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β-secretase 1, one of the most important proteins, is an aspartate protease. This membrane-associated protein is used for treating Alzheimer’s disease (AD). Several inhibitors have been pursued against β-secretase 1, but they still have not resulted effectively. Virtual screening based on pharmacophores has been shown to be useful for lead optimization and hit identification in the preliminary phase of developing a new drug. Here, we screen the commercially available databases to find the hits against β-secretase 1 for drug discovery against AD. Virtual screening for 200,000 compounds was done using the database from the Vitas-M Laboratory. The phase screen score was utilized to assess the screened hits. Molecular docking was performed on compounds with phase scores >1.9. According to the study, the 66H ligand of the crystal structure has the maximum performance against β-secretase 1. The redocking of the co-crystal ligand showed that the docked ligand was seamlessly united with the crystal structure. The reference complex had three hydrogen bonds with Asp93, Asp289, and Gly291; one van der Waals interaction with Gly74; and three hydrophobic interactions. After equilibration, the RMSD of the reference compound sustained a value of ∼1.5 Å until 30 ns and then boosted to 2.5 Å. On comparison, the RMSD of the S1 complex steadily increased to ∼2.5 Å at 15 ns, displayed slight aberrations at approximately ∼2.5–3 Å until 80 ns, and then achieved steadiness toward the end of the simulation. The arrangements of proteins stayed condensed during the mockup when bonded to these complexes as stable Rg values showed. Furthermore, the MM/GBSA technique was employed to analyze both compounds’ total binding free energies (ΔGtotal). Our research study provides a new understanding of using 66H as anti-β-secretase 1 for drug development against AD.

Abstract Background This research aimed to investigate the prognostic factors of oral squamous cell carcinoma (OSCC), especially the role of age. Methods A total of 33,619 cases of OSCC were received from the Surveillance, Epidemiology, and End Results (SEER) database during 2005–2015. Kaplan–Meier curves of 5-year overall survival rates and 5-year cancer-specific survival rates were performed, and univariate and multivariate Cox regression analyses as well as competing risk model were used to help understand the relationship between various factors and mortality of OSCC. Results Compared to 18–39-year-old group, the older age was an important predictor of worse prognosis. The multivariate analysis of overall survival (OS) was 50–59 years (HR, 1.32; 95% CI 1.17–1.48; p ≤ .001), 60–69 years (HR, 1.66; 95% CI 1.42–1.87; p ≤ .001) and 70 + years (HR, 3.21; 95% CI 2.86–3.62; p ≤ .001), respectively, while the specific value of competing risk model was 60–69 years (HR, 1.21; 95% CI 1.07–1.38; p = .002) and 70 + years (HR, 1.85; 95% CI 1.63–2.10; p ≤ .001). In addition, female gender, unmarried, Blacks, tumor in floor of mouth, size and higher Tumor Node Metastasis (TNM) classification were also other predictors that signify significant clinically deterioration of OS/cancer-specific survival (CSS). Conclusions Our research revealed that age was an important factor in explaining the difference of survival in the whole process of OSCC. It is suggested that we should pay attention to the influence of age on diagnosis, treatment and prognosis in the clinical process.

With the rapid development of integrated circuits, glass substrates are frequently utilized for prototyping various functional electronic circuits due to their superior stability, transparency, and signal integrity. In this experiment, copper wire was printed on a glass substrate using inkjet printing, and the electronic circuit was sintered through laser irradiation with a 532 nm continuous green laser. The relationship between resistivity and microstructure was analyzed after laser sintering at different intensities, scanning speeds, and iterations. The experimental results indicate that the conductivity of the sintered lines initially increases and then decreases with an increase in laser power and scanning speed. At the same power level, multiple sintering runs at a lower scanning speed pose a risk of increased porosity leading to reduced conductivity. Conversely, when the scanning speed exceeds the optimal sintering speed, multiple sintering runs have minimal impact on porosity and conductivity without altering the power.

BackgroundNeoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations.MethodsThis review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model.ResultsSixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle.ConclusionThis study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

BackgroundThe prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer).MethodsWe selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions.ResultsWe have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors.ConclusionsThe current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.

