectively (cutoff value, 191 pg/mL). Serum TFPI2 levels were significantly elevated along with the stage progression (stage I, 189.6 pg/mL; stage III, 230.9 pg/mL; stage IV, 312.5 pg/mL; p < 0.001). Patients with high-risk histology showed significantly elevated serum TFPI2 levels than those with low-risk histology (220.8 pg/mL vs. 187.7 pg/mL; p < 0.001). The positivity rate for TFPI2 was the highest among tumor markers, including CA125, CA19-9, and CEA. Serum TFPI2 and CA125 levels were almost independent (r = 0.203, p < 0.001), and the combined sensitivity increased to 58.8%. The 5-year survival rate was significantly worse in TFPI2-positive patients (≥ 191 pg/mL, n = 178) than in TFPI2-negative patients (< 191 pg/mL, n = 150) (hazard ratio, 8.22; 95% confidence interval, 2.49-27.1; p < 0.001). TFPI2 immunostaining revealed that 37.1% (39/105) of the samples were positive for TFPI2, with an IHC score of > 0. There was no significant difference in the immunostaining score according to histological type. Serum TFPI2 levels and immunostaining score showed poor agreement (kappa coefficient, -0.039). CONCLUSIONS: The serum TFPI2 level is a promising marker for diagnosing and predicting the prognosis of endometrial cancer. No correlation exists between serum and tissue TFPI2 levels. Further multicenter clinical trials are needed to test the utility of TFPI2 as a diagnostic marker.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

Gender Differences in Lung Neuroendocrine Tumors: A Single-Center Experience.

INTRODUCTION: Gender difference may affect lung neuroendocrine tumor (L-NET) onset, progression, and outcomes as emerged in other cancers. This study aimed to analyze gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies. METHODS: Patients with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023, were retrospectively evaluated. RESULTS: Among 48 patients with L-NEN, 38 (79.2%) with sporadic L-NET were enrolled: 22 typical (57.9%) and 16 atypical (42.1%) carcinoids, 22 (57.9%) female and 16 (42.1%) male, mean age at diagnosis 57.3 years (range 16-84). Median follow-up was 70.5 months (range 12-305). No statistical difference resulted regarding smoking habit, BMI, primary site (left/right and central/peripheral), and histological characteristics, between cohorts. Metastasis at diagnosis was found in 20 patients (52.3%), 10 female (10%) and 10 male (10%) (p: 0.20). Progressive disease (PD) was observed in 14 (36.8%) patients, and male sex developed PD more frequently 9/14 (64.3%) than female 5 (35.7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistical difference, 7 male/10 (70%), p: 0.06. Among 9 deaths (23.7%), 7 (77.8%) were men and 7 died for PD, p < 0.03. Male had a poorer prognosis than female regarding progression-free survival (PFS) (p: 0.04) and overall survival (p: 0.001), also when sub-groups of patient metastatic at diagnosis were compared (p: 0.02 and p: 0.02). CONCLUSIONS: This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumor type, stage, and treatment, with regard to PFS, OS, and metastatic spread. These findings may suggest a closer follow-up in men, with potential positive impact on outcomes.

Patient's self-reported quality of life as a prognostic factor in metastatic renal cell carcinoma initially treated with TKI: nomogram proposal.

BACKGROUND: Numerous prognostic factors have been described for metastatic renal cell carcinoma (mRCC). There are nomograms to assist in clinical decision-making and inform patients of their disease progression. However, they have a limited capacity and moderate concordance rates. Performance status (PS) is one of the most widely used prognostic factors and most closely related to overall survival (OS), but this is a subjective assessment based solely on the clinician's opinion. Patients must be at the center of care. Patient-reported outcomes (PROs) have shown benefits but are not widespread in daily clinical practice. METHODS: We analyzed 78 consecutive patients diagnosed with mRCC who initiated treatment at our institution between September 2012 and September 2019. We performed a descriptive analysis of the sample's baseline characteristics and the NCCN FKSI 19 questionnaire. We also conducted a survival analysis. RESULTS: The baseline FKSI 19 score demonstrates its prognostic potential, HR of 0.94 (95% CI 0.92-0.97). Our prognostic model would include: FKSI < 58 (HR 3.61 95% CI 1.97-6.61), anemia, thrombocytosis, non-clear cell histology, and metastatic hepatic involvement. AUC 0.86 (95%CI 0.77-0.95). CONCLUSION: Although it would need external validation, the proposed nomogram could be an alternative to other previously described models. The NCCN FKSI 19 baseline score could replace the clinician's subjective determination of PS. CLINICAL TRIAL REGISTRATION: Not applicable.

Establishment of Prognostic Nomogram for Male Breast Cancer Patients: A Surveillance, Epidemiology and End Results Database Analysis.

BACKGROUND: Male breast cancer (MBC) represents a rare subtype of breast cancer, with limited prognostic factor studies available. The purpose of this research was to develop a unique nomogram for predicting MBC patient overall survival (OS) and breast cancer-specific survival (BCSS). METHODS: From 2010 to 2020, clinical characteristics of male breast cancer patients were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Following univariate and multivariate analyses, nomograms for OS and BCSS were created. Kaplan-Meier plots were further generated to illustrate the relationship between independent risk variables and survival. The nomogram's ability to discriminate was measured by employing the area under a time-dependent receiver operating characteristic curve (AUC) and calibration curves. Additionally, when the nomogram was used to direct clinical practice, we also used decision curve analysis (DCA) to evaluate the clinical usefulness and net clinical benefits. RESULTS: A total of 2143 patients were included in this research. Univariate and multivariate analysis showed that age, grade, surgery, chemotherapy status, brain metastasis status, subtype, marital status, race, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with OS. Lung metastasis, age, marital status, grade, surgery, and AJCC-T, AJCC-N, and AJCC-M stages were significantly correlated with BCSS. By comprising these variables, a predictive nomogram was constructed in the SEER cohort. Then, it could be validated well in the validation cohort by receiver operating characteristics (ROCs) curve and calibration plot. Furthermore, the nomogram demonstrated better decision curve analysis (DCA) results, indicating the ability to forecast survival probability with greater accuracy. CONCLUSION: We created and validated a unique nomogram that can assist clinicians in identifying MBC patients at high risk and forecasting their OS/BCSS.