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Background. Breast cancer is an important cause of cancer‐related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple‐negative breast cancer (TNBC) patients with brain metastasis (BM). Methods. We retrospectively reviewed a cohort of patients diagnosed with TNBC at the "Instituto Nacional de Enfermedades Neoplasicas" (period 2000–2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan–Meier method, and prognostic factors were identified with the Cox regression analysis. Results. Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I–III patients with a median age of 45 years (range:21–78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea‐vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30‐0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15–2.48, and p = 0.007). Conclusion. Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM. [ABSTRACT FROM AUTHOR]

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed. [ABSTRACT FROM AUTHOR]

Background. In this research, programmed cell death protein 1 (PD-1) inhibitors, including toripalimab, sintilimab, and camrelizumab, were evaluated for the treatment of non-small-cell lung cancer (NSCLC). Methods. This retrospective research was conducted on patients with locally advanced and advanced NSCLC receiving various PD-1 inhibitors including toripalimab, sintilimab, and camrelizumab, between April 2019 and March 2023. Results. In total, the ORR and DCR of 167 patients included in this research were 40.72% (68/167) and 92.81% (155/167), respectively, while the statistical median PFS was 13.90 months (95% CI, 10.657–17.143), and the median OS was 30.10 months (95% CI, 22.142–38.058). Multifactorial analysis showed that two factors, line of treatment and history of smoking, had a statistically significant benefit on the patients' PFS benefit P < 0.05 , while the factor that had a statistically significant benefit on the patients' OS benefit was the presence of serious adverse events (AEs) during treatment. 83.83% and 24.55% of patients experienced any grade AEs and grade 3–5 AEs, respectively. Conclusions. In our research, therapy lines and history of smoking had influence on the efficacy of immunotherapy, while serious AEs during treatment were prognostic factors that affected the OS benefit of immunotherapy. Patients we studied did not die from treatment-related causes, and PD-1 inhibitors did not cause additional toxicity in elderly patients. However, further investigations and multicenter studies are needed. [ABSTRACT FROM AUTHOR]

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001 ; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001 ; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P = 0.02 ; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P = 0.04 ; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P = 0.02 ; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P = 0.01 ; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion. Young age seems to positively influence patients' survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636. [ABSTRACT FROM AUTHOR]

Purpose. Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods. Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results. Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion. G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma. [ABSTRACT FROM AUTHOR]

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses. [ABSTRACT FROM AUTHOR]

Background. Female cancers cover common breast cancers, relatively common endometrial, ovarian, and cervical cancers and rare vulvar cancer. Survival in these cancers is known to be relatively good compared to all cancers but long-term studies for these cancers are rare, and to fill the gap, here, we generate survival data through 50 years. Materials and Methods. We applied generalized additive models to data from the NORDCAN database and analyzed 1- and 5-year relative survival for these cancers in Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) over half a century (1971–2020). Conditional 5/1-year survival for patients who survived the 1st year after diagnosis and annual survival changes was also estimated. Results. In 2016–20, 5-year survival was best for breast cancer reaching 92.3% (in SE), followed by endometrial cancer at 86.1% (SE) and cervical cancer at 75.6% (NO). Improvement in 5-year survival over the 50 years was the largest for ovarian cancer (20% units), finally reaching 52.9% (SE). For vulvar cancer, the final survival was between 70 and 73%. The best 5-year survival rate in 2016–20 was recorded for SE in breast, endometrial, and ovarian cancers; NO showed the highest rate for cervical and DK for vulvar cancers. DK had the lowest survival for breast and ovarian cancers, and FI, for the other cancers. Conclusions. The overall survival development appeared to consist of continuous improvements, most likely because of novel treatment and imaging techniques as well as overall organization of patient care. The large survival improvement for ovarian cancer was probably achieved by a surgical focus on tumors spread in the peritoneal cavity. For cervical and vulvar cancers, the high early mortality requires attention and could be helped by raising increasing public awareness of early symptoms in these cancers and developing pathways for fast initiation of treatment. [ABSTRACT FROM AUTHOR]

Objective. Metformin is a common antidiabetic drug that has been reported to serve as an anticancer agent in combination with other therapies. But the effect of the addition of metformin on the survival of non-small cell lung cancer (NSCLC) patients undergoing chemotherapy is still controversial. We conducted this systematic review to evaluate the survival effect of metformin added to chemotherapy in NSCLC patients. Methods. Electronic literature search was performed in the PubMed, Embase, and Web of Science databases from their inception up to April 2023. The study region, study design, histological subtype of the NSCLC, tumor stage, treatment strategy, sample size, follow-up duration, diabetes status, and HR of OS or PFS of the included studies were extracted. The quality was assessed through Cochrane collaboration's tool for RCT and the Newcastle–Ottawa scale (NOS) for observational studies, respectively. Results and conclusions. Eleven studies with a total of 4606 patients were finally included. Five RCTs showed a high risk of bias due to the open-label nature while six retrospective studies were of high quality. Two studies of NSCLC patients with diabetes reported significant benefits in overall survival from metformin addition, while one study of patients without diabetes reported a negative effect on the survival of metformin addition. The survival impact of metformin added to chemotherapy on unresectable NSCLC patients remains inconclusive. The survival benefit might be more prominent in patients with diabetes, awaiting further evidence. [ABSTRACT FROM AUTHOR]

Purpose. Paclitaxel and carboplatin are novel anticancer drugs that have emerged in recent years, while there is still a lack of clinical consensus on these two drugs. The study conducted a meta-analysis and systematic review to analyze the efficacy and safety of paclitaxel and carboplatin for platinum-sensitive ovarian cancer. Methods. A systematic search was carried out in three databases of the Cochrane Library, Embase, and PubMed from the inception of each database to March 2021, and defined the progression-free survival and overall survival as the primary outcomes. Data analysis was performed using STATA 15.1. Results. Altogether, five randomized controlled trials (RCTs) were included in the meta-analysis, involving 2,740 patients, including 1317 in the CD (carboplatin doxorubicin) group and 1423 in the CP (carboplatin plus paclitaxel) group. It was found that pooled OS demonstrated no significant differences between the CD group and CP group (HR = 1.02, 95% CI = 0.89–1.18, P = 0.340), and the differences were not statistically significant in progression-free survival (HR = 0.84, 95% CI = 0.71–0.99, P = 0.140), thrombocytopenia (OR = 0.23, 95% CI = 0.09−0.58, P = 0.775), and grade II alopecia between the two groups (OR = 9.41, 95% CI = 6.57–13.47, P = 0.215). Conclusion. Current evidence suggests that paclitaxel and carboplatin do not produce more satisfactory results with respect to overall survival and reduction of side effects in treating platinum-sensitive ovarian cancer, and further studies are needed. [ABSTRACT FROM AUTHOR]