Background: Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for monitoring early non-small cell lung cancer (ENSCLC), particularly after radical surgery. However, the prognostic value of postoperative ctDNA is still being investigated due to the small sample size and heterogeneity of patients with ENSCLC in current trials. Moreover, the potential clinical utility of ctDNA assessment for administering adjuvant therapy (AT) in patients with ENSCLC is also an important area of active research. Objectives: We aimed to identify the prognostic value of postoperative ctDNA detection in ENSCLC patients with stages I–III. Design: This study type is a systematic review and meta-analysis. Data sources and methods: We conducted a search in the Cochrane Library, Embase, PubMed, and ScienceDirect for prospective or retrospective investigations involving patients with ENSCLC, gathering outcomes based on predefined end points. The literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Newcastle–Ottawa scale was employed to carry out a quality evaluation of the included studies. The primary end point of the study was to evaluate the association of ctDNA status in two time points (within 1 month after surgery and long-term postoperative monitoring with more than 3 months) with relapse-free survival (RFS) and overall survival (OS). In addition, the study investigated the role of ctDNA in predicting the response to AT. The secondary end points of the study were to determine the impact of ctDNA on RFS and OS in different subgroups of ENSCLC patients based on pathological subtypes and TNM staging. Results: In total, 2149 studies were screened, and 11 studies met the inclusion criteria for the analysis. The presence of ctDNA within 1 month after surgery as well as long-term postoperative ctDNA were both associated with poorer RFS [hazard ratio (HR) = 4.43; 95% CI: 3.23–6.07 and HR = 7.99; 95% CI: 3.28–19.44, respectively] and worse OS (HR = 5.07; 95% CI: 2.80–9.19 and HR = 7.49; 95% CI: 3.42–16.43, respectively). Most subgroup analyses yielded similar results. Moreover, ctDNA-positive patients could acquire survival benefits from AT (HR = 0.30; 95% CI: 0.16–0.54), while ctDNA-negative patients that received AT did not show significant improvement in RFS (HR = 1.18; 95% CI: 0.67–2.09). Conclusion: The postoperative ctDNA assessment is a promising approach to stratify the risk of relapse and death in ENSCLC patients. Our data suggest that patients with negative ctDNA in the postoperative setting may not benefit from AT, which warrants further investigation. This finding, if validated in prospective trials with a larger sample size, could aid in better-individualized treatment for patients and avoid potential side effects of AT. Registration: This study was designed in accordance with PRISMA and registered with PROSPERO (CRD42022311615).

BackgroundRenal cell carcinoma (RCC) is the most common renal malignancy, and may metastasize to different sites in the body via hematogenous and lymphomatous routes. The pancreas is a rare metastatic site of metastatic RCC (mRCC) and isolated pancreatic metastasis of RCC (isPMRCC) is even rarer.ResultsThe present report describes a case of isPMRCC that recurred 16 years after surgery. The patient responded well to the treatment with pancreaticoduodenectomy and systemic therapy, and no recurrence was recorded after 2 years.ConclusionsisPMRCC is a distinct subgroup of RCC with unique clinical characteristics that may be explained by its underlying molecular mechanisms. Surgery and systemic therapy confer survival benefits to patients with isPMRCCs, although the recurrence problem has to be paid attention to.

Abstract Background Esophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis. Methods A total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram’s risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared. Results A better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45–0.68, P

The aim of this study was to compare the clinical safety and efficacy of robotic hepatectomy (RH) versus conventional laparoscopic hepatectomy (LH) for malignancy using meta-analysis. A systematic literature search was performed using PubMed, EMBASE, Medline and the Cochrane Library databases up to September 2020 for studies, which limited to comparative articles of RH or LH for malignant tumors. Stata14.0 was performed in the meta-analysis. Six studies with a total of 1093 patients (345 RH and 748 LH) were eligible for inclusion. Operative time, tumor size, open procedure rate and the proportion of right hepatectomy were found to be significantly different between RH and LH in the pooled analysis (P 0.05). For malignant tumors that require hepatectomy, robotic approaches have demonstrated similar safety and feasibility to laparoscopy, with lower open procedure rate, were suitable for larger tumor size, and have a high right hepatectomy utilization rate. These results still need to be confirmed by multicenter, high-quality randomized controlled studies.

BackgroundMetabolic syndrome (MetS) has been related to increased risks of a variety of cancers. However, the association between MetS and the risk of renal cell cancer (RCC) remains not fully determined. This meta-analysis was conducted to investigate whether MetS is independently associated with the risk of RCC in adults.MethodsRelevant observational studies were obtained by searching PubMed, Embase, Cochrane’s Library, and Web of Science databases. Study characteristics and outcome data were extracted independently by two authors. The random-effect model was used for meta-analysis considering the possible influence of between-study heterogeneity. Predefined subgroup analyses were used to evaluate the possible influences of study characteristics on the outcome.ResultsEight studies involving 10,601,006 participants contributed to the meta-analysis. Results showed that MetS was independently associated with a higher risk of RCC in adult population (risk ratio [RR]: 1.62, 95% confidence interval [CI]: 1.41 to 1.87, p0.05).ConclusionsMetS may be independently associated with RCC in adult population.

Abstract Background Metastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the survival. Some other special method might need to be found out. Methods We reviewed 1011 MACUP patients diagnosed by pathological examination and immunohistochemistry based on the Surveillance, Epidemiology, and End Results (SEER) database during 2010–2016. Kaplan–Meier curves and Cox proportional hazard model were analyzed to compare the survival. Logistic regression models and relevant nomograms were performed to predicting the probability of the primary site which including digestive system, respiratory system, and female breast. The validation and clinical utility of models were measured with relevant statistical approaches. Results About 324 (32.1%), 299 (29.6%), and 203 (20.1%) of MACUP patients were identified as the primary sites of digestive system, respiratory system, and female breast, respectively. Patients derived from digestive system and respiratory system showed poorer survival than these with other sites. Digestive system was significantly associated with liver (Odds ratio =13.21 [95% confidence interval =8.48–21.02]) or lung (2.36 [1.40–3.97]) metastasis, while respiratory system was linked to brain (11.68 [6.68–21.26]) or lymph node (3.39 [2.26–5.13]) metastasis. Patients identified as female breast were prone to occur bone metastasis (5.85 [3.68–9.45]). Logistic regression nomograms were developed to help clinicians intuitively predict the probabilities of tumor site origin with 0.867, 0.824, and 0.753 of the C‐index, respectively. Decision curve analysis and clinical impact curves both revealed the clinical effectiveness. Conclusions We profiled different tumor site origin of MACUP patients and established prediction models. These features might be significant for clinicians to improve the probabilities of predicting the primary sites, and to decide subsequent treatment strategy.

Abstract Second primary malignancy (SPM) ranks the second leading cause of death in patients with head and neck cancer (HNC), while studies exploring the risk factors for SPM are limited. To clarify this, we investigated the relationship between the chemotherapy and SPM using the Surveillance, Epidemiology, and End Results (SEER) database. 11 345 patients initially diagnosed with HNC between 1998 and 2016 were selected from the SEER database. First, these patients were divided into two groups according to chemotherapy or not. With Fine and Gray model, the subdistribution hazard ratio (sHR) of chemotherapy was calculated based on Propensity Score Matching (PSM). Second, the 11 345 cases were randomized into a training set and a validation set. Based on the training set, the different cumulative incidence of SPMs between the patients with and without chemotherapy was estimated respectively in the high‐ and low‐risk group according to the scores derived from a nomogram. Chemotherapy was negatively correlated to the SPMs (sHR: 0.847, 95% CI: 0.733‐0.977, P = .023) by conducting competing risk analysis. With chemotherapy, forest plots showed subgroups of squamous cell carcinoma (SCC, sHR: 0.815, 95% CI: 0.7‐0.948, P = .008), 50‐64 years old (sHR:0.794, 95% CI: 0.655‐0.962, P = .019), male (sHR:0.828, 95% CI: 0.703‐0.974, P = .023), and well/moderate histological grade (sHR:0.828, 95% CI: 0.688‐0.996, P = .045) were negatively correlated to SPMs; the nomogram showed the high‐risk population characterized as SCC, elder age, male, and well/moderate histological grade also tended to have lower incidence of SPMs (sHR: 0.805, 95% CI: 0.669‐0.969, P = .022). Despite HNC patients with characteristics of SCC, increased age, male, and well/moderate histological grade had higher risk of a SPM, they were also more likely to be benefitted from chemotherapy to avoid it.