Background. To investigate the value of SMO and GLI1 genes in the hedgehog pathway in malignant mesothelioma specimens. Further study on the expression and prognosis of SMO and GLI1 in malignant mesothelioma tissues and the relationship between the two and the molecular mechanisms of mesothelioma immunity and to further investigate the prognostic value of mesothelioma expression. Materials and Methods. Immunohistochemistry and RT-qPCR were applied to detect the expression of SMO and GLI1 proteins and mRNA in biopsy specimens and plasma cavity effusion specimens from malignant mesothelioma (n = 130) and benign mesothelial tissues (n = 50) and to analyze the clinicopathological significance and survival risk factors of SMO and GLI1 protein expression in mesothelioma. The mechanisms of mesothelioma cell expression and immune cell infiltration were investigated using bioinformatics methods. Results. SMO and GLI1 in mesothelioma tissues detected high concordance between the diagnostic results of mesothelioma biopsy specimens and plasma cavity effusion specimens. The expression levels of SMO and GLI1 protein and mRNA in mesothelioma tissues were higher than those in benign mesothelioma tissues. The expression levels of SMO and GLI1 protein were correlated with the age, site, and asbestos exposure history of patients with mesothelioma. The expression levels of SMO and GLI1 protein were correlated with the expressions of ki67 and p53 (P < 0.05). SMO and GLI1 gene expression levels were negatively correlated with good prognosis in mesothelioma patients (P < 0.05). Cox proportional risk model indicated that protein expressions of invasion, lymph node metastasis, distant metastasis, staging, and genes were independent prognostic factors of mesothelioma. The GEPIA database showed the overall survival rate and the disease-free survival rate of mesothelioma patients in the high SMO and GLI1 expression groups; the UALCAN database analysis showed lower SMO expression levels in mesothelioma patients with more pronounced TP53 mutations (P = 0.001); GLI1 gene expression levels were strongly correlated with lymph node metastasis in mesothelioma patients (P = 0.009). Timer database analysis showed that the mechanism of immune cell infiltration was closely related to SMO and GLI1 expression. The degree of immune cell infiltration was strongly correlated with the prognosis of mesothelioma patients (P < 0.05). Conclusion. The expression levels of both SMO and GLI1 proteins were higher than those of normal mesothelial tissues, and the mRNA expression levels also changed in the same direction. SMO and GLI1 gene expressions in mesothelioma were negatively correlated with age, site of occurrence, and history of asbestos exposure. Positive expression of SMO and GLI1 was negatively correlated with patient survival. The Cox proportional risk model showed that gender, history of asbestos exposure, site of occurrence, SMO, and GLI1 were independent prognostic factors for mesothelioma. The mechanism of immune cell infiltration in mesothelioma is closely related to the gene expression of both and the survival prognosis of mesothelioma patients. [ABSTRACT FROM AUTHOR]

The prognosis of patients with colorectal cancer (CRC) is affected by invasion and metastasis. Leucyl-tRNA synthetase (LARS) was shown to be related to the growth and migration of lung cancer cells. Dickkopf 4 (DKK4) is known as a Wnt/β-catenin pathway inhibitor, and its upregulation was reported in several cancers. However, the clinical significance of LARS and DKK4 in human CRC has not been clearly defined. We investigated the expression of LARS and DKK4 by immunohistochemical staining in tissue microarrays from 642 primary CRC patients and analyzed the relationship between their expression and the clinicopathological characteristics of CRC patients. LARS and DKK4 expressions were not related to gender, age at surgery, histologic grade, size, tumor location, tumor invasion, or metastasis, but LARS expression was significantly correlated with TNM stage, N stage, and lymph node metastasis. DKK4 expression was inversely related to the TNM stage and N stage. Survival analysis demonstrated that the OS and DFS in the LARS high expression group were not different compared to the LARS low expression group. OS and DFS in the DKK4 high expression group were significantly higher than in the DKK4 low expression group. In addition, OS and DFS in the group with the combination of the LARS high/DKK4 low expression were significantly lower than in the LARS high/DKK4 high expression group. The low expression of DKK4 alone can be used as a predictor of relapse in CRC patients. In addition, DKK4 low expression in the case of LARS high expression can be used as a poor prognostic factor in CRC patients. Thus, our findings suggest that DKK4 alone or in combination with LARS at diagnosis may be a useful prognostic factor for CRC. [ABSTRACT FROM AUTHOR]

Background. Hypoxia is regarded as a key factor in promoting the occurrence and development of ovarian cancer. In ovarian cancer, hypoxia promotes cell proliferation, epithelial to mesenchymal transformation, invasion, and metastasis. Long non-coding RNAs (lncRNAs) are extensively involved in the regulation of many cellular mechanisms, i.e., gene expression, cell growth, and cell cycle. Materials and Methods. In our study, a hypoxia-related lncRNA prediction model was established by applying LASSO-penalized Cox regression analysis in public databases. Patients with ovarian cancer were divided into two groups based on the median risk score. The survival rate was analyzed in the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and the mechanisms were investigated. Results. Through the prognostic analysis of DElncRNAs (differentially expressed long non-coding RNAs), a total of 5 lncRNAs were found to be closely associated with OS (overall survival) in ovarian cancer patients. It was evaluated through Kaplan–Meier analysis that low-risk patients can live longer than high-risk patients (TCGA: p = 1.302 e − 04 ; ICGC: 1.501e − 03). The distribution of risk scores and OS status revealed that higher risk score will lead to lower OS. It was evaluated that low-risk group had higher immune score (p = 0.0064) and lower stromal score (p = 0.00023). Conclusion. It was concluded that a hypoxia-related lncRNA model can be used to predict the prognosis of ovarian cancer. Our designed model is more accurate in terms of age, grade, and stage when predicting the overall survival of the patients of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background. Metformin is one of the most common drugs for type 2 diabetes mellitus (T2DM) treatment. In addition, metformin intends to have a positive effect on the prognosis of several cancers. However, the therapeutic effect of metformin on gastric cancer (GC) remains controversial. This study explores and updates the therapeutic effect of metformin in GC patients with T2DM. Methods. We searched through PubMed, Embase, Web of Science, and the Cochrane Library for relevant articles by July 2022. The relationship between metformin therapy and the prognosis of GC patients with T2DM was evaluated based on the hazard ratio (HR) at a 95% confidence interval (95% CI). Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were the primary outcomes analyzed. Results. Seven retrospective cohort studies with a combined 2,858 patients met the inclusion criteria. OS and CSS were reported in six studies, and PFS was reported in four studies. Pooled results showed that, compared to the nonmetformin group, the prolonged OS (HR = 0.72, p = 0.001), CSS (HR = 0.81, p = 0.001), and PFS (HR = 0.70, p = 0.008) of the experimental group may be associated with the exposure to metformin. Conclusion. Metformin may have a beneficial effect on the prognosis of GC patients with T2DM. [ABSTRACT FROM AUTHOR]