Abstract Background Lymph nodes metastasis (LNM) and distant metastasis (DM) are important prognostic factors in colorectal cancer (CRC) and determine the following treatment approaches. We aimed to find clinicopathological factors associated with LNM and DM, and analyze the prognosis of CRC patients with T1 stage. Methods A total of 17 516 eligible patients with T1 CRC were retrospectively enrolled in the study based on the Surveillance, Epidemiology, and End Results (SEER) database during 2004‐2016. Logistic regression analysis was performed to identify risk factors for LNM and DM. Unadjusted and adjusted Cox proportional hazard models were used to identify prognostic factors for overall survival. We performed the cumulative incidence function (CIF) to further determine the prognostic role of LNM and DM in colorectal cancer‐specific death (CCSD). LNM, DM, and OS nomogram were constructed based on these models and evaluated by the C‐index and calibration plots for discrimination and accuracy, respectively. The clinical utility of the nomograms was measured by decision curve analyses (DCAs) and subgroups with different risk scores. Results Tumor grade, mucinous adenocarcinoma, and age accounted for the first three largest proportion among the LNM nomogram scores (all, P

BackgroundBreast cancer (BC) has become the most common malignancy worldwide, accounting for 11.7% of newly diagnosed cancer cases last year. Invasive ductal carcinoma (IDC) is the most common pathological type of BC. However, there were few studies to predict distant metastatic sites and overall survival (OS) of IDC patients.MethodsPost-operative IDC patients from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Nomograms were developed to predict the specific distant metastatic sites and OS of IDC patients. The performance of nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of IDC patients with distant metastases.ResultsA total of 171,967 post-operative IDC patients were enrolled in our study. Univariate and multivariate analyses were used to establish the nomograms of significant variables. The AUC of the nomograms for the prediction of liver, lung, bone, and brain metastases was 0.903, 0.877, 0.863, and 0.811, respectively. In addition, the AUC of the nomogram for the prediction of 1-, 3-, and 5-year OS was 0.809, 0.813, 0.787, respectively. Calibration curves and DCA showed good consistency and clinical benefits, respectively.ConclusionsWe constructed new predictive models for liver, lung, brain, bone metastases and 1-, 3-, and 5-year OS in IDC patients. These can help clinicians to individualize the treatment of IDC patients, so that patients can get the more appropriate treatment options.

Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4’-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

Background: Non-cancer causes of death in patients with colorectal cancer (CRC) have not received much attention until now. The purpose of the current study is to investigate the non-cancer causes of death in patients with CRC at different periods of latency.Methods: Eligible patients with CRC were included from the Surveillance, Epidemiology, and End Results (SEER) database, and standardized mortality ratios (SMRs) were calculated using the SEER*Stat software 8.3.8.Results: A total of 475,771 patients with CRC were included, of whom 230,841 patients died during the follow-up period. Within 5 years, CRC was the leading cause of death. Over time, non-cancer causes of death account for an increasing proportion. When followed up for more than 10 years, non-cancer deaths accounted for 71.9% of all deaths worldwide. Cardiovascular diseases were the most common causes of non-cancer deaths, accounting for 15.4% of the total mortality. Patients had a significantly higher risk of death from septicemia within the first year after diagnosis compared with the general population (SMR, 3.39; 95% CI, 3.11–3.69). Within 5–10 years after CRC diagnosis, patients had a significantly higher risk of death from diabetes mellitus (SMR, 1.27; 95% CI, 1.19–1.36). During the course of more than 10 years, patients with CRC had a significantly higher risk of death from atherosclerosis (SMR 1.47; 95% CI, 1.11–1.9).Conclusions: Although CRC has always been the leading cause of death in patients with CRC, non-cancer causes of death should not be ignored. For patients with cancer, we should not only focus on anti-tumor therapies but also pay attention to the occurrence of other risks to prevent and manage them in advance.

Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been widely used for clinical treatment in recent years, which has a better survival benefit. However, not all patients can derive clinical benefit from combination immunotherapy. Therefore, it is necessary to explore the biomarkers of combination immunotherapy.Methods: We retrieved articles from electronic databases including PubMed, EMBASE and Cochrane. The statistical analysis was performed using RevMan software. Progression free survival (PFS), overall survival (OS) and objective response rate (ORR) were the outcome indicators. In the unselect population, we compared combination therapy with other treatments. In addition, we also conducted subgroup analysis on PFS, OS and ORR according to PD-L1 status.Results: Seven studies were included in the analysis for a total of 3,515 cases. In the unselected population, we found that combination therapy has longer PFS, OS, and better ORR than other treatments for cancer patients. The longer PFS was showed in PD-L1 ≥ 5% cases (HR = 0.64, 95% CI: 0.56–0.76; p < 0.001) than PD-L1 ≥ 1% cases (HR = 0.72, 95% CI: 0.66–0.79; p < 0.001), while ORR and OS have not related to the status of PD-L1.Conclusion: This study supported the efficacy of combination therapy with immune checkpoint inhibitors (ICIs), and also showed that PFS in patients with malignant tumors is positively correlated with PD-L1 expression. Due to the limited number of trials included, more high-quality clinical randomized controlled trials should be conducted to confirm the review findings.

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism. Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC. Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated. Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

BackgroundThe incidence of colon cancer in young patients is on the rise, of which adenocarcinoma is the most common pathological type. However, a reliable nomogram for early onset colon adenocarcinoma (EOCA) to predict prognosis is currently lacking. This study aims to develop nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with EOCA.MethodsPatients diagnosed with EOCA from 2010 to 2015 were included and randomly assigned to training set and validation set. Cox regression models were used to evaluate prognosis and identify independent predictive factors, which were then utilized to establish the nomograms for predicting 3- and 5-year OS and CSS. The discrimination and calibration of nomograms were validated using the calibration plots, concordance index, receiver operating characteristics curve, and the decision curve analysis.ResultsA total of 2,348 patients were screened out, with 1,644 categorized into the training set and 704 into the validation set. Multivariate analysis demonstrated that gender, age, tumor size, T stage, M stage, regional node, tumor deposits, lung metastasis and perineural invasion were significantly correlated with OS and CSS. The calibration plots indicated that there was good consistency between the nomogram prediction and actual observation. The C-indices for training set of OS and CSS prediction nomograms were 0.735 (95% CI: 0.708–0.762) and 0.765 (95% CI: 0.739–0.791), respectively, whereas those for validation set were 0.736 (95% CI: 0.696–0.776) and 0.76 (95% CI: 0.722–0.798), respectively. The results of ROC analysis revealed the nomograms showed a good discriminate power. The 3- and 5-year DCA curves displayed superiority over TNM staging system with higher net benefit gains.ConclusionsThe nomograms established could effectively predict 3- and 5-year OS and CSS in EOCA patients, which assisted clinicians to evaluate prognosis more accurately and optimize treatment strategies.

Background: Second primary malignancy (SPM) attracts a growing attention. However, the clinical features of colon cancer (CC) survivors with SPMs are not clear and could help guide clinicians to develop a better surveillance strategy.Methods: We reviewed 56,930 CC survivors treated with colectomy from the Surveillance, Epidemiology, and End Results (SEER) database during 1998–2011. Competing risk models and nomograms were conducted for predicting the risk of occurring SPMs. The clinical utility of the models was measured by decision curve analysis (DCA) using net benefit approaches.Results: Five thousand thirteen (17.1%) of male patients developed SPMs and sites of SPMs included prostate (32.2%), lung and bronchus (11.6%), urinary bladder and kidney (10.8%), colon (10.0%), and melanoma of the skin (3.9%), while 3,592 (13.0%) of female patients occurred SPMs and sites of SPMs involved breast (25.8%), lung and bronchus (13.6%), colon (11.6%), uterus (8.2%), urinary bladder, and kidney (5.6%). Survivors with a second carcinoma of lung and bronchus showed the worst prognosis. Older age increased the risk of SPMs in both male (Subdistribution hazard ratio =2.85 [95% confidence interval = 2.53–3.21]) and female (1.80 [1.59–2.04]) survivors, especially for the risk of a second prostate carcinoma in male (5.33 [4.03–7.03]). Compared with white race, black male survivors remained at higher risk to develop the second prostate carcinoma (1.98 [1.74–2.26]). Competing-risk nomograms for CC survivors were established to help clinicians predict the probabilities of overall SPMs and prostate carcinoma. Validation of nomograms showed good discrimination and accuracy, and DCAs revealed the clinical effectiveness.Conclusions: We profiled the clinical characteristics of a large population-based cohort of CC survivors with SPMs. These features may improve future follow-up management, especially for the surveillance of second prostate cancer in men and second breast cancer in women.