Background. There is controversy regarding whether patients with single hepatocellular carcinoma (HCC) should be offered radiofrequency ablation (RFA) as a first-line treatment option. Thus, this study compared overall survival after surgical resection (SR) and RFA for single HCC. Methods. The Surveillance, Epidemiology, and End Results (SEER) database was used for this retrospective study. The study included 30- to 84-year-old patients diagnosed with HCC from 2000 to 2018. Selection bias was reduced via propensity score matching (PSM). The study compared the overall survival (OS) and cancer-specific survival (CSS) of patients with single HCC who were treated with SR and RFA. Results. Before and after PSM, the median OS and median CSS were significantly longer in the SR group than in the RFA group (p < 0.05). In the subgroup analysis, the median OS and median CSS for male and female patients with male and female patients with tumor sizes <3, 3–5, and>5 cm, age at diagnosis between 60 and 84 years, and grades I–IV tumors were longer than in the SR group than in the RFA group (p < 0.05). Similar results were reported for patients who received chemotherapy (p < 0.05). Univariate and multivariate analyses revealed that compared with RFA, SR was an independent favorable factor for OS and CSS (p < 0.05) before and after PSM. Conclusion. Patients with SR who had a single HCC showed higher OS and CSS compared with patients who received RFA. Hence, SR should be used as a first-line treatment in cases of single HCC. [ABSTRACT FROM AUTHOR]

Background. Stomach adenocarcinoma (STAD) has an extremely high fatality rate worldwide, and survival after metastasis is extremely poor. Cytokine-like protein 1 (CYTL1) has prognostic significance in various tumors. We aimed to explore the impact and underlying molecular mechanisms of CYTL1 in STAD through bioinformatics analysis. Methods. We used R software to analyze CYTL1 expression in STAD samples (n = 375) and normal samples (n = 32) in The Cancer Genome Atlas database. Kaplan–Meier analysis was used to verify the relationship between CYTL1 expression and overall survival (OS) and disease-specific survival (DSS) based on the clinical characteristics and subgroups of patients with STAD. Furthermore, univariate and multivariate Cox regression analyses were used to verify the outcome variables of OS and DSS in patients with STAD. Receiver operating characteristic curves were used to test the predictive power of CYTL1. The biological functions and signaling pathways of CYTL1 were determined using gene set enrichment analysis (GSEA), and the immune infiltration patterns of CYTL1 and correlation of immune-related markers were analyzed using single-sample GSEA (ssGSEA) and an estimate algorithm. Results. In our research, low CYTL1 expression (tumor vs. normal) was noted in patients with STAD. High CYTL1 expression was detrimental to OS and DSS and had good diagnostic performance (AUC = 0.731). In the subtype analysis of STAD, T3 and T4 stages, N0 and N1 stages, M0 stage, gender (female), and age (≤65 years) showed different performances between OS and DSS. Univariate and multivariate Cox analyses identified CYTL1 as an independent factor, and logistic regression analysis indicated that CYTL1 was associated with M stage (OR = 3.406) and sex (OR = 1.535). GSEA of the differential genes of CYTL1 showed the possible involvement of immunity. ssGSEA and estimation algorithms were used to further evaluate whether immune cells were closely related to CYTL1 expression, and many markers of immune cells also had statistical significance with the expression of CYTL1. Conclusion. CYTL1 may, thus, act as an independent prognostic factor for STAD and regulate STAD progression by affecting the immune microenvironment. [ABSTRACT FROM AUTHOR]

Objective. Multiple myeloma (MM) represents a malignant tumor with abnormal proliferation of plasma cells. The current study sought to investigate the changes in serum lncRNA MIR17HG (long noncoding RNA miR-17-92a-1 cluster host gene) levels in MM patients and its values in assessing the accuracy of MM diagnosis and predicting diagnosis. Methods. First, 108MM patients and 85 healthy controls were enrolled as the study subjects. The serum levels of MIR17HG in all subjects were determined by RT-qPCR. MM patients were clinically staged according to the Durie-Salmon (DS) and international staging system (ISS), and the levels of serum MIR17HG were compared among patients at different stages. The correlation of serum MIR17H level with serum creatinine (Scr), lactate dehydrogenase (LDH), and albumin (ALB) was analyzed using the Pearson method. The accuracy of the serum MIR17HG level in identifying MM was evaluated using receiver operating characteristic curves. The progression-free survival (PFS) and overall survival (OS) curves of MM patients were plotted using the Kaplan–Meier method. Results. Serum MIR17HG levels were up-regulated in MM patients and elevated with the development of DS and ISS stages. The serum MIR17HG was positively correlated with Scr and LDH and negatively correlated with ALB in MM patients. Serum MIR17HG level >1.485 could evaluate the accuracy of identifying MM. The PFS and OS were significantly shortened in MM patients with elevated MIR17HG levels. Conclusion. Our findings collectively indicate that the serum MIR17HG can aid the evaluation of accurate MM identification, and a high serum MIR17HG level can predict poor prognosis of patients with MM. [ABSTRACT FROM AUTHOR]

Objective. Radiofrequency coblation (RFC) is a relatively new method that has opened up new perspectives in treating oropharyngeal squamous cell carcinoma (OPSCC). Our study was designed to explore the feasibility and effectiveness of RFC-assisted transoral surgery (RFC-TOS) for primary OPSCC. Methods. Sixty-nine cases of OPSCC from February 2005 to November 2020 were retrospectively analyzed, including 31 in the RFC-TOS group and 38 in the open surgery group. No difference was observed in demographic and oncological characteristics. Results. The significance between the RFC-TOS group and the open surgery group was proved in intraoperative bleeding volume (34.10 ± 10.10 ml vs. 193.68 ± 21.00 ml, P < 0.001), durations of surgery (79.58 ± 8.45 min vs. 217.87 ± 17.65 min, P < 0.001), time to resume oral feeding (1.64 ± 0.41 d vs. 11.58 ± 1.41 d, P < 0.001), duration of hospitalization (7.84 ± 0.66 d vs. 15.66 ± 1.62 d, P < 0.001), and the total costs (22846.22 ± 1821.55¥ vs. 41792.24 ± 4150.86¥, P < 0.001). The rates of 5-year overall survival (OS), 5-yeardisease-specific survival (DSS), and 5-year local control rate (LC) were 69.1%, 71.7%, and 75.7%, respectively, in the RFC-TOS group and 71.0%, 73.4%, and 73.7% in the open surgery group (P > 0.05). Conclusions. RFC-TOS is a feasible alternative transoral approach for OPSCC. The reported perioperative and oncologic outcomes are satisfactory. [ABSTRACT FROM AUTHOR]

Background. The SMYD family comprises a group of genes encoding lysine methyltransferases, which are closely related to tumorigenesis. However, a systematic understanding of their role in gastric cancer (GC) is lacking. Methods. Using databases and tools such as the Cancer Genome Atlas, Human Protein Atlas, Kaplan–Meier Plotter, Gene Expression Profiling Interactive Analysis, and Metascape, we comprehensively analyzed differences in SMYD expression and its prognostic value as well as the association of SMYDs with immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). We conducted functional enrichment analysis and explored a competing endogenous RNA mechanism regulating SMYD mRNA and protein levels in patients with GC. Results. In GC, the expression of SMYD2/3/4/5 mRNA was significantly upregulated, as opposed to that of SMYD1 mRNA, which was significantly downregulated. The protein levels of SMYDs were consistent with mRNA levels. SMYD1/2/4/5 was negatively correlated with overall survival; SMYD1/2/3/5 was negatively correlated with progression-free survival. Our SMYD-based signature and nomogram model may be useful for inferring the prognosis of GC. All SMYDs were closely associated with the infiltration of six immune cell types: uncharacterized, CD8+T, CD4+T, macrophage, endothelial, and B cells. TMB was significantly negatively correlated with SMYD1 expression, while a significant positive correlation was observed with SMYD2/5. Furthermore, MSI was significantly positively correlated with SMYD2/5 expression. Long non-coding RNAs, such as chr22-38_28785274-29006793.1, XLOC_002309, and CTD-2008N3.1, were suggested to regulate SMYD expression by sponging multiple microRNAs. Conclusion. SMYDs are differentially expressed in GC and are thus potential prognostic markers. SMYD expression is closely related to immune infiltration, TMB, and MSI, all of which are closely related to the response to targeted immune therapy. [ABSTRACT FROM AUTHOR]

Objective. This study was conducted to compare the efficacy of standard therapy (radiotherapy/RT/CT) with that of antiepidermal growth factor receptor (anti-EGFR) monoclonal antibody (NPC) therapy in patients with advanced nasopharyngeal cancer. Methods. A meta-analysis was performed to meet the objective of this study. The English databases PubMed, Cochrane Library, and Web of Science were searched. The literature review compared anti-EGFR-targeted therapy with conventional therapy practices. The main outcome measure was overall survival (OS). Secondary goals were progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and adverse events (grade 3). Results. The database search resulted in 11 studies, with a total of 4219 participants. It was found that combining an anti-EGFR regimen with conventional therapy did not enhance OS (hazard ratio HR = 1.18 ; 95 % confidence interval CI = 0.51 – 2.40 ; p = 0.70) or PFS appreciably (HR = 0.95 ; 95 % CI = 0.51 – 1.48 ; p = 0.88) in patients with nasopharyngeal carcinoma. While LRRFS increased considerably (HR = 0.70 ; 95 % CI = 0.67 – 1.00 ; p = 0.01), the combined regimen did not improve DMFS (HR = 0.86 ; 95 % CI = 0.61 – 1.12 ; p = 0.36). Treatment-related adverse events included haematological toxicity (RR = 0.2 ; 95 % CI = 0.08 – 0.45 ; p = 0.01), cutaneous reactions (RR = 7.05 ; 95 % CI = 2.15 – 23.09 ; p = 0.01), and mucositis (RR = 1.96 ; 95 % CI = 1.58 – 2.09 ; p = 0.01). Conclusions. Individuals who have nasopharyngeal cancer do not have an increased chance of surviving until a local recurrence of their disease if they get normal therapy in addition to an anti-EGFR regimen. However, this combination does not enhance overall survival. On the other hand, this factor adds to an increase in the number of adverse effects. [ABSTRACT FROM AUTHOR]

Cancer has been a significant threat to human health and well-being, posing the biggest obstacle in the history of human sickness. The high death rate in cancer patients is primarily due to the complexity of the disease and the wide range of clinical outcomes. Increasing the accuracy of the prediction is equally crucial as predicting the survival rate of cancer patients, which has become a key issue of cancer research. Many models have been suggested at the moment. However, most of them simply use single genetic data or clinical data to construct prediction models for cancer survival. There is a lot of emphasis in present survival studies on determining whether or not a patient will survive five years. The personal issue of how long a lung cancer patient will survive remains unanswered. The proposed technique Naive Bayes and SSA is estimating the overall survival time with lung cancer. Two machine learning challenges are derived from a single customized query. To begin with, determining whether a patient will survive for more than five years is a simple binary question. The second step is to develop a five-year survival model using regression analysis. When asked to forecast how long a lung cancer patient would survive within five years, the mean absolute error (MAE) of this technique's predictions is accurate within a month. Several biomarker genes have been associated with lung cancers. The accuracy, recall, and precision achieved from this algorithm are 98.78%, 98.4%, and 98.6%, respectively. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficiency and safety of sentinel lymph node biopsy (SLNB) in patients with breast cancer with complete response to neoadjuvant chemotherapy (NAC). Methods. Ninety-two consecutive (T1-4 and N1-2) patients with breast cancer who had pathologic and/or clinical and radiologic axillary lymph node involvement were included. All patients received NAC. Patients with a clinical and radiologic complete response in the axilla after NAC underwent SLNB. Pathologic complete response (ypCR) was defined as the absence of residual invasive and in situ cancer, and near-complete response (ypNCR) represented in situ and/or ≤ 1 mm residual tumor in the breast and/or presence of malignant cell clusters (≤0.2 mm) and/or micrometastases (≤2.0 mm) in the axillary lymph nodes (ALN) (ypTis/T1mi, ypN0i+/pN1mi). Results. The mean age of the 92 patients was 49.6 ± 10.3 years and the mean follow-up was 34.0 ± 17.8 months. With respect to breast tumors, 23 (25.0%) patients had complete and 14 (15.2%) had a near-complete response to NAC. Complete response in ALN was obtained in 39 (42.4%) patients and near-complete in six (6.5%) patients. The overall survival of the 33 patients who achieved ypCR and ypNCR was 100% and the remaining 59 patients with partial or no response to NAC was 83.1% at a mean follow-up of 34 months (p = 0.063). Conclusions. In this study, no event developed in cases with ypCR and ypNCR in the breast and axilla. The persistence of the same results in long-termfollow-ups may enable the use of ypNCR as a positive prognostic marker in addition to ypCR. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Programmed cell death protein‐1 (PD‐1) inhibitors synergize apatinib for anti‐tumour effect by regulating tumour microenvironment, vascular endothelial growth factor, hypoxia condition, immune response, etc. This study aimed to investigate the treatment efficacy and safety of camrelizumab (PD‐1 inhibitor) plus apatinib as third‐line or above therapy in metastatic colorectal cancer (mCRC) patients. Methods: Totally, 64 unresectable mCRC patients receiving camrelizumab plus apatinib (N = 31) and apatinib (N = 33) were retrospectively enrolled. Results: Disease control rate (80.6% vs. 57.6%) (P = 0.047) was elevated in camrelizumab plus apatinib group compared to apatinib group; however, objective response rate (22.6% vs. 6.1%) (P = 0.078) only showed an increasing trend but did not achieve statistical significance. Besides, the median (95% confidence interval [CI]) progressive‐free survival (PFS) and overall survival (OS) were 6.9 (3.7–10.1) and 11.5 (7.7–15.3) months in camrelizumab plus apatinib group; meanwhile, the median (95% CI) PFS and OS were 3.6 (1.7–5.5) and 6.7 (5.0–8.4) months in the apatinib group. Additionally, PFS (P = 0.017) and OS (P = 0.006) were prolonged in camrelizumab plus apatinib group compared with apatinib group, which was confirmed by further multivariate Cox's proportional hazards regression analysis (hazard ratio [HR] = 0.340, P < 0.001 for PFS; HR = 0.271, P < 0.001 for OS). The incidence of total, grade 1–2, and grade 3–4 adverse events did not differ between groups (all P > 0.05). Conclusion: Camrelizumab (PD‐1 inhibitor) plus apatinib achieves a better treatment efficacy than apatinib as third‐line or above therapy with a good safety profile in mCRC patients. [ABSTRACT FROM AUTHOR]

What is Known and Objective: Solute Carrier (SLC) transporters are known mediators of drug disposition that facilitate the influx of substrates and various chemotherapeutic agents into cells. Polymorphisms in the SLC19A1, SLCO1B1, and SLCO1B3 gene influence the prognosis in the cancer patients, but little is known about their role in lung cancer in Asians. So, the current study aims to investigate the polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 genes in Northern Indian lung cancer patients. Methods: Patients with lung cancer who had a confirmed histology and cytology diagnosis were enrolled in the study. SLC polymorphisms were assessed by Polymerase Chain Reaction‐Restriction Fragment Length Polymorphism (PCR‐RFLP) for variations in SLC19A1 (G80A), SLCO1B1 (A388G, T521C), and SLCO1B3 (A1683‐5676G). Results and Discussion: Our results showed that mutant genotype for SLC19A1 G80A polymorphism had higher median survival time (MST) compared to wild genotype. ADCC patients with mutant genotype showed better survival compared to wild genotype for SLC19A1 G80A. SCLC patients G80A polymorphism showed increased survival in patients with mutant genotype (p = 0.04). In SLCO1B3, A1683‐5676G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p = 0.006). In T521C variant, patients with carrier genotype had reduced chances of developing anaemia (p = 0.04). Patients with SLC19A1 and SLCO1B3 variants showed lower incidence of thrombocytopenia and nephrotoxicity. What is New and Conclusion: Our findings imply that Solute Carrier gene polymorphisms modulate the overall survival in lung cancer patients undergoing platin‐based doublet chemotherapy, also these polymorphisms have a modifying impact on the associated adverse events/toxicity. [ABSTRACT FROM AUTHOR]

Background: Microbiotas affected the prognosis of cancer patients by regulating programmed death ligand-1 (PD-L1) expression. However, the relationship between gastric fungi and PD-L1 expression is still unclear in gastric cancer (GC). We aimed at exploring the association of gastric fungi with PD-L1 expression and overall survival in GC.Methods: A total of 61 GC patients were divided into the two groups based on the PD-L1 combined positive scores (CPS). Fungal profiling was performed by internal transcribed spacer rDNA sequencing, and the survival analyses were performed by Kaplan-Meier curves.Results: We observed a taxonomic difference of fungi between the PD-L1-High (CPS ≥ 10) and PD-L1-Low group (CPS < 10) by principal coordinates analysis (PCoA) (P = 0.014 for Bray-Curtis and P = 0.042 for Jaccard). Malassezia had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group (P = 0.045). Malassezia globosa elevated significantly in the PD-L1-High group. GC patients with PD-L1 low expression and low abundance of Malassezia globosa had a longer overall survival (OS) than others (P = 0.047). Malassezia globosa was associated with PD-L1 expression (Odds Ratio = 3.509, 95% Confidence Interval: 1.056-11.656, P = 0.040). Malassezia globosa was associated with the tumor size (P = 0.031) and PD-L1 status (P = 0.024). GC patients with a high abundance of Malassezia globosa had shorter OS than others (P = 0.028). Malassezia globosa was an independent factor (Hazard Ratio = 3.080, 95% Confidence Interval: 1.140-8.323, P = 0.027) for OS after adjusting for tumor stage. Malassezia globosa was figured out to be associated with- fatty acid and lipid biosynthesis and degradation via LIPASYN pathway. Conclusions. Malassezia globosa was identified as a PD-L1 expression-associated gastric fungus and associated with OS of GC patients, which calls for more studies to further explore its potential in PD-L1/PD-1 targeted immunotherapy. [ABSTRACT FROM AUTHOR]

What is known and objective: Chemotherapy is the primary pharmacotherapy of triple‐negative breast cancer (TNBC). But the benefit of adjuvant chemotherapy in the oldest old TNBC patients remains controversial. Hence, we designed this population based observational study in order to assess the survival benefit of adjuvant chemotherapy in oldest old TNBC patients with early‐stage disease. Methods: TNBC patients aged 80 years and older that with stage I to III invasive disease were identified in the surveillance, epidemiology, and end results cancer database from 2010 to 2016. Results and discussion: Of 1611 patients enrolled, 1356 (84.17%) did not receive chemotherapy. Age, race, histology, grade, T stage, N stage, and radiation were found to be strong predictors of chemotherapy recipient by multivariate logistic regression analysis. Chemotherapy significantly prolonged overall survival (OS) (HR, 0.62, 95% CI: 0.49–0.79, p < 0.001), but did not significantly reduce breast cancer specific death (BCSD) (HR, 0.92, 95% CI: 0.63–1.35, p = 0.675). These results were further confirmed by propensity score matching analysis. Chemotherapy was associated with better OS in the subgroup of patients aged 80–84 years old (HR, 0.54, 95% CI: 0.40–0.74, p < 0.001), T2‐4 stage disease (HR, 0.58, 95% CI: 0.44–0.76, p < 0.001), or grade 3–4 disease (HR, 0.54, 95% CI: 0.41–0.71, p < 0.001). However, chemotherapy did not reduce the cumulative incidence of BCSD in any subgroup. What is new and conclusion: Chemotherapy should be considered for TNBC patients aged 80–84 years old, T2‐4 disease, or grade 3–4 disease. [ABSTRACT FROM AUTHOR]

Aim. Salivary gland adenoid cystic carcinoma (SACC) is the second highest incidence of malignant salivary gland tumor. The purpose of this study was to establish nomograms combined with SACC patients based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods. Patients with SACC were included in the SEER ∗ Stat Database from 2004 to 2016. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to filter potential prognostic clinical variables. Multivariate analysis from the Cox proportional hazards model was performed to determine the independent prognostic factors on overall survival (OS) and disease-specific survival (DSS), applied to develop nomograms. The Schönfeld residual test verified the proportional hazard assumption. The discrimination and consistency of nomograms was assessed and validated according to concordance index (C -index), receiver operating characteristic (ROC) curves, and calibration curves using an internal 1,000 times bootstrap resampling. The nomogram's net clinical benefit was assessed through decision curve analysis (DCA). Results. A total of 658 patients with SACC were included. Age, T stage, N stage, M stage, histologic grade, and surgery were independent prognostic factors for OS and DSS. Based on these independent prognostic factors, nomograms were developed to predict 3-, 5-, and 10-year OS and DSS. In the validation of 1,000 times bootstrap resampling, the C -index and ROC curves had good discriminatory ability. The calibration curves indicated excellent consistency between the predicted and actual survival results in the nomograms. The DCA curves demonstrated that the nomograms had good clinical benefit and were superior to the TNM stage and other variables. Conclusions. Two nomograms developed in this study precisely predicted the 3-, 5-, and 10-year OS and DSS rates of patients with SACC in accordance with independent prognostic factors, and their clinical value is better than TNM staging, providing a prognostic reference for other SACC patients. [ABSTRACT FROM AUTHOR]

Objective. Clear cell sarcoma of the kidney (CCSK) is a lethal pediatric renal malignancy with poor prognosis. A prognostic nomogram needs to be established for overall survival (OS) prediction of patients with CCSK. Methods. Eligible 2588 CCSK patients (age 0–19) diagnosed between 2000 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomized into training and validation cohorts (7 : 3). Independent prognostic factors were identified by univariate and multifactorial Cox regression analyses and used to construct a nomogram. Receiver operating characteristics (ROC) analysis, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram. Moreover, a risk classification system was established based on the risk scores of the nomogram. Results. Cox analyses revealed that age, combined stage, and origin were most significant prognostic factors. Based on these prognostic factors, a nomogram was established for predicting 3- and 5-year OS of patients with CCSK. The area under the ROC curve (AUC) of 3- and 5-year OS was 0.733 and 0.728 in the training cohort, corresponding to 0.69 and 0.674 in the validation cohort. The C-index of calibration curves in the training and validation cohorts was 0.724 and 0.686. DCAs indicated the clinical utility of this nomogram. A risk classification system stratified CCSK patients into three different risk cohorts. The OS time of low-, intermediate-, and high-risk patients was 76, 68, and 65 months in the training cohort, corresponding to 69.5, 66, and 72 months in the validation cohort. Conclusion. A nomogram-based risk classification system has high accuracy for the prognostic prediction of CCSK. [ABSTRACT FROM AUTHOR]

Background. Necroptosis is a type of programmed cell death mode and it serves an important role in the tumorigenesis and tumor metastasis. The purpose of this study is to develop a prognostic model based on necroptosis-related genes and nomogram for predicting the overall survival of patients with lung cancer. Method. Differentially expressed necroptosis-related genes (NRDs) between lung cancer and normal samples were identified. Univariate and LASSO regression analyses were performed to establish a risk score (RS) model, followed by validation within TCGA and GSE37745. The correlation between RS model and tumor microenvironment, mutation status, or drug susceptibility was analyzed. By combining clinical factors, nomogram was developed to predict 1-, 3-, and 5-year survival probability of an individual. The biological function involved by different risk groups was conducted by GSEA. Results. A RS model containing six NRDs (FLNC, PLK1, ID1, MYO1C, SERTAD1, and LEF1) was constructed, and patients were divieded into low-risk (LR) and high-risk (HR) groups. Patients in HR group were associated with shorter survival time than those in the LR group; this model had better prognostic performance. Nomogram based on necroptosis score, T stage, and stage had been confirmed to predict survival of patients. The number of resting NK cells and M0 macrophages was higher in HR group. In addition, higher tumor mutational burden and drug sensitivity were observed in the HR group. Patients in HR group were involved in p53 signaling pathway and cell cycle. Conclusion. This study constructed a robust six-NRDs signature and established a prognostic nomogram for survival prediction of lung cancer. [ABSTRACT FROM AUTHOR]

Objective. To investigate into the clinical factors associated with posttreatment recurrence and death patterns in patients with advanced esophageal cancer. Methods. Clinical information of patients with recurrence/metastasis and death after radical resection of esophageal cancer at our hospital between January 1, 2005, and December 31, 2015, were retrospectively collected and followed up. Postoperative recurrence-free survival time, postrelapse survival time, and overall survival time were compared among the metabolic-associated, organ failure-associated, and anastomotic recurrence-associated mortality groups. Results. Five hundred and ninety-five qualified patients were retrieved, including 456 males and 139 females, with an average age of 58 ± 7.56 years. There were 57 cases of TNM-1 stage, 131 cases of TNM-2 stage, 365 cases of TNM-3 stage, and 42 cases of TNM-4 stage. There were 547 cases of squamous cell cancer and 48 cases of nonsquamous cell cancer. There were significant differences in age (p < 0.01), tumor location (p < 0.01), and lymph node metastasis (p = 0.04), recurrence type (p < 0.01) by one-way ANOVA, and recurrence-free survival (p = 0.02) and postrecurrence survival (p < 0.01) by Kaplan-Meier survival curve analysis among the three main death causes. Conclusions. Age, tumor location, and lymph node metastasis were significantly different among metabolic-associated, organ failure-associated, and anastomotic recurrence-associated mortality of recurrent EC patients. [ABSTRACT FROM AUTHOR]

Background. FOLFIRINOX chemotherapy is the current Dutch standard of care for locally advanced (LAPC) and metastatic pancreatic cancer (PDAC) patients with good performance status. The objective of this study was to evaluate real-world response rates and survival in advanced PDAC and to assess conditional survival after FOLFIRINOX. Methods. A multicenter, retrospective cohort study was conducted in four hospitals in the Netherlands. Consecutive patients with LAPC or metastatic PDAC, treated with FOLFIRINOX, were included. Results. Between 2012 and 2018, 284 patients were included: n = 136 with LAPC and n = 148 with metastatic PDAC. Objective response rates were similar in both the groups: 14.0% in LAPC and 18.2% in metastatic patients. The disease control rate was higher in LAPC patients (77.2%) compared to metastatic PDAC (51.4%, P < 0.001). Median overall survival (OS) in LAPC patients was 12.7 months (95% CI 11.4–14.1 months). Their 2-year survival probability increased from 14% to 26% one year after the completion of FOLFIRINOX. Median OS in metastatic PDAC patients was 8.1 months (95% CI 6.5–9.6 months); 2-year survival probability increased from 10% to 29% after one year. Discussion. Our study provides real-world estimates of response rates, survival, and conditional survival in patients with advanced PDAC treated with FOLFIRINOX. These results are useful for patient counseling and clinical decision making. [ABSTRACT FROM AUTHOR]

Objective: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health‐related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. Methods: Patients with mucosal HNSCC were prospectively included. HRQOL and 2‐year overall survival were analysed using linear mixed‐model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. Results: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL‐scores (indicating better HRQOL) during 2‐year follow‐up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score—β: 2.62, 95% CI: 0.57–4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65–15.76, p = 0.005) and stage‐IV tumours (HR: 12.37, 95% CI: 2.81–54.39, p = 0.001). Delay was not associated with worse overall survival. Conclusion: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL‐scores or decreased overall survival during 2‐year follow‐up. [ABSTRACT FROM AUTHOR]

Noncoding ribonucleic acids (ncRNAs) are involved in various functions in the formation and progression of different tumors. However, the association between N6-methyladenosine-related ncRNAs (m6A-related ncRNAs) and gastric cancer (GC) prognosis remains elusive. As such, this research was aimed at identifying m6A-related ncRNAs (lncRNAs and miRNAs) in GC and developing prognostic models of relevant m6A-related ncRNAs and identifying potential biomarkers regulated by m6A. In this study, the m6A2Target database, Starbase database, and The Cancer Genome Atlas (TCGA) were used to screen m6A-related ncRNAs. And then, we performed integrated bioinformatics analyses to determine prognosis-associated ncRNAs and to develop the m6A-related ncRNA prognostic signature (m6A-NPS) for GC patients. Finally, five m6A-related ncRNAs (including lnc-ARHGAP12, lnc-HYPM-1, lnc-WDR7-11, LINC02266, and lnc-PRIM2-7) were identified to establish m6A-NPS. The predictive power of m6A-NPS was better in the receiver operating characteristic (ROC) curve analysis of the training set (area under the curve (AUC), >0.6). The m6A-NPS could be utilized to classify patients into high- and low-risk cohorts, and the Kaplan-Meier analysis indicated that participants in the high-risk cohort had a poorer prognosis. The entire TCGA dataset substantiated the predictive value of m6A-NPS. Significant differences in TCGA molecular GC subtypes were observed between high- and low-risk cohorts. The ROC curve analysis indicated that m6A-NPS had better predictive power than other clinical characteristics of GC prognosis. Uni- and multivariate regression analyses indicated m6A-NPS as an independent prognostic factor. Furthermore, the m6A status between the low-risk cohort and high-risk cohort was significantly different. Differential genes between them were enriched in multiple tumor-associated signaling pathways. In summary, five m6A-related ncRNA signatures that could forecast the overall survival of patients with GC were identified. [ABSTRACT FROM AUTHOR]

Purpose. To analyze the effects of dosimetric parameters and clinical characteristics on overall survival (OS) by machine learning algorithms. Methods and Materials. 128 patients with cervical cancer were treated with definitive pelvic radiotherapy with or without chemotherapy followed by image-guided brachytherapy. The elastic-net models with integrating DVH parameters and baseline clinical factors, only DVH parameters and only baseline clinical factors were constructed in 5-folds cross-validations for 100 iteration bootstrapping, and then were compared using concordance index (C-index) criteria. Finally, the selected important factors were used to build multivariable Cox-pH models for OS and also shown in nomograms for clinical usage. Results. The median OS occurred was 25.78 months with 25 (19.53%) deaths. The elastic-net models integrating clinical and DVH factors had the best prediction performances (C-index 0.76 in the train set and C-index 0.74 in the test set). Three important factors were selected, including baseline hemoglobin level as the protective factor, primary tumor volume (GTV_P) volume, and body V5 as the risk factors. The final multivariable Cox-pH models were constructed using these important factors and had prediction performance (C-index: 0.78, 95%CI: 0.73–0.81). Conclusions. This is the first attempt to establish elastic-net models to study the contributions of DVH parameters for predicting OS in patients with cervical cancer. These results can facilitate individualized tailoring of radiation treatment in cervical cancer patients. [ABSTRACT FROM AUTHOR]

Objective. To identify and validate effective clinical predictors for the long-term prognosis of patients with cervical cancer. Methods. Cervical cancer patients were retrieved from the TCGA database, and patients' clinical data were collected and analyzed for the predictive value of long-term prognosis. In the other branch of the study, patients with cervical cancer and admitted to our hospital between January 1, 2016, and December 31, 2016, were retrieved and followed up for prognosis analysis. Results. In the database patient cohort of our study, 607 cases with cervical cancer were analyzed. Aneuploidy score (p = 0.012), Buffa hypoxia score (p = 0.013), histologic grade (p = 0.01), fraction genome altered >0.4 (p < 0.001), weight > 60 kg (p < 0.001), height > 160 cm (p = 0.047), BMI <18.5 (p = 0.023), Winter hypoxia score (p = 0.002), and adjuvant postoperative radiotherapy were good predictors for disease-free survival (DFS), while aneuploidy score (p = 0.001), MSI sensor score > 0.5 (p = 0.035), person neoplasm status (p < 0.001), race (p = 0.006), Ragnum hypoxia score (p = 0.012), weight (p < 0.001), height (p < 0.001), and BMI < 18.5 (p = 0.04) were good predictors for overall survival (OS). In the admitted patient cohort, age over 60 years old at the time of diagnosis was the only clinical factor influencing the long-term DFS (p = 0.004). TNM stage above III (p = 0.004), body weight > 70 kg (p < 0.001), and complicated with other cancer (p < 0.001) were clinical factor influencing the long-term OS. Conclusions. Clinical factors, especially common to both cohorts, could be used to show the long-term prognosis of cervical cancer. [ABSTRACT FROM AUTHOR]

Background. Solitary plasmacytoma of bone (SPB) is an isolated plasmacytoma of bone origin, most commonly seen in the elderly, with a poor prognosis. So far, there is no precise nomogram to predict the overall survival (OS) of elderly patients with SPB. Our goal is to construct and validate a nomogram for elderly patients with SPB. Methods. This study collected all elderly patients with SPB in the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2018, and the variables included were age, sex, race, marital status, primary site, grade, stage, surgery, chemotherapy, and radiotherapy. Independent prognostic factors were identified using univariate and multivariate Cox analysis. The nomogram was constructed to predict 1-, 2-, and 3-year OS of elderly patients with SPB. The receiver-operating characteristic (ROC) and the calibration curves were used to differentiate and calibrate the nomogram. The clinical validity of the nomogram was evaluated by decision curve analysis (DCA). The total OS scores of all elderly SPB patients were calculated and divided into two risk subgroups for comparison. Results. A total of 1837 patients diagnosed with SPB were screened from the SEER database, with a final inclusion of 1180 patients (age ≥ 60 years). Age, radiotherapy, and marital status were significantly correlated with OS. These characteristics were further incorporated into the creation of the nomogram for predicting 1-, 2-, and 3-year OS of elderly patients with SPB. For this predictive model, the area under the ROC curves, calibration curves, and DCA have good performance in terms of differentiation, consistency, and validity, respectively. In addition, patients in the high-risk group (≥96) had a worse prognosis than those in the low-risk group (<96). Conclusion. We constructed a nomogram and a risk classification system that could provide an intuitive and effective tool for clinicians to better predict the OS of elderly SPB patients. [ABSTRACT FROM AUTHOR]

Objective. To determine the efficacy of clinical characteristics in the prediction of prognosis in patients with ovarian cancer. Methods. Clinical data were collected from 3 datasets from TCGA database, including 1680 cases of ovarian serous cystadenocarcinoma, and were analyzed. Patients with ovarian cancer admitted to our hospital in 2016 were retrieved and followed up for prognosis analysis. Results. From the datasets, for patients > 75 years old at the time of diagnosis, histologic grade and mutation count were good predictors for disease-free survival, while for patients > 50 years old at the time of diagnosis, histologic grade, race, fraction genome altered, and mutation count were good predictors for overall survival. In the patients (n = 38) retrieved from our hospital, the longest dimension of lesion (cm) and body weight at admission were good predictors for overall survival. Conclusions. Those clinical factors, together with the two predictive equations, could be used to comprehensively predict the long-term prognosis of patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective. To explore a novel Immune-associated gene signature for overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). Methods. Expression profiles of genes and corresponding clinical materials of OSCC patients were obtained through the TCGA database. With a LASSO Cox regression model, a multigene signature was established to predict the OS of OSCC patients. Some molecular experiments including RNA interference, MTT, and Transwell assay were applied to verify the role of the risk gene FGF9 in OSCC. Results. 43 immune-related prognostic DEGs were identified in OSCC. A 17-gene signature was established to assign the patients to either a high-risk group (HG) or a low-risk group (LG). The HG presented a shorter OS than the LG (P < 0.05). According to multivariate Cox regression analyses, the risk score was considered an independent factor for OS prediction (training set: HR = 3.485, 95% CI = 2.037–5.961, P < 0.001 ; test set: HR = 4.531, 95% CI = 2.120–9.682, P < 0.001). ROC curve-based analysis revealed the signature's ability for prediction. According to functional analysis, the immune cell expression and immune function of the HG were significantly inhibited. After knocking down the high-risk gene FGF9, the migration, proliferation, and invasion capabilities of OSCC cells HSC6 were significantly suppressed (P < 0.05). Conclusion. A novel immune-associated gene signature was identified for predicting the prognosis of OSCC. These risk genes show great potential as targets for OSCC treatment. [ABSTRACT FROM AUTHOR]

The role of 5-methylcytosine-related long noncoding RNAs (m5C-lncRNAs) in bladder cancer (BLCA) remains unclear. Here, we aim to study the prognostic value, gene expression characteristics, and correlation between the m5C-lncRNA risk model and the tumor microenvironment, immune infiltration, and tumor mutations in BLCA. After collecting BLCA patient RNA sequence transcriptome data, clinical information and mutation data from the Cancer Genome Atlas (TCGA) database, 17 m5C-related lncRNAs independently correlated with OS were obtained by Lasso and multivariate Cox regression analysis, and a risk model was constructed. Univariate Cox, multivariate Cox regression analysis, and the C-index curve proved that the risk model was a significant independent prognostic indicator for patients with BLCA. ESTIMATE and CIBERSORT indicated that the higher the number of immune cells and stromal cells in TME, the higher the prognostic risk. We found that in the low-risk group, the expression levels of immune cells that predicted a good prognosis were higher, including plasma cells, regulatory T cells, and CD 8 T cells. There is a negative correlation between TMB and risk score. The TMB of the low-risk group is significantly higher than that of the high-risk group. In conclusion, the m5C-related risk model is crucial to predict the prognosis of patients with BLCA. [ABSTRACT FROM AUTHOR]

Background. Recent studies have shown that nicotinamide adenosine dinucleotide phosphate oxidase 4 (NOX4) is related to cancer development, proliferation, invasion, epithelial-to-mesenchymal transition, and metastasis. The prognostic value of NOX4 expression although has been reported in various cancers, it remains unclear as several studies have reported conflicting results. Therefore, the purpose of this study was to systematically investigate the prognostic value of NOX4 expression in cancer patients. Method. Appropriate studies were collected by searching the PubMed, EMBASE, and Cochrane library databases, and the prognostic value of NOX4 expression in cancer patients was assessed through a meta-analysis. Results. Nine eligible studies involving 2675 cancer patients were included in this meta-analysis. We found that NOX4 expression is related to prognosis in cancer patients. In particular, high expression of NOX4 was significantly associated with overall survival in patients with gastrointestinal cancer (hazard ratio [HR]: 1.83, 95% confidence interval [CI]: 1.39–2.42, p < 0.001). Conclusion. NOX4 expression is significantly correlated with overall survival in patients with gastrointestinal cancer, indicating that it could be a potential prognostic marker. [ABSTRACT FROM AUTHOR]

Background. Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. Methods. We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. Results. High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P = 0.03), presence of perineural invasion (P = 0.02), presence of vascular invasion (P = 0.05), distant metastases (P < 0.001), advanced TNM stage (P = 0.001), the occurrence of relapse (P = 0.04), and the high number of deceased cases (P = 0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (P = 0.005) and harbor more KRAS mutations (P = 0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (P = 0.007). In all stages, high tumor budding was correlated with poorer overall survival (P = 0.04) and decreased relapse-free survival with a difference close to significance ((P = 0.09). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions. Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective. Earlier research has illustrated prognostic significance of pathologic complete response (pCR) in neoadjuvant therapy (NAT) for breast cancer, whereas correlation between treatment after achieving pCR and survival improvement remains underexplored. We attempted to measure the relation between pCR achieved after NAT and breast cancer recurrence or patient's survival. Methods. We searched PubMed, EMBASE, Web of Science, and The Cochrane Library databases to find relevant articles from their inception to November 2020. According to eligibility criteria, studies were selected and basic data were extracted. The primary endpoint was the correlation between pCR achieved after NAT and event-free survival (EFS) or overall survival (OS). The results were obtained by directly extracting specific information from the literature or estimating individual data by survival curves on DigitizeIt software, presented with HR and 95% CI. All data were processed on Stata 14.0 software. Results. Among 4338 articles, there were 25 eligible articles involving 8767 patients. The EFS of patients achieved pCR after NAT improved obviously (HR = 0.27 ; 95% CI, 0.24-0.31), especially in triple negative (HR = 0.17 ; 95% CI, 0.12-0.24) and HER2 positive (HR = 0.24 ; 95% CI, 0.20-0.30) breast cancer patients. As such, pCR after NAT was implicated in significantly increased OS (HR = 0.32 ; 95% CI, 0.27–0.37). Conclusion. Achieving pCR after NAT was notably related to the improvement of EFS and OS, especially for patients with triple-negative and HER2-positive breast cancer. pCR can be a surrogate indicator for outcome of breast cancer patients after NAT, as well as a predictor of treatment efficacy after NAT. Besides, well-designed studies are still warranted for confirmation. [ABSTRACT FROM AUTHOR